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To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.

DOI： 10.18926/AMO/65978

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Here we describe our experience with a rare case of methotrexate (MTX)-associated lymphoproliferative disorder (LPD) initially diagnosed as follicular lymphoma (FL) and then in relapse as classic Hodgkin lymphoma (CHL). A 66-year-old man was admitted to the hospital with fever and abdominal and lower back pain after a transient remission of MTX-associated FL (MTX-FL) following MTX withdrawal. Computed tomography (CT) showed para-aortic lymphadenopathy, which was compatible with one of the previous FL lesions. We considered a relapse of FL and started bendamustine and rituximab. Although his initial symptoms and para-aortic lymphadenopathy regressed after the first course, he began to have dorsal pain, and multiple osteolytic lesions were detected on CT. We biopsied a Th4 vertebra osteolytic lesion, and the results indicated MTX-associated CHL (MTX-CHL). We successfully treated advanced MTX-CHL with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD). This case suggests the importance of repeat biopsy of a new lesion arising after resolution of previously affected sites in MTX-LPD and the effectiveness of A+AVD in treating advanced MTX-CHL.

DOI： 10.3960/jslrt.23016

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The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry.

DOI： 10.18926/AMO/65740

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An ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas. The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation. To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells.

DOI： 10.1016/j.heliyon.2023.e18241

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Recent studies have advanced our understanding of the pathophysiology of autoimmune gastritis, particularly its molecular aspects. The most noteworthy recent advancement lies in the identification of several candidate genes implicated in the pathogenesis of pernicious anemia through genome-wide association studies. These genes include PTPN22, PNPT1, HLA-DQB1, and IL2RA. Recent studies have also directed attention towards other genes such as ATP4A, ATP4B, AIRE, SLC26A7, SLC26A9, and BACH2 polymorphism. In-depth investigations have been conducted on lymphocytes and cytokines, including T helper 17 cells, interleukin (IL)-17A, IL-17E, IL-17F, IL-21, IL-19, tumor necrosis factor-α, IL-15, transforming growth factor-β1, IL-13, and diminished levels of IL-27. Animal studies have explored the involvement of roseolovirus and H. pylori in relation to the onset of the disease and the process of carcinogenesis, respectively. Recent studies have comprehensively examined the involvement of autoantibodies, serum pepsinogen, and esophagogastroduodenoscopy in the diagnosis of autoimmune gastritis. The current focus lies on individuals demonstrating atypical presentations of the disease, including those diagnosed in childhood, those yielding negative results for autoantibodies, and those lacking the typical endoscopic characteristics of mucosal atrophy. Here, we discuss the recent developments in this field, focusing on genetic predisposition, epigenetic modifications, lymphocytes, cytokines, oxidative stress, infectious agents, proteins, microRNAs, autoantibodies, serum pepsinogen, gastrin, esophagogastroduodenoscopy and microscopic findings, and the risk of gastric neoplasm.

DOI： 10.3390/cimb45070334

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Primary cardiac sarcomas are rare diseases with very poor prognoses. In this report, we present a case of coronary artery intimal sarcoma in a patient who survived for a long time after diagnosis. A 57-year-old female underwent percutaneous coronary intervention of the right coronary artery due to acute myocardial infarction caused by thrombotic occlusion and was diagnosed as having coronary artery intimal sarcoma. She underwent surgical resection and coronary artery bypass surgery of the artery, cryothermy coagulation, and postoperative adjuvant chemotherapy for 1 year. After 3 years, focal recurrence was detected in the caudal region of the left ventricular inferior wall. Radiotherapy was performed. The tumor shrank significantly after radiotherapy. Four years later, there was no significant abnormal uptake on positron-emission tomography/computed tomography. At 7 years after diagnosis, when this case report was submitted, the patient was alive and her performance had maintained a good status. Intimal sarcoma occurring in a coronary artery is extremely rare. The efficacy of treatments for cardiac intimal sarcoma, which include surgical resection, chemotherapy and radiotherapy, has been reported to be limited. To the best of our knowledge, this is the first report of a case of coronary artery intimal sarcoma with long-term survival after comprehensive therapies including surgical resection and radiotherapy.

DOI： 10.1536/ihj.22-578

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Language：Japanese   Publisher：金原出版(株)  

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Herein, we present a case of collagenous colitis in a patient who underwent chemotherapy for gastric cancer, comprising five cycles of S-1 plus oxaliplatin and trastuzumab, followed by five cycles of paclitaxel and ramucirumab and seven cycles of nivolumab. The subsequent initiation of trastuzumab deruxtecan chemotherapy led to the development of grade 3 diarrhea after the second cycle of treatment. Collagenous colitis was diagnosed via colonoscopy and biopsy. The patient's diarrhea improved following the cessation of lansoprazole. This case highlights the importance of considering collagenous colitis as a differential diagnosis, in addition to chemotherapy-induced colitis and immune-related adverse event (irAE) colitis, in patients with similar clinical presentations.

DOI： 10.7759/cureus.39466

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BACKGROUND: An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). METHODS: To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. RESULTS: The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21-7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06-5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07-5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. CONCLUSIONS: We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy.

DOI： 10.21037/jgo-22-870

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Patients with primary intestinal follicular lymphoma are often followed-up without a specific treatment, and this approach is called the "watch-and-wait approach." However, the long-term outcomes of this patient group have not been sufficiently investigated. We enrolled patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression. Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II1). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%. In conclusion, an indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients.

DOI： 10.1038/s41598-023-32736-9

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We report a 63-year-old male, Helicobacter pylori-negative patient with mucosa-associated lymphoid tissue (MALT) lymphoma of the second part of the duodenum that regressed after antibiotic treatment. Esophagogastroduodenoscopy (EGD) showed flat elevation with shallow depression on the contralateral side of the ampulla of Vater. The lesion was limited to the duodenal second part. The patient had a history of Helicobacter pylori positivity, with successful eradication at 41 years of age. Twelve months after vonoprazan (VPZ)-based antibiotic treatment, the duodenal lesion had obviously regressed, and the pathological diagnosis was complete histological response (ChR). This case suggests that certain bacteria may promote the development of duodenal MALT lymphoma.

DOI： 10.7759/cureus.37194

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The presentation, subtype, and macroscopic images of lymphoma vary depending on the site of the tumor within the gastrointestinal tract. We searched PubMed for publications between January 1, 2012 and October 10, 2022, and retrieved 130 articles relating to duodenal lymphoma. A further 22 articles were added based on the manual screening of relevant articles, yielding 152 articles for full-text review. The most predominant primary duodenal lymphoma was follicular lymphoma. In this review, we provide an update of the diagnosis and man-agement of representative lymphoma subtypes occurring in the duodenum: Follicular lymphoma, diffuse large B-cell lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, mantle cell lymphoma, and T-cell lymphomas.

DOI： 10.3748/wjg.v29.i12.1852

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Herein, we report two patients with autoimmune gastritis who had undergone multiple esophagogastroduodenoscopy procedures for 17 and 9 years, respectively, before their diagnosis. Instead, they had been diagnosed with and treated for Helicobacter pylori-associated gastritis. The correct diagnosis was made when scatterings of tiny whitish protrusions in the gastric mucosa were detected on esophagogastroduodenoscopy. Our findings suggest that scattered tiny whitish bumps may be a clue to the diagnosis of autoimmune gastritis.

DOI： 10.18926/AMO/64365

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Endometrial carcinoma with hepatoid differentiation is rare and <20 reported cases have been reported as endometrial hepatoid carcinoma (EHC). We present a case of EHC associated with serous carcinoma in a 76-yr-old Japanese woman. The hepatoid component showed trabecular, pseudoglandular, and diffuse proliferation of hepatoid cells. The hepatoid cells were positive for α-fetoprotein, Hep-Per-1, glypican 3, and HNF-1β, weakly and focally positive for SALL4, and negative for PAX8. Both of the serous and hepatoid components showed overexpression of p53. The serum α-fetoprotein on postoperative day 5 was 3691 ng/mL. The postoperative course has remained uneventful for 4 yr. These findings suggested that EHC developed from serous carcinoma by acquiring hepatocytic features and losing Müllerian features. Both serous and hepatoid components showed p53 overexpression, suggesting they share a TP53 mutation as a common primary driver.

DOI： 10.1097/PGP.0000000000000852

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Introduction Gastric cancer is divided into four subtypes by their molecular features linked with genetic alterations, e.g., Epstein-Barr virus (EBV), microsatellite instability-high (MSI-high), chromosomal instability (CIN), and genomically stable (GS), called as TCGA classification. In this study, we tried to clarify the epigenetic features of the four GC subtypes according to aberrant methylation status in 23 loci. Methods A total of 98 gastric cancers and their normal gastric mucosa samples were included in this study. We divided gastric cancers into TCGA subtypes which were determined in line with MSI-high, EBV, CIN, to GS by their molecular features. The 13 loci of polymorphic microsatellite sequences were used to determine loss of heterogeneity (LOH) for the detection of CIN. The MSI status was determined by three mononucleotide repeat markers. Infection of EBV was determined by recovering EBV BNRF1 sequence from genomic DNA collected from gastric cancers. Methylation status of 23 loci was investigated by the combined bisulfite restriction analysis (COBRA). Status of other findings, e.g., KRAS mutations, HER2 expression status and infection of helicobacter pylori were confirmed. Results Gastric cancers were divided into MSI (13%), EBV (7%), CIN (53%), and GS (27%). By histological classification, poorly differentiated adenocarcinoma (por) was more in tumors categorized in MSI-high, and GS and signet-ring cell carcinoma (sig) was more in GS. Among the 23 loci investigated their methylation status, 18 loci were significantly hypermethylated in caner tissues. A unsupervised clustering divided gastric cancers into two clusters, and revealed that most GS tumors clustered together in a cluster that exhibited lower methylation levels, distinct from the other subtypes. The inter-variable clustering revealed that a cluster contained the three loci (SFRP2-region 1/2 and APC) belonging to the Wnt signal cascade (Wnt-associated loci). The mean methylation score of Wnt-associated loci was the lowest in GS tumors (MSI-high: 2.7 [95% confidence interval (CI), 2.3-2.9]; EBV:2.1[1.2-3.1]; CIN: 2.4 [2.2-2.7]; GS: 1.3 [0.8-0.7]). In contrast, the mean methylation score of the other 15 loci was significantly higher in MSI-high, while that in GS was as same as that in EBV or CIN (MSI- high: 10.4 [8.3-12.4]; EBV:5.7 [1.7-9.7]; CIN: 4.4 [3.6-5.1]; GS: 3.4 [2.2-4.6]). Additionally, the lower methylation score of Wnt-associated loci was observed only in sig tumors. Conclusions GS subtype tumors have the potential to possess distinct signatures in DNA hypomethylation profiles in Wnt signaling pathway, especially in signet-ring cell carcinoma.

DOI： 10.1159/000527098

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A 41-year-old woman showed a palpable mass at the superonasal orbital edge on the right side. Magnetic resonance imaging demonstrated a lobulated fluid-containing tubular mass which extended anteriorly to posteriorly along the medial orbital wall, nasal to the eyeball. She was followed once a year for 8 years until the age of 49 years when she decided to undergo surgical resection because of the enlarged mass. The lobulated large mass was resected and the pathology showed sparsely distributed spindle cells, positive for CD34, in alcian blue-positive mucous substances, indicative of myxoma. Postoperative magnetic resonance imaging showed residual lobulated tubular mass along the optic nerve on the medial side and superior to the eyeball. The residual orbital mass showed stable structure with more evident connection with the ethmoid sinus lesion, suggestive of the ethmoid origin, in 12 years until the age of 61 years. In the review of 20 patients with orbital myxomas in the literature, in addition to this case, roughly classified locations in the orbit were retrobulbar in 8 patients, on the lateral side of the orbit in 4, on the superior side in 6, on the medial side in 1 (this patient), and in the orbit with no specific description in 2. In pathological examinations, immunohistochemistry was not done in 8 patients, done but all negative in 2, and positive in 11 patients: nerve sheath myxoma was diagnosed in 3 patients based on positive S100 staining. Orbital myxoma is rare but considered in differential diagnosis of orbital masses.

DOI： 10.1177/23247096231201013

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A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.

DOI： 10.1177/23247096231185483

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BACKGROUND: Cancer-associated fibroblasts (CAFs) reportedly enhance the progression of gastrointestinal surgery; however, the role of CAFs in ampullary carcinomas remains poorly examined. This study aimed to investigate the effect of CAFs on the survival of patients with ampullary carcinoma. MATERIALS AND METHODS: A retrospective analysis of 67 patients who underwent pancreatoduodenectomy between January 2000 and December 2021 was performed. CAFs were defined as spindle-shaped cells that expressed α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). The impact of CAFs on survival, including recurrence-free (RFS) and disease-specific survival (DSS), as well as prognostic factors associated with survival, was analyzed. RESULTS: The high-α-SMA group had significantly worse 5-year RFS (47.6% vs. 82.2%, p = 0.003) and 5-year DSS (67.5% vs. 93.3%, p = 0.01) than the low-α-SMA group. RFS (p = 0.04) and DSS (p = 0.02) in the high-FAP group were significantly worse than those in the low-FAP group. Multivariable analyses found that high α-SMA expression was an independent predictor of RFS [hazard ratio (HR): 3.68; 95% confidence intervals (CI): 1.21-12.4; p = 0.02] and DSS (HR: 8.54; 95% CI: 1.21-170; p = 0.03). CONCLUSIONS: CAFs, particularly α-SMA, can be useful predictors of survival in patients undergoing radical resection for ampullary carcinomas.

DOI： 10.3389/fonc.2023.1072106

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We report a patient with sarcoidosis who developed diffuse large B-cell lymphoma. A 71-year-old woman with persistent cough was diagnosed pathologically with sarcoidosis by resection of the right upper lung lobe with a nodule after an unsuccessful attempt of transbronchial needle aspiration for mediastinal lymphadenopathy. She was referred for an eye examination and found to have spotty retinal degeneration on the lower fundi of both eyes, together with residual macular edema and vitreous opacity in the left eye. At 76 years, she underwent cataract surgery and vitrectomy to gain a visual acuity of 0.6 in the left eye. At 77 years, she developed a cough and fever, and showed leukopenia and thrombocytopenia. Computed tomography showed multiple small nodular lesions in both lungs, and bilateral hilar, mediastinal, and hepatic lymphadenopathy. Fluorodeoxyglucose positron emission tomography demonstrated high uptake in the liver, spleen, pancreatic head, and lymph nodes. Bone marrow biopsy was intact, but liver biopsy revealed anomalous large lymphoid cells in the sinusoids which were positive for CD20 and showed a high Ki-67 index, leading to the diagnosis of diffuse large B-cell lymphoma. Chemotherapy with 8 courses of THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with rituximab, followed by intrathecal injection of methotrexate, cytarabine, and dexamethasone, resulted in complete remission. She maintained complete remission for 10 years until 88 years old at present. The literature review found 30 patients, including this case, who developed lymphoma in the course of sarcoidosis. A novel pathological diagnosis is required in the setting of acute symptomatic changes and novel lesions on imaging in patients with sarcoidosis.

DOI： 10.3960/jslrt.22015

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It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases). We analyzed the CG/RLH and MALT lymphoma groups. The median percentage of IRTA1-positive cells was 0% (range 0%-90.6%) in the CG/RLH group and 43.5% (range 0%-97.6%) in the MALT lymphoma group (p < 0.0001). The median percentage of MNDA-positive cells was 32.4% (range 0%-97.6%) in the CG/RLH group and 55.1% (range 0%-97.6%) in the MALT lymphoma group (p = 0.0044). These results indicate that immunohistochemistry for IRTA1 and MNDA can help differentiate gastric MALT lymphoma from CG/RLH.

DOI： 10.3960/jslrt.22021

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We report two cases of multiple white plaques in the esophagus that emerged after the administration of immune checkpoint inhibitors. Both patients developed enterocolitis as immune-related adverse events associated with immune checkpoint inhibitors. Esophagogastroduodenoscopy revealed duodenal involvement and multiple white plaques in the esophagus. A biopsy of the esophagus showed predominant CD3+ lymphocyte infiltration, suggesting that esophageal mucosal alterations were associated with immune-related adverse events. In addition, histopathology showed keratinized stratified squamous epithelium in the first case while increased inflammatory cell infiltration in the intraepithelial and subepithelial layers was observed in the second case. These data suggest a different pathogenesis of the multiple esophageal white plaques between the two cases. Although further investigation is needed to elucidate the significance of these observations, recognition of the esophageal plaques may be important for prompt diagnosis of immune-related adverse events when associated with immune checkpoint inhibitors.

DOI： 10.7759/cureus.32710

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Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10-10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.

DOI： 10.1371/journal.pone.0273749

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The composition of lymphocytes in the gastric mucosa following the eradication of Helicobacter pylori (H. pylori) in patients with and without gastric cancer has not been compared. This study performed a single spot analysis of gastric mucosal lymphocytes after H. pylori eradication in patients with (n = 13) and without (n = 20) gastric cancer. Our comprehensive analysis of lymphocyte composition in the gastric mucosa revealed that: i) the proportion of CD8+/CD3+ cells was relatively higher in the peri-tumor mucosa than in the background mucosa; ii) the proportion of CCR4+/CD3+ cells was higher, and the ratio of CD62L+/CD3+CD4+ cells was relatively lower in the gastric mucosa of cancer patients than in non-cancer patients; and iii) the proportion of CD45RA-CD62L+/CD3+CD4+ cells, namely, the central memory CD4+ T-cell fraction, was lower in the gastric mucosa of cancer patients than in non-cancer patients. Although the exact mechanism of the altered proportions of CCR4+/CD3+ and central memory CD4+ cells in the gastric mucosa of patients with cancer is unknown, focusing on lymphocytes in the gastric mucosa might help improve our understanding of gastric cancer development after H. pylori eradication.

DOI： 10.7759/cureus.31713

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Patients with familial adenomatous polyposis (FAP) are at increased risk of developing gastric neoplasms. However, endoscopic findings have not been sufficiently investigated. We investigated the phenotypic expression of gastric adenoma (low-grade dysplasia) and gastric cancer (high-grade dysplasia or carcinoma) in patients with FAP and clarified their relationships to endoscopic findings. Of 29 patients with FAP who underwent esophagogastroduodenoscopy between 2005 and 2020, 11 (38%) had histologically confirmed gastric neoplasms, including 23 lesions of gastric adenoma and 9 lesions of gastric cancer. The gastric neoplasms were classified into 3 phenotypes (gastric, mixed, or intestinal type) according to the immunostaining results and evaluated for location (U or M region: upper or middle third of the stomach or L region: lower third of the stomach), color (same as the background mucosa, whitish, or reddish), macroscopic type (elevated, flat, or depressed), background mucosal atrophy (present or absent), fundic gland polyps in the surrounding mucosa (present or absent), and morphologic changes in tumor size. Elevated whitish gastric adenomas were further subdivided by macroscopic type (flat elevated, protruded, or elevated with a central depression) and color (milky- or pinkish-white). The gastric adenomas included gastric (11/23, 48%), mixed (4/23, 17%), and intestinal (8/23, 35%) phenotypes. In contrast, no lesions of gastric cancers showed a gastric phenotype (0/9, 0%), while 5 (56%) and 4 (44%) lesions were intestinal and mixed phenotypes, respectively. Gastric cancers were significantly more likely than gastric adenomas to present as reddish depressed lesions with gastric atrophy. All gastric-type adenomas occurred in non-atrophic mucosa, in mucosa with fundic gland polyps in the periphery, in the U or M region, and as flat elevated or protruded lesions with a milky-white color. Half of the lesions increased in size. Meanwhile, the typical endoscopic features of intestinal-type adenomas included occurrence in the L region and elevated pinkish-white lesions with central depression. None of the intestinal-type adenomas increased in size during the observation period. We believe that these endoscopic features will be useful for the prompt diagnosis and appropriate management of gastric neoplasms in patients with FAP.

DOI： 10.1097/MD.0000000000030997

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Diagnostic utility of fluorescence microscopy for lanthanum phosphate deposition in the gastrointestinal mucosa has not been reported previously. In this study, we comparatively assessed the light, electron, and fluorescence microscopy features of gastroduodenal lanthanum phosphate deposition in 10 patients with deposits in the stomach and 5 patients with deposits in the duodenum. During light microscopy, lanthanum deposits were observed as dark-brown, needle-shaped, or crystalloid structures and pale red amorphous materials. During electron microscopy, the deposited material appeared as bright aggregates. Fluorescence microscopy also revealed lanthanum deposits as bright areas under green, red, and blue filters. The deposits were more easily recognizable on electron and fluorescence microscopy than on light microscopy. Furthermore, during fluorescence microscopy, the green filter provided the most clear visualization of lanthanum phosphate. In conclusion, fluorescence microscopy with a green filter is useful in determining the degree and extent of lanthanum deposition in the gastroduodenal mucosa.

DOI： 10.7759/cureus.30729

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Language：Japanese   Publisher：(一財)日本消化器病学会  

82歳男性.食後の胃もたれを主訴に上部消化管内視鏡検査を実施.胃体部小彎に白苔付着をともなうびらんと周囲に発赤を認め,生検で中分化管状腺癌が疑われたため当院紹介となった.初回より3週間後の内視鏡検査では,体部小彎の異なる位置に白苔付着をともなうびらんを認め,生検では非腫瘍であった.酢酸亜鉛起因性胃粘膜傷害を疑い,同薬剤の内服を中止したところ,胃粘膜傷害は改善した.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01118&link_issn=&doc_id=20220922450009&doc_link_id=1390574876232671104&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390574876232671104&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

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In our earlier work, we revealed that inflammation of the lesser curvature of the gastric body and antrum could constitute independent risk factors for gastric cancer development, while inflammation of the greater curvature was not. The aims of this study were as follows: first, to reveal the differences between T lymphocyte populations of the gastric antrum and the greater and lesser curvatures of the gastric body in patients after Helicobacter pylori eradication; second, to analyze the correlation between the composition of the stomach-resident T lymphocytes and time from H. pylori eradication; and third, to evaluate the sex differences in T lymphocyte subsets after H. pylori eradication. To investigate site-specific differences in stomach-resident T lymphocytes after H. pylori eradication, we performed flow cytometry analysis on samples taken from the gastric antrum, greater curvature of the gastric body, and lesser curvature of the gastric body of 20 patients. We also analyzed the correlation between the composition of the stomach-resident T lymphocytes and the time from H. pylori eradication. The lymphocyte subsets of the antrum and lesser curvature of the body were similar. In contrast, compared to those in the greater curvature of the gastric body, CD4+/CD3+ lymphocyte subsets (43.8 ± 19.4% vs 31.7 ± 14.6%) were elevated in the lesser curvature of the body, whereas CD8+/CD3+ (67.1 ± 21.3% vs 80.4 ± 12.0%), CD7+/CD3+ (91.2 ± 4.6% vs 93.7 ± 3.8%), CCR4+/CD3+ (7.7 ± 8.1% vs 10.4 ± 7.0%), CD45RA+/CD3+CD4+ (27.2 ± 24.8% vs 39.5 ± 20.8%), and CD45RA+/CD3+CD4- (14.2 ± 11.1% vs 18.7 ± 11.5) were lower. Linear regression analysis showed a negative correlation between the time after H. pylori eradication and CD4+/CD3+ (P < .05, R2 = 0.198). There were no significant differences between men and women with respect to the lymphocyte populations. These results indicate that there are site-specific differences in lymphocyte composition in the stomach after H. pylori eradication.

DOI： 10.1097/MD.0000000000030241

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DOI： 10.3960/jslrt.22007.

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BACKGROUND: Verrucous carcinoma of the esophagus (VCE) is a rare tumor that is difficult to diagnose. In most cases, biopsies show nonspecific inflammatory and hyperkeratotic changes and do not show malignant findings. Most VCEs are slowly growing, locally advanced tumors with few metastases. Treatments for VCE are the same as for normal esophageal cancer, involving combined chemotherapy, surgical resection, and radiation therapy. However, it has been reported that VCE has a poor response to radiation or chemoradiotherapy (CRT). A case of VCE with complete response (CR) after CRT is presented. CASE PRESENTATION: A 70-year-old man was found to have white, irregular esophageal mucosa 4 years earlier. He had been followed up as an outpatient as having candidal esophagitis. However, his tumor grew gradually, and biopsy was performed by endoscopic mucosal resection (EMR). He was finally diagnosed with VCE. He had no metastases to distant organs, but some lymph node metastases were suspected. The tumor invaded his left bronchus. The esophagostomy and gastrostomy were constructed as emergent procedures. The patient then underwent definitive CRT. 4 weeks after the end of CRT, two-stage esophagectomy was performed. First, he underwent esophagectomy with thoracic lymph node dissection. A latissimus dorsi flap was patched to the bronchus after primary suture of the hole. 6 weeks later, reconstruction of the gastric tube was performed through the antethoracic route. The pathological findings showed CR to CRT, with no proliferative cancer cells in the specimen. The patient has had no recurrence for three and half years after the resection. CONCLUSIONS: We presented a locally advanced VCE that achieved CR to CRT. In cases that have some difficulty for local resection, CRT might be an appropriate treatment for VCE.

DOI： 10.1186/s40792-022-01486-7

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BACKGROUND: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. METHODS: We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). RESULTS: The average age was older in the Hp group than in the uninfected group (68.1 ± 8.1 vs. 63.4 ± 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). CONCLUSIONS: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection.

DOI： 10.1186/s12876-022-02368-w

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BACKGROUND: Diffuse redness is a characteristic endoscopic finding that indicates current infection of Helicobacter pylori, which is reduced after successful eradication. Linked color imaging (LCI) has been reported to improve the visibility of diffuse redness compared to white light imaging (WLI); however, quantitative evaluation has not been reported. AIMS: This study aimed to objectively evaluate the color change of the gastric mucosa after H. pylori eradication. METHODS: Images of the greater curvature of the antrum and corpus were captured, and the sites were biopsied during esophagogastroduodenoscopy (EGD) before and 1 year after eradication. The region of interest (ROI) was set around the biopsied area on the images. The color difference (ΔE) before and after eradication was calculated using the CIE L*a*b* color space. The association between the histological evaluation and the color value of the corresponding ROI was determined. RESULTS: At the antrum, there was no significant color change with either mode. At the corpus, the a* value, which reflected redness, decreased significantly after eradication with both modes (WLI: 41.2 to 36.0, LCI: 37.5 to 25.5); the b* value, reflecting yellowish, decreased with WLI, but increased significantly with LCI (WLI: 44.6 to 41.6, LCI: 23.9 to 29.2). The ΔE was significantly larger with LCI than with WLI (16.5 vs. 8.6). The a* values at the corpus were generally associated with histological neutrophil infiltration. CONCLUSIONS: Quantitative evaluation revealed that LCI emphasizes the change in color of the gastric mucosa due to the reduction in diffuse redness.

DOI： 10.1007/s10620-021-07030-1

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Background and study aims  Because the endoscopic treatment for non-ampullary duodenal adenoma (NADA) has a non-negligible risk of adverse events (AEs), a safe and easy treatment for NADA is desirable. This was a multicenter prospective trial evaluating the efficacy and safety of cold forceps polypectomy (CFP) for diminutive NADAs. Patients and methods  This study was prospectively conducted at six general hospitals and one university hospital. The inclusion criteria were histologic and endoscopic diagnosis of low-grade NADA measuring ≤ 6 mm. A second endoscopy was scheduled for 1 month after CFP. After confirmation of the success of CFP, 6-month and 12-month surveillance endoscopies were scheduled. The primary endpoint was the endoscopic and histologic disease disappearance rates at the 12-month endoscopy. Results  Thirty-nine lesions from 38 patients were prospectively included. Median tumor size at enrollment was 5 mm (range 3-6 mm). There were four cases of remnant lesions at the second endoscopy, and the lesion disappearance rate of single CFP was 89.7 % (35 /39; 95 % confidence interval (CI), 76.9 %-97.9 %). In three cases, complete removal of the lesion was achieved with a single re-CFP, but one case required four repeat CFPs. The lesion disappearance rate at 12-month endoscopy was 97.4 % (38 /39; 95 %CI, 86.8 %-99.5 %). During the follow-up period, no AEs related to CFP were observed. Conclusions  CFP for NADA ≤ 6 mm was safe and effective in this study. This common endoscopic method to remove lesions may be an option for treatment of diminutive NADAs.

DOI： 10.1055/a-1793-9439

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[This corrects the article DOI: 10.1055/a-1793-9439.].

DOI： 10.1055/a-1895-1758

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BACKGROUND AND AIM: Although endoscopic resection with careful surveillance instead of total proctocolectomy become to be permitted for visible low-grade dysplasia, it is unclear how accurately endoscopists can differentiate these lesions, as classifying neoplasias occurring in inflammatory bowel disease (IBDN) is exceedingly challenging due to background chronic inflammation. We evaluated a pilot model of an artificial intelligence (AI) system for classifying IBDN and compared it with the endoscopist's ability. METHODS: This study used a deep convolutional neural network, the EfficientNet-B3. Among patients who underwent treatment for IBDN at two hospitals between 2003 and 2021, we selected 862 non-magnified endoscopic images from 99 IBDN lesions and utilized 6 375 352 images that were increased by data augmentation for the development of AI. We evaluated the diagnostic ability of AI using two classifications: the "adenocarcinoma/high-grade dysplasia" and "low-grade dysplasia/sporadic adenoma/normal mucosa" groups. We compared the diagnostic accuracy between AI and endoscopists (three non-experts and four experts) using 186 test set images. RESULTS: The diagnostic ability of the experts/non-experts/AI for the two classifications in the test set images had a sensitivity of 60.5% (95% confidence interval [CI]: 54.5-66.3)/70.5% (95% CI: 63.8-76.6)/72.5% (95% CI: 60.4-82.5), specificity of 88.0% (95% CI: 84.7-90.8)/78.8% (95% CI: 74.3-83.1)/82.9% (95% CI: 74.8-89.2), and accuracy of 77.8% (95% CI: 74.7-80.8)/75.8% (95% CI: 72-79.3)/79.0% (95% CI: 72.5-84.6), respectively. CONCLUSIONS: The diagnostic accuracy of the two classifications of IBDN was higher than that of the experts. Our AI system is valuable enough to contribute to the next generation of clinical practice.

DOI： 10.1111/jgh.15904

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Data regarding the in-depth surface marker profiles of gastric tissue-resident lymphocytes in autoimmune and Helicobacter pylori-associated gastritis are lacking. In this study, we investigated potential differences in lymphocyte composition between these profiles. We enrolled patients with autoimmune (n = 14), active (current infection of H. pylori in the stomach; n = 10), and inactive gastritis (post-eradication of H. pylori; n = 20). Lymphocytes were isolated from the greater curvature of the stomach and lesser curvature of the body and analyzed using flow cytometry. The CD8+/CD3+ and CD4+/CD3+ ratios differed between the samples. Body CD4+/antrum CD4+, which is calculated by dividing the CD4+/CD3+ ratio in the body by that in the antrum, was significantly higher in autoimmune gastritis (3.54 ± 3.13) than in active (1.47 ± 0.41) and inactive gastritis (1.42 ± 0.77). Antrum CD8+/CD4+ in autoimmune gastritis (7.86 ± 7.23) was also higher than that in active (1.49 ± 0.58) and inactive gastritis (2.84 ± 2.17). The area under the receiver operating characteristic curve of antrum CD8+/CD4+ was 0.842, and the corresponding optimal cutoff point was 4.0, with a sensitivity of 71.4% and a specificity of 93.3%. We propose that an antrum CD8+/CD4+ ratio &gt; 4.0 is a potential diagnostic marker for autoimmune gastritis.

DOI： 10.3390/cimb44060167

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Background and study aims  Small colorectal polyps are removed by various methods, including cold snare polypectomy (CSP), hot snare polypectomy (HSP), and underwater endoscopic mucosal resection (UEMR), but the indications for using these methods are unclear. We retrospectively assessed the efficacy of CSP, HSP, and UEMR for small polyps, focusing on the depth of the resected specimens. Patients and methods  Outpatients with non-pedunculated small polyps (endoscopically diagnosed as 6 to 9 mm), resected by two endoscopists between July 2019 and September 2020, were enrolled. We histologically evaluated the specimens resected via CSP, HSP, and UEMR. The main outcome was the containment rate of the muscularis mucosa (MM) and submucosa (SM) tissues. Results  Forty polyps resected via CSP (n = 14), HSP (n = 12), or UEMR (n = 14) were enrolled after excluding 13 polyps with resection depths that were difficult to determine. The rates of specimens containing MM and SM tissue differed significantly (57 % and 29 % for CSP, 92 % and 83 % for HSP, and 100 % and 100 % for UEMR, respectively ( P  = 0.005 for MM and P  < 0.001 for SM tissue). Multiple logistic regression analysis showed UEMR was an independent factor relating to the containment of SM tissue. The thickness of SM tissue by CSP, HSP, and UEMR were 52 μm, 623 μm, and 1119 μm, respectively ( P  < 0.001). The thickness by CSP was significantly less than those by HSP and UEMR ( P  < 0.001, Bonferroni correction). Conclusions  UEMR could be the best method to contain SM tissue without injection. Further studies are needed to evaluate the indication of UEMR for small polyps.

DOI： 10.1055/a-1785-8616

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OBJECTIVES: Transient fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD) remain a challenge. The aim of this study was to assess the risk factors of post-ESD fever and post-ESD coagulation syndrome (PECS), focusing on the involvement of immunosuppressive drugs and steroids (IM). METHODS: This retrospective analysis included 510 patients who underwent colorectal ESD at Okayama University Hospital from 2015 to 2020. The incidence rate, clinical outcome, and factors associated with post-ESD fever and PECS were investigated. RESULTS: Post-ESD fever and PECS occurred in 63 patients (12.4%) and 43 patients (8.4%), respectively. In multivariate analysis, the American Society of Anesthesiologists Physical Status ≥3, the use of immunosuppressants or prednisolone ≥5mg (IM group), and injury to muscle layer/perforation were significantly associated with post-ESD fever. In PECS, IM group, tumors located on the right side, treatment time ≥60 min, injury to the muscle layer, and multiple lesions were independent risk factors. Both post-ESD fever and PECS improved conservatively in the IM group, and no serious complication was observed. CONCLUSIONS: The use of IM was a risk factor for both post-ESD fever and PECS. However, there were no serious complications in colorectal ESD for patients taking IM.

DOI： 10.1002/deo2.83

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We report the case of a 63-year-old man who underwent annual surveillance esophagogastroduodenoscopy, during which a small squamous cell carcinoma and a tiny yellowish granular lesion were found in the middle esophagus, slightly apart from each other. Magnifying endoscopy with narrow-band imaging of the yellowish granular lesion showed yellowish spots and blots scattered within an approximately 2-mm area. The larger spots appeared nodular and were overlaid with tortuous microvessels. Subsequently, both the lesions were excised en masse via endoscopic submucosal dissection, and the yellowish lesion was determined to be xanthoma. Histologically, an aggregated nest of foam cells surrounded by intrapapillary capillary vessels filled the intraepithelial papillae; the foam cells also extended inferiorly, below the rete ridges, and were sparsely distributed through the lamina propria mucosae. To our knowledge, the latter finding is the first to be described in literature, which leads us to postulate that the number of foam cells in the lamina propria mucosae may affect how thick and yellow a xanthoma appears on endoscopy. We believe that this case that presents a highly detailed comparison between endoscopic and histologic findings improves our understanding of the endoscopic appearance of esophageal xanthomas and may facilitate a precise diagnosis of this rare disease.

DOI： 10.1007/s12328-021-01583-4

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Electron microscopy has long been used in research in the fields of life sciences and materials sciences. Transmission and scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDX) analyses have also been performed in the field of gastroenterology. Electron microscopy and EDX enable (1) Observation of ultrastructural differences in esophageal epithelial cells in patients with gastroesophageal reflux and eosinophilic esophagitis; (2) Detection of lanthanum deposition in the stomach and duodenum; (3) Ultrastructural and elemental analyses of enteroliths and bezoars; (4) Detection and characterization of microorganisms in the gastrointestinal tract; (5) Diagnosis of gastrointestinal tumors with neuroendocrine differentiation; and (6) Analysis of gold nanoparticles potentially used in endoscopic photodynamic therapy. This review aims to foster a better understanding of electron microscopy applications by reviewing relevant clinical studies, basic research findings, and the state of current research carried out in gastroenterology science.

DOI： 10.4291/wjgp.v13.i2.41

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The present study describes proton beam therapy as a clinical option to achieve local control of giant conjunctival melanoma in an aged person, instead of orbital exenteration. An 80-year-old woman with one-year history of left-eye injection and hemorrhage experienced rapid growth of the ocular surface black mass. At the initial visit, a black, elastic hard, hemorrhage-prone, thickened mass in the size of 30x40 mm with a presumed wide stalk covered the total area of the lid fissure on the left side. Biopsy of the mass demonstrated anomalous melanin-containing cells in fibrin and hemorrhage, which were positive for cocktail-mix antibodies against tyrosinase, melanoma antigen recognized by T cells-1 and human melanoma black-45, indicative of malignant melanoma. One month after the initial visit, the patient underwent proton beam therapy at the total dose of 70.4 Gy (relative biological effectiveness) in 32 fractions (~10 min each) in one and a half months. One month after the end of proton beam therapy, 3.5 months from the initial visit, the patient was found by computed tomographic scan to have multiple metastatic lesions in bilateral lung fields. With the evidence of absent BRAF mutation, the patient underwent intravenous administration of pembrolizumab 77.2 mg every three weeks five times in total. Then, three months after proton beam therapy, ocular surface melanoma almost subsided and the clear cornea allowed visualization of the intraocular lens inside the eye. In three weeks, spontaneous corneal perforation was plugged with iris incarceration. The patient died suddenly of unknown cause 7.5 months from the initial visit. The local control of giant conjunctival melanoma was achieved by proton beam therapy, leading to patient's satisfaction and better quality of life. Proton beam therapy, followed by immune checkpoint inhibitors, would become the future standard of care for unresectable giant conjunctival melanoma.

DOI： 10.3892/mco.2021.2445

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

Objectives

To investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis.

Methods

We performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients ( n = 13) and control patients ( n = 5).

Results

CD62L⁺/CD3⁺CD4⁺ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L⁺/CD3⁺CD4⁻ cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA⁻CD62L⁺/CD3⁺CD4⁺, that is, central memory T cell fraction in CD4⁺ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56⁺/CD3⁺ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56⁺/CD3⁺ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%).

Conclusion

We demonstrated that CD62L⁺ T lymphocytes, particularly the CD45RA⁻CD62L⁺ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56⁺/CD3⁺ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.

DOI： 10.1177/20587384211051982

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A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis.

DOI： 10.1177/23247096221086450

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Although high-dose methotrexate (HD-MTX) is the standard therapy for primary central nervous system lymphoma (PCNSL), the prognosis remains poor. Because 90% of PCNSL is diffuse large B-cell lymphoma (DLBCL), chimeric antigen receptor (CAR)-T cell therapy is expected to be beneficial. However, there are limited reports on CAR-T cell therapy for PCNSL because of the concern of neurotoxicity. Here, we report a case of relapsed PCNSL treated with anti-CD19 CAR-T cell therapy. A 40-year-old woman presenting with visual disturbance in her left eye was initially diagnosed with bilateral uveitis. Her histological diagnosis was DLBCL, and she was positive for CD19. Although she received chemotherapy including HD-MTX, the tumor relapsed in her right occipital lobe. She underwent remission induction therapy and then anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) grade 2 occurred, but there were no complications of CAR-T cell-related encephalopathy syndrome (CRES). She has achieved complete response for more than 1 year. Anti-CD19 CAR-T cell therapy is a revolutionary immunotherapy for treating relapsed or refractory (R/R) B lineage malignancies. Although there are concerns regarding CRS and CRES in central nervous system lymphoma, the use of anti-CD19 CAR-T cells to treat R/R PCNSL is safe and feasible.

DOI： 10.2176/jns-nmc.2022-0134

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Objective This study aimed to determine the prevalence and endoscopic features of zinc acetate dihydrate tablet-associated gastric lesions. Methods We retrospectively examined the endoscopic features of 47 patients taking zinc acetate dihydrate tablets who underwent esophagogastroduodenoscopy. Results Gastric mucosal alterations, including redness, erosions, ulcers, and adhesion of the white coat, were observed in 29 of 47 patients (61.7%). Among patients with gastric lesions (group A), there was a significantly higher percentage of symptomatic patients in comparison to patients without lesions (group B) (65.5% vs. 22.2%; p<0.01). The background characteristics of the two groups did not differ to a statistically significant extent. On esophagogastroduodenoscopy, mucosal redness (n=27, 93.1%), erosions (n=26, 90.0%), adhesion of the white coat (n=25, 86.2%), and ulcers (n=9, 31.0%) were observed. None of the 19 patients who previously underwent esophagogastroduodenoscopy had gastric lesions before starting zinc acetate dihydrate. Esophagogastroduodenoscopy was performed after the cessation of zinc acetate dihydrate intake in six patients, and revealed the resolution of gastric lesions. Conclusion Gastric lesions were observed in 29 of 47 patients who were taking zinc acetate dihydrate tablets. The most common endoscopic findings were mucosal redness (93.1%), erosions (90.0%), adhesion of the white coat (86.2%), and ulcers (31.0%). Although the exact pathogenesis is uncertain, we believe that understanding the unique manifestations of this gastric lesion will help physicians manage adverse events in patients taking zinc acetate dihydrate tablets.

DOI： 10.2169/internalmedicine.8625-21

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A 45-year-old Japanese man underwent esophagogastroduodenoscopy, which revealed spotty redness at the gastric fornix, mucosal swelling, diffuse redness in the corpus, and mucosal atrophy in the gastric angle and antrum. Histological examination showed rod-shaped bacteria that appeared larger than Helicobacter pylori. The patient tested positive for rapid urease test, and serum anti-H. pylori IgG antibody test results were negative. Further examination of the bacteria revealed that H. suis antibody test was positive, and the presence of H. suis was confirmed using H. suis-specific real-time PCR. H. suis was successfully eradicated after triple therapy with vonoprazan, amoxicillin, and clarithromycin. This case reinforces the notion that non-H. pylori Helicobacter species such as H. suis and H. heilmannii may be involved in the pathogenesis of active gastritis in patients who test negative for H. pylori antibodies.

DOI： 10.1155/2022/4254605

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Language：Japanese   Publishing type：Research paper (scientific journal)  

An 82-year-old Japanese man underwent esophagogastroduodenoscopy for postprandial epigastric discomfort. The patient was diagnosed with hypozincemia with a serum zinc level of 63μg/dL (normal range:80-130μg/dL), and he had commenced oral intake of zinc acetate 1 month before the esophagogastroduodenoscopy. Endoscopy showed erosions with white-coated mucosa surface adhesions and erythema on the lesser curvature of the gastric body. Moderately differentiated tubular adenocarcinoma was suspected based on the biopsy examination findings;therefore, he was referred to our hospital for further examination and treatment. A repeat endoscopy showed two erosions with white-coated mucosa surface adhesion and erythema on the lesser curvature of the gastric body. However, the lesion location was different from that detected in the initial endoscopy. The biopsy showed no neoplastic changes. Therefore, based on the endoscopic findings and history of oral zinc acetate administration, we diagnosed the gastric mucosal injury as zinc acetate-associated gastric lesions. The cessation of zinc acetate intake resulted in the resolution of gastric lesions. Reassessment of the biopsy specimen from the initial endoscopy revealed erosions, epithelial cells showing infarct-like necrosis, degenerative atypical cells, and necrotic substances, which were misdiagnosed as neoplastic changes. This case highlights the importance of recognizing the typical endoscopic features of a zinc acetate-associated gastric lesion to enable its prompt diagnosis during esophagogastroduodenoscopy.

DOI： 10.11405/nisshoshi.119.853

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A 65-year-old Japanese woman underwent umbilical cord blood transplantation for acute myeloid leukemia. Zinc acetate dihydrate tablets were administered for hypozincemia after transplantation, and vomiting and appetite loss occurred soon thereafter. Esophagogastroduodenoscopy revealed mucosal redness, erosion, white coat adhesion, and ulcers. Although graft-versus-host disease, intestinal transplant-associated microangiopathy, and cytomegalovirus infection were considered as possible causes, we diagnosed the patient with zinc acetate dihydrate tablet-associated gastric mucosal alterations based on the endoscopic features. This case reinforces the notion that medication-associated gastric lesions should be suspected in patients taking zinc acetate dihydrate tablets.

DOI： 10.1155/2022/4637707

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PURPOSE: Nonampullary duodenal adenocarcinoma (NADA) is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive NADA, focusing on the microsatellite instability (MSI) phenotype, programmed cell death-ligand 1 (PD-L1) expression, and prognostic factors. METHODS: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25, and BAT-26) were amplified for MSI assessment by PCR. RESULTS: The incidence of MSI in invasive NADA was 35.2%. No significant correlation between the MSI phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (p = 0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (p = 0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival (OS) in patients with MSI (p = 0.013) and at early-stage disease (p = 0.000) than in those with microsatellite-stable or at late tumor stages. Univariate and multivariate analyses showed that MSI (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106-0.751, p = 0.011) and early tumor stage (stage I-II) (HR: 8.81, 95% CI: 2.545-30.500, p = 0.001) were independent better prognostic factors of OS. CONCLUSIONS: MSI and early tumor stage (stage I-II) were independent better prognostic factors of OS. A high proportion of MSI phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.

DOI： 10.1159/000519805

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IgG4-related disease is a recently established clinical entity. The disease might serve as the background for later development of systemic lymphoma. This study aims to confirm the diagnosis of IgG4-related disease by re-staining lacrimal gland lesions diagnosed previously with low-grade lymphoma in a patient who developed systemic diffuse large B-cell lymphoma (DLBCL) 18 years later. A 53-year-old man developed bilateral lacrimal gland swelling and right submandibular gland swelling and was diagnosed by excision as low-grade lymphoma. In follow-up, positron emission tomography showed high uptake in the median hyoid 11 years later but no malignancy was detected by laryngeal submucosal biopsy. He was well with no treatment until 18 years later when he had palatal swelling and was diagnosed with DLBCL by oral floor biopsy. He had systemic lymphadenopathy, infiltration in paranasal sinuses, hypopharynx, small intestine, kidney, and prostate. He underwent 8 courses of R-CHOP and 3 courses of high-dose methotrexate and achieved complete remission with no relapse for 1 year thereafter. Re-immunostaining of paraffin blocks of bilateral lacrimal gland lesions showed IgG and IgG4-positive lymphocytes and plasma cells among lymphoid follicles separated by fibrous bundles, with 10 or more IgG4-positive cells in high-power field. The IgG4/IgG-positive cell ratio was 100% and the number of κ chain-positive cells and λ chain-positive cells was the same. The bilateral lacrimal lesions were thus re-diagnosed as IgG4-related disease. In conclusion, systemic DLBCL occurred approximately 20 years after lacrimal gland IgG4-related disease. Literature review revealed 12 patients with IgG4-related disease, including the present patient, who later developed lymphoma in the other organs.

DOI： 10.1177/23247096211067894

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Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations. Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER). Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 to December 2017. Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 μm experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005). Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.

DOI： 10.2169/internalmedicine.6942-20

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The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases.

DOI： 10.3390/life11121433

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INTRODUCTION: The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors. METHODS: One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining. RESULTS: The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P < 0.01). In univariate analysis of primary deaths from duodenal adenocarcinoma, TNM stage II or higher, undifferentiated, KRAS mutations, gastric phenotype, intestinal phenotype, and PD-L1 status were significant factors. In multivariate analysis, TNM stage II or higher (hazard ratio: 1.63 × 1010, 95% confidence interval: 18.66-6.69 × 1036) and KRAS mutation (hazard ratio: 3.49, confidence interval: 1.52-7.91) were significant factors. DISCUSSION: Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered.

DOI： 10.14309/ctg.0000000000000424

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BACKGROUND: It remains unclear which factors, such as tumor volume and tumor invasion, influence circulating tumor DNA (ctDNA), and the origin of ctDNA in liquid biopsy is always problematic. To use liquid biopsies clinically, it will be very important to address these questions. AIM: To assess the origin of ctDNA, clarify the dynamics of ctDNA levels, assess ctDNA levels by using a xenograft mouse after treatment, and to determine whether tumor volume and invasion are related to ctDNA levels. METHODS: Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line. Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis. Analysis of ctDNA was performed by droplet digital PCR, using the human telomerase reverse transcriptase (hTERT) gene. RESULTS: Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8. No hTERT was detected at week 4, but it was detected at week 8. However, in four-site xenograft mice, hTERT was detected both at week 4 and week 6. These experiments revealed that both tumor invasion and tumor volume were associated with the detection of ctDNA. In resection experiments, hTERT was detected at resection, but had decreased by 6 h, and was no longer detected 1 and 3 d after resection. CONCLUSION: We clarified the origin and dynamics of ctDNA, showing that tumor volume is an important factor. We also found that when the tumor was completely resected, ctDNA was absent after one or more days.

DOI： 10.3748/wjg.v27.i41.7134

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ABSTRACT: There is no practical predictive model for the diagnosis of gastrointestinal stromal tumors (GISTs). To establish a practical predictive model for the diagnosis of subepithelial lesions in the stomach, we reviewed patients with GISTs (n = 89), schwannomas (n = 7), and leiomyomas (n = 28).The tumor was more frequently found along the gastric cardia in the leiomyoma group (57.1%) than in the GIST/schwannoma group (2.1%, P < .01). Contrast enhancement (57.3% vs 0%, P < .01) and intra-tumoral necrosis (34.4% vs 0.0%, P < .01) were more frequently observed in the GIST/schwannoma group than in the leiomyoma group. On endoscopic ultrasonography, 58.3% of GISTs/schwannomas showed uneven echogenicity, whereas the echogenicity was uneven in 21.4% of leiomyomas (P < .01). There were no differences between the tumor color and the presence or absence of ulcer formation, tumor bleeding, irregularity of the tumor margin, cystic spaces, and hyperechoic spots between the 2 groups. Based on these results, we developed a 2-step diagnostic algorithm for GISTs/schwannomas. The first step comprises 1 endoscopic feature: a cardiac or non-cardiac location. Tumors with a cardiac location were judged as leiomyomas and those with a non-cardiac location were judged as GISTs/schwannomas, with 96.9% sensitivity and 57.1% specificity for GIST/schwannoma diagnosis. The second step comprises a combination of endoscopic (non-cardiac location), radiologic (positive contrast enhancement and intra-tumoral necrosis), and endosonographic (uneven echogenicity) features for a total of 4 points. We assigned 1 point to each feature. Tumors with scores of 2 to 4 were judged as GISTs/schwannomas, with 81.3% sensitivity and 92.9% specificity for GIST/schwannoma diagnosis.Our predictive model will be a practical guide for the management of gastric subepithelial lesions.

DOI： 10.1097/MD.0000000000027520

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ABSTRACT: Sporadic non-ampullary duodenal adenoma (SNADA) is a rare disease, and therefore, its clinical characteristics have not been comprehensively investigated. Furthermore, owing to the high complication rates and severity of endoscopic resection, treatment strategies vary among facilities. In the present study, we aimed to clarify the clinical characteristics and course of SNADA.We extracted clinical and histological records of SNADA cases diagnosed in 11 hospitals between September 1999 and August 2014. The patients were divided into "no-resection" and "resection" groups based on the initial treatment approach. We investigated the long-term outcome of the "no-resection" group and treatment results of the "resection" group, with particular interest in endoscopic resection.Overall, 299 patients were diagnosed with SNADA. The median age at diagnosis was 67 years (range, 31-88 years), with approximately twice as many men as women. The median tumor size was 8.0 mm (2-60 mm). In total, 161 patients were initially selected for no-resection and 138 underwent resection. Age >70 years and the presence of either severe illness or poor performance status were significantly related to opting for no-resection. In the no-resection group, 101 patients underwent endoscopic follow-up for at least 1 year. During the observational period (2.5 ± 2.2 years), 27 lesions (27%) disappeared following cold forceps biopsy, and 13 lesions (14%) presented lateral growth. Four lesions (4%) changed to mucosal carcinoma, 3 were treated endoscopically, and 1 was surgically resected. Nineteen patients died; however, no one died of duodenal carcinoma. In the endoscopic resection group, en bloc resection was achieved in 78% of patients. However, the complication rate for perforation was 7%, and endoscopic submucosal dissection was associated with a 36% perforation rate.With the low incidence of cancer development and no disease specific death, the strategy of initially not performing resection could be considered especially for the older adults, poor-prognosis patients, or small lesions.

DOI： 10.1097/MD.0000000000027382

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DOI： 10.2169/internalmedicine.7307-21

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DOI： 10.1055/a-1559-2158

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BACKGROUND AND STUDY AIMS: The propriety of cold forceps polypectomy (CFP) using jumbo biopsy forceps for diminutive polyps remains controversial. We conducted a prospective study to evaluate the complete CFP resection rate of 3-5-mm polyps using additional endoscopic mucosal resection (EMR) specimens following CFP. PATIENTS AND METHODS: Patients with 3-5-mm protruded or flat elevated colorectal polyps diagnosed endoscopically as adenomas or serrated lesions were prospectively enrolled. CFP using jumbo biopsy forceps was used to remove the eligible polyps and repeated until the absence of residuals were confirmed via image-enhanced endoscopy or chromoendoscopy. After CFP, saline was injected at the defect, and the marginal specimen of the defect was resected using EMR to histologically evaluate the residue. The primary outcome was the complete CFP resection rate, which was defined as no residue at the EMR site. Other outcomes were the number of CFP bites and the complete resection rate by lesion size. RESULTS: Eighty patients with 120 polyps were enrolled. The mean polyp size was 4.1 ± 0.7 mm. The overall complete resection rate was 96.7% (95% confidence interval [CI], 91.7-98.7), and the rates for 3-, 4- and 5-mm polyps were 100% (95% CI, 86.7-100), 96.0% (95% CI, 86.5-98.9) and 95.5% (95% CI, 85.1-98.8), respectively. The one-bite CFP rates were 92%, 60% and 31% for the 3-, 4- and 5-mm polyps, respectively. CONCLUSIONS: The complete CFP resection rate for 3-5-mm polyps was acceptable, although the one-bite clearance rate decreased as the polyp size increased (UMIN000028841).

DOI： 10.1111/den.13895

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The intraoperative pathological diagnosis (IPD) plays an important role in determining the optimal surgical treatment for spinal cord tumors. The final pathological diagnosis (FPD) is sometimes different from the IPD. Here, we sought to identify the accuracy of the IPD of spinal cord tumors compared to the FPD. We retrospec-tively analyzed the cases of 108 patients with spinal cord tumors treated surgically in our institute; the IPD, FPD, mismatched cases, and concordance rate between the IPD and FPD were investigated. Five cases involved a mismatch between the IPD and FPD. The overall concordance rate was 95.4%, with 90.9% for extra-dural lesions, 98.5% for intradural extramedullary lesions, 84.2% for intramedullary lesions, and 100% for dumbbell-type tumors. The concordance rate of intramedullary lesions tended to be lower than that of other lesions (p = 0.096). A lower concordance rate was revealed for intramedullary lesions compared to the other lesions. Despite the IPD clearly remaining a valuable tool during operative procedures, surgeons should recog-nize the limitations of IPDs and make comprehensive decisions about surgical treatments.

DOI： 10.18926/AMO/62397

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The characteristics of gastric polyps in patients with Peutz-Jeghers (PJ) syndrome (PJS) have not been fully investigated. The objective of this study was to reveal the endoscopic and pathologic findings of gastric polyps in patients with PJS. We reviewed 11 patients with PJS treated at 6 institutions, and summarized the endo-scopic and pathologic features of their gastric polyps. The polyps were mainly classified into 2 types: (i) soli-tary or sporadic polyps > 5 mm, reddish in color with a sessile or semi-pedunculated morphology (n = 9); and (ii) multiple sessile polyps ≤ 5 mm with the same color tone as the peripheral mucosa (n = 9). Patients who underwent endoscopic mucosal resection for polyps > 5 mm were diagnosed with PJ polyps (n = 2), whereas those who underwent biopsy were diagnosed with hyperplastic polyps. Polyps ≤ 5 mm were pathologically diagnosed as fundic gland polyps or hyperplastic polyps. This study revealed that patients with PJS present with 2 types of polyps in the stomach. Endoscopic mucosal resection of polyps > 5 mm seems necessary for the pathologic diagnosis of PJ polyps.

DOI： 10.18926/AMO/62399

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BACKGROUND: Numerous basic studies have shown a relationship between interleukin-6 (IL-6) and the development or severity of myocarditis. However, there has been no study in which the effect of IL-6 levels in patients with myocarditis was evaluated. METHODS: We enrolled control patients (n = 12) and consecutive patients with acute myocarditis (n = 13), including lymphocytic, eosinophilic, and giant cell myocarditis, and investigated the pathological and clinical effects of IL-6 on human myocarditis. RESULTS: The serum IL-6 level in patients with myocarditis (16.7 [9.9, 103.8] pg/mL) was significantly higher than that in the control patients (1.4 [1.0, 1.9] pg/mL) (P<0.001). Immunohistochemical analysis showed that IL-6 was expressed in infiltrating inflammatory cells of endomyocardial biopsy samples from all patients with myocarditis. Moreover, the log-transformed value of serum IL-6 level showed significant positive correlations with serum creatine kinase (CK) level, CK-MB level, peak CK level, peak CK-MB level and C-reactive protein level (all P ≤ 0.005) and a negative correlation with the left ventricular (LV) ejection fraction (p = 0.014). We divided the patients with myocarditis into a low IL-6 group (9.9 [4.5, 14.2] pg/dL, n = 7) and a high IL-6 group (108.9 [51.1, 130.9] pg/dL, n = 6). The degree of infiltration of IL-6-expressing inflammatory cells in myocardial samples obtained from patients in the high IL-6 group was significantly more severe than that in samples obtained from patients in the low IL-6 group. Furthermore, patients in the high IL-6 group significantly more frequently received catecholamine therapy (P = 0.005), venoarterial extracorporeal membrane oxygenation (P = 0.029), and artificial respirator support (P = 0.021) in the acute phase of myocarditis. CONCLUSION: The results suggest that there is a strong impact of IL-6 on cardiac injury and dysfunction in patients with myocarditis.

DOI： 10.1016/j.jjcc.2021.03.003

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We herein report a patient who presented with follicular lymphoma. Although the stomach was initially intact, mucosal redness and multiple erosions appeared in the gastric body owing to infiltration of the follicular lymphoma cells. Subsequently, a slightly depressed, white area lacking gastric mucosal structure was detected in the lesser curvature of the gastric cardia and body, where lymphoma cell infiltration was also pathologically observed beneath the stratified squamous epithelium. This case indicated that, although infrequent, prolonged mucosal injury owing to lymphoma infiltration can cause squamous metaplasia in the stomach.

DOI： 10.2169/internalmedicine.6271-20

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BACKGROUND: The effects of the Franseen needle size in endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) of solid pancreatic masses remain unclear. This study aimed to compare 25G and 22G Franseen needles in terms of adequate tissue acquisition from solid pancreatic masses. METHODS: In this single-center, crossover, randomized noninferiority trial, eligible patients underwent EUS-FNB with both 25G and 22G Franseen needles in a randomized order between November 2018 and August 2020. Tissue specimens from each pass were separately evaluated based on the cellularity scoring system. The primary outcome was the proportion of acquired specimens allowing adequate histological assessment (cellularity score ≥3). A -15% noninferiority margin was assumed. RESULTS: Data from 88 patients were analyzed, which showed malignant and benign lesions in 84 (95.5%) and four (4.5%) patients, respectively. Of the 88 specimens, 62 (70.5%) and 69 (78.4%) acquired using 25G and 22G needles, respectively, allowed adequate histological assessment. The adjusted proportion difference was -6.6% (95% confidence interval -8.8% to -4.5%), indicating noninferiority of the 25G Franseen needle (P < 0.001). The diagnostic accuracies of the 25G and 22G needles were 86.4% and 89.8%, respectively, with no significant difference (P = 0.180). Adverse events occurred in one patient. CONCLUSIONS: The 25G Franseen needle showed a noninferior adequate tissue acquisition and similar diagnostic performance compared to that of the 22G Franseen needle. However, a 15% noninferiority margin was high for clinical use; thus, further consideration is needed (Clinical Trial Registry no. UMIN000034596).

DOI： 10.1111/den.14079

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BACKGROUND AND AIM: Fusobacterium nucleatum (Fn) is involved in colorectal cancer (CRC) growth and is a biomarker for patient prognosis and management. However, the ecology of Fn in CRC and the distribution of intratumoral Fn are unknown. METHODS: We evaluated Fn and the status of KRAS and BRAF in 200 colorectal neoplasms (118 adenomas and 82 cancers) and 149 matched adjacent normal mucosas. The differentiation status between "surface" and "deep" areas of cancer tissue and matched normal mucosa were analyzed in 46 surgical samples; the Ki-67 index was also evaluated in these samples. RESULTS: Fusobacterium nucleatum presence in the tumor increased according to pathological stage (5.9% [adenoma] to 81.8% [stage III/IV]), while Fn presence in normal mucosa also increased (7.6% [adenoma] to 40.9% [stage III/IV]). The detection rates of Fn on the tumor surface and in deep areas were 45.7% and 32.6%, while that of normal mucosa were 26.1% and 23.9%, respectively. Stage III/IV tumors showed high Fn surface area expression (66.7%). Fn intratumoral heterogeneity (34.8%) was higher than that of KRAS (4.3%; P < 0.001) and BRAF (2.2%; P < 0.001). The Ki-67 index in Fn-positive cases was higher than that in negative cases (93.9% vs 89.0%; P = 0.01). CONCLUSIONS: Fusobacterium nucleatum was strongly present in CRC superficial areas at stage III/IV. The presence of Fn in the deep areas of adjacent normal mucosa also increased. The intratumoral heterogeneity of Fn is important in the use of Fn as a biomarker, as Fn is associated with CRC proliferative capacity.

DOI： 10.1111/jgh.15361

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BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

DOI： 10.12659/AJCR.932241

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We herein report two patients with endometriosis in the cecum. Both patients presented with a protruding, subepithelial tumor on colonoscopy and were diagnosed with cecal endometriosis after surgical resection. It is notable that the cecal lesions were not initially identified on computed tomography (CT), while CT colonography with air/carbon dioxide insufflation resulted in the detection of the cecal tumor. These cases highlight the possibility of false-negative results on conventional CT in patients with cecal endometriosis. We consider CT colonography with air/carbon dioxide insufflation useful for detecting cecal tumors in such cases.

DOI： 10.2169/internalmedicine.6418-20

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

DOI： 10.1038/s41598-021-90441-x

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BACKGROUND: Mutations in the POLE gene result in an ultra-hypermutated phenotype in colorectal cancer (CRC); however, the molecular characterisation of epigenetic alterations remains unclear. We examined the genetic and epigenetic profiles of POLE-mutant CRC to elucidate the clinicopathological features of the associated genetic and epigenetic alterations. RESULTS: Tumour tissues (1,013) obtained from a cohort of patients with CRC were analysed to determine associations between the proofreading domain mutations of POLE with various clinicopathological variables, microsatellite instability (MSI) status, BRAF and KRAS mutations, and the methylation status of key regions of MLH1, MGMT, and SFRP2 promoters by calculating the methylation scores (range 0-6). Only four cases (0.4%) exhibited pathogenic POLE hotspot mutations (two p.P286R [c.857C > G], one p.V411L [c.1231G > C], and p.S459F [c.1376C > T] each), which were mutually exclusive to BRAF and KRAS mutations and MSI. CRC patients were divided into four subgroups: patients with POLE mutations (POLE, 0.4%, n = 4), patients with both MSI and extensive methylation in MLH1 (MSI-M, 2.9%, n = 29), patients with MSI but no extensive methylation in MLH1 (MSI-U, 3.6%, n = 36), and patients without MSI (non-MSI, 93.2%, n = 944). The POLE group was younger at diagnosis (median 52 years, P < 0.0001), with frequent right-sided tumour localisation (frequency of tumours located in the right colon was 100%, 93.1%, 36.1%, and 29.9% in POLE, MSI-M, MSI-U, and non-MSI, respectively; P < 0.0001), and was diagnosed at an earlier stage (frequency of stages I-II was 100%, 72.4%, 77.8%, and 46.6% in POLE, MSI-M, MSI-U, and non-MSI, respectively, P < 0.0001). The mean methylation score in POLE was not different from that in MSI-U and non-MSI, but the methylation signature was distinct from that of the other subgroups. Additionally, although the examined number of POLE-mutant tumours was small, the number of CD8-positive cells increased in tumours with partial methylation in the MLH1 gene. CONCLUSIONS: CRC patients with POLE proofreading mutations are rare. Such mutations are observed in younger individuals, and tumours are primarily located in the right colon. Diagnosis occurs at an earlier stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.

DOI： 10.1186/s13148-021-01104-7

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BACKGROUND: Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. CASE PRESENTATION: A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller-Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. CONCLUSIONS: Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor.

DOI： 10.1186/s40792-021-01199-3

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Objective The eradication of Helicobacter pylori (H. pylori) reduces the risk for gastric cancer (GC) development, but it cannot prevent GC completely. We investigated the risk factors of early GC development after the eradication of H. pylori, based on the histological characteristics of gastric mucosa. Methods Sixty-one patients who underwent endoscopic submucosal dissection for early GC after successful H. pylori eradication (Group A) and 122 patients without developing a gastric neoplasm over 3 years after successful H. pylori eradication (Group B) were analyzed. We compared the histological findings of the patients enrolled in Group A and Group B before and after the propensity score-matching. Results Comparing the characteristics of two the groups, Group A consisted predominantly of males, had significantly more elderly patients, and the years after successful eradication tended to be longer. We performed score matching for these three factors to reduce the influence of any confounding factors. After matching, the scores of inflammation for Group A (n=54) was significantly higher than those of Group B (n=54) at the greater curvature of the antrum, the lesser curvature of the corpus, and the greater curvature of the corpus. According to a multivariate analysis, inflammation of the greater curvature of the antrum and lesser curvature of the corpus were found to be independent risk factors. The risk ratio and 95% CI were 5.92 (2.11-16.6) (p<0.01), and 3.56 (1.05-13.2) (p=0.04), respectively. Conclusion A continuous high level of inflammation of the background gastric mucosa may be a risk factor for gastric cancer onset after H. pylori eradication.

DOI： 10.2169/internalmedicine.5486-20

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The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n = 42) or endoscopic submucosal dissection (ESD, n = 72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (≥ 500 μm) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG.

DOI： 10.1038/s41598-021-86893-w

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Targeted therapies for malignant melanoma have improved patients' prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years. Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma.

DOI： 10.18926/AMO/61906

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BACKGROUND AND AIMS: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS). METHODS: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma. RESULTS: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P < 0.0001). Early CP findings ≥2 and atrophic parenchyma were significantly correlated with I-type (P < 0.0001). PB-type was significantly associated with pancreatic parenchyma without early CP findings or fatty degeneration in comparison to the other subtypes (P < 0.0001). Using the above characteristic EUS findings, the sensitivity, specificity, and accuracy were as follows: 63%, 92% and 74%, respectively, in G-type, 57%, 96% and 87% in I-type, and 90%, 94% and 94% in PB-type. CONCLUSIONS: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN.

DOI： 10.1016/j.pan.2021.01.026

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BACKGROUND: Recent improvements in the prognosis of patients with esophageal cancer have led to the increased occurrence of gastric tube cancer (GTC) in the reconstructed gastric tube. However, there are few reports on the treatment results of endoscopic submucosal dissection (ESD) for GTC. AIM: To evaluate the efficacy and safety of ESD for GTC after esophagectomy in a multicenter trial. METHODS: We retrospectively investigated 48 GTC lesions in 38 consecutive patients with GTC in the reconstructed gastric tube after esophagectomy who had undergone ESD between January 2005 and December 2019 at 8 institutions participating in the Okayama Gut Study group. The clinical indications of ESD for early gastric cancer were similarly applied for GTC after esophagectomy. ESD specimens were evaluated in 2-mm slices according to the Japanese Classification of Gastric Carcinoma with curability assessments divided into curative and non-curative resection based on the Gastric Cancer Treatment Guidelines. Patient characteristics, treatment results, clinical course, and treatment outcomes were analyzed. RESULTS: The median age of patients was 71.5 years (range, 57-84years), and there were 34 men and 4 women. The median observation period after ESD was 884 d (range, 8-4040 d). The median procedure time was 81 min (range, 29-334 min), the en bloc resection rate was 91.7% (44/48), and the curative resection rate was 79% (38/48). Complications during ESD were seen in 4% (2/48) of case, and those after ESD were seen in 10% (5/48) of case. The survival rate at 5 years was 59.5%. During the observation period after ESD, 10 patients died of other diseases. Although there were differences in the procedure time between institutions, a multivariate analysis showed that tumor size was the only factor associated with prolonged procedure time. CONCLUSION: ESD for GTC after esophagectomy was shown to be safe and effective.

DOI： 10.3748/wjg.v27.i11.1043

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DOI： 10.1016/j.dld.2020.05.019

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OBJECTIVE: The rare incidence of submucosal invasive non-ampullary duodenal carcinoma has led to scant information in literature; therefore, we compared the clinicopathological features between submucosal invasive carcinoma (SM-Ca), mucosal carcinoma (M-Ca), and advanced carcinoma (Ad-Ca). MATERIALS: We retrospectively analyzed 165 patients with sporadic non-ampullary duodenal carcinomas (SNADCs) from four institutions between January 2003 and December 2018. The SNADCs were divided to three groups according to histological diagnosis: SM-Ca, M-Ca, and Ad-Ca. The clinicopathological characteristics and mucin phenotypes were compared between groups. RESULTS: Among the 165 SNADCs, 11 (7%) were classified as SM-Ca, 70 (42%) as M-Ca, and 84 (51%) as Ad-Ca. We found that all SM-Ca (P = 0.013) and most Ad-Ca (P = 0.020) lesions were located on the oral-Vater; however, an almost equal distribution of M-Ca lesions was found between the oral- and anal-Vater. No significant difference was observed between the tumor diameter of M-Ca and SM-Ca; however, 45% (5/11) of SM-Ca were ≤10 mm. A total of 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were classified as intestinal phenotype; whereas most M-Ca were classified as intestinal phenotype (67%, 8/12). CONCLUSIONS: SM-Ca lesions were all located on the oral-Vater and were highly associated with the gastric mucin phenotype, which were different from the features of most M-Ca.

DOI： 10.1371/journal.pone.0256797

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INTRODUCTION: Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. METHODS: This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. RESULTS: This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. DISCUSSION/CONCLUSION: Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.

DOI： 10.1159/000515213

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In this report, we describe a patient with myoepithelial hamartoma, which is regarded as synonymous with adenomyosis and heterotopic pancreas. Endoscopy revealed a submucosal tumor in the antrum of the stomach. Subsequently, distal gastrectomy with Roux-en-Y reconstruction was performed. Histological findings of adenomyomatous lesion and heterotopic pancreatic tissue were observed in this lesion. The distribution of OCT4, which is a pluripotency marker, varied in each part.

DOI： 10.1155/2021/6617370

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The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

DOI： 10.3960/jslrt.20048

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A 77-year-old Japanese woman who had been treated for follicular lymphoma for 8 years developed abdominal pain and intra-abdominal lymphadenopathies. Colonoscopy revealed an elevated lesion in the rectum, which presented as two humps with erosions. A diagnosis of histologic transformation of follicular lymphoma to diffuse large B-cell lymphoma was made by endoscopic biopsy. This case underscores the importance of endoscopy examinations and biopsy of newly emerged gastrointestinal lesions for the prompt diagnosis of histologic transformation, since salvage chemotherapy must be initiated quickly in such cases.

DOI： 10.18926/AMO/62775

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis.

DOI： 10.3960/jslrt.19041

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BACKGROUND: It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. METHODS: Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. RESULTS: Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. CONCLUSION: Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

DOI： 10.1186/s12885-020-07699-z

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We herein report four patients with desquamative esophagitis that developed one to nine days after peripheral blood stem cell transplantation (PBSCT). Three patients underwent allogeneic PBSCT for leukemia, and the other underwent autologous PBSCT for pineoblastoma. Esophagogastroduodenoscopy revealed mucosal sloughing and fresh blood in the esophagus. Fasting and intravenous proton pump inhibitor therapy in addition to blood transfusion improved the esophageal lesions within five to seven days in three patients. These cases indicate that desquamative esophagitis can occur in patients who receive hematopoietic stem cell transplantation. Although blood transfusions may be required, it can be resolved within seven days.

DOI： 10.2169/internalmedicine.4977-20

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DOI： 10.1111/pin.13022

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DOI： 10.2169/internalmedicine.5183-20

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DOI： 10.2169/internalmedicine.4940-20

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BACKGROUND: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. METHODS: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017. RESULTS: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). CONCLUSIONS: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.

DOI： 10.1186/s12876-020-01465-y

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Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is mainly associated with Helicobacter pylori infection, and H. pylori eradication therapy is often effective. However, 20-30% of the cases of MALT lymphoma are resistant to the eradication therapy, and translocation of the API2-MALT1 gene is often found in these cases. Most cases without translocation of API2-MALT1 are localized to the stomach, whereas some cases with this translocation are a more advanced stage of MALT lymphoma that spreads to other organs. The c-Met receptor is a prognostic factor involved in infiltration and metastasis in many malignant tumors, including gastric, pancreatic, lung, and kidney cancer. In the present study, the expression of c-Met in 43 cases of gastric MALT lymphomas was immunohistochemically examined and compared with clinicopathological factors. To elucidate the significance of c-Met in MALT lymphoma, the expression intensity of c-Met in 22 API2-MALT1 translocation-positive and 21 API2-MALT1 translocation-negative cases was scored, compared, and examined. The immunohistochemistry analysis revealed strong staining for c-Met in 21 API2-MALT1 translocation-positive cases and in 1 translocation-negative case (P = 0.00). This result indicates the relationship between strong expression of c-Met and the progression of MALT lymphoma with API2-MALT1 gene translocation.

DOI： 10.1007/s00795-019-00241-6

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Purpose: To evaluate the histological findings in both tumor and surrounding non-tumoral liver parenchyma after trans-arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) in patients who subsequently underwent hepatectomy.Material and methods: This study included six patients with an HCC (size 15-61 mm). DEB-TACE was performed using polyvinyl alcohol-based hydrogel microspheres loaded with epirubicin. Radiological tumor response was evaluated after DEB-TACE and before hepatectomy, according to the Modified Response Evaluation Criteria in Solid Tumors. Surgical specimens were histologically evaluated with hematoxylin and eosin, and elastic Van Gieson's staining.Results: Segmental, sub-segmental, or partial hepatectomy were performed 14-58 days after DEB-TACE. There was no remarkable destructive change and minimal to absent inflammatory cell infiltration in the surrounding non-tumoral liver parenchyma. There was no evidence of biliary tract or arterial wall impairment. Complete and partial histological tumor necrosis were found in three cases, respectively, in agreement with the complete and partial responses seen during the radiological evaluation.Conclusion: Histological examination of resected liver specimens after DEB-TACE showed substantial tumor necrosis without any severe inflammatory or destructive changes in the non-tumoral liver parenchyma.

DOI： 10.1080/13645706.2019.1626250

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PURPOSE: Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer. METHOD: We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen. RESULT: There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08). CONCLUSION: Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study.

DOI： 10.1007/s00280-020-04092-2

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BACKGROUND AND AIM: Underwater endoscopic mucosal resection (UEMR) has become widespread for treating colorectal polyps. However, which observational mode is best suited for determining polyp margins underwater remains unclear. To determine the best mode, we analyzed three imaging modes: white light imaging (WLI), blue laser imaging (BLI) and linked color imaging (LCI). METHODS: Images of consecutive colorectal polyps previously examined by these three modes before UEMR were analyzed according to the degree of underwater turbidity (transparent or cloudy). Color differences between the polyps and their surroundings were calculated using the Commission Internationale d'Eclairage Lab color space in which 3-D color parameters were expressed. Eight evaluators, who were blinded to the histology, scored the visibility from one (undetectable) to four (easily detectable) in both underwater conditions. The color differences and visibility scores were compared. RESULTS: Seventy-three polyps were evaluated. Sixty-one polyps (44 adenomatous, 17 serrated) were observed under transparent conditions, and 12 polyps (seven adenomatous, five serrated) were observed under cloudy conditions. Under transparent conditions, color differences for the BLI (8.5) and LCI (7.9) were significantly higher than that of WLI (5.7; P < 0.001). Visibility scores for BLI (3.6) and LCI (3.4) were also higher than that of WLI (3.1; P < 0.0001). Under cloudy conditions, visibility scores for LCI (2.9) and WLI (2.7) were significantly higher than that of BLI (2.2; P < 0.0001 and P = 0.04, respectively). CONCLUSIONS: BLI and LCI were better observational modes in transparent water; however, BLI was unsuitable for cloudy conditions.

DOI： 10.1111/den.13581

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There have been no comparative studies investigating the results of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with gastric mesenchymal tumors, including leiomyomas, leiomyosarcomas, schwannomas, and gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 142 patients with pathologically diagnosed gastric mesenchymal tumors treated at 11 institutions. We analyzed the correlation between the maximum standardized uptake value (SUVmax) evaluated using fluorodeoxyglucose-positron emission tomography (FDG-PET) and the tumor size. The correlation between the SUVmax and mitotic index was also investigated in GISTs. The SUVmax (mean ± standard deviation) was 0.5 ± 0.6 in very low-risk GISTs (n = 42), 2.1 ± 0.7 in low-risk GISTs (n = 26), 4.9 ± 0.8 in intermediate-risk GISTs (n = 22), 12.3 ± 0.8 in high-risk GISTs (n = 20), 1.0 ± 1.0 in leiomyomas (n = 15), 6.9 ± 1.2 in schwannomas (n = 10), and 3.5 in a leiomyosarcoma (n = 1). The SUVmax of GISTs with an undetermined risk classification was 4.2 ± 1.3 (n = 8). Linear associations were observed between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax of GISTs with a high mitotic index was significantly higher than that of GISTs with a low mitotic index (9.6 ± 7.6 vs. 2.4 ± 4.2). In conclusion, we observed positive correlations between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax also positively correlated with the mitotic index and risk grade in GISTs. Schwannomas showed a higher FDG uptake than GISTs and leiomyomas.

DOI： 10.3390/jcm9051301

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DOI： 10.1016/j.gie.2019.12.006

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OBJECTIVE: Flow cytometry has not been widely used in routine clinical practice for the diagnosis of gastrointestinal lymphoma; this is mainly because of the absence of an appropriate protocol. Here, we established a protocol for flow cytometric analysis of a single biopsy specimen from the gastrointestinal mucosa and investigated its sensitivity and specificity. DESIGN: In this prospective study, we enrolled patients with previously diagnosed gastrointestinal lymphoma and patients with gastrointestinal lesions that were suspected to be lymphoma. RESULTS: Overall, 15 patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (N=8), duodenal follicular lymphoma (grade 1; N=5), and benign lymphoid hyperplasia (ileum, N=1, and rectum, N=1) were included in this study. Of these, lymphocytes were isolated from 14 patients (93.3%). There were 200,000-1,500,000 viable cells per patient. Biopsy specimens from 10 out of the 12 patients with lymphoma were positive for light chain restriction; the two patients with benign lymphoid hyperplasia showed negative results. CONCLUSIONS: An adequate number of lymphocytes for flow cytometry could be isolated from a single specimen of endoscopic mucosal biopsy from 93.3% of the patients. Overall, the sensitivity of flow cytometric analysis of light chain expression for the diagnosis of B-cell lymphoma was 83.3%, and the specificity was 100%. Although further investigation is required as the sample size of the present study was small, our study suggests a potential option for diagnosing B-cell lymphoma in the gastrointestinal mucosa.

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Lanthanum carbonate is used for treatment of hyperphosphatemia mostly in patients with chronic renal failure. Although lanthanum carbonate is safe, recently, lanthanum deposition in the gastrointestinal mucosa of patients has been reported in the literature. This review provides an overview of gastroduodenal lanthanum deposition and focuses on disease's endoscopic, radiological, and histological features, prevalence, and outcome, by reviewing relevant clinical studies, case reports, and basic research findings, to better understand the endoscopic manifestation of gastrointestinal lanthanum deposition. The possible relationship between gastric lanthanum deposition pattern and gastric mucosal atrophy is also illustrated; in patients without gastric mucosal atrophy, gastric lanthanum deposition appears as diffuse white lesions in the posterior wall and lesser curvature of the gastric body. In the gastric mucosa with atrophy, lanthanum-related lesions likely appear as annular or granular whitish lesions. Moreover, these white lesions are probably more frequently observed in the lower part of the stomach, where intestinal metaplasia begins.

DOI： 10.3748/wjg.v26.i13.1439

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The aim of this study was to explore enhancement patterns of different types of primary lung cancers on 2-phase dynamic computed tomography (CT). This study included 217 primary lung cancer patients (141 adenocarcinomas [ADs], 48 squamous cell carcinomas [SCCs], 20 small cell lung carcinomas [SCLCs], and 8 others) who were examined using a 2-phase dynamic scan. Regions of interest were identified and mean enhancement values were calculated. After excluding the 20 SCLCs because these lesions had different clinical stages from the other cancer types, the mean attenuation values and subtractions between phases were compared between types of non-small cell lung carcinomas (NSCLCs) using the Kruskal-Wallis test. Late phase attenuation and attenuation of the late minus unenhanced phase (LMU) of SCCs were significantly higher than those of ADs (p<0.05). To differentiate SCC and AD in the late phase, a threshold of 80.21 Hounsfield units (HU) gave 52.9% accuracy. In LMU, a threshold of 52.16 HU gave 59.3% accuracy. Dynamic lung CT has the potential to aid in differentiating among NSCLC types.

DOI： 10.18926/AMO/58271

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Intestinal graft-vs.-host disease (GVHD) is a serious complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Villous atrophy in the terminal ileum is considered a useful diagnostic indicator for GVHD. However, the inter- and intra-observer agreement regarding the ileocolonoscopic findings indicative of acute intestinal GVHD, i.e., villous atrophy in the terminal ileum, are currently insufficient in multiple institutions. Thus, the present study aimed to investigate the incidence of villous atrophy in the terminal ileum to diagnose acute intestinal GVHD and determine the inter- and intra-observer agreement regarding this result for experienced endoscopists from multiple institutions. Consecutive patients who underwent allo-HSCT were referred to our institution between May 2008 and September 2015. A total of 54 patients underwent total ileocolonoscopy after allo-HSCT due to suspected intestinal acute GVHD. Subsequently, three observers from different institutions evaluated the cases for the presence of villous atrophy in the terminal ileum. In this study, the pathology results were a gold standard to evaluate the predictive value of ileocolonoscopy detection. Definitive pathological and non-pathological GVHD was diagnosed in 22 and 32 cases, respectively. The results of examining whether villous atrophy could predict GVHD were as follows. For three observers (A, B and C), the sensitivity of villous atrophy in the terminal ileum was 86.4, 77.3 and 79.2%, respectively, whereas the specificity was 62.5, 62.5 and 86.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of villous atrophy for GVHD were as follows: The PPV of appearance was 61.3, 58.6 and 82.6%, respectively, whereas the NPV was 87.0, 80.0 and 83.9%, respectively. Kappa coefficients for the inter-observer reliability were 0.85, 0.63 and 0.63 for observers A and B, A and C, and B and C, respectively. The intra-observer kappa coefficient was 0.88 for observer A, 0.73 for observer B and 0.75 for observer C. A substantial observer agreement was achieved for the analysis of villous atrophy in the terminal ileum and the agreement for the predictive histological diagnosis was also excellent. Based on the results of the present study, identification of villous atrophy in the terminal ileum was a clinically effective diagnostic parameter, even if different endoscopists were involved in the diagnosis at multiple institutions. The present study was registered as a trial with the University Hospital Medical Information Network (UMIN; registration no. UMIN000025390).

DOI： 10.3892/etm.2020.8538

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The aim of this study was to evaluate the ability of pretreatment 90-min 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to predict the extranodular spread of lymph node metastases in oral squamous cell carcinoma. We retrospectively reviewed the cases of 56 patients who underwent pretreatment 18F-FDG PET/CT and surgery with neck dissection. Maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were measured for the 56 primary sites and maximum standardized uptake value was measured for 115 lymph node levels. Extranodular spread was present at 9 lymph node levels in 7 patients. Significant differences were found in metabolic tumor volume and total lesion glycolysis of the primary site, and in lymph node maximum standardized uptake value, between patients with and without extranodular spread (p<0.05). Combining primary site total lesion glycolysis and lymph node maximum standardized uptake volume at their respective optimal cutoffs, the sensitivity, specificity, and accuracy for predicting extranodular spread were 89%, 92%, and 92%, respectively. Pretreatment 18F-FDG PET/CT is useful for predicting extranodular spread in patients with oral squamous cell carcinoma. The combined use of primary site total lesion glycolysis and lymph node maximum standardized uptake value showed greater predictive value than either predictor singly.

DOI： 10.18926/AMO/58270

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A 64-year-old Japanese man suffered cardiopulmonary arrest, which may have resulted from sepsis and/or hyperosmolar hyperglycemic non-ketonic coma, and was admitted after successful resuscitation. He had watery diarrhea on day 18 and was diagnosed with cytomegalovirus enterocolitis. In addition, computed tomography performed on day 27 and colonoscopy revealed gastric emphysema and intestinal pseudolipomatosis, respectively. This report is the first to describe a patient with cytomegalovirus enterocolitis and subsequent gastric emphysema and pseudolipomatosis. Gastrointestinal cytomegalovirus infection may underlie gastric emphysema and intestinal pseudolipomatosis, particularly in patients with relative or obvious immune dysfunction.

DOI： 10.2169/internalmedicine.3633-19

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DOI： 10.1016/j.cgh.2018.09.023

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A 55-year-old Japanese woman, who had been diagnosed with ulcerative colitis at 18 years of age, underwent screening endoscopy examinations. Esophagogastroduodenoscopy revealed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the stomach. Colonoscopy showed a slightly elevated reddish lesion with dilated microvessels but no erosions or ulcers. Although MALT lymphoma in the cecum was endoscopically suspected, flow cytometry and pathological analyses led to the diagnosis of appendiceal orifice inflammation in ulcerative colitis. This case highlights the diversity of the endoscopic appearance of appendiceal orifice inflammation in ulcerative colitis.

DOI： 10.1155/2020/8893604

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In this paper, we introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment. For lymphocyte isolation, an endoscopically harvested specimen and 5 mL of normal saline solution were placed in a wire mesh strainer set in a porcelain bowl. To obtain the lymphocyte suspension, the solid specimen was crushed using the rubber portion of a plunger of a 10 mL injection syringe. Flow cytometry was performed using the lymphocyte suspension. For validating our methods, the one-step lymphocyte isolation technique was used to perform flow cytometry on samples from 23 patients with (n = 12) or without (n = 11) gastrointestinal lymphoma. Flow cytometry of light chain expression was performed in all patient samples (feasibility: 100%). Sensitivity was 83.3% (10/12) and specificity was 100% (11/11). In conclusion, lymphocytes isolated from a single endoscopic biopsy specimen using our simplified and quick procedure are suitable for flow cytometry. Considering that flow cytometry has an important advantage of providing the results on the examination day itself, the results of this study suggest that flow cytometric analysis using our single-step lymphocyte isolation technique can be potentially used to diagnose lymphoma in the gastrointestinal mucosa. •We introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment.•Our technique is feasible for flow cytometric analysis in patients with gastrointestinal lymphoma as well as those with gastrointestinal lesions that are suspected to be lymphoma.

DOI： 10.1016/j.mex.2020.101095

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A 44-year-old Japanese woman with systemic lupus erythematosus (SLE) presented to our hospital with abdominal pain. Radiological and endoscopic examinations led to the diagnosis of diffuse large B-cell lymphoma of the jejunum, which was subsequently resected. Patients with SLE reportedly have an increased risk of non-Hodgkin lymphoma, as demonstrated by our patient. Hence, lymphoma should be considered in the differential diagnosis of neoplastic lesions emerging in SLE patients. In addition, flow cytometry using endoscopically biopsied fragments is useful for the immediate diagnosis of lymphoma, leading to timely and accurate preoperative staging.

DOI： 10.1155/2020/7947540

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A 77-year-old Japanese man with bronchial asthma was treated with dupilumab. Dupilumab treatment was discontinued at the patient's request after two injections separated by a 2-week interval. The blood eosinophil count was elevated, and an esophagogastroduodenoscopy performed 3 months after dupilumab treatment revealed gastric ulcers; subsequently, eosinophilic gastritis was diagnosed from biopsy examinations. The gastric lesions were resolved by steroid administration. This case report underscores that eosinophil-associated gastrointestinal diseases should be considered in the differential diagnosis of gastric lesions occurring in patients who were treated with dupilumab.

DOI： 10.1155/2020/6381670

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BACKGROUND/AIMS: The Kyoto Classification of Gastritis was published in 2014. Although this classification is now widely used in Japan, its usefulness and convenience have not been sufficiently evaluated. This study aimed to evaluate the usefulness and convenience of this classification in the endoscopic diagnosis of Helicobacter pylori infection. METHODS: We made a test for the endoscopic diagnosis of H. pylori infection comprising 30 cases who had representative endoscopic features of non-, active, or inactive gastritis. Thirty-eight participants took the test before and after a brief mini-lecture on the Kyoto Classification of Gastritis. Eighteen participants took the test again 3 months later. We investigated the accuracy before, just after, and 3 months after the mini-lecture. RESULTS: The accuracy of endoscopists after the lecture was significantly improved in comparison to before the lecture (77.6 vs. 83.3%). Medical students also showed significantly improved accuracy after the lecture (56.7 vs. 71.7%). Among endoscopists, this improvement was maintained after 3 months. Before the lecture, the accuracy of diagnosing non-gastritis was 90.3%; it tended to be further improved 3 months later (96.5%). A >10% point increase was observed in diagnosing active (72.7-83.3%) and inactive gastritis (73.2-84.3%) at 3 months after the lecture in comparison to before the lecture. CONCLUSION: A brief mini-lecture on the Kyoto Classification of Gastritis improved the accuracy in the endoscopic diagnosis of gastritis, indicating that understanding this classification is useful for the prompt diagnosis of H. pylori infection during esophagogastroduodenoscopy.

DOI： 10.1159/000502573

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Primary intraocular lymphomas frequently develop into central nervous system lymphomas and vice versa. This study reviewed 22 consecutive patients with primary intraocular lymphoma diagnosed by immunostaining of vitrectomy cell blocks, and examined whether they developed central nervous system lymphoma. Seventeen patients developed central nervous system lymphoma: 3 patients developed intraocular and central nervous system lymphoma simultaneously, 9 patients developed central nervous system lymphoma 1 month to 5 years (median, 3 months) after intraocular lymphoma, and 5 patients developed central nervous system lymphoma preceding the diagnosis of intraocular lymphoma by 3 months to 9 years and 8 months (median, 1.5 years). In contrast, 5 patients did not develop central nervous system lymphoma: 2 patients did not develop local recurrence or central nervous system lymphoma in the follow-up period of 5 years and 11 years, respectively, after vitrectomy alone without additional local or systemic treatment. The remaining 3 patients with intraocular lymphoma had insufficient follow-up periods to determine the prognosis. The results of CD5 immunostaining of vitrectomy specimens were found in pathology reports of 8 patients: 3 patients with CD5-positive large cells and 4 patients with CD5-negative large cells developed central nervous system lymphoma. In summary, only a small number of patients did not develop central nervous system lymphoma based on long-term follow-up after vitrectomy alone. CD5 was not a marker of central nervous system involvement in this study population.

DOI： 10.3960/jslrt.19019

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A 60-year-old Caucasian male was diagnosed with lung adenocarcinoma and multiple metastases to the bone, spleen, and brain. He underwent radiotherapy for the brain and lumbar spine metastases, plus chemotherapy (cisplatin and pemetrexed). The chemotherapy was discontinued due to vomiting and hyponatremia, and nivolumab was then administered. Eight months later, 18F-fluorodeoxyglucose positron emission tomography showed tracer uptake in the colon. Colonoscopy revealed a reddish multinodular polyp in the sigmoid colon. The polyp showed irregular microvessels. No colonic mucosal surface structures were observed. Colonic metastasis of the lung carcinoma was highly suspected; the polyp was therefore surgically removed. The histological analysis revealed granulation tissue and suppurative inflammation without neoplastic changes. We diagnosed the lesion as a granulation polyp. Despite the difficulty in diagnosing these lesions due to their rarity and similarity to metastatic colon tumors, we suggest that recognizing the endoscopic features of the polyp surface may allow a preoperative diagnosis.

DOI： 10.18926/AMO/57377

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Castleman-Kojima disease, also known as idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO), is a recently recognized systemic inflammatory disorder with a characteristic series of clinical symptoms, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Patients with iMCD-TAFRO often develop severe abdominal pain, elevated alkaline phosphatase levels, and systemic inflammation, but the etiological factors are unknown. To investigate the potential role of bacterial infection in the pathogenesis of iMCD-TAFRO, we performed polymerase chain reaction (PCR) for the bacterial 16S rRNA gene with DNA extracted from liver specimens of three patients with iMCD-TAFRO, four patients with amyotrophic lateral sclerosis, and seven patients with inflammatory conditions. Sequencing of the PCR product showed 99% DNA sequence identity with Campylobacter jejuni in all three patients with iMCD-TAFRO and in two patients with inflammatory conditions. Immunohistochemical and electron microscopy analyses could not identify C. jejuni in patients with iMCD-TAFRO. The findings indicated that C. jejuni infection is not the pathological cause of iMCD-TAFRO; however, this ubiquitous bacterium may play a role in uncontrolled systemic hypercytokinemia, possibly through the development of cross-reactive autoantibodies.

DOI： 10.1111/pin.12856

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OBJECTIVE: Gastrointestinal tract lymphomas are currently detected more frequently due to advances in endoscopic technology. The aim of this study was to assess the feasibility of flow cytometric analysis of restricted light chain in endoscopic biopsy specimens for the diagnosis of gastrointestinal tract B-cell lymphoma. We prepared viable cell suspensions from unfixed specimens obtained from 10 consecutive patients who had a previous histological diagnosis of gastrointestinal tract B-cell lymphoma. We performed immunophenotypic studies with multi-color flow cytometry and assessed clonality through examination of immunoglobulin light chain expression exclusively in a population identified by anti-CD45 or CD20 antibodies. RESULTS: We could perform light chain expression analysis with 2 endoscopic biopsy specimens from all 10 patients with gastrointestinal tract B-cell lymphoma. We conclude that flow cytometric analysis of endoscopic biopsy specimens is feasible and thus likely useful for the diagnosis of gastrointestinal tract B-cell lymphoma in clinical settings. Trial registration UMIN Clinical Trials Registry, UMIN000027730. Registered 12 June 2017.

DOI： 10.1186/s13104-019-4578-4

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BACKGROUND AND AIM: Although sporadic non-ampullary duodenal adenoma is speculated to be precancerous lesion, the relationship between adenoma and carcinoma remains unclear due to their rarity. Previous studies on sporadic non-ampullary duodenal epithelial neoplasm (SNADEN) have mainly targeted superficial tumors, like adenoma and early carcinoma. The clinicopathological features, including those of advanced carcinoma, remain poorly investigated. We assessed the clinicopathological features of SNADEN, including advanced carcinoma, focusing on tumor location. METHODS: We retrospectively collected the data of 410 patients who had been clinically and pathologically diagnosed with SNADEN at 11 institutions in Japan between June 2002 and March 2014. RESULTS: The SNADEN was mucosal neoplasia and invasive carcinoma in 321 (78.3%) and 89 (21.7%) patients, respectively. The proportion of invasive carcinomas in SNADEN was significantly higher on the oral side of the papilla of Vater (oral-Vater) than on the anal side (anal-Vater) (27.9% vs 14.4%, P < 0.001). Undifferentiated-type carcinoma was significantly more frequent with oral-Vater than anal-Vater (38.7% vs 14.8%, P = 0.026). The recurrence rate of surgically R0 resected locally advanced carcinomas was significantly higher with oral-Vater than anal-Vater (46.4% vs 8.3%, P = 0.021). Furthermore, the relapse-free survival with oral-Vater was significantly shorter than with anal-Vater (hazard ratio: 2.35; 95% confidence interval: 1.09-5.50; P = 0.028). CONCLUSIONS: The clinicopathological features of SNADEN on oral-Vater were different from those on anal-Vater. SNADEN on oral-Vater was more likely to be invasive carcinomas and might behave more aggressively due to biologically higher malignancy than that on anal-Vater.

DOI： 10.1111/jgh.14640

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DOI： 10.1016/j.gie.2019.04.221

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Objective This study aimed to investigate the endoscopic features of lanthanum-associated duodenal lesions and the prevalence of duodenal involvement among patients with pathologically proven lanthanum deposition in the gastrointestinal tract. Methods We retrospectively reviewed 24 patients with pathologically proven lanthanum deposition in the gastrointestinal tract. Patients were subdivided into three groups: Group A, patients with pathologically-proven lanthanum deposition in the duodenum; Group B, patients without lanthanum deposition in the duodenum; and Group C, patients without a biopsy of the duodenum. Results A biopsy examination of the duodenum was performed in 19 patients, and lanthanum deposition was detected in 17 patients (17/19, 89.5%). In group A (n=17), whitish duodenal villi were detected in 15 patients during esophagogastroduodenoscopy (15/17, 88.2%). While the other two patients showed no whitish villi, a biopsy of the duodenal mucosa revealed lanthanum deposition. The deposition of a white substance showing a clear margin was visible within multiple villi under magnified observation in some patients of group A. Group B patients (n=2) also showed whitish villi. However, the whitish color was faint in one case and sparse in the other case. Conclusion Lanthanum deposits in the duodenum may resemble white villi. However, in some cases, these deposits may be unrecognizable during esophagogastroduodenoscopy due to the subtle degree of deposition. Endoscopists should biopsy the duodenum as well as the stomach, regardless of the presence or absence of white villi, for an accurate determination of lanthanum deposition in the gastrointestinal tract.

DOI： 10.2169/internalmedicine.2398-18

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Objective: Keratin 19 (K19) expression is a potential predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). To clarify the feature of K19-proficient HCC, we traced epigenetic footprints in cultured cells and clinical materials. Patients and Methods: In vitro, KRT19 promoter methylation was analyzed and 5-aza-2'-deoxycytidine with trichostatin A (TSA) treatment was performed. Among 564 surgically resected HCCs, the clinicopathological relevance of K19-proficent HCCs was performed in comparison with hepatocytic (HepPar-1 and arginase-1), epithelial-mesenchymal transition (E-cadherin and vimentin), biliary differentiation-associated (K7 and NOTCH-1) markers, and epigenetic markers (KRT19 promoter/long interspersed nucleotide element-1 [LINE-1] methylation status). Results: KRT19 promoter methylation was clearly associated with K19 deficiency and 5-aza-2'-deoxycytidine with TSA treatment-stimulated K19 re-expression, implicating DNA methylation as a potential epigenetic process for K19 expression. After excluding HCCs with recurrence, TNM stage as IIIB or greater, preoperative therapy, transplantation, and combined hepatocellular cholangiocarcinoma, we assessed 125 of 564 HCC cases. In this cohort, K19 expression was found in 29 HCCs (23.2%) and corresponded with poor survival following surgery (p = 0.025) and extrahepatic recurrence-free survival (p = 0.017). Compared with K19-deficient HCCs, lower KRT19 promoter methylation level was observed in K19-proficient HCCs (p < 0.0001). Conversely, HCC with genome-wide LINE-1 hypermethylation was frequently observed in K19-proficient HCCs (p = 0.0079). Additionally, K19 proficiency was associated with K7 proficiency (p = 0.043), and reduced E-cadherin and HepPar-1 expression (p = 0.043 and p < 0.0001, respectively). Conclusions: K19-proficient HCC exhibited poor prognosis owing to extrahepatic recurrence, with molecular signatures differing from those in conventional cancer stem cells, providing novel insights of the heterogeneity underlying tumor development.

DOI： 10.1159/000490806

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Here, we report a highly unusual case of high-grade glioneuronal tumor with a neurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. The tumor was diagnosed as a high-grade glioneuronal tumor, unclassified. Methylation profiling classified it as a diffuse leptomeningeal glioneuronal tumor (DLGNT) with low confidence. This tumor showed genotypes frequently found in DLGNT such as 1p/19q codeletion without IDH mutation and, however, did not have the typical DLGNT clinical and histological features. RNA sequencing identified an ARHGEF2 (encoding Rho/Rac guanine nucleotide exchange factor 2)-NTRK1 fusion gene. The presence of recurrent NTRK fusion in glioneuronal tumors has an important implication in the clinical decision making and opens up a possibility of novel targeted therapy.

DOI： 10.1007/s10014-019-00345-y

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Intrapulmonary solitary fibrous tumors (SFTs) are extremely rare neoplasms. We report a case of an intrapulmonary SFT and describe the findings of computed tomography (CT) and F-18 fluorodeoxyglucose positron emission tomography. The case indicates that a benign intrapulmonary SFT can present as a ground-glass nodule in the early stages of disease and may appear as a well-defined, lobular, homogeneously enhanced mass with slow growth on chest CT images. To our knowledge, this is the first report describing the natural course of an intrapulmonary SFT over 16 years based on the findings of chest CT and F-18 fluorodeoxyglucose positron emission tomography/CT.

DOI： 10.1016/j.radcr.2019.03.023

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DOI： 10.1016/j.gie.2019.02.007

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BACKGROUND: The details of gastric cancer in young patients remain unclear because of the low prevalence of the disease. This study aimed to clarify the clinicopathological features and prognosis of gastric cancer in young patients. METHODS: From January 2007 to January 2016, patients in their 20s and 30s who were diagnosed with primary gastric cancer at 4 hospitals were enrolled. Their clinical characteristics and prognosis were evaluated. RESULTS: The total number of patients was 72. The median age was 36 years, and the ratio of males to females was 1:1. The dominant histological type was undifferentiated type (66/72, 92%). Helicobacter pylori (H. pylori) was positive in 81% (54/67). Although there were some asymptomatic patients in stages I-III, all stage IV patients had some clinical symptoms at the diagnosis. The percentage of stage IV was significantly higher in patients in their 20s than in those in their 30s (75% vs. 25%, P < 0.001). The Kaplan-Meier method showed that the overall survival of patients in their 20s was significantly lower than that of patients in their 30s (P = 0.037). CONCLUSIONS: A high rate of H. pylori infection was revealed in young gastric cancer patients. The patients in their 20s had a worse prognosis than those in their 30s. We should consider examining the H. pylori infection status for young patients as well as older patients to identify high-risk populations.

DOI： 10.1007/s00535-018-1525-4

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Pulmonary pleomorphic carcinoma (PPC) is a rare very aggressive subtype of non-small cell lung cancer. We herein report a case of PPC that showed a rapid response to nivolumab. The patient, whose multiple tumors had progressed very aggressively, was treated with nivolumab, an anti-programmed cell death-1 (PD-1) antibody. The tumors dramatically shrank after one cycle of nivolumab. The tumors were positive for programmed cell death ligand 1 (PD-L1). An immunohistochemical analysis revealed numerous PD-1+, CD68+ and CD206+ macrophages. This PD-1 antibody may be a good treatment option, especially in tumors that express PD-L1 and which show PD-1+ macrophage infiltration.

DOI： 10.2169/internalmedicine.0890-18

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The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of superficial pharyngeal cancer, and the efficacy and safety of ESD, we retrospectively assessed 70 pharyngeal cancers in 59 patients who underwent ESD. Of these patients, 61.0% and 50.8% had a history of esophageal cancer and head and neck cancer, respectively. The median tumor size was 15 mm, and 75.7% of the lesions were located at the piriform sinus. The en bloc resection rate was 94.9%. Treatment-related adverse events occurred in 8 cases, but there was no treatment-related death. The lateral margin was positive for neoplasm in 3 lesions (4.3%) and inconclusive in 27 lesions (38.6%), but no local recurrence was observed. Cervical lymph node metastasis was observed in 6 patients, and was successfully treated by cervical lymph node dissection. The three-year overall survival rate was 91.5% (95%CI: 76.6-97.3%) and the cause-specific survival rate was 97.6% (95%CI: 84.9-99.7%). In conclusion, ESD for superficial pharyngeal cancer was safe and effective. "Resect and watch" is probably a feasible and rational strategy for treatment of patients with superficial pharyngeal cancer.

DOI： 10.18926/AMO/56646

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While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

DOI： 10.1038/s41598-019-41177-2

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DOI： 10.1016/j.diii.2018.12.001

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DOI： 10.1016/j.gie.2018.08.044

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DOI： 10.1016/j.dld.2018.07.031

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DOI： 10.1177/2324709619888052

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In this report, we describe two cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the stomach, which presented with multiple small, whitish nodules in the gastric body. The endoscopic appearance was similar to that of lymphoid follicular hyperplasia found in follicular gastritis or nodular gastritis. Both patients were positive for Helicobacter pylori, and the eradication treatment resulted in complete remission of the lymphoma. However, recurrence was noted in one patient. These cases indicate that, although infrequent, gastric MALT lymphoma can show a nodular appearance resembling that of follicular gastritis.

DOI： 10.3332/ecancer.2019.933

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Background: Clinical characteristics and prognosis of patients with a solitary Peutz-Jeghers polyp (PJP) have not been fully investigated. Methods: Solitary PJP was diagnosed when a single hamartomatous lesion was identified in the gastrointestinal tract of patients without mucocutaneous pigmentation or a family history of Peutz-Jeghers syndrome. We retrospectively reviewed 51 patients (32 men and 19 women) with a solitary PJP and analyzed the sex, age at diagnosis, endoscopic features, and outcomes in this patient group. The STK11/LKB1 germline mutation was not investigated in any of the patients. Results: The mean age of the 51 patients was 66.1 years. The polyp was found in the duodenum (N = 10), jejunum (N = 2), cecum (N = 2), transverse colon (N = 5), sigmoid colon (N = 21), or rectum (N = 11). Most of the polyps presented as a pedunculated lesion (N = 40), followed by semipedunculated (N = 9) and sessile (N = 2) morphologies. The mean size of a solitary PJP was 15.6 mm (range: 5 to 33 mm). During a mean endoscopic follow-up period of 4.5 years (range: 0.1 to 16.1 years), no recurrence was identified. Eighteen of the enrolled patients had a history of cancer or concomitant cancer. Five patients died due to non-gastrointestinal-related causes. No additional cancer or death directly related to solitary PJP was observed. Conclusions: Solitary PJPs did not recur in this study. Although examination of the entire gastrointestinal tract using esophagogastroduodenoscopy, enteroscopy, and colonoscopy is desirable to exclude Peutz-Jeghers syndrome, follow-up endoscopy after endoscopic polyp resection may be unnecessary, once the diagnosis of a solitary PJP is made.

DOI： 10.1155/2019/8159072

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DOI： 10.3960/jslrt.18026

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The incidence of lymphoma has rapidly increased over the last 40 years in Japan, following a trend that is very similar to that of breast cancer. In particular, the relative frequency of follicular lymphoma (FL) has reached that in Western countries. Given its indolence, a "watch-and-wait" approach is often applied to FL patients. We have shown that FL is often detected in the second portion of the duodenum and has a distinct follicular dendritic cell distribution and heavy chain variable usage similar to mucosa-associated lymphoid tissue (MALT) lymphoma. Although the t(14;18)(q32;q21) frequency is the same as in the nodal subtype of FL, there are also ongoing mutations, immunopositivity for cluster of differentiation 10 and B-cell lymphoma (BCL)6, and overexpression of BCL2. Gene expression profiling has shown that it is more similar to gastric MALT lymphoma than to nodal FL. Duodenal-type FL lacks the activation-induced cytidine deaminase (AID) expression observed in nodal ones, although this may be compensated for by BTB domain and CNC homolog 2. Based on these findings, duodenal-type FL has been included in the Revised 4th edition of the World Health Organization classification published in late 2017.

DOI： 10.1111/pin.12733

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Pancreatic cancer has a poor prognosis; hence, novel prognostic markers and effective therapeutic targets should be identified. We aimed to evaluate folate receptor alpha (FR-α) expression in pancreatic cancer and examine its association with clinicopathological features. We utilized tissue samples from 100 primary pancreatic cancer patients who underwent surgery. FR-α was expressed in 37 of 100 cases (37%). The FR-α-positive group (median, 18.8 months) had a significantly poorer prognosis than the FR-α-negative group [median 21.3 months; HR 1.89 (1.12-3.12); P = 0.017]. These groups were not significantly different regarding progression-free survival (P = 0.196). Furthermore, other serum tumor markers including CA19-9 (mean, 186 vs. 822 U/ml; P = 0.001), Dupan-2 (286 vs. 1133 U/ml; P = 0.000), and Span-1 (69.7 vs. 171.9 U/ml; P = 0.006) were significantly downregulated in the FR-α-positive group. CA19-9 was another prognostic factor, in addition to FR-α, and patient prognosis showed clear stratification curves with the expression of these two molecules. Along with CA19-9, FR-α expression was an independent prognostic factor for the overall survival. FR-α and CA19-9 helped predict patient prognosis based on stratification curves.

DOI： 10.1007/s00795-018-0197-8

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A 74-year-old Japanese woman was diagnosed with pseudolipomatosis of the cecum and ascending colon. Colonoscopy was performed, which revealed the presence of slightly elevated white lesions, while a magnifying observation showed microbubbles within the mucosa. A month after colonoscopy, the patient was diagnosed with pneumatosis intestinalis. Although the exact pathogenesis is unclear, pneumatosis intestinalis may arise secondary to pseudolipomatosis. This case also indicates that a magnifying observation during colonoscopy may aid in the diagnosis of pseudolipomatosis of the large intestine, since it shows microbubbles within the mucosa, which may be a distinctive feature reflecting the pathology of this disease.

DOI： 10.2169/internalmedicine.0730-17

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A 72-year-old Japanese woman presented with a fever, diarrhea, intermittent spotting, and constant fluid discharge from the vagina. Imaging studies revealed an enterovaginal fistula. She underwent radical hysterectomy and radiotherapy 35 years previously. She also had a surgical history of nephrostomy, nephrectomy, ileoascending anastomosis, and colostomy. As bleeding from the enterovaginal fistula was uncontrollable, ileocecal resection was performed. However, a colovesical fistula with urinary tract infection occurred 3 months later. The present case indicates that fistula formation occurs and causes various symptoms in patients who underwent postpelvic radiotherapy, particularly in those with prior surgeries in the irradiated field.

DOI： 10.1002/jgf2.184

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A 69-year-old Japanese woman presented to our hospital for the further investigation of an esophageal subepithelial tumor. A diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was made by an endoscopic biopsy. The patient had no involvement other than the esophagus. The tumor was resected using endoscopic submucosal dissection. Lymphoma recurrence has not been documented in the 57 months since resection. This case suggests that although a detailed preoperative evaluation is required to determine the extent of tumor, endoscopic resection may be an option for the long-term disease control of MALT lymphoma of the esophagus.

DOI： 10.2169/internalmedicine.0487-17

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BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Endoscopic biopsy can provide a definitive diagnosis, but the optimal endoscopic approach for diagnosis remains uncertain. This study evaluated whether ileocolonoscopic imaging can predict acute GVHD severity after allo-HSCT. METHODS: Consecutive patients who underwent allo-HSCT were referred to our institution, and those diagnosed with acute GVHD by pathology were included in this retrospective study. RESULTS: Fifty-one of 261 patients who underwent ileocolonoscopy were suspected to have acute intestinal GVHD. We performed univariate and multivariate conditional logistic regression with stepwise variable selection; villous atrophy in the terminal ileum remained a statistically significant predictor of GVHD severity (odds ratio, 4.69; 95% confidence interval, 1.07-20.60, P = 0.04). Patients were classified into three groups based on ileal endoscopic findings in the terminal ileum: group S, GVHD with severe villous atrophy; group M, mild atrophy; and group N, no atrophy. Compared with patients in groups M and N, those in group S had significant clinical GVHD at diagnosis (P = 0.03). In group S, three of four, compared with five of 13 patients in groups M and N, required the addition of second-line agents (P = 0.02). CONCLUSIONS: This study showed that severe atrophy of the terminal ileum predicts severe clinical GVHD that is likely to be refractory to steroid treatment. Thus, the severity of terminal ileum atrophy may serve as a tool in predicting clinically severe GVHD. TRIAL REGISTRATION: Trial Registration Number UMIN 000022805 , Registration date July 1, 2016.

DOI： 10.1186/s12876-018-0829-4

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OBJECTIVE: Although lanthanum deposition in the stomach has been most frequently reported to occur as white lesions, no study has investigated whether the white lesions observed during esophagogastroduodenoscopy are truly lanthanum-related. Here, we retrospectively investigated the amount of lanthanum in endoscopic biopsy specimens. METHODS: We reviewed four patients showing gastric white spots or annular whitish mucosa in the gastric white lesions (Bw) and peripheral mucosa where the white substance was not endoscopically observed (Bp) during biopsy. We also reviewed three patients with diffuse whitish mucosa and three patients with no whitish lesions. We performed scanning electron microscopy and energy dispersive X-ray spectrometry to quantify the lanthanum elements (wt%) in the biopsy specimens. RESULTS: The amount of lanthanum in the Bw ranged from 0.15-0.31 wt%, whereas that of Bp was 0.00-0.13 wt%. The difference was statistically significant (P < 0.05). The amount of lanthanum in the Bw, endoscopically presented with white spots or annular whitish mucosa, was significantly higher than that of no whitish lesions (0.05-0.14 wt%, P < 0.05). The amount of lanthanum was also higher in the diffuse whitish mucosa (0.21-0.23 wt%) compared with no whitish lesions (P < 0.01). CONCLUSIONS: This study is the first to reveal that pathological lanthanum deposition corresponds to the endoscopically observed white lesions in the gastric mucosa. Therefore, during esophagogastroduodenoscopy, physicians should pay attention to possible presence of white lesions in patients treated with oral lanthanum carbonate to ensure prompt identification of associated issues.

DOI： 10.1016/j.prp.2018.05.024

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Objective Although esophageal granular cell tumors have been reported to present as hypoechoic tumors, we noticed that their echogenicity is similar to that of the submucosal layer. We investigated the sonographic features of esophageal granular cell tumors and the diagnostic accuracy of the features. Methods Seven patients with esophageal granular cell tumors who underwent endoscopic ultrasonography were retrospectively reviewed. Thirteen patients with esophageal leiomyoma were selected as historical control subjects. The brightness of the tumor on ultrasonography images was measured and the echogenicity was standardized according to the echogenicity of the proper muscle and submucosal layers. Ten board-certified endoscopists then independently evaluated the endoscopic pictures of the 20 patients (Test 1), as well as the endoscopic ultrasonography images together with endoscopic pictures of the same patient set (Test 2). Results The standardized echogenicity in granular cell tumors was significantly higher than that in leiomyomas. The diagnostic accuracy of the 10 evaluators using endoscopic pictures alone (Test 1) was 72.0%. The addition of endoscopic ultrasonography images (Test 2) significantly improved the accuracy to 93.0%. Conclusion The echogenicity of granular cell tumors was similar to that of the submucosal layer, and it was significantly higher than that of leiomyomas. Endoscopic ultrasonography images facilitate the accurate identification of esophageal granular cell tumors.

DOI： 10.2169/internalmedicine.9816-17

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© 2018 The Author(s). Immune checkpoint inhibitors such as ipilimumab, a cytotoxic T-lymphocyte-Associated antigen-4 inhibitor, have been widely used for advanced malignancies. As these inhibitors improve antitumor immunity via T-cell modulation, immune-mediated adverse events associated with T-cell activation, such as colitis, might occur. Herein, we describe a 75-year-old Japanese woman with metastatic malignant melanoma who developed hemorrhagic gastritis after ipilimumab treatment. There was no macroscopic or clinical improvement of gastritis after proton pump inhibitor treatment. However, her condition improved after approximately 3 weeks of corticosteroid therapy and Helicobacter pylori eradication. This case suggests a potential association between severe gastritis and immune checkpoint inhibitor treatment. Although several reports have mentioned ipilimumab-Associated colitis, gastritis is considered to be rare. In the present case, H. pylori-Associated gastritis might have been exacerbated by the T-cell modulation effect of ipilimumab. To date, no report has clarified the mechanism by which ipilimumab modifies H. pylori infection. The present treatment course provides a helpful perspective for similar cases.

DOI： 10.1159/000491862

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To analyze the clinical characteristics of patients with ulcerative colitis who have upper gastrointestinal lesions, we retrospectively reviewed the data of 216 patients with ulcerative colitis who underwent esophagogastroduodenoscopy at our institute in April 2008-March 2016. We investigated the endoscopic features and compared the clinical characteristics between the patients with and without upper gastrointestinal lesions. Forty-two patients (19.4%) had upper gastrointestinal lesions, including multiple erosions (n=18), bamboo joint-like appearance (n=17), mucosa with white spots (n=4), friable mucosa (n=2), ulcer (n=1), and purulent deposits within the mucosa (n=1) in the stomach and/or duodenum. Compared to the patients without upper gastrointestinal lesions, those with upper gastrointestinal lesions showed significantly more frequent extraintestinal manifestations (19.0% vs. 8.0%, p<0.05) and a significant history of colectomy (33.3% vs. 12.1%, p<0.01). There were no significant differences with regard to the sex ratio, age at esophagogastroduodenoscopy, gastrointestinal symptoms, time since the diagnosis of ulcerative colitis, type of colitis at the initial diagnosis of ulcerative colitis, or gastric atrophy between the groups. In conclusion, gastroduodenal lesions were identified in 19.4% of the patients with ulcerative colitis. Esophagogastroduodenoscopy is particularly recommended for ulcerative colitis patients who show extraintestinal manifestations and for those who have undergone a colectomy.

DOI： 10.18926/AMO/55850

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Immunoglobulin G4 (IgG4)-related disease is characterized by elevated serum IgG4 levels and increased numbers of IgG4-positive cells. However, its pathogenesis is not fully understood. We previously suggested that mast cells may play an important role in IgG4-related disease. In this study, we confirmed the characteristics of mast cells in IgG4-related lymphadenopathy by using immunohistochemistry and dual immunofluorescence. We analyzed 23 cases of IgG4-related lymphadenopathy and compared them with 23 cases of non-specific lymphoid hyperplasia. The majority of patients with IgG4-related lymphadenopathy had cervical lesions with involvement of other organs. Immunohistologically, mast cells with strong cytoplasmic staining for immunoglobulin E and high affinity immunoglobulin E receptor were significantly increased in IgG4-related lymphadenopathy as compared to those in non-specific lymphoid hyperplasia (mean: 3.83 ± 3.99 cells per high power field and 7.14 ± 8.21 cells per high power field, respectively; P = 0.007 and P = 0.011). In addition, dual immunofluorescence assay showed that immunoglobulin E and high affinity immunoglobulin E receptor staining exhibited a cytoplasmic granular pattern in IgG4-related lymphadenopathy, suggesting internalization of the antibodies and receptors. Our findings showed that mast cell activation might be involved in the pathogenesis of IgG4-related disease.

DOI： 10.1038/s41598-018-23043-9

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In this case report, we describe two patients who showed a diffusely whitish mucosa in the posterior wall and the lesser curvature of the gastric body. The patients were serologically- and histopathologically-negative for Helicobacter pylori. Random biopsy specimens from the stomach revealed no regenerative changes, intestinal metaplasia, and/or foveolar hyperplasia in either of the patients. Although lanthanum deposition in the gastric mucosa has been reported to occur in close association with H. pylori-associated gastritis, our patients tested negative for H. pylori. These cases suggest that lanthanum deposition presents as whitish lesions in the gastric body in H. pylori-negative patients.

DOI： 10.2169/internalmedicine.9665-17

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s12328-017-0795-3

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Other Link： http://link.springer.com/content/pdf/10.1007/s12328-017-0795-3.pdf

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BACKGROUND AND AIM: The safety of gastric endoscopic submucosal dissection (ESD) in the antithrombotic drug users remains controversial. METHODS: Patients who underwent gastric ESD at Okayama University Hospital between March 2006 and February 2016 were enrolled. This study investigated the risk of post-ESD bleeding according to the management of the antithrombotic drugs. RESULTS: One thousand twenty lesions (872 patients) were enrolled. In a multivariate analysis, heparin replacement (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.8-14), multiple antithrombotic drug use (OR 2.9, 95% CI 1.1-6.9), a resected specimen of ≥ 33 mm in diameter (OR 2.7, 95% CI 1.5-5.4), Helicobacter pylori negativity (OR 2.2, 95% CI 1.3-3.7), and tumors located in the lower third of the stomach (OR 1.7, 95% CI 1.0-2.9) were significant risk factors for post-ESD bleeding, while the continuation of aspirin or cilostazol was not (OR 2.6, 95% CI 0.72-7.8). The bleeding rate of the continuation group was comparable with that of the all cessation group among single antithrombotic drug users (4.5% vs 4.4%, P = 1.0); however, the rate of the continuation group was significantly higher than that of the all cessation group among multiple antithrombotic drug users (67% vs 15%, P = 0.020). CONCLUSIONS: The risk of post-ESD bleeding differed according to the management of the antithrombotic drugs. The gastric ESD under the cessation or continuation of aspirin or cilostazol monotherapy was acceptable. However, multiple antithrombotic drug use or heparin replacement was associated with a higher risk of post-ESD bleeding.

DOI： 10.1111/jgh.13872

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OBJECTIVE: To retrospectively evaluate the safety, diagnostic yield, and risk factors of diagnostic failure of computed tomography (CT) fluoroscopy-guided biopsies of anterior mediastinal masses. MATERIALS AND METHODS: Biopsy procedures and results of anterior mediastinal masses in 71 patients (32 women/39 men; mean [±standard deviation] age, 53.8±20.0years; range, 14-88years) were analyzed. Final diagnoses were based on surgical outcomes, imaging findings, or clinical follow-up findings. The biopsy results were compared with the final diagnosis, and the biopsy procedures grouped by pathologic findings into diagnostic success and failure groups. Multiple putative risk factors for diagnostic failure were then assessed. RESULTS: Seventy-one biopsies (71 masses; mean size, 67.5±27.3mm; range 8.6-128.2mm) were analyzed. We identified 17 grade 1 and one grade 2 adverse events (25.4% overall) according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Sixty-nine biopsies (97.2%) provided samples fit for pathologic analysis. Diagnostic failure was found for eight (11.3%) masses; the 63 masses diagnosed successfully included thymic carcinoma (n=17), lung cancer (n=14), thymoma (n=12), malignant lymphoma (n=11), germ cell tumor (n=3), and others (n=6). Using a thinner needle (i.e., a 20-gauge needle) was the sole significant risk factor for diagnostic failure (P=0.039). CONCLUSION: CT fluoroscopy-guided biopsy of anterior mediastinal masses was safe and had a high diagnostic yield; however, using a thinner biopsy needle significantly increased the risk of a failed diagnosis.

DOI： 10.1016/j.diii.2017.10.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a key therapy used for patients with EGFR-mutant non-small cell lung cancer (NSCLC), some of whom do not respond well to its therapy. Cytokine including IL-6 secreted by tumour cells is postulated as a potential mechanism for the primary resistance or low sensitivity to EGFR-TKIs. Fifty-two patients with advanced EGFR-mutant NSCLC who had received gefitinib were assessed retrospectively. The protein expression of IL-6 in the tumour cells was assessed by immunostaining and judged as positive if >= 50 of 100 tumour cells stained positively. Of the 52 patients, 24 (46%) and 28 (54%) were defined as IL-6-postitive (group P) and IL-6 negative (group N), respectively. Group P had worse progression-free survival (PFS) than that of group N, which was retained in the multivariate analysis (hazard ratio: 239; 95 %CI: 1.00-5.68; p < 0.05). By contrast, the PFS after platinum-based chemotherapy did not differ between groups P and N (p = 0.47). In cell line-based model, the impact of IL-6 on the effect of EGFR-TKIs was assessed. The combination of EGFR-TKI and anti-IL-6 antibody moderately improved the sensitivity of EGFR-TKI in lung cancer cell with EGFR mutation. Interestingly, suppression of EGFR with EGFR-TKI accelerated the activation of STAT3 induced by IL-6. Taken together, tumour IL-6 levels might indicate a subpopulation of EGFR-mutant NSCLC that benefits less from gefitinib monotherapy. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2017.10.175

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In this report, we described two patients with white globe appearance in autoimmune atrophic gastritis. Endoscopy revealed multiple white substances in the stomach in both cases. Biopsied specimens from the lesions contained dilated glands and showed a decrease in parietal cells. Intraglandular necrotic debris and carcinoma were absent. These results confirmed that white globe appearance can be observed in autoimmune atrophic gastritis. Moreover, microscopic features for white globe appearance observed in these cases were different from those reported previously in gastric cancer lesions and were similar to those observed for noncancerous stomach.

DOI： 10.1155/2018/7091520

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We describe two cases of leiomyoma in the colon that were diagnosed histologically after endoscopic resection. The first case was a 79-year-old Japanese woman who presented with a pedunculated polyp of 14 mm length at the splenic flexure. Preoperative diagnosis suggested a colonic mucosubmucosal elongated polyp. The second case was a 29-year-old Japanese woman who presented with a pedunculated polyp of 40 mm length at the hepatic flexure and had an ulcer on top of the polyp. Preoperative diagnosis suggested an inflammatory fibroid polyp. A pathological diagnosis of colonic leiomyoma was made after endoscopic resection in both cases. Both tumors were confirmed to originate, not from the proper muscle layer, but from the muscularis mucosae. These cases underscore that although colonic involvement is infrequent, leiomyomas can display pedunculated morphology in the colon rather than the typical gross appearance of gastrointestinal submucosal tumors seen with sessile morphology.

DOI： 10.1155/2018/8272313

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In this report, we describe two patients with white globe appearance in the non-cancerous stomach. The patient in Case 1 was an 82-year-old Japanese man who had been taking vonoprazan, dimethicone, acotiamide, sitagliptin, candesartan, dutasteride, etizolam and zolpidem. The patient in Case 2 was a 74-year-old Japanese woman who had been taking esomeprazole, rebamipide, sitagliptin, candesartan, ezetimibe, mirabegron, levocetirizine, zolpidem and lactobacillus preparation. In both cases, endoscopy revealed multiple white spots in the stomach. Magnifying endoscopy and blue laser imaging revealed a slightly elevated, round, white substance. Biopsied specimens from the lesions contained parietal cell protrusions and fundic gland cysts. Intraglandular necrotic debris was absent. Consequently, microscopic features in these cases were different from those reported previously for white globe appearance observed in gastric cancer lesions. These results indicate that white globe appearance can be observed in non-cancerous stomach. Although the macroscopic features could be confusing or misleading, thorough endoscopic observation and pathological analysis of white globe appearance will aid oncologists and endoscopists in differentiating between cancer-related lesions and non-cancerous lesions.

DOI： 10.3332/ecancer.2018.856

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A 62-year-old woman was diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with increased plasma cell differentiation of the stomach. Esophagogastroduodenoscopy showed slightly elevated, whitish lesions in the gastric body. Magnifying endoscopic observation revealed that the gastric surface epithelium was swollen, but the structure was not destroyed or diminished. Elongated, tortuous vasculature was observed on the surface of the whitish lesions. The patient underwent eradication treatment for Helicobacter pylori, which resulted in complete remission. Although the appearance of abnormal vessels and the destruction of gastric epithelial structure are the typical features of gastric MALT lymphoma during magnifying endoscopy, the present case showed different features, which were rather similar to those observed in a previously reported case of gastric plasmacytoma. The current case indicates that magnifying endoscopic features are not uniform among gastric MALT lymphomas.

DOI： 10.1155/2018/8054284

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 40-year-old Japanese man with abdominal pain was referred to our hospital. The patient had been diagnosed with Crohn's disease at the age of 21 years and had since then received treatment with mesalazine and had been advocated an elemental diet. About 30 months before his visit to the hospital, he had swallowed a patency capsule, the retention of which in the ileum was subsequently detected on abdominal ultrasonography. The patient was advised to undergo the evaluation of stenosis, but he refused further investigation at that time. Computed tomography scanning performed at our institution revealed stenosis of the ileum and the presence of a high-density material in the proximal side of the stenosis. Double-balloon enteroscopy and enterography with contrast media revealed multiple stenoses of the ileum. The stenotic ileum was surgically resected, and a foreign body was removed. Electron microscopy analysis revealed that the foreign body was the cellophane wall of the PillCamTM patency capsule. Thus, the retention of the cellophane wall of a patency capsule after consumption was diagnosed for the current case on the basis of the study findings.

DOI： 10.11405/nisshoshi.115.203

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 75-year-old woman visited our hospital for the examination of esophagogastroduodenoscopy (EGD) without any major complaint. The patient's medical history included hypertension, but no carcinoma. EGD revealed a 30-mm elevated lesion located in the anterior wall of the upper region of the stomach. The lesion, which was a 0-IIa+I type lesion with fading-like and light flare-like domains, was surgically removed using endoscopic submucosal dissection (ESD) and then the patient was diagnosed with gastric type adenoma with submucosal invasive carcinoma. To the best of our knowledge, this is the first report of a gastric type adenoma with submucosal invasive carcinoma and may therefore provide significant insights into the malignant potential of gastric type adenoma lesions.

DOI： 10.11405/nisshoshi.115.283

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A 67-year-old Japanese man with neurofibromatosis type 1 underwent right hemicolectomy owing to abscess formation around the cecum. A pathological analysis revealed diffuse intestinal ganglioneuromatosis in the cecum and colon. Colonoscopy performed eight months after hemicolectomy revealed multiple ulcers throughout the colon and rectum. The colorectal ulcers failed to respond to conservative treatment and ultimately required surgical resection. Diffuse ganglioneuromatosis was observed again in the resected specimen. This report illustrates a rare manifestation of diffuse intestinal ganglioneuromatosis in a patient with neurofibromatosis type 1.

DOI： 10.2169/internalmedicine.8671-16

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Background and study aims:  Linked color imaging (LCI) and blue laser imaging (BLI) are novel image-enhanced endoscopy technologies with strong, unique color enhancement. We investigated the efficacy of LCI and BLI-bright compared to conventional white light imaging (WLI) by measuring the color difference between early gastric cancer lesions and the surrounding mucosa. Patients and methods:  Images of early gastric cancer scheduled for endoscopic submucosal dissection were captured by LCI, BLI-bright, and WLI under the same conditions. Color values of the lesion and surrounding mucosa were defined as the average of the color value in each region of interest. Color differences between the lesion and surrounding mucosa (ΔE) were examined in each mode. The color value was assessed using the CIE L*a*b* color space (CIE: Commission Internationale d'Eclairage). Results:  We collected images of 43 lesions from 42 patients. Average ΔE values with LCI, BLI-bright, and WLI were 11.02, 5.04, and 5.99, respectively. The ΔE was significantly higher with LCI than with WLI ( P  < 0.001). Limited to cases of small ΔE with WLI, the ΔE was approximately 3 times higher with LCI than with WLI (7.18 vs. 2.25). The ΔE with LCI was larger when the surrounding mucosa had severe intestinal metaplasia ( P  = 0.04). The average color value of a lesion and the surrounding mucosa differed. This value did not have a sufficient cut-off point between the lesion and surrounding mucosa to distinguish them, even with LCI. Conclusion:  LCI had a larger ΔE than WLI. It may allow easy recognition and early detection of gastric cancer, even for inexperienced endoscopists.

DOI： 10.1055/s-0043-117881

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Language：English   Publisher：OXFORD UNIV PRESS  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBLISHING GROUP INC  

AIM
To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1.
METHODS
This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11; 18) translocation. Patients were subdivided into patients without t(11; 18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11; 18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated.
RESULTS
Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (p = 0.10).
CONCLUSION
Patients with t(11; 18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11; 18) translocation or extra copies of MALT1.

DOI： 10.3748/wjg.v23.i33.6155

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BACKGROUND: Although ectopic pancreatic tissue is common in the upper gastrointestinal tract, the incidence of ectopic pancreatic tissue in the jejunum is low, and malignant transformation in ectopic pancreatic tissue is rare. Furthermore, pancreatic-type acinar cell carcinoma (ACC) developing in the jejunum and ACC accompanied by tumor thrombus are extremely rare. CASE PRESENTATION: A 78-year-old-woman presented with melena. Abdominal computed tomography images and endoscopic examination revealed a submucosal jejunal mass with tumor thrombus extending into a jejunal vein. The patient underwent a curative resection combined with a partial jejunectomy and partial pancreatectomy. Histopathological examination of the resected tissue showed tumor cells with a homogeneous acinar architecture identical to pancreatic-type ACC and tumor thrombus. Postoperatively, she was followed for 10 months and had no recurrence. CONCLUSION: We present an extremely rare case of pancreatic-type ACC in the jejunum with extensive tumor thrombus invading into the mesenteric venous system. This type of cancer has not been reported previously but should be considered in the differential diagnosis of a jejunal mass.

DOI： 10.1186/s12893-017-0273-3

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BACKGROUND: Endoscopic resection (ER) has been widely accepted as the standard treatment for early gastric cancer (EGC). However, in patients considered to have undergone non-curative ER due to their potential risk of lymph node metastasis (LNM), additional gastrectomy is recommended. The aim of the present study was to identify EGC patients after non-curative ER at high risk of LNM. METHODS: A total of 150 patients who had undergone ER for EGC were diagnosed as non-curative ER due to their potential risk of LNM. Clinicopathological data and clinical outcomes were examined retrospectively. RESULTS: Additional gastrectomy with lymph node dissection was performed in 73 patients, and the remaining 77 patients were followed-up without additional gastrectomy. In patients who underwent additional gastrectomy, 8 patients had local residual tumor, and 8 patients had LNM, which were limited in the peritumoral nodes. Only lymphatic invasion (p = 0.012) was a statistically significant factor for LNM. The 5-year overall survival and recurrence-free survival were not significantly different between patients with and without additional gastrectomy. CONCLUSION: Additional gastrectomy with lymph node dissection is recommended for patients who were diagnosed as non-curative ER with lymphatic invasion, and minimizing the extent of lymph node dissection may be allowed for these patients.

DOI： 10.1186/s12893-017-0268-0

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Language：English   Publisher：WILEY  

Patients with Down syndrome (DS) have a markedly higher incidence of childhood leukemia, but a lower incidence of most solid tumors, compared with age-matched euploid individuals. Trisomy 21 might be protective against tumorigenesis because of several tumor suppressive mechanisms. Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterized by a variable clinical course. In recent reports, almost all cases of DF involved genomic alterations associated with activation of the Wnt/β-catenin pathway. Here, we report the case of a boy with DS who developed DF without activation of the Wnt/β-catenin pathway. To the best of our knowledge, this is the first case of DS involving DF.

DOI： 10.1111/ped.13241

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Language：English   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2016.06.012

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INTRODUCTION: We presented the first case in the literature of inter-horn bridge formation involved in ring-shaped lateral meniscus after anterior cruciate ligament (ACL) reconstruction. PRESENTATION OF CASE: A 22-year-old man underwent anatomic double-bundle ACL reconstruction using semitendinosus tendon autograft. At the surgery, the lateral meniscus showed a normal appearance without meniscal tears and had no instability. There were no meniscal anomalies such as discoid meniscus and ring-shaped meniscus. Magnetic resonance image examination was performed before second-look arthroscopy at 1 year postoperatively. A coronal plane showed a small triangular fragment located at the medial border of the lateral tibial plateau. An axial plane demonstrated a ring-shaped lateral meniscus. On second-look arthroscopy, there was a meniscus-like tissue formation that connected the anterior horn to the posterior horn of the lateral meniscus at the lateral intercondylar tubercle. DISCUSSION: Ring-shaped meniscus is an extremely rare malformation of the meniscus. Our hypothesis was that drilling debris and remaining remnant of ACL might induce a scar tissue formation. CONCLUSION: This is the first case in the literature of inter-horn bridge formation involved in ring-shaped lateral meniscus following ACL reconstruction.

DOI： 10.1016/j.ijscr.2017.01.060

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We retrospectively analyzed the cases of 14 patients (9 women, 5 men, mean age: 51.6 years) with cytomegalovirus (CMV) involvement in the esophagus, stomach, and/or duodenum diagnosed at a single center, to determine their endoscopic features and clinical backgrounds. Thirteen patients (92.9%) had hematologic disease; the other had rheumatoid arthritis. Of the former, 12 patients underwent allogeneic hematopoietic stem cell transplantation, and 9 of these patients had graft-versus-host disease (GVHD) before undergoing esophagogastroduodenoscopy (EGD). All 14 patients had been taking one or more immunosuppressive agents including cyclosporine (n=10), corticosteroids (n=9), mycophenolic acid (n=6), tacrolimus (n=3), and methotrexate (n=1). Tests for CMV antigenemia were positive in 11 patients (78.6%). EGD examinations revealed esophageal (n=3), gastric (n=9), and duodenal involvement (n=6). Macroscopically, esophageal lesions by CMV infection presented as redness (n=1), erosions (n=1), and ulcers (n=1). Gastric lesions manifested as redness (n=7), erosions (n=3), exfoliated mucosa (n=2), and verrucous erosions (n=1). Mucosal appearances in the duodenum varied: redness (n=2), ulcers (n=2), multiple erosions (n=2), single erosion (n=1), edema (n=1). CMV was detected even in the intact duodenal mucosa (n=1). In conclusion, physicians must recall the relevance of CMV infection when any mucosal alterations exist in the upper gastrointestinal tract of immunosuppressed patients.

DOI： 10.18926/AMO/54977

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BACKGROUND AND AIM: Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. METHODS: In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. RESULTS: By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P < 0.0001) and pathological grade (P = 0.0074). CONCLUSIONS: Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.

DOI： 10.1111/jgh.13594

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem cell (CSC) marker that is easily evaluable. The expression and clinical significance of ALDH1 in ipsilateral breast tumor recurrence (IBTR) has yet to be investigated. In the present study, the expression profile of ALDH1 and its correlation with prognosis in IBTR tissues was examined. Patients with IBTR from eight institutions were retrospectively enrolled in the study. Immunohistochemistry was used to examine ALDH1 expression patterns in the tissue specimens of primary cancers and IBTRs. ALDH1 expression levels were investigated in 182 IBTR tumors, which included cases of invasive carcinoma selected from 271 consecutive patients with IBTR. ALDH1 was expressed in 23% of the IBTR tissue samples. The rate of concordant expression between primary cancer and IBTR tissues was 68%. There was no significant association between disease-free survival (DFS) and ALDH1 expression levels in IBTR. IBTRs that expressed ALDH1 and Ki-67 had a poorer prognosis and this expression pattern was significantly associated with DFS (P=0.0073). The percentages of ALDH1 positive expression in each tissue subtype were as follows: Luminal A, 20%; luminal B, 24%; human epidermal growth factor 2 (HER2), 35%; triple-negative, 21%. There was a significant correlation between DFS and ALDH1 expression levels in HER2-type IBTR tissue specimens (P=0.034). In conclusion, it is possible that ALDH1 and Ki-67 expression levels may be useful for predicting prognosis in patients with HER2-type tumors.

DOI： 10.3892/ol.2016.5538

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After having been treated with lanthanum carbonate administration for 4 years for hyperphosphatemia, a 75-year-old Japanese woman undergoing hemodialysis was diagnosed with lanthanum phosphate deposition in the stomach. The deposition, seen as white microgranules, was observed using esophagogastroduodenoscopy with magnifying observation. To the best of our knowledge, these are the minutest endoscopy images of lanthanum phosphate deposition in the gastric mucosa. Scanning electron microscopy (SEM) observation enabled easier identification of the deposited material, which was visible as bright areas. The present case suggests the usefulness of SEM observation in the detection of lanthanum phosphate deposition in the gastrointestinal tract.

DOI： 10.18926/AMO/54828

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A 42-year-old man with eosinophilia and high serum immunoglobulin E (IgE) developed a lacrimal gland mass on the left side. Excisional biopsy revealed hyperplasia of lymphoid follicles, and infiltration with lymphocytes and eosinophils around lacrimal gland acini, leading to the pathological diagnosis of Kimura disease. IgE-positive cells were mainly found along follicular dendritic cells, and a small number of IgG4-positive cells was present. One month after oral prednisolone was started at 40 mg daily and tapered to 10 mg daily, he developed lower leg edema on both sides and marked proteinuria (10.8 g/day). Renal biopsy showed no glomerular abnormalities, no immunoglobulin deposition, and no tubulointerstitial infiltration with eosinophils, leading to the diagnosis of minimal change nephrotic syndrome. Proteinuria subsided in response to an increased dose of prednisolone to 30 mg daily. Proteinuria relapsed three times in the following 5 years when oral prednisolone was tapered. In conclusion, Kimura disease manifested as an orbital mass and did not relapse. However, nephrotic syndrome relapsed frequently with background eosinophilia and high serum IgE. This study reviewed the clinical features of 10 Japanese patients with Kimura disease associated with proteinuria.

DOI： 10.3960/jslrt.17028

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Two cases of rectal xanthomas are described. One case is that of a 56-year-old Japanese man in whom multiple yellowish spots measuring approximately 3 to 5 mm were observed in the rectum during colonoscopy. The other case is that of a 78-year-old Japanese man in whom colonoscopy showed a whitish plaque of 4 mm in diameter in the rectum. Biopsy examinations performed on both patients revealed the deposition of xanthoma cells within the rectal mucosa. Within the gastrointestinal tract, xanthomas most frequently arise in the stomach, whereas the colorectum is rarely affected. Despite this infrequency, the two cases indicate that xanthomas should be recalled when yellowish to whitish lesions are observed in the colorectum.

DOI： 10.1155/2017/5975107

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Language：Japanese   Publishing type：Research paper (scientific journal)  

An 83-year-old Japanese man underwent esophagogastroduodenoscopy for screening purposes. He had a medical history of hypertension, chronic kidney disease, chronic heart failure, and chronic myeloid leukemia, and he had been taking the following medications:ferrous citrate, furosemide, spironolactone, tolvaptan, bisoprolol, nicorandil, warfarin, nilotinib, febuxostat, esomeprazole, digestive enzyme complex, ambroxol, carbocysteine, and potassium L-aspartate. Esophagogastroduodenoscopy revealed a brownish speckled pigmentation in the duodenal bulb. Biopsy specimens from the duodenal villi revealed a brown pigment deposition, which appeared bright on scanning electron microscopy. Energy dispersive X-ray spectroscopy and elemental mapping revealed the presence of iron and sulfur in the duodenal villi. Consequently, pseudomelanosis duodeni was diagnosed based on these findings.

DOI： 10.11405/nisshoshi.114.1264

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A 68-year-old Japanese woman underwent radiotherapy for gastric lymphoma. Although lymphangiectasia was sparsely observed in the second portion of the duodenum before radiotherapy, the number of pinpoint white spots obviously increased after the treatment. Although the duodenal lymphangiectasia gradually progressed, the patient had no features of protein-losing enteropathy. This case highlights the importance of endoscopic observation of the duodenum after irradiation to the abdomen as radiotherapy may secondarily cause intestinal lymphangiectasia.

DOI： 10.3332/ecancer.2017.752

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 46-year-old woman presented with massive hematemesis, caused by the rupture of esophageal varices. The laboratory investigations showed pancytopenia, and imaging tests revealed hepatosplenomegaly and ascites. A diagnosis of systemic sarcoidosis was made based on biopsies of the liver, stomach, lungs, heart, and skin. Although fat deposition was predominant, non-caseating granuloma and cirrhotic changes were found in the liver. Non-caseating granuloma was also identified in a biopsy specimen from minute depressions of the gastric folds. This case illustrates the rare involvement of the digestive system in a case of systemic sarcoidosis.

DOI： 10.2169/internalmedicine.8768-16

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Language：English   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/54817

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Other Link： http://search.jamas.or.jp/link/ui/2017326194

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10-30% of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60-75 disease-free survival; however, a relatively high relapse rate was observed (25-30% ). We report 2 patients with Stage III ALCL who relapsed 6-18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients. However, antibodies against the ALK protein appeared to be relatively low in the serum of both patients (×100 and ×750). An increase in chemotherapy intensity may be beneficial if Stage III ALCL patients are shown to be NPM-ALK chimera-positive in the first diagnostic bone marrow sample.

DOI： 10.18926/AMO/54815

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

A 61-year-old Japanese man with IgG4-related autoimmune pancreatitis was referred to our hospital because of perspiration during food intake. Abdominal computed tomography (CT) with contrast media revealed multiple mesenteric lymphadenopathies. An open surgical abdominal biopsy and subsequent histopathological analysis revealed abnormally large lymphoid cells that were negative for CD3, CD5, and c-myc and positive for CD20 and bcl-2, leading to a diagnosis of diffuse large B-cell lymphoma. Here, we discuss the risk of malignancies, particularly malignant lymphoma in patients with IgG4-related disease. The importance of pathological analysis to reach the appropriate diagnosis in such cases should be emphasized.

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Other Link： http://orcid.org/0000-0003-0995-9405

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Although limited understanding exists for the presence of specific genetic mutations and aberrantly methylated genes in pancreatobiliary intraductal papillary mucinous neoplasms (IPMNs), the fundamental understanding of the dynamics of methylation expansion across CpG dinucleotides in specific gene promoters during carcinogenesis remains unexplored. Expansion of DNA methylation in some gene promoter regions, such as EFEMP1, one of the fibulin family, with tumor progression has been reported in several malignancies. We hypothesized that DNA hypermethylation in EFEMP1 promoter would expand with the tumor grade of IPMN.A sample of 65 IPMNs and 30 normal pancreatic tissues was analyzed. IPMNs were divided into the following three subsets according to pathological findings: 31 with low-grade dysplasia (low grade), 11 with high-grade dysplasia (high grade), and 23 with associated invasive carcinoma (invasive Ca). Mutations in the KRAS or GNAS genes were analyzed by Sanger sequencing, and methylation status of two discrete regions within the EFEMP1 promoter, namely region 1 and region 2, was analyzed by bisulfite sequencing and fluorescent high-sensitive assay for bisulfite DNA (Hi-SA). Expression status of EFEMP1 was investigated by immunohistochemistry (IHC).KRAS mutations were detected in 39, 55, and 70 % of low-grade, high-grade, and invasive Ca, respectively. GNAS mutations were observed in 32, 55, and 22 % of low-grade, high-grade, and invasive Ca, respectively. The methylation of individual regions (region 1 or 2) in the EFEMP1 promoter was observed in 84, 91, and 87 % of low-grade, high-grade, and invasive Ca, respectively. However, simultaneous methylation of both regions (extensive methylation) was exclusively detected in 35 % of invasive Ca (p = 0.001) and five of eight IPMNs (63 %) with extensive methylation, whereas 20 of 57 (35.1 %) tumors of unmethylation or partial methylation of the EFEMP1 promoter region showed weak staining EFEMP1 in extracellular matrix (p = 0.422). In addition, extensive EFEMP1 methylation was particularly present in malignant tumors without GNAS mutations and associated with disease-free survival of patients with IPMNs (p < 0.0001).Extensive methylation of the EFEMP1 gene promoter can discriminate invasive from benign IPMNs with superior accuracy owing to their stepwise accumulation of tumor progression.

DOI： 10.1007/s00432-016-2164-x

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

背景:耳下腺に発生したmammary analogue secretory carcinoma(以下MASC)の1例を経験したので細胞像を中心に報告する。症例:60歳代、男性。左耳前部の腫脹を主訴に他院を受診。超音波検査にて左耳下腺内に約3cmの腫瘍を認め、穿刺吸引細胞診を施行、悪性判定となり、手術目的で当院紹介受診となった。穿刺吸引細胞診では、乳頭状構造を示す細胞集塊やライトグリーン淡染性で豊富な細胞質を有する細胞が疎な結合性を呈し散見された。これらの細胞の核は偏在し、一部の細胞では細胞質内小腺腔(intracytoplasmic lumina、以下ICL)を認めた。ICLや腺腔内の貯留物質は、パパニコロウ染色では淡い桃色を呈し、Hema-color染色では、異染性を呈した。細胞学的には、腺房細胞癌や低悪性度篩状嚢胞腺癌、腺癌の鑑別が困難であった。結論:腺房細胞癌や低悪性度篩状嚢胞腺癌、腺癌の鑑別が困難であったが、MASCというまれな組織型と診断された。腺房細胞癌様の細胞が認められた場合は、鑑別診断の一つとしてMASCを念頭に置くことが肝要であると考えられた。(著者抄録)

DOI： 10.5795/jjscc.55.112

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01209&link_issn=&doc_id=20160824210005&doc_link_id=%2Few5saibo%2F2016%2F005502%2F006%2F0112-0116%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Few5saibo%2F2016%2F005502%2F006%2F0112-0116%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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BACKGROUND AND STUDY AIMS: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time - intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time - intensity curve parameters and tumor microvessel density. PATIENTS AND METHODS: Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time - intensity curve analysis were evaluated retrospectively. Time - intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time - intensity curve parameters was evaluated. RESULTS: The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (P = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (r = 0.803, P < 0.001). CONCLUSIONS: CH-EUS with time - intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD.

DOI： 10.1055/s-0034-1393563

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

A 77-year-old Japanese man underwent endoscopic submucosal dissection twice over a 5-year period for the treatment of two separate early gastric cancers. He had been taking lanthanum carbonate, an orally administered phosphate binder, for 3 years. Esophagogastroduodenoscopy revealed reddish mucosa in the greater curvature and anterior wall of the gastric angle, while granular, white deposits were also observed in some areas of this reddish mucosa. Additionally, biopsy specimens from the gastric mucosa revealed the deposition of fine, amorphous, eosinophilic material, which appeared bright on scanning electron microscopy. Energy dispersive X-ray spectroscopy revealed the presence of lanthanum and phosphate in these bright areas, and elemental mapping confirmed that their distribution was identical to that seen in the bright areas. Based on these findings, the diagnosis of lanthanum phosphate deposition in the gastric mucosa was determined.

DOI： 10.11405/nisshoshi.113.1216

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Language：Japanese   Publisher：Okayama Medical Association  

A 43-year-old Japanese woman was diagnosed with ectopic sebaceous glands in the esophagus by esophagogastroduodenoscopy and biopsy. At the age of 46, typical ectopic sebaceous glands were recognized in the upper esophagus, whereas yellowish white granules were faintly observed in the lower esophagus. Esophagogastroduodenoscopy examinations were repeated when she was 47 and again at 50 years old, and the lesions in the lower esophagus had become more evident over the ensuing 3 years. Esophageal ectopic sebaceous glands are relatively infrequent, and there have been few case reports describing the progression of the endoscopic features. We also report the clinical and endoscopic features of the five similar cases with pathologically proven ectopic sebaceous glands in the esophagus.

DOI： 10.4044/joma.128.201

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Language：Japanese   Publisher：Okayama Medical Association  

Esophageal neuroendocrine carcinoma (ECC) is rare and has a poor prognosis when presenting with vascular invasion and distant metastasis from an early stage. Multidisciplinary therapy with surgery, chemotherapy, and radiation therapy may prolong survival in patients with advanced ECC, but there is as yet no standard therapy for advanced ECC. We treated two patients who have achieved long-term survival (> 4 years) who underwent multidisciplinary therapy, including chemotherapy, for ECC. Our experience with these two cases suggests that multidisciplinary therapy, including chemotherapy, may be effective for treating ECC at an advanced stage.

DOI： 10.4044/joma.128.207

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A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus (HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated.

DOI： 10.2169/internalmedicine.55.6287

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An 82-year-old Japanese man presented with a gastric involvement of peripheral T-cell lymphoma, not otherwise specified. Although gastrointestinal lesions were not detected on computed tomography, oesophagogastroduodenoscopy revealed a slight elevation of the gastric mucosa, with changes in mucosal colour and the presence of abnormal microvessels. This led to the prompt detection of gastric involvement in lymphoma. This case highlights the usefulness of detailed observation of the gastric mucosa for the endoscopic detection of gastric involvement of peripheral T-cell lymphoma.

DOI： 10.3332/ecancer.2016.625

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BACKGROUND/AIMS: Patients who are Helicobacter pylori antibody negative and have normal pepsinogen (PG) levels (group A of ABC (D) stratification) are considered unlikely to develop gastric cancer. This study aimed to clarify the involvement (uninfection, present infection or previous infection) of H. pylori in group A patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) by examining their background gastric mucosa endoscopically and histologically. METHODS: This study included 166 patients with gastric cancer who were treated by ESD. Patients were classified according to PG levels and H. pylori antibody titers. Three biopsies (greater curvature of the antrum, lesser curvature of the middle corpus and greater curvature of the middle corpus) from group A were histologically analyzed and compared with those of groups B, C, D and after eradication). RESULTS: In group A (34 patients), 32 patients had endoscopic atrophy (group A'). Histological neutrophil activity, chronic inflammation and atrophy scores were lower in group A' than in other groups. Group A' scores were similar to those of the after eradication group. CONCLUSION: Most of the group A patients with early gastric cancer were not uninfected with H. pylori, but had previous infections, thus carrying carcinogenic risk.

DOI： 10.1159/000446771

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI LTD  

A 52-year-old woman presented with stage IIB primary breast cancer (cT2N1M0), which was treated using neoadjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel). However, the tumor persisted in patchy areas; therefore, we performed modified radical mastectomy and axillary lymph node dissection. Routine endoscopy at 8 months revealed a depressed lesion on the gastric angle's greater curvature, and histology revealed signet ring cell proliferation. We performed endoscopic submucosal dissection for gastric cancer, although immunohistochemistry revealed that the tumor was positive for estrogen receptor, mammaglobin, and gross cystic disease fluid protein-15 (E-cadherin-negative). Therefore, we revised the diagnosis to gastric metastasis from the breast cancer.

DOI： 10.1155/2016/2085452

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A 68-year-old Japanese woman presented with a solitary pedunculated polyp in the duodenum. Endoscopic ultrasonography showed multiple cystic structures in the polyp. The polyp was successfully resected by endoscopic snare polypectomy and pathologically diagnosed as Brunner's gland hamartoma. Because hamartomatous components were not identified in the stalk of the polyp, we speculate that the stalk developed from traction of the normal duodenal mucosa. When a solitary, pedunculated polyp with cystic structure within the submucosa is found in the duodenum, Brunner's gland hamartoma should be considered in the differential diagnosis, despite the rarity of the disease. This case underscores the usefulness of endoscopic ultrasonography for the diagnosis of duodenal subepithelial tumors.

DOI： 10.1155/2016/6707235

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.55.6993

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Language：English   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2015.05.021

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DOI： 10.18926/AMO/53679

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OBJECTIVES: We previously showed that a quantitative fecal immunochemical test (FIT) can predict mucosal healing (MH) in ulcerative colitis (UC). Fecal calprotectin (Fcal) has also been reported as an important biomarker of UC activity. The aim of this study was to compare the predictive ability of these two fecal markers for MH in UC. METHODS: FIT and Fcal were examined in stool samples from consecutive UC patients who underwent colonoscopy. Mucosal status was assessed via the Mayo endoscopic subscore (MES). RESULTS: In total, 105 colonoscopies in 92 UC patients were evaluated in conjunction with the FIT and Fcal results. Both FIT and Fcal results were significantly correlated with MES (Spearman's rank correlation coefficient: 0.61 and 0.58, respectively). The sensitivity and specificity of the FIT values (<100 ng/ml) for predicting MH (MES 0 alone) were 0.95 and 0.62, respectively, whereas those of Fcal (<250 μg/g) were 0.82 and 0.62, respectively. The sensitivities became similar when MH was defined as MES 0 or 1 (0.86 vs. 0.86). Although the predictability of MH evaluated by the area under the receiver operating characteristics curve was similar for the two fecal markers (FIT 0.83 vs. Fcal 0.82 for MES 0 alone), the FIT results were relatively robust regardless of the cutoff value selected. CONCLUSIONS: Both FIT and Fcal can efficiently predict MH in UC, but FIT appears to be more sensitive than Fcal for predicting MES 0 alone.

DOI： 10.1038/ajg.2015.66

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BACKGROUND: Differentiating sessile serrated adenoma/polyp (SSA/P) from hyperplastic polyp (HP) is clinically important in determining the necessity of endoscopic resection or recommending appropriate surveillance. There are few reports of characterization of SSA/P using narrowband imaging and chromoendoscopy with and without magnification. We aimed to establish imaging criteria to aid real-time diagnosis of SSA/P. METHODS: Patients with pale sessile or flat lesions of 6 mm or greater were prospectively enrolled in this multicenter trial. Nine endoscopic criteria, determined in real time, were investigated for possible association with SSA/P. Endoscopic mucosal resection was performed; specimens were retrieved and analyzed by histopathological examination. RESULTS: In 63 patients, 89 lesions were detected, including 41 HP, 38 SSA/P, five mixed polyps, and five other lesions. Right-side colon location, lesion size of 10 mm or greater, excessive mucus, the presence of a varicose microvascular vessel (VMV) noted with high-magnification narrowband imaging, and type III(H) pit pattern were each commonly associated with SSA/P compared with HP. Multivariate analysis substantiated three independent endoscopic criteria for SSA/P: the presence of VMV (p = 0.001), lesion size of 10 mm or greater (p = 0.0017), and right-side location (p = 0.0041), with odds ratios of 8.2, 7.2, and 6.1, respectively. The presence of VMV had a significantly higher specificity (87.8%) than the other two independent endoscopic criteria (p = 0.0007 and p = 0.0008, respectively), but a lower sensitivity (57.9%), whereas a combination of the three criteria (two or more positive) increased the sensitivity significantly (89.5% and p = 0.0033) and had a higher degree of accuracy (82.3%). CONCLUSIONS: Three endoscopic criteria individually and in combination were effective in predicting a diagnosis of SSA/P without the need for chromoendoscopy.

DOI： 10.1007/s00535-014-0999-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation. Recently, in addition to Th2 cells, Th1 and Th17 cells have been shown to contribute to chronic GVHD progression. IL-12 induces Th1 cells and IL-23 plays a role in stabilizing and/or amplifying Th17 cells, as well as in inducing IFN-gamma/IL-17 double-producing cells. Because mAb targeting the p40 subunit common to both IL-12 and IL-23 can inhibit both IL-12R and IL-23R-mediated signaling, we investigated the effects of anti-p40 mAb on a well-defined chronic GVHD mice model. Treatment of anti-p40 mAb in allogeneic recipients significantly reduced the severity of clinical and pathological chronic GVHD. Intracellular staining revealed that IFN-gamma single-positive (IL-17(-)) and IFN-gamma/IL-17 double-positive cells were suppressed in anti-p40 mAb-treated allogeneic recipients compared with control recipients. The cytokine levels of IFN-gamma and IL-17 were also decreased in serum from anti-p40 mAb-treated allogeneic recipients. T-bet expression of donor IL-17(+) CD4(+) T cells was reduced significantly in anti-p40 mAb-treated recipients, and this reduction in T-bet expression was associated with IL-22 production by donor T cells. These results suggested that anti-p40 mAb attenuated chronic GVHD via suppression of IFN-gamma/IL-17-producing cells, and that targeting the IL-12/IL-23 pathway may represent a promising therapeutic strategy for preventing and treating chronic GVHD.

DOI： 10.4049/jimmunol.1400973

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

A cell line named PRU-1, derived from a Langerhans cell (LC) histiocytosis (LCH) skull lesion of a 7-year-old boy, was established and characterized. PRU-1 is an adherent spindle-shaped cell line that shows no Birbeck granules on electron microscopy. Flow cytometric analysis of cells collected from the early seventh passage showed no LC phenotypes of CD1a and S100 protein. Immunostaining of PRU-1 cells also revealed no expression of LC markers but showed expression of CD11c, CD54 (ICAM-1) and CD68, which was also observed in some peripherally located cells of the original LCH lesion. The PRU-1 cells stained positive for factor XIIIa and negative for CD34, suggesting a dermal dendritic cell phenotype. Cytogenetic analyses revealed abnormalities such as 39, XY, -2, -4, -8, -12, -12, -14, add (18)(q21), 20, +mar and 44, XY, -11, -14, add(18)(q21). TCR rearrangement in the PRU-1 cells was not amplified by PCR. Tumorigenicity was not proven by xenografting into SCID mice. A conditioned medium from PRU-1 culture induced the proliferation of peripheral blood lymphocytes as well as the activation of monocytes from a healthy donor into CD1a-positive LC-like cells. Because the phenotypic characteristics of PRU-1 differed from those of CD1a-positive abnormal LC-like cells (LCH cells), it was likely that the PRU-1 cells were derived from peripherally located cells of the LCH lesion rather than LCH cells. LCH has been regarded as a type of granulomatous neoplasm with several intermingled inflammatory cells and influenced by stimuli such as Merkel cell polyomavirus (MCPyV) infection or cigarette smoking. However, in the PRU-1 cells, MCPyV-DNA was not detected by PCR. Stromal cell-like PRU-1 cells are likely to produce some growth or differentiation factors, which may play important roles in LCH lesion formation, cell maintenance and LC-like cell induction.

DOI： 10.3892/or.2014.3567

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

A 67-year-old woman was diagnosed with ileocolic Crohns disease at 61 years of age. Remission had been induced by the monoclonal antibody adalimumab, and maintenance therapy had continued since her diagnosis. However, she developed respiratory symptoms, including a dry cough. A chest CT scan revealed interstitial shadows in the lower pulmonary lobes. Although no sicca symptoms were noted, she was serologically positive for both anti-Sjögrens syndrome-related antigen A and B antibodies, and salivary gland biopsy showed lymphocytic infiltration. Consequently, she was diagnosed as having asymptomatic Sjögrens syndrome. Infection or drug-induced pulmonary disease was considered unlikely, and the interstitial pneumonia was considered an extra-glandular presentation of Sjögrens syndrome. Thus, interstitial shadows, which appear during immunotherapy for Crohns disease, could indicate asymptomatic Sjögrens syndrome; clinicians should consider this rare clinical picture when assessing such a patient.

DOI： 10.11405/nisshoshi.112.1326

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Other Link： http://search.jamas.or.jp/link/ui/2015305791

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.

DOI： 10.2169/internalmedicine.54.3784

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The sensitivity and specificity of magnified endoscopic features for differentiating follicular lymphoma from other diseases with duodenal whitish lesions have never been investigated. Here we compared the magnified endoscopic features of duodenal follicular lymphoma with those of other whitish lesions. We retrospectively reviewed the cases of patients with follicular lymphoma (n＝9), lymphangiectasia (n＝7), adenoma (n＝10), duodenitis (n＝4), erosion (n＝1), lymphangioma (n＝1), and hyperplastic polyp (n＝1). The magnified features of the nine follicular lymphomas included enlarged villi (n＝8), dilated microvessels (n＝5), and opaque white spots of various sizes (n＝9). The lymphangiectasias showed enlarged villi, dilated microvessels, and white spots, but the sizes of the white spots were relatively homogeneous and their margin was clear. Observation of the adenoma and duodenitis revealed only whitish villi. Although the lymphangioma was indistinguishable from the follicular lymphomas by magnified features, it was easily diagnosed based on the macroscopic morphology. In conclusion, magnified endoscopic features, in combination with macroscopic features, are useful for differentiating follicular lymphomas from other duodenal diseases presenting whitish lesions.

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A 32-year-old Japanese man presented with a gastric submucosal tumor. Esophagogastroduodenoscopy showed a sessile submucosal tumor measuring approximately 10 mm in diameter on the greater curvature of the gastric antrum. Endoscopic ultrasonography examination revealed a solid tumor with a diameter of 11.8 mm, which was located in the deep mucosal and submucosal layers. The internal echogenicity was homogenous and hypoechoic. Biopsy examinations were performed twice but were not diagnostic since only the intact mucosal layer was obtained. The patient was subsequently diagnosed with ectopic pancreas in the stomach by endoscopic submucosal dissection (ESD). This case underscores the usefulness of the ESD technique for the pathological diagnosis of gastric submucosal tumors.

DOI： 10.1155/2015/147927

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A 78-year-old Japanese man underwent routine esophagogastroduodenoscopy, during which a reddish, flat elevated lesion was observed in the middle third of the esophagus. A bright red area of protrusion appeared in the center of the elevated lesion three months later, and the protruded nodule grew to be a blood blister six months after the initial endoscopy examination. The morphology of the lesion changed from a protruded nodule to a mass with two humps that subsequently returned to a single hump during the three-year observation period. A histological diagnosis of pyogenic granuloma was made based on a biopsy performed at six months. This report illustrates a rare case of an esophageal pyogenic granuloma presenting with a unique endoscopic appearance and morphologic changes. Endoscopic ultrasonography images are also presented.

DOI： 10.2169/internalmedicine.54.4265

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BACKGROUND: The gene expressions of netrin-1 dependence receptors, DCC and UNC5C, are frequently downregulated in many cancers. We hypothesized that downregulation of DCC and UNC5C has an important growth regulatory function in gastric tumorigenesis. RESULTS: In the present study, a series of genetic and epigenetic analyses for DCC and UNC5C were performed in a Japanese cohort of 98 sporadic gastric cancers and corresponding normal gastric mucosa specimens. Loss of heterozygosity (LOH) analyses and microsatellite instability (MSI) analysis was applied to determine chromosomal instability (CIN) and MSI phenotypes, respectively. More than 5 % methylation in the DCC and UNC5C promoters were found in 45 % (44/98) and 32 % (31/98) gastric cancers, respectively, and in 9 % (9/105) and 5 % (5/105) normal gastric mucosa, respectively. Overall, 70 % (58 of 83 informative cases) and 51 % (40 of 79 informative cases) of gastric cancers harbored either LOH or aberrant methylation in the DCC and UNC5C genes, respectively. In total, 77 % (51 of 66 informative cases) of gastric cancers showed cumulative defects in these two dependence receptors and were significantly associated with chromosomal instability. Both DCC and UNC5C were inactivated in 97 % of CIN-positive gastric cancers and in 55 % of CIN-negative gastric cancers. CONCLUSIONS: Defect in netrin receptors is a common feature in gastric cancers. DCC alterations are apparent in the early stages, and UNC5C alterations escalate with the progression of the disease, suggesting that the cumulative alterations of netrin-1 receptors was a late event in gastric cancer progression and emphasizing the importance of this growth regulatory pathway in gastric carcinogenesis.

DOI： 10.1186/s13148-015-0096-y

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Language：English   Publishing type：Research paper (scientific journal)  

Composite tumors in the stomach composed of adenocarcinoma and neuroendocrine carcinoma are rare. We herein report a case of intramucosal gastric mixed adenoneuroendocrine carcinoma (MANEC) that was treated with endoscopic submucosal dissection (ESD). A 77-year-old man who had previously received ESD for early gastric adenocarcinoma underwent esophagogastroduodenoscopy for screening, which showed a depressed lesion on the lesser curvature of the antrum. The tumor was removed en bloc via ESD and pathologically diagnosed as MANEC. The tumor was located within the mucosal layer, and no lymphovascular invasion was evident. Seven months after the ESD procedure, the patient is currently feeling well without recurrence or metastasis.

DOI： 10.2169/internalmedicine.54.3469

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Language：English  

Total hip arthroplasty (THA) is the most effective treatment for advanced or end-stage hip osteoarthritis. However, venous thromboembolism (VTE) remains one of its unresolved complications. We reviewed the records of 322 patients undergoing primary THA and investigated the efficacy of anticoagulant prophylaxis for VTE. Our study cohort consisted of 60 patients who received no anticoagulants, 100 patients who received a factor Xa inhibitor (fondaparinux), 100 patients who received low molecular weight heparin (enoxaparin), and 62 patients who selectively received no anticoagulant prophylaxis due to perioperative bleeding, weight, and/or hemoglobin concentration. Enhanced 64-slice multidetector row computed tomography was performed postoperatively for 7 days in all cases. The incidence of VTE in the four groups was 15%, 9.0%, 6.0%, and 6.4%, respectively. The incidence of VTE was significantly lower in the groups receiving anticoagulant prophylaxis and the group selectively receiving no anticoagulant prophylaxis than in the group receiving no anticoagulants. Complications of fondaparinux therapy included hepatic dysfunction in 4 cases (4.0%), minor bleeding in 2 cases (2.0%), persistent wound drainage in 3 cases (3.0%), and eruption in 1 case (1.0%). The complications of enoxaparin therapy were persistent wound drainage in 1 case (1.0%) and progression of anemia in 1 case (1.0%). The incidence of VTE was low in patients who selectively received no anticoagulant prophylaxis, so we conclude that anticoagulant prophylaxis should be used selectively in THA cases.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Hepatic intracystic hemorrhage is a rare complication of polycystic liver diseases, such as autosomal dominant polycystic kidney disease (ADPKD). A hepatic cyst with mural nodules and septation may suggest the presence of a cystic malignancy, such as biliary cystadenocarcinoma. We herein report a case of hepatic intracystic hematoma with a mural nodule mimicking biliary cystadenocarcinoma in a patient with ADPKD. Hepatic intracystic hemorrhage with a mural nodule is a very rare occurrence. A fat-saturated T1-weighted magnetic resonance image may be useful for making an accurate diagnosis of intracystic hematoma.

DOI： 10.2169/internalmedicine.54.4218

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Language：Japanese   Publisher：岡山県臨床細胞学会  

背景 頭蓋内Rosai-Dorfman diseaseは画像上、髄膜腫と鑑別困難である。今回我々は、術中迅速組織検査と並行して行った圧挫細胞診が診断に有用であった頭蓋内Rosai-Dorfman diseaseの一例を経験したので、その細胞像を中心に報告する。症例 50代、男性。頸部リンパ節腫脹に対し、Rosai-Dorfman diseaseと診断確定された病歴がある。MRIにて硬膜内の脳実質外にガドリニウムで造影される病変があり、画像上、髄膜腫との術前診断により腫瘍摘出術が施行された。圧挫細胞診標本では、巨大な組織球が散在性に認められ、その細胞質内にはリンパ球がみられ、emperipolesisを呈していた。免疫染色では、巨大組織球はS-100蛋白(+)、CD68(+)、CD1a(-)であった。結論 本例では圧挫細胞診で特徴的なemperipolesisが明瞭に観察されたことから、Rosai-Dorfman diseaseを推定するのに有用な所見を得ることができた。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は62歳、男性。貧血精査のため近医にて上部消化管内視鏡検査行い、胃癌の診断で当院紹介受診した。噴門部小彎に食道浸潤を伴う3型胃癌を認め、治療前診断は、胃癌cT4b(Panc)N1M0、Stage IIIBと診断した。根治度を高めるためS-1+CDDPによる術前化学療法(neoadjuvant chemotherapy:NAC)を2コース行い、胃全摘術を施行した。病理組織学的検査所見では、原発巣、リンパ節ともに癌細胞の残存は認めず、組織学的効果判定Grade3であった。術後経過は良好で、術後4ヵ月経過した現在、再発所見認めず経過観察中である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00296&link_issn=&doc_id=20141217480280&doc_link_id=%2Fab8gtkrc%2F2014%2F004112%2F280%2F2282-2284%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2014%2F004112%2F280%2F2282-2284%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)  

A 6 2-year-old man with advanced gastric cancer was referred to our hospital. A gastroscopy revealed a type 3 tumor invading the esophagus in the lesser curvature of the stomach cardia. We diagnosed the tumor as cStageIIIB(T4bN1M0) gastric cancer. For the best chance of a pathological complete response, we selected neoadjuvant chemotherapy (NAC) with S-1+CDDP (SP therapy). A total gastrectomy with lymph node dissection was performed after 2 courses of SP therapy. Pathological evaluation of the resected stomach and lymph nodes indicated an absence of cancerous cells, confirming a pathological complete response (pCR). The patient has been followed up for 4 months without evidence of recurrence.

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BACKGROUND: We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients. METHODS: We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors. RESULTS: None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively. CONCLUSION: There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.

DOI： 10.1007/s12282-013-0445-7

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Language：English   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/52900

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Other Link： http://search.jamas.or.jp/link/ui/2015229718

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the role of the programmed death-1 (PD-1) pathway in chronic GVHD using a well-defined mouse model of B10.D2 (H-2(d)) donor to BALB/c (H-2(d)) recipients. PD-1 expression on allogeneic donor T cells was upregulated continuously in chronic GVHD development, whereas PD-L1 expression in host tissues was transiently upregulated and declined to basal levels in the late posttransplant period. Blockade of the PD-1 pathway by anti-PD-1, anti-PD-L1, or anti-PD-L2 mAbs exacerbated clinical and pathologic chronic GVHD. Chimeric mice revealed that PD-L1 expression in host tissues suppressed expansion of IL-17(+)IFN-gamma(+) T cells, and that PD-L1 expression on hematopoietic cells plays a role in the development of regulatory T cells only during the early transplantation period but does not affect the severity of chronic GVHD. Administration of the synthetic retinoid Am80 overcame the IL-17(+)IFN-gamma(+) T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1(-/-) recipients. Stimulation of the PD-1 pathway also alleviated chronic GVHD. These results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronic GVHD.

DOI： 10.4049/jimmunol.1400954

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Other Link： http://orcid.org/0000-0003-0995-9405

Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

While the use of polymerase chain reaction (PCR)-based clonality analysis of formalin-fixed paraffin-embedded (FFPE) tissue has recently become widespread, the detection sensitivity for lymphoma subtypes using FFPE samples is not well known. Here, we analyzed T-cell receptor gamma chain (TCRG) gene rearrangement clonality in 100 cases of T-or natural killer (NK)/T-cell lymphoma and examined detection sensitivity according to lymphoma subtype. Clonality was detected in approximately 80% of the major T-cell lymphoma subtypes: peripheral T-cell lymphoma, not otherwise specified, 84% (21/25 cases); angioimmunoblastic T-cell lymphoma, 71% (15/21 cases); and adult T-cell leukemia/lymphoma, 80% (8/10 cases). The number of clonal peaks differed according to subtype. TCRG gene rearrangement was not detected in 63 cases of B-cell lymphoma or reactive lesions. Thus, clonality analysis can effectively and reliably detect TCRG gene rearrangement in T-cell lymphoma cases and could, therefore, be a useful diagnostic tool in routine practice.

DOI： 10.3109/10428194.2013.871634

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

A 55-year-old woman underwent a total thyroidectomy for carcinoma showing thymus-like differentiation (CASTLE). The patient was referred to our hospital after the tumor was found to have directly invaded the cervical esophagus and the entire circumference of the trachea. A total thyroidectomy was performed, followed by end-to-end anastomosis of the trachea, suprahyoid release and dissection of bilateral pulmonary ligaments. No major complications, including anastomotic dehiscence or stenosis, were observed. The patient experienced some swallowing disturbances and hoarseness during the perioperative period but fully recovered. Radiotherapy to the neck was performed as an adjuvant therapy. Eleven months after surgery, lower back pain and right leg numbness developed and led to gait inability. Multiple lung and bone recurrences were observed, but no local recurrence. Palliative radiotherapy to the bone metastasis was performed. The patient died of pleural metastasis 14 months after the initial diagnosis of CASTLE.

DOI： 10.1159/000370306

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT. (C) 2014 American Society for Blood and Marrow Transplantation.

DOI： 10.1016/j.bbmt.2013.11.018

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Other Link： http://orcid.org/0000-0003-0995-9405

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer. METHODS: From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS). RESULTS: Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037). CONCLUSION: Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1-3 metastatic lymph nodes.

DOI： 10.1007/s12282-012-0350-5

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Language：Japanese   Publisher：Japan Surgical Association  

A 41-year-old woman noticed a tumor on the left side of her neck. Cervical ultrasonography showed a cystic mass in the left lateral neck region. The mass was further enlarged at follow-up, and hence, the patient was referred to our hospital. A cystic tumor with an internal anechoic area and clear boundary was seen outside the thyroid gland. No abnormal cells were observed on aspiration cytology. The patient underwent tumorectomy. The tumor was present on the outside of the left internal jugular vein. It could be exfoliated easily. Pathologically, a follicular gland with poor dysplasia in the mural nodule and cyst wall was observed, so a pathological diagnosis of ectopic adenomatous goiter was made. Lateral cervical cystic tumors should be treated by surgical resection because of the possibility of malignancy as well as recurrence after aspiration.

DOI： 10.3919/jjsa.75.2971

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Other Link： http://search.jamas.or.jp/link/ui/2015106655

Language：English   Publishing type：Research paper (scientific journal)   Publisher：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Systemic lupus erythematosus is a systemic autoimmune disorder that sometimes involves the gastrointestinal tract. The aim of this study is to describe the clinical characteristics of patients with systemic lupus erythematosus with colorectal involvement, and to provide criteria for colonoscopy. Methodology: Among 288 patients with systemic lupus erythematosus, 29 patients underwent colonoscopy. The clinical backgrounds were comparatively analyzed between the patients with colorectal involvements (n = 11, group A) and the patients without colorectal involvements (n = 18, group B). Endoscopic features were also evaluated in group A patients. Results: The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) of the group A patients was higher than that of the group B patients. Abdominal pain (n = 6) and diarrhea (n = 5) were significantly correlated with the presence of colorectal involvements, and other manifestations in group A patients included visible blood in stools (n = 5) and fever (n = 1). In colonoscopy, discrete ulcers (n = 5), longitudinal ulcers (n = 1), erosions and/or small ulcers (n = 2), edematous mucosa (n = 2), and concurrent ulcerative colitis (n = 1) were identified. Conclusions: Patients with systemic lupus erythematosus with SLEDAI scores &gt;= 5, or with gastrointestinal symptoms, particularly those who present with abdominal pain or diarrhea should undergo colonoscopy, because these patients are likely to have mucosal damage in the colorectum.

DOI： 10.5754/hge.11013

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BACKGROUND: There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR). METHODS: One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR. RESULTS: There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model). CONCLUSIONS: Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).

DOI： 10.1245/s10434-012-2825-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p&lt;0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1382856320966453

DOI： 10.1186/1746-1596-8-81

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

Background &amp
Aim: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene that is expressed in gastric and other cancers including pancreatic cancer. However, the precise function of RUNX3 in pancreatic cancer has not been fully elucidated. In this study, we aimed to determine the effect of decreased RUNX3 expression in pancreatic cancer. Methods: This study included 36 patients with primary pancreatic cancer, who had undergone pancreaticoduodenectomy. All patients were treated with 1000mg/m2 gemcitabine after the surgery. The pancreatic cancer cell lines PANC-1, MIAPaCa-2, BxPC-3, SUIT-2, and KLM-1 were used for immunoblotting analysis of RUNX3 and multidrug resistance protein (MRP) expressions. Ectopic RUNX3 expression was achieved by cDNA transfection of the cells, and small interfering RNA (siRNA) against RUNX3 was used to knock down endogenous RUNX3. Cell growth in the presence of gemcitabine was assessed using the MTT assay. Results: Patients with RUNX3-positive and RUNX3-negative pancreatic cancer had a median survival of 1006 and 643 days, respectively. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5 in endogenous RUNX3-negative cells, whereas RUNX3 siRNA increased the expressions of these genes in endogenous RUNX3-positive cells. Exogenous RUNX3 expression decreased gemcitabine IC50 in RUNX3-negative cells. Conclusion: Loss of RUNX3 expression contributes to gemcitabine resistance by inducing MRP expression, thereby resulting in poor patient survival. © 2013 Federation of European Biochemical Societies.

DOI： 10.1016/j.molonc.2013.04.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBL GRP CO LTD  

AIM: To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barrett's adenocarcinoma in Japan.METHODS: We performed immunohistochemical analysis of HER2 in 30 samples taken from patients with Barrett's adenocarcinoma and dual color in situ hybridization in cases showing 2+ reactions. We compared the clinicopathological characteristics of HER2-positive and HER2-negative patients.RESULTS: HER2 positivity was identified in 8 (27%) carcinoma samples. We found that HER2 expression was associated with p53 overexpression (100% vs 52.6% in pT1 tumor; 100% vs 54.5% in all stage tumor, P < 0.05) and protruding lesions at the early disease stage. There was no association between the mucin phenotype of the carcinomas and prognosis. HER2 expression and low clinical stage were unexpectedly different between Barrett's adenocarcinoma patients and gastric cancer patients, but the macroscopic features may be associated with earlier diagnosis in these patients.CONCLUSION: Our results suggest that HER2-positive Barrett's adenocarcinomas are associated with p53 overexpression and lesion protrusion at the early disease stage. (C) 2012 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v18.i43.6263

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Carcinosarcomas of the gallbladder are rare tumors that are characterized by malignant epithelial and mesenchymal components, and preoperative diagnosis of carcinosarcoma of the gallbladder remains difficult.
We recently encountered a case of carcinosarcoma of the gallbladder with osteoid and chondroid differentiation, manifesting as cholangitis due to hemobilia.
Preoperative computed tomography and magnetic resonance imaging indicated the cause of cholangitis and provided qualitative information regarding the two components of the tumor.

DOI： 10.1007/s11605-012-1836-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Serrated polyps have been considered to be precursors of colorectal cancer with microsatellite instability. However, the biological and/or morphological changes which occur during the course of serrated polyp to cancer remain to be elucidated.
Twenty-eight colorectal serrated polyps including five mixed polyps (MP) from 20 patients were observed by chromoendoscopy with magnification, and subsequently resected endoscopically. The presence of mutations in two genes (K-ras and BRAF) and the methylation status of six genes (MLH1-A, MLH1-C, ESR1, P16, SOCS1, and IGFBP7) were examined.
The 28 polyps included 32 histological serrated lesions (22 sessile serrated adenomas [SSA], six hyperplastic polyps [HP], and four traditional serrated adenoma [TSA]-like lesions). BRAF mutation was frequently observed in SSAs (19/22), while K-ras mutation was dominant in HPs (5/6). The externalization of saw-tooth architecture in serrated polyps was endoscopically observed more frequently in those with high levels of IGFBP7 methylation (P = 0.03). Moreover, the endoscopic finding was observed in five of six small serrated lesions (&lt; 10 mm) which contained both BRAF mutation and high levels of IGFBP7 methylation. TSA-like lesions in small MPs demonstrated the endoscopic finding with no or little MLH1 methylation, while the counterparts in the mixed polyps had high levels of MLH1 methylation with relatively low levels of IGFBP7 methylation.
Our data suggests two distinct pathways may be involved in the early stages of the serrated pathway: one where MLH1 is primarily methylated, and a second where methylated IGFBP7 is associated with an externalization of saw-tooth architecture.

DOI： 10.1007/s10620-011-2008-0

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Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-gamma-deficient and IL-17-deficient mice as donors. Infusion of IFN-gamma(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-beta expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD. (Blood. 2012; 119(1): 285-295)

DOI： 10.1182/blood-2011-01-332478

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BACKGROUND/AIMS: Few studies exist on the efficacy and long-term outcome of radiation therapy (RT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Twenty-two patients with stage I or stage II(1) disease were prospectively evaluated, including 14 patients without Helicobacter pylori(H. pylori) infection and 8 patients with persistent lymphoma after H. pylori eradication. RT dose was 30 Gy in daily fractions of 1.5 Gy. All patients underwent endoscopic and histological follow-up regularly. RESULTS: The study included 22 patients with a mean age of 63 years. The t(11;18)(q21;q21) translocation occurred in 8 of the 22 cases. All patients showed complete remission without any serious toxicity. At a median follow-up evaluation 74 months (range 27-159) after completion of RT, the overall and relapse-free survival rates after 5 years were 91 and 84%, respectively. Although no patient showed local recurrence of lymphoma, distant recurrence was detected in 3 patients, all of whom were H. pylori negative; MALT lymphoma relapsed in two patients with the t(11;18)(q21;q21) translocation, and diffuse large-cell lymphoma developed in one patient without the translocation. CONCLUSION: RT provides excellent local control of the gastric MALT lymphoma. However, continuous follow-up is mandatory as relapse may occur in other sites.

DOI： 10.1159/000339497

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Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. Although many investigations have been performed on the prognostic factors of DLBCL, no reports have focused on localized nodal DLBCL. We examined the prognostic significance of 39 Japanese patients with localized nodal DLBCL with special reference to the germinal center B-cell-like (GCB) versus non-germinal center B-cell-like (NGCB) types. The median age was 65 years with 23 males and 16 females. Using Hans algorithm of immunohistochemistry, 18 patients (46%) exhibited GCB type and 21 (54%) exhibited NGCB type. Twenty-nine patients (74%) presented with disease in the neck (neck group) and 10 (26%) had disease in non-neck regions (non-neck group). Comparing Hans, Choi, and Muris algorithms, patients with GCB type showed statistically significant progression-free survival (PFS) only with Hans algorithm (P = 0.022, P = 0.100, and P = 0.130, respectively). Patient survival analyses revealed that GCB-type patients by Hans algorithm had a better PFS (P = 0.012), and neck-group patients had better PFS and overall survival (OS) (P = 0.018 and P = 0.012, respectively). Univariate analysis revealed that only neck vs. non-neck exhibited a significant difference in terms of OS (P = 0.026). Multivariate analysis revealed that GCB type by Hans algorithm and neck vs. non-neck were significantly different in terms of PFS (P = 0.025 and P = 0.033, respectively). Therefore, the subclassifications of GCB type vs. NGCB type and neck vs. non-neck are important predictive prognostic factors in localized nodal DLBCL.

DOI： 10.3960/jslrt.52.91

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A 72-year-old woman was referred to our hospital for palliative care. Fifteen years earlier, she had undergone total hysterectomy and radiotherapy for cervical cancer. One year before her referral, she visited a hospital due to a gait disturbance and was diagnosed with lymphangiosarcoma. The level of coagulation factor VIII plasma activity was &gt;201% (normal range: 62-145%) and the immunohistochemical results were positive for factor VIII-related antigen in a tumor specimen. To the best of our knowledge, this is the first report of high coagulation factor VIII plasma activity in a patient with lymphangiosarcoma.

DOI： 10.2169/internalmedicine.51.8083

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Language：Japanese   Publisher：岡山県臨床細胞学会  

70歳代女。検診にて左乳房に異常を指摘され、超音波検査で左CD境界部に境界不明瞭な腫瘤を認め、マンモグラフィーではC領域にspiculaを伴う腫瘤として描出されカテゴリーVと診断した。穿刺吸引細胞診を行い、細胞所見で異型の乏しい小型細胞からなる重積著明な細胞集塊を多数認め、一部は腺管状または篩状構造様を呈し粘液様物質を有していた。また、硬癌様の配列を示す小集塊、明らかな構造を示さない大型充実性の集塊、網目状構造を呈する大型の集塊、折れ曲がった腺管様の集塊等を認めた。乳頭腺管癌と判断して乳房部分切除術および腋窩リンパ節郭清を施行し、組織所見で中心部に硝子化を伴う腫瘤形成を認め、真の腺腔とともに粘液物質を含む間質を囲む偽腺腔の形成がみられ、病変中には索状配列を示す大小の胞巣が浸潤性増殖し、無構造な充実性胞巣、網状構造の浸潤巣、篩状構造を伴う管腔や嚢胞状腺管等もみられた。

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80歳代男。頸部エコーで右耳下腺内に不整形腫瘤を認め、穿刺吸引細胞診を施行した。壊死物を伴う嚢胞内容を背景に、シート状ないし管状配列を示す小型で細胞質に乏しい上皮細胞集塊、小集塊〜散在性に出現する大型裸核状筋上皮細胞を認め、筋上皮細胞が粘液球を取り囲む構造がみられた。筋上皮細胞の核は裸核状で大型、不整形、クロマチン細顆粒状で、大型核小体を認めた。以上より腺様嚢胞癌と推定したが、組織学的に腫瘍は嚢胞内に上皮細胞と筋上皮細胞が明瞭な二層構造を示して乳頭状あるいは充実性に増生していたことから上皮筋上皮癌と診断した。腫瘍細胞には腺腔形成、偽腺腔形成を認めた。免疫組織化学的に上皮細胞はEMA陽性、筋上皮細胞はα-smooth muscle actin、p63陽性、偽腺腔、基底膜様物質がType IV collagen陽性であった。

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Diffuse large B-cell lymphoma (DLBCL) rarely involves the duodenum, and its clinicopathological characteristics have not been well elucidated. We performed clinicopathological examinations and identified 15 patients with duodenal DLBCL using 18 gastric or colonic DLBCL as a control. Eleven of the 15 patients (73%) were subclassified by immunohistochemical analysis according to the Choi algorithm as germinal center B-cell-like (GCB) type, whereas the 18 control gastric and colonic DLBCL were predominantly subclassified as activated B-cell-like (ABC) type. The classifications according to organ involvement were statistically significant (P= 0.011 and P= 0.035). Macroscopically, the GCB lesions were varied, while all ABC lesions were ulcerative. Fluorescence in situ hybridization analysis revealed a higher frequency of t(14;18) translocation in patients with duodenal DLBCL (3 of 13) as compared with non-duodenal gastrointestinal tract DLBCL (0 of 18), however, the difference was not significant (P = 0.064). Furthermore, the three patients with t(14;18) translocations were classified as GCB. In addition, overall survival of patients was statistically different between those with and without t(14;18) translocation (P= 0.040). In conclusion, duodenal DLBCL predominantly exhibits GCB-type tumors and the frequency of t(14;18) translocation appears to be higher in duodenal GCB-type DLBCL compared to non-duodenal tumors.

DOI： 10.1111/j.1440-1827.2011.02748.x

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DOI： 10.1038/hr.2011.29

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Other Link： http://www.nature.com/articles/hr201129

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The CD79 molecule, encoded by the CD79a and CD79b genes, is a signaling unit of the B-cell receptor complex, which transmits signals of B-cell activation, growth, and differentiation. They are B-cell-specific and expressed at most stages of B-cell development. Although plasma cells have been believed to lack these gene products, the regulation of CD79 expression in plasma cells is still controversial. In particular, the regulation of CD79b expression remains unclear. We sought to examine CD79b expression in normal and neoplastic plasma cells by immunohistochemical analysis. Out of the 23 clinical samples and 11 cell lines of plasma cell myeloma (PCM), none of the clinical samples and only 1 of 11 cell lines expressed CD79b immunohistologically, whereas non-neoplastic plasma cells in reactive hyperplastic lymph nodes exhibited loss of CD79b protein expression. This finding is quite different from our previous report on CD79a. Not only immunocytochemistry, but also RT-PCR and Western blot analysis of PCM cell lines gave identical results. Interestingly, we detected mRNA transcripts of CD79b in PCM cell lines, although protein translation was lacking. These findings suggest that expression of CD79b is downregulated in both plasma cells and plasma cell myeloma, and this process is possibly under post transcriptional regulation.

DOI： 10.1111/j.1440-1827.2010.02634.x

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The purpose of this study is to report on a patient who developed conjunctival lesions of blastic plasmacytoid dendritic cell neoplasm (BPDCN) after radiation to skin lesions of the same pathological type. A 79-year-old man developed salmon-pink lesions in the lower fornix of the conjunctiva of both eyes and biopsy revealed BPDCN. One and a half years previously, he noticed an erythematous plaque with a 30-mm diameter, which later became multiple, on the left chest, and the biopsy revealed BPDCN. The bone marrow was negative for CD56-positive cells, but fluorescence-activated cell sorting analysis of peripheral blood cells revealed a group of cells positive for CD4 and CD56, or CD4 and CD123. The monocyte fraction, in an increased percentage of white blood cell counts, did contain atypical cells positive for the three markers. Whole-body 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography demonstrated no abnormal uptake lesions. He received 30 Gy of radiation to the chest lesions, and later, the same dose of radiation to novel skin lesions on the back, waist, and chest, and also to pharyngeal lesions. In conclusion, the conjunctiva could be involved with BPDCN and pathological differential diagnosis by biopsy is mandatory to establish the correct diagnosis.

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Language：Japanese   Publisher：岡山県臨床細胞学会  

症例1は59歳女で、出血持続の内膜細胞診classVで紹介となった。細胞所見は出血性背景の中に淡明な胞体を有する腫瘍細胞が孤立散在性から小集塊状、シート状に認められた。核は円形から一部不整形、大小不同を伴い、クロマチン細顆粒状・密で、著明な核小体と核縁肥厚が観察された。また、hobnail様構造も認めた。組織所見は淡明な胞体を有した乳頭状〜腺管増殖を示し、明細胞腺癌clear cell adenocarcinomaと診断し、一部にendometrioid adenocarcinoma像も認めた。症例2は71歳女で、不正出血のclassIVで紹介となった。細胞所見は壊死性背景の中に明るく豊富な細胞質を有する腫瘍細胞がシート状に認められた。核は円形から類円形、大小不同を伴い、クロマチン細顆粒状で、著明な核小体が確認された。また、ライト緑好性、オレンジG好性の基底膜様物質も認められた。組織所見は、一部に扁平上皮への分化を示す腫瘍細胞が管状〜充実性に増殖し、endometrioid adenocarcinoma G2相当像を認めた。明るい胞体を有する細胞の充実性増殖を認め、clear cell adenocarcinomaの成分が合併し、ER染色では類内膜腺癌で強陽性、明細胞腺癌で弱陽性、P53は明細胞腺癌で高陽性率が高かった。

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Language：Japanese   Publisher：岡山県臨床細胞学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：B M J PUBLISHING GROUP  

Background Differentiation between multicentric Castleman&apos;s disease and systemic immunoglobulin (Ig) G4-related lymphadenopathy is sometimes difficult. It has been suggested that measurement of the IgG4-/IgG-positive cell ratio is useful for the differential diagnosis of the two diseases. However, the authors present a detailed report of six patients with multicentric Castleman&apos;s disease with abundant IgG4-positive cells (IgG4-/IgG-positive cell ratio, &gt;40%).
Results In the present series, the patients showed systemic lymphadenopathy, polyclonal hypergammaglobulinaemia and elevated serum interleukin-6 (IL-6) and C-reactive protein levels. Further, anaemia, hypoalbuminaemia, hypocholesterolaemia and thrombocytosis were observed. These findings were consistent with those of multicentric Castleman&apos;s disease. Although five patients showed elevated serum IgG4 levels, only two patients showed an increased serum IgG4/IgG ratio. However, the two patients showed highly elevated serum IgG4 levels, but the serum IgG4/IgG ratios were, although increased, not very high. Also, a patient with increased serum IgG4/IgG ratio showed a good response to antihuman IL-6 receptor monoclonal antibody (tocilizumab). Histologically, the germinal centres were mostly small and regressive, and frequently penetrated by hyalinised blood vessels, and there was no eosinophil infiltration. These findings were different from those of IgG4-related lymphadenopathy.
Conclusions The authors conclude that multicentric Castleman&apos;s disease sometimes occurs with abundant IgG4-positive cells and elevated serum IgG4 levels. Therefore, the two diseases cannot be differentially diagnosed by immunohistochemical staining alone. Laboratory findings, especially IL-6 level, C-reactive protein level and platelet count, are important for the differential diagnosis of the two diseases.

DOI： 10.1136/jcp.2010.082958

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

B-cell activating factor receptor (BAFF-R) is one of three known receptors for BAFF. BAFF-R is required for B-cell maturation and survival. We tried to determine the normal pattern of BAFF-R expression in non-neoplastic and neoplastic B- and T-cells. We used immunohistochemistry to evaluate the expression pattern of BAFF-R in non-neoplastic and neoplastic lymphoid tissues of routinely fixed paraffin-embedded samples, and examined the relationships among BAFF-R and expressions of CD10, bcl-6, MUM-1, and MIB-1. BAFF-R expression was detected on B-cells of the mantle zones, some cells within germinal centers, and scattered cells in the interfollicular areas of reactive lymph nodes. BAFF-R expression was only found in B-cell lymphoma (60/120, positive samples/examined samples), but not in T/NK cell lymphoma (0/10) or Hodgkin lymphoma (0/10). The proportions were as follows : follicular lymphoma (14/16), diffuse large B-cell lymphoma (DLBCL) (27/61), mantle cell lymphoma (4/4), and Burkitt lymphoma (0/4). According to Hans' criteria, DLBCLs were subclassified into germinal center B-cell-like (GCB) and non-germinal center B-cell-like (non-GCB) types. Interestingly, in nodal lymphomas, in the GCB subgroup (n=12), 9 of 12 (75%) were positive for BAFF-R, while 6 of 20 (30%) were positive in the non-GCB subgroup (n=20) (p < 0.05). In addition, expression of BAFF-R related to lower MIB-1 index was associated with GCB-type DLBCL. In conclusion, BAFF-R was only found in some B-cell lymphomas, which was closely associated with the expression pattern in normal counterparts, although BAFF-R expression on follicular lymphoma is different from that on germinal center cells, which is similar to bcl-2. BAFF-R was rather specifically related to low growth activity of GCB-type DLBCL of nodal origin.

DOI： 10.3960/jslrt.50.121

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Plasma cell myeloma is a frequent hematogeneous disorder that occurs mainly in older people. Not only bone marrow smears but also clots and/or biopsied specimens are often taken for confirmation of pathological diagnosis. Some specimens show sheet-like plasma cell proliferation associated with immunoglobulin monotype on immunohistology, which readily leads to diagnosis, but many samples do not clearly show light-chain restriction. The aim of the present study was therefore to examine CD79a expression because some samples had reduced expression or none at all. The immunoreactivity of CD79a was categorized into three groups: positive, weakly positive and negative, compared with scattering non-neoplastic plasma cells in the same specimen. Out of 100 specimens of plasma cell myeloma, 48% were positive for CD79a, 15% were weakly positive, and 37% were negative. In contrast, overexpression of cyclinD1 was detected in 26% of examined samples. CD79a-negative cases had a significantly lower percentage of positive staining for cyclinD1 than CD79a-positive or weakly positive cases. Clinicopathological data showed that CD79a-negative expression was associated with decreased platelet numbers in patients. The present study indicates that downregulation or loss of CD79a and/or overexpression of cyclin D1, observed in 59% of neoplastic plasma cell samples, could provide a strong diagnostic clue without regard to the results of immunoglobulin light-chain restriction.

DOI： 10.1111/j.1440-1827.2009.02448.x

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DOI： 10.1016/j.jvir.2009.07.029

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Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activation-induced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (P<0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas. Modern Pathology (2009) 22, 940-949; doi: 10.1038/modpathol.2009.51; published online 24 April 2009

DOI： 10.1038/modpathol.2009.51

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Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma. Although many studies have attempted to identify prognostic factors, most have focused on conventionally treated patients. The influence of anti-CD20 antibody (rituximab) should be considered now. We evaluated the prognostic significance of serum soluble interleukin-2 receptor levels and germinal center B-cell-like or non-germinal center B-cell like subgroups in 80 patients with diffuse large B-cell lymphoma, who had been treated with rituximab. Serum soluble interleukin-2 receptor levels ranged from 322 to 39900 U/mL (median 1365 U/mL). Sixteen (20%) were germinal center B-cell-like subgroups, and the remainder (80%) non-germinal center B-cell-like. Survival analysis associated lower serum soluble interleukin-2 receptor level and germinal center B-cell-like phenotype with better overall survival (P = 0.015), whereas multivariate analysis, including International Prognostic Index factors, revealed that only higher performance status score and higher serum lactate dehydrogenase levels significantly affected survival. However, serum soluble interleukin-2 receptor levels were elevated in patients with higher International Prognostic Index scores as well as in the non-germinal center B-cell-like subgroup. Serum soluble interleukin-2 receptor levels, International Prognostic Index, and subphenotypes were strongly correlated with each other. Our study showed that soluble interleukin-2 receptor is quite useful and may serve as a substitute for the International Prognostic Index, especially for patients undergoing treatment. Moreover, the differentiation between the germinal center B-cell-like and non-germinal center B-cell-like phenotypes is also useful for predicting patients with diffuse large B-cell lymphoma, even among those treated with rituximab. (Cancer Sci 2009; 100: 1255-1260)

DOI： 10.1111/j.1349-7006.2009.01167.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Nature  

Cholangiolocellular carcinoma (CLC) is a rare malignant primary liver tumor, categorized as a subtype of cholangiocellular carcinoma. CLC is considered to originate from hepatic progenitor cells, and sometimes accompanies a component of cholangiocellular carcinoma and/or hepatocellular carcinoma (HCC). We report herein a case of a 53-year-old Japanese male with CLC occurring asynchronously after a resection of HCC. At the age of 50, the patient underwent a first hepatectomy due to HCC, followed by intrahepatic recurrence. At 53, a new type of hepatic tumor was detected. Dynamic computed tomography revealed a multinodular enhanced tumor in the hepatic arterial phase, and an iso-density tumor in the portal venous and delayed phases. Living donor liver transplantation was performed for the treatment of this liver tumor because of his poor liver function. Histological findings confirmed the diagnosis of CLC. Nineteen months after the liver transplantation, bone metastasis of CLC was detected. Although the preoperative diagnosis of CLC is difficult in general, CLC should be considered as a differential diagnosis when a tumor with atypical image findings for HCC is observed after the resection of HCC. Once the diagnosis of CLC is made, postoperative surveillance of the patient must be performed, including the bone. © 2009 Springer.

DOI： 10.1007/s12328-009-0064-1

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IgG4-related disease sometimes involves regional and/or systemic lymph nodes, and often clinically and/or histologically mimics multicentric Castleman's disease or malignant lymphoma. In this study, we examined clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy. None of these cases were associated with human herpes virus-8 or human immunodeficiency virus infection, and there was no T-cell receptor or immunoglobulin gene rearrangement. Histologically, systemic IgG4-related lymphadenopathy was classified into two types by the infiltration pattern of IgG4-positive cells: interfollicular plasmacytosis type and intra-germinal center plasmacytosis type. The interfollicular plasmacytosis type showed either Castleman's disease-like features or atypical lymphoplasmacytic and immunoblastic proliferation-like features. By contrast, the intra-germinal center plasmacytosis type showed marked follicular hyperplasia, and infiltration of IgG4-positive cells mainly into the germinal centers, and some cases exhibited features of progressively transformed germinal centers. Interestingly, eight of our nine (89%) cases showed eosinophil infiltration in the affected lymph nodes, and examined patients showed high elevation of serum IgE. Laboratory examinations revealed elevation of serum IgG4 and soluble interleukin-2 receptors. However, the levels of interleukin-6, C-reactive protein, and lactate dehydrogenase were within normal limits or only slightly elevated in almost all patients. One patient showed a high interleukin-6 level whereas C-reactive protein was within the normal limit. Autoantibodies were examined in five patients and detected in four. Compared with the previously reported cases of multicentric Castleman's disease, our patients with systemic IgG4-related lymphadenopathy were significantly older and had significantly lower C-reactive protein and interleukin-6 levels. In conclusion, in our systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman's disease, and serum data (especially C-reactive protein and interleukin-6) are useful for differentiating the two. Our findings of eosinophil infiltration in the affected tissue and elevation of serum IgE may suggest an allergic mechanism in the pathogenesis of systemic IgG4-related lymphadenopathy.

DOI： 10.1038/modpathol.2009.17

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Diffuse large B-cell lymphomas are detected frequently in the oral cavity. Although tonsillar lymphomas have been rather well characterized, lymphomas originating from non-tonsillar regions, such as the gingiva, palate, and tongue, have not been well studied. We examined the pathology of clinical samples obtained from 21 patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma. Immunohistological examination of CD10, Bcl-6, and MUM1 determined that 17 of 21 (81%) samples exhibited non-germinal center B-cell type, an increased proportion of non-germinal center B-cell type compared with previous reports in samples of tonsillar origin (P < 0.05). The four remaining samples exhibited germinal center B-cell type, although one sample expressed MUM1. Follow-up clinical survival data were obtained from the 17 patients over a range from 4 to 173 months (mean 52 months). All patients were treated with chemotherapies, irradiation, or surgical resection. Sixteen patients achieved complete remission and two patients relapsed, but no patient has died of disease. Extranodal diffuse large B-cell lymphomas of non-germinal center B-cell type are generally characterized by poor prognosis, regardless of localized disease. Interestingly, our results indicate that, unlike similar lymphomas of tonsillar origin, localized primary non-tonsillar oral diffuse large B-cell lymphomas exhibit favorable prognosis, suggesting that these lymphomas may be clinicopathologically distinct. © 2009 Japanese Cancer Association.

DOI： 10.1111/j.1349-7006.2008.00995.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. Little is known about lymphomagenesis in the context of IgG4-related disease, we recently first reported the ocular adnexal marginal zone B-cell lymphomas arising from IgG4-related disease. To the best of our knowledge, no existing study has ever established the neoplastic potential of IgG4-producing cells. In the present report, we describe the first IgG4-producing lymphoma. The patient was a 72-year-old male who was being followed for an asbestos-related pleural plaque. During follow-up, computed tomography revealed bilateral renal masses and multiple swollen retroperitoneal lymph nodes. A retroperitoneal lymph node biopsy was performed. Histologically, the interfollicular areas were expanded by medium to large plasmacytoid cells. These plasmacytoid cells showed nuclear pleomorphism and had prominent Russell bodies. Immunohistochemistry and double immunofluorescence staining of these cells revealed IgG4 positivity and monotypic lambda-light chain predominance. A portion of these cells were partially positive for CD20, negative for CD3, and somewhat faintly positive for CD138. In addition, serum IgG4 was elevated. Southern blot analysis of the lymph node specimen detected immunoglobulin heavy chain gene rearrangement. The present study indicates that, not only can malignant lymphomas occur in the setting of IgG4-related disease, but IgG4-producing cells can also be neoplastic.

DOI： 10.1007/s12185-008-0170-8

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4-related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39-86 years) with ocular adnexal IgG4-related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4-related disease. Immunostaining detected numerous aggregates of IgG4-positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4-related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B-cell lymphoma arising in a background of IgG4-related chronic inflammation.

DOI： 10.1111/j.1440-1827.2008.02257.x

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Language：English   Publishing type：Research paper (scientific journal)  

Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. Here, we examine growth suppression efficiency of human glioblastomas by dual-peptide targeting. We did simultaneous introduction of two tumor suppressor peptides (p14(ARF) and p16(INK4a) or p16(INK4a) and p21(CIP1) functional peptides) compared with single-peptide introduction using Wr-T-mediated peptide delivery. Wr-T-mediated transport of both p14(ARF) and p16(INK4a) functional peptides (p14-1C and p16-MIS, respectively) into human glioblastoma cell line, U87DeltaEGFR, reversed specific loss of p14 and p16 function, thereby drastically inhibiting tumor growth by >95% within the first 72 h, whereas the growth inhibition was approximately 40% by p14 or p16 single-peptide introduction. Additionally, the combination of p16 and p21(CIP1) (p21-S154A) peptides dramatically suppressed the growth of glioblastoma line Gli36DeltaEGFR, which carries a missense mutation in p53, by >97% after 120 h. Significantly, our murine brain tumor model for dual-peptide delivery showed a substantial average survival enhancement (P < 0.0001) for peptide-treated mice. Wr-T-mediated dual molecular targeting using antitumor peptides is highly effective against growth of aggressive glioblastoma cells in comparison with single molecule targeting. Thus, jointly restoring multiple tumor suppressor functions by Wr-T-peptide delivery represents a powerful approach, with mechanistic implications for development of efficacious molecular targeting therapeutics against intractable human malignancies.

DOI： 10.1158/1535-7163.MCT-07-2010

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：B M J PUBLISHING GROUP  

Background: Follicular lymphomas occasionally arise in the extra-nodal organs and are frequently found in the duodenum. They are often localised tumours with multiple polyps around the ampulla of Vater.
Aims: To examine a IgH/bcl-2 hybrid gene and VH gene to investigate the nature of the lymphoma cells and how they differ from nodal follicular lymphomas and MALT lymphomas.
Methods: Of 40 patients reported previously, 35 with duodenal follicular lymphoma were studied in detail with respect to clinicopathological characteristics.
Results: 37/40 patients were in clinical stage I (n= 30) or stage II (n= 7). Clonal immunoglobulin gene rearrangement was detected in 53.3% of examined cases, and rearrangement of IgH/bcl-2 gene at the major break point was detected in 27% of cases. Three of 8 examined cases were VH4 (38%); 2 out of them were VH4-34. As VH4 deviation is one of the common characteristics of MALT lymphomas and 2/3 were identical, duodenal follicular lymphomas have a similar aetiology to MALT lymphomas. Clinical course was also similar to that of MALT lymphomas.
Conclusions: Results suggest that duodenal follicular lymphomas have intermediate characteristics of MALT lymphomas and nodal follicular lymphomas.

DOI： 10.1136/jcp.2007.049825

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Language：English  

It remains unclear whether or not diffuse large B-cell lymphomas of extranodal sites arise from mucosa-associated lymphoid tissue (MALT) lymphomas. We studied the clinicopathological features of MALT lymphoma and diffuse large B-cell lymphoma in the thyroid gland, with special reference to VH usage of immunoglobulin gene rearrangement, to clarify the relationships between these two types of lymphomas. In addition, t(11; 18) (q21; q21) translocation was examined by multiplex reverse transcription-polymerase chain reaction. We examined 58 patients with primary thyroid lymphoma: 31 (male seven and female 24) with MALT lymphoma and 27 (male three and female 24) with diffuse large B-cell lymphoma. Interestingly, the sequence of VH genes revealed that the two subtypes differed significantly in their use of the VH4 family (P < 0.05). Of the seven MALT lymphomas, three used the VH4 family and the other four used the VH3 family, whereas eight out of nine diffuse large B-cell lymphoma used the VH3 family, one used the VH1 family, and none used the VH4 family. It was also interesting that, in one diffuse large B-cell lymphoma patient with MALT lymphoma, the diffuse large B-cell lymphoma component used the VH3 family and the MALT lymphoma component used the VH4 family. These data imply that, in a subset of cases, these two subtypes do not share a common origin and that at least some diffuse large B-cell lymphomas have a de novo origin. No t(11; 18) (q21; q21) was detected in thyroid lymphomas, which are different from MALT lymphoma of the stomach, lungs, large intestine and ocular adnexa. This strongly indicated that the presence of t(11; 18) (q21; q21) in MALT lymphoma is organ-specific.

PubMed

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Language：English  

We investigated the relationship of gastric mucosa-associated lymphoid tissue (MALT) lymphoma tumorigenesis to Helicobacter pylori infection, the t (11;18) translocation, and alterations in cell cycle regulators. We sought to assess the implications of altered expression of p27(Kip1), a cyclin-dependent kinase inhibitor, on high-grade transformation and responsiveness to eradication therapy. We used immunohistochemistry to examine p27(Kip1), p53, and Ki-67 expression in 23 MALT lymphomas, five diffuse large B-cell lymphomas (DLBCLs), and four DLBCLs with associated MALT lymphoma. All of the MALT lymphomas were positive for p27(Kip1) expression and negative for p53 with a low Ki-67 index, regardless of the sensitivity of these cells to eradication. All DLBCLs were negative for p27(Kip1) and positive for p53, exhibiting a high Ki-67 index. In DLBCLs with MALT lymphoma, p27(Kip1) expression was absent from both the MALT and large cells components. In all of these lymphomas, the MALT components were negative for p53 and displayed a low Ki-67 index, while the large cell components were positive for p53 with a high Ki-67 index. The expression patterns of the DLBCLs differed significantly from those of the MALT lymphomas. p27(Kip1) was not detected in either component of DLBCL with MALT lymphoma, suggesting that decreased expression of p27(Kip1) in the MALT component may be related to high-grade transformation. Thus, p27(Kip1) expression in morphological MALT lymphomas could be useful tool to predict high-grade transformation to DLBCL.

PubMed

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Language：English  

PURPOSE: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bcl-2. EXPERIMENTAL DESIGN: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. RESULTS: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positivity 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P < 0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P < 0.05) and correlated with clinical stages and lymph node metastasis (P < 0.05 and P < 0.05, respectively). CONCLUSIONS: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.

DOI： 10.1158/1078-0432.CCR-05-0274

PubMed

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper (scientific journal)  

High-frequent silencing of hematopoietic cell-specific protein-tyrosine phosphatase SHP1 gene by promoter methylation was detected in various kinds of leukemias and lymphomas, as well as in many hematopoietic cell lines, which is supported by our previous observation of strong decrease of SHP1 mRNA and protein. The promoter methylation of the SHP1 gene was clearly correlated with the clinical stage. Loss of heterozygosity with microsatellite markers near the SHP1 gene was shown in 79% of informative acute lymphoblastic leukemia cases. These results suggest that functional loss of SHP1 is associated with the pathogenesis of leukemias/lymphomas.

PubMed

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：岡山県臨床細胞学会  

背景:子宮内膜の二次性腫瘍は子宮外を原発とする腫瘍の子宮内膜への転移であり,極めて稀である.二次性腫瘍としては婦人科原発や乳癌の小葉癌,胃癌が多い.今回,特徴的な細胞所見が確認できた胃癌子宮転移の一例を報告する.症例:40代,女性.3型進行胃癌の疑いで精査のために他院より紹介受診した.CTにて胃体下部から胃角部大彎を中心に約7cm大の壁肥厚病変や卵巣の低度腫大が認められ,胃生検,子宮腟部細胞診,子宮体部細胞診が施行された.胃生検では,卵円形に腫大した核と粘液に富む胞体をもつ異型細胞が索状あるいは孤在性に増殖しており,印環細胞癌と診断された.子宮腟部,子宮体部細胞診では異型が強く,細胞質内に粘液を大量に含み,核が偏在し,いわゆる印環細胞癌の特徴を示す異型細胞が多数存在しており,これらの所見と既往歴から,胃癌の子宮転移と推定した.結語:子宮の二次性腫瘍の中でも,細胞診標本中に腫瘍細胞を認めることは稀であるが,今回の症例では子宮腟部,子宮体部細胞診にて胃生検と同様に印環細胞型の異型の強い腺癌細胞が孤在性または集塊で出現しており,臨床情報と併せて転移性腫瘍の診断が可能であった.(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

症例は87歳男性.75歳時に逆流性食道炎に対して下部食道および胃噴門部切除,空腸間置法再建を実施.87歳時の上部消化管内視鏡検査にて,穹窿部に境界明瞭な約10mmの白色調の領域を認め,narrow-band imaging観察では白色～緑色調であり,腺管構造は不明瞭であった.生検にて胃扁平上皮化生と診断した.以後,1年毎に上部消化管内視鏡検査を施行.経過中に扁平上皮化生領域は軽度増大し,92歳時点では地図状の形態となっていた.胃扁平上皮化生が食道粘膜から非連続性に発生することはまれであるが,上記の内視鏡所見を認める場合は,本症を鑑別に挙げるべきと考えられた.(著者抄録)

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Language：Japanese   Publisher：広島医学会  

症例は69歳、女性。便潜血陽性にて下部消化管内視鏡検査を施行した。横行結腸にφ6mm大のIspポリープを認め、NBI観察ではJNET分類Type 2Aで、腺腫病変と考え切除した。病理組織学所見では高度異型腺腫に約10%の割合で印環細胞癌の増殖を認め、深達度はM癌で断端陰性であった。その後の検討では免疫組織化学的染色で、印環細胞癌においてMLH1の発現低下を認めマイクロサテライト不安定性(microsatellite instability:MSI)大腸癌の可能性を考えた。また腺腫部分でもMLH1の発現低下を認めたことから、腺腫は高分化型腺癌相当と考え高分化型腺癌を背景とした印環細胞癌と考えた。MSI大腸癌は比較的予後良好なものが多いが、大腸印環細胞癌はM癌でも再発・転移を認めた症例も報告されている。大腸に発生する印環細胞癌の報告例は極めて少なく、今後のさらなる症例の蓄積や検討が必要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

【背景・目的】胃癌と非癌粘膜の白色球状外観(white globe appearance:WGA)の違いを明らかにする.【方法】胃WGA症例の内視鏡所見と臨床的特徴を後ろ向きに解析した.【結果】胃癌18例,非癌23例にWGAを認めた.胃癌症例は7例(38.9%),非癌症例は17例(73.9%)がプロトンポンプ阻害剤(proton pump inhibitor:PPI)を内服していた.病理学的には,胃癌症例(18例)のうち腺管の嚢胞状拡張は12例(66.7%),腺腔内壊死物質は12例(66.7%),壁細胞の過形成と内腔への鋸歯状の突出(parietal cell protrusion:PCP)は1例(5.6%)でみられた.一方,非癌症例のうち14例で生検が実施され,腺管の嚢胞状拡張は8例(57.1%),PCPは7例(50.0%)でみられたが,腺腔内壊死物質は指摘できなかった.非癌群において,自己免疫性胃炎を2例,内視鏡的粘膜下層剥離術後瘢痕を2例,腺腫を1例,ランタン沈着を1例,胃MALTリンパ腫を1例に認めた.【結論】胃癌粘膜と非癌粘膜ではWGAの成因は異なり,非癌症例ではPPI服用が関与している可能性が示唆された.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00192&link_issn=&doc_id=20220125370003&doc_link_id=10.11280%2Fgee.64.29&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.64.29&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

J-GLOBAL

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：岡山医学会  

70歳男性。健診の上部消化管内視鏡検査にて十二指腸病変を指摘され、当院へ紹介となった。精査の結果、十二指腸・空腸病変を伴うIV期の濾胞性リンパ腫と診断されたが、FLIPI2で中間リスクに分類され、また無症状でbulky病変がないため経過観察の方針となった。だが、14ヵ月後の拡大鏡を含めた内視鏡所見では十二指腸に濾胞性リンパ腫、リンパ濾胞過形成、リンパ管腫、リンパ管拡張の4種の白色病変が確認された。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00175&link_issn=&doc_id=20211206090005&doc_link_id=10.4044%2Fjoma.133.175&url=https%3A%2F%2Fdoi.org%2F10.4044%2Fjoma.133.175&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)東京医学社  

悪性リンパ腫の診断はHE染色標本による組織所見ならびに免疫染色による検討が必須であるが、それですべてが解決できるものではない。EBウイルスやHTLV-1ウイルスのようなリンパ腫の発生に関与するウイルスの検索が必要となる場合もあるし、Burkittリンパ腫のように遺伝子転座の検索が必須となる場合やMYD88の変異のように特定の遺伝子変異が診断上重要となるものもあり、免疫染色を含めた組織診断だけでは確定診断に至らない状況が生じてきており、生検材料をホルマリン瓶に入れて病理検査室に提出するだけでは不十分なことが起こりうる。診断に必要な検討を過不足なく行うには、ホルマリン固定組織、冷蔵状態の生組織、凍結組織の3つの検体が必要である。(著者抄録)

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Language：Japanese   Publisher：医学図書出版(株)  

岡山大学病院では胆膵疾患診療に対する診療科横断的なチーム医療を積極的に行っている。膵癌の集学的治療においては、術前後の化学療法は内科が担当し、周術期においては外科、麻酔科、歯科などの医師のみならず、看護師、理学療法士、薬剤師などからなる周術期管理センターが患者のサポートにあたる。術後には病理を検討するカンファレンスを行い、外科、内科、放射線科、病理診断科の医師が一堂に会して症例の振り返りを行い明日への診療に役立てている。肝移植後の胆管狭窄はしばしば患者の予後にかかわるものであり、積極的な治療介入が必要である。当院では移植開始当初から術後胆管狭窄に対し内視鏡治療を行ってきた。肝移植の胆道再建は症例ごとに異なるので、内視鏡治療前の外科との協議による情報収集が重要である。また、胆管炎が起こった際などは免疫抑制剤の調整が必要であり、内視鏡治療前後の管理は外科が行っている。(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(株)医学書院  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

【背景・目的】内視鏡的な胃ランタン沈着様式と胃粘膜萎縮の関係を明らかにする。【方法】胃ランタン沈着症症例の内視鏡所見を後ろ向きに解析した。【結果】ヘリコバクター・ピロリ未感染の4症例のうち3例で白色病変を認め、びまん性白色病変が体部後壁と小彎に優位に分布していた。萎縮性胃炎を認める10症例のうち9例で白色病変を認めた。萎縮を伴う領域では前庭部(5例)、角部(5例)に白色病変がみられる頻度が高く、環状白色病変と顆粒状白色病変がみられた。また体部の萎縮領域にも3例で白色病変がみられ、内訳は環状1例、顆粒状1例、びまん性1例であった。胃ランタン沈着は、非萎縮粘膜では体部後壁〜小彎のびまん性白色病変として捉えられた。萎縮粘膜では、前庭部〜角部に環状白色病変または顆粒状白色病変を呈する症例が多かった。【結論】内視鏡的な胃ランタン沈着様式は萎縮の有無によって異なると考えられた。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

十二指腸腺腫・腺癌は大きく乳頭部/非乳頭部に分けられ、臨床病理学的特徴や臨床的対応が異なる。非乳頭部十二指腸腺腫・腺癌はその粘液形質から腸型/胃型に分類される。腸型は十二指腸のどこでも発生しうるが、胃型は十二指腸近位側(乳頭より口側)に好発し、悪性度が高いことが示唆されている。非乳頭部十二指腸腺腫や粘膜内癌に対する内視鏡的切除はその合併症の頻度や重篤性から積極的には行われていなかったが、近年の内視鏡治療法の開発により徐々に普及しつつある。一方で低異型度腺腫では長期間の経過観察がなされている症例においても癌化のリスクは高いものではない。治療方針は切除による合併症と経過観察による癌化リスクならびに患者の全身状態や予後を含めて検討されるべきであり、十二指腸腺腫・腺癌の特徴や自然史を考慮し、病変への適切な評価をもとにした治療方針の選択が必要である。(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

計6施設より14症例(男性7例、女性7例)のPeutz-Jeghers(PJ)症候群症例の情報を収集し、悪性腫瘍の合併率およびその特徴を解析した。平均観察期間は10.1年(0〜34年)であり、1例は原発不明癌で死亡したが、残りの13例は生存中であった。悪性腫瘍の合併は6例(42.9%)で認めた。内訳は子宮頸癌3例、乳癌1例、十二指腸癌1例、横行結腸癌1例、原発不明癌1例であり、1例は子宮頸癌で29歳時に手術されたのち、35歳時に乳癌と診断された。PJ症候群では、消化管のみならず子宮や乳房など他臓器にも癌が発生することを念頭に置き、計画的な全身諸臓器のサーベイランスを行う必要があると考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01118&link_issn=&doc_id=20191213380006&doc_link_id=130007760308&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007760308&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)南江堂  

症例は78歳男性で、心房細動に対してdabigatranを内服中である。2年前に2ヶ所の胃腺腫を指摘され、以後は定期的に内視鏡検査を行い経過観察中であった。腺腫の増大を認め、生検でgroup 4と判定されたため内視鏡的粘膜下層剥離術(ESD)を施行した。DabigatranはESD前日および当日のみ休薬し、ESD翌日より内服を再開した。術後経過に問題はなく、ESDの7日後に上部消化管内視鏡検査を実施したところ、中部〜下部食道にび漫性に白色の膜様物の付着を認めダビガトラン起因性食道炎と診断した。Dabigatran内服は継続し、十分な飲水量での服用と内服後30分の臥位を避けるよう指導した。また、ESD後の潰瘍底はフィブリンで被覆されており、出血や露出血管は認めなかったため、クリニカルパスに従ってESD 8日後に退院となった。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00974&link_issn=&doc_id=20190227030030&doc_link_id=issn%3D0022-1961%26volume%3D123%26issue%3D3%26spage%3D465&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D123%26issue%3D3%26spage%3D465&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：広島県臨床細胞学会  

患者は40代女性で、検診によりatypical squamous cells、cannot exclude、HSIL(ASC-H)とHuman papilloma virus(HPV)ハイリスク型陽性を指摘された。その後、当院で2年間にわたり、子宮頸部細胞診でatypical glandular cells(AGC)とnegative for intraepithelial lesion or malignancy(NILM)を繰り返した。AGCと判定された異型腺系細胞には、核の腫大や重積が認められたが、腺癌との判定に至る明らかな所見はなかった。また、子宮内膜細胞診や頸管キュレット生検が繰り返し行われたが、異常はみられなかった。しかし、HPVハイリスク型陽性でもあり、AGCを繰り返すために子宮頸部円錐切除が行われ、最終的にAdenocarcinoma in situ(AIS)と診断された。本症例では、細胞診でのAGC判定が有用であり、結果的にAISの完全切除につながった。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06778&link_issn=&doc_id=20190325050008&doc_link_id=%2Fdt2jhiro%2F2018%2F003900%2F008%2F0045-0051%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdt2jhiro%2F2018%2F003900%2F008%2F0045-0051%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：西日本泌尿器科学会  

症例は64歳、女性。2007年に関節リウマチの診断を受け、2008年よりメトトレキサート(MTX)内服中であった。2015年に繰り返す発熱で近医を受診。CTで子宮頸癌および両肺多発転移を疑われた。当院婦人科で子宮頸部パンチ生検を施行するも悪性所見なく、肺結節も自然消退したため経過観察となっていた。2017年2月、症状が再燃し近医を受診した。CTで左下葉結節影、右肺門リンパ節腫脹、腹腔内リンパ節腫脹および左腎盂拡張を認め、PET-CTで左腎門部リンパ節、尿道、上咽頭に高集積を認めた。MTX関連リンパ増殖性疾患(MTX-LPD)を疑い、施行した上咽頭生検はHodgkinリンパ腫の像を呈し、EBER-ISH陽性であった。MTX中止後は左尿管病変および尿道病変に著変はないものの、肺腫瘤とリンパ節は縮小傾向で現在経過観察中である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01004&link_issn=&doc_id=20181228180007&doc_link_id=%2Fer9niuro%2F2018%2F008012%2F007%2F0678-0683%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2018%2F008012%2F007%2F0678-0683%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：岡山県臨床細胞学会  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞十二指腸リンパ腫は組織型によって特徴的な内視鏡像を呈する例も多い.過半数を占める濾胞性リンパ腫は,十二指腸下行脚の白色調のびまん性小顆粒状所見が特徴的であり,小腸病変も高率に併存するため,小腸内視鏡検査も施行すべきである.びまん性大細胞型B細胞性リンパ腫は潰瘍型が多いが,隆起型や混在型もみられる.MALTリンパ腫はMLP(multiple lymphomatous polyposis)型,隆起型が多く,Helicobacter pylori感染陽性例では除菌により寛解に至る例も多い.マントル細胞リンパ腫は診断時既に進行期であることが多く,また,消化管にも広範囲に分布していることが多い.十二指腸ではMLP型を呈しているものが多い.

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(株)学研メディカル秀潤社  

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Language：Japanese   Publisher：(独)国立病院機構岡山医療センター  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

症例は75歳・女性。定期検査目的に上部消化管内視鏡を施行し、胃体上部前壁に30mm大の褪色調領域と淡い発赤調領域の混在した境界明瞭なO-IIa+I型の病変を認めた。内視鏡的粘膜下層剥離術を施行し、胃型腺腫から発生した粘膜下組織浸潤をともなった腺癌と診断した。胃型腺腫の癌化報告例はいずれも粘膜内癌であり、本症例は粘膜下組織浸潤をともなった初めての症例であった。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01118&link_issn=&doc_id=20180329470006&doc_link_id=130006483386&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130006483386&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

高齢化社会の進展とともに85歳以上の超高齢者に対し胃ESDを行う機会が増加している。2009年9月から2016年6月に75歳以上の高齢者に対して当科でESDを施行した早期胃癌340例を対象とし、高齢者群(75歳以上85歳未満)、超高齢者群(85歳以上)の2群に分類し、両群における安全性と有効性を比較検討した。併存疾患、麻酔関連合併症発生率、偶発症発生率において両群間に有意差は認めず、85歳以上の超高齢者においてもESDの安全性が示唆された。病理組織学的な根治性評価および3年生存率において有意差はなく、ESDの有効性に関して超高齢者においても良好な成績が得られていた。胃ESDは超高齢者においても高齢者と同等の安全性、有効性が期待される。(著者抄録)

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