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

PURPOSE: Biliary reconstruction remains a technically demanding and complicated procedure in minimally invasive hepatopancreatobiliary surgeries. No optimal hepaticojejunostomy (HJ) technique has been demonstrated to be superior for preventing biliary complications. This study aimed to investigate the feasibility of our unique technique of posterior double-layer interrupted sutures in robotic HJ. METHODS: We performed a retrospective analysis of a prospectively collected database. Forty-two patients who underwent robotic pancreatoduodenectomy using this technique between September 2020 and November 2022 at our center were reviewed. In the posterior double-layer interrupted technique, sutures were placed to bite the bile duct, posterior seromuscular layer of the jejunum, and full thickness of the jejunum. RESULTS: The median operative time was 410 (interquartile range [IQR], 388-478) min, and the median HJ time was 30 (IQR, 28-39) min. The median bile duct diameter was 7 (IQR, 6-10) mm. Of the 42 patients, one patient (2.4%) had grade B bile leakage. During the median follow-up of 12.6 months, one patient (2.4%) with bile leakage developed anastomotic stenosis. Perioperative mortality was not observed. A surgical video showing the posterior double-layer interrupted sutures in the robotic HJ is included. CONCLUSIONS: Posterior double-layer interrupted sutures in robotic HJ provided a simple and feasible method for biliary reconstruction with a low risk of biliary complications.

DOI： 10.1007/s00423-023-03020-1

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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The use of virtual reality for simulations plays an important role in the initial training for robotic surgery. This randomized controlled trial aimed to investigate the impact of educational video on the performance of robotic simulation. Participants were randomized into the intervention (video) group that received an educational video and robotic simulation training or the control group that received only simulation training. The da Vinci® Skills Simulator was used for the basic course, including nine drills. The primary endpoint was the overall score of nine drills in cycles 1-10. Secondary endpoints included overall, efficiency, and penalty scores in each cycle, as well as the learning curves evaluated by the cumulative sum (CUSUM) analysis. Between September 2021 and May 2022, 20 participants were assigned to the video (n = 10) and control (n = 10) groups. The video group had significantly higher overall scores than the control group (90.8 vs. 72.4, P < 0.001). Significantly higher overall scores and lower penalty scores were confirmed, mainly in cycles 1-5. CUSUM analysis revealed a shorter learning curve in the video group. The present study demonstrated that educational video training can be effective in improving the performance of robotic simulation training and shortening the learning curve.

DOI： 10.1007/s11701-023-01556-4

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Studies remain limited on the role of the Pfannenstiel incision in minimally invasive hepato-pancreato-biliary (HPB) surgery, especially robotic surgery. The role of various extraction sites in robotic HPB surgery should be understood. Herein, we describe the surgical techniques, outcomes, advantages, and disadvantages of the Pfannenstiel incision in robotic pancreatic surgery. Seventy patients underwent robotic pancreatectomy at our institution between September 2020 and October 2022. The Pfannenstiel incision was used for specimen retrieval in 55 patients. Advantages of the Pfannenstiel incision include less pain, cosmetic benefits, and a lower incidence of complications. Moreover, the specimen could be removed using the robotic system docked. However, all complex reconstructions should be performed intra-abdominally during robotic pancreatoduodenectomies. The incidence of mortality and postoperative pancreatic fistula (grade B) was 0% and 9.1%, respectively. During the median follow-up (11.2 months) after surgery, complications at the Pfannenstiel incision site included surgical site infection (n = 1, 1.8%) and incisional hernia (n = 1, 1.8%). The Pfannenstiel incision can be a useful option for specimen retrieval in minimally invasive HPB surgery, according to the surgeon's preferences and the patient's condition.

DOI： 10.3390/jcm12051971

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Language：Japanese   Publisher：(株)へるす出版  

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TECHNIQUE: Minimally invasive congenital biliary dilatation (CBD) surgery is technically demanding. However, few studies have reported surgical approaches of robotic surgery for CBD. This report presents robotic CBD surgery using a scope-switch technique. Our robotic surgery technique for CBD consisted of four steps: step 1, Kocher's maneuver; step 2, dissection of the hepatoduodenal ligament using the scope switch technique; step 3, preparation for the Roux-en-Y loop; and step 4, hepaticojejunostomy. RESULTS: The scope switch technique can provide different surgical approaches for dissecting the bile duct, including anterior approach by the standard position and right approach by the scope switch position. When approaching the ventral and left side of the bile duct, anterior approach with the standard position is suitable. In contrast, the lateral view by the scope switch position is preferable for approaching the bile duct laterally and dorsally. Using this technique, the dilated bile duct can be dissected circumferentially from four directions: anterior, medial, lateral, and posterior. Thereafter, complete resection of the choledochal cyst can be achieved. CONCLUSIONS: The scope switch technique in robotic surgery for CBD can be useful for dissecting around the bile duct with different surgical views, leading to the complete resection of the choledochal cyst.

DOI： 10.1016/j.asjsur.2023.02.021

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Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy.

DOI： 10.1038/s41598-023-29397-z

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BACKGROUND: Delayed gastric emptying (DGE) is a major complication of pancreatoduodenectomy (PD). Several efforts have been made to decrease the incidence of DGE. However, the optimal anastomotic method for gastro/duodenojejunostomy (GJ) remains debatable. Moreover, few studies have reported the impact of GJ surgical techniques on outcomes following robotic pancreatoduodenectomy (RPD). This study aimed to investigate the surgical outcomes of robot-sewn and stapled GJ anastomoses in RPD. METHODS: Forty patients who underwent RPD at the Okayama University Hospital between September 2020 and October 2022 were included. The outcomes between robot-sewn and stapled anastomoses were compared. RESULTS: The mean [standard deviation (SD)] operative and GJ time were 428 (63.5) and 34.0 (15.0) minutes, respectively. Postoperative outcomes included an overall incidence of DGE of 15.0%, and the mean postoperative hospital stays were 11.6 (5.3) days in length. The stapled group (n = 21) had significantly shorter GJ time than the robot-sewn group (n = 19) (22.7 min versus 46.5 min, p &lt; 0.001). Moreover, stapled GJ cases were significantly associated with a lower incidence of DGE (0% versus 21%, p = 0.01). Although not significant, the stapled group tended to have shorter postoperative hospital stays (9.9 days versus 13.5 days, p = 0.08). CONCLUSIONS: Our findings suggest that stapled GJ anastomosis might decrease anastomotic GJ time and incidence of DGE after RPD. Surgeons should select a suitable method for GJ anastomosis based on their experiences with RPD.

DOI： 10.3390/jcm12020732

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The incidence and mortality rates of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years worldwide [...].

DOI： 10.3390/jcm12020465

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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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Language：Japanese   Publisher：(一社)日本臨床栄養代謝学会  

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Language：Japanese   Publisher：日本分子腫瘍マーカー研究会  

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The concept of the superior mesenteric artery (SMA)-first approach has been widely accepted in pancreatoduodenectomy. However, few studies have reported surgical approaches to the SMA in robotic pancreatoduodenectomy (RPD). Herein, we present our surgical strategies to dissect around the SMA in RPD. Among the various approaches, our standard protocol for RPD included the right approach to the SMA, which can result in complete tumor resection in most cases. In patients with malignant diseases requiring lymphadenectomy around the SMA, we developed a novel approach by combining the left and right approaches in RPD. Using this approach, circumferential dissection around the SMA can be achieved through both the left and right sides. This approach can also be helpful in patients with obesity or intra-abdominal adhesions. The present study summarizes the advantages and disadvantages of both the approaches during RPD. To perform RPD safely, surgeons should understand the different surgical approaches and select the best approach or a combination of different approaches, depending on demographic, anatomical, and oncological factors.

DOI： 10.3390/jcm11237112

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BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

DOI： 10.1186/s12887-022-03706-3

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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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Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

DOI： 10.21037/ls-22-39

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Minimally invasive spleen-preserving distal pancreatectomy (SPDP) is technically challenging, and only a few reports have described surgical approaches for minimally invasive SPDP. This report demonstrates our novel gastrohepatic ligament approach in robotic SPDP with preservation of the splenic vessels (the superior window approach in the Kimura technique). Our gastrohepatic ligament approach for robotic SPDP included four steps. First, the gastrohepatic ligament was divided extensively, and the pancreas was confirmed (step 1). In this step, we did not lift the stomach, nor did we divide the gastrocolic ligament. Next, the superior and inferior borders of the pancreas were dissected, and tunneling of the pancreas on the superior mesenteric vein was performed (step 2). Following the division of the pancreas (step 3), the pancreatic body and tail were dissected from the medial to the lateral side with preservation of the splenic vessels (step 4). Using this approach, the pancreas can be directly accessed via the gastrohepatic ligament route and dissected without division of the gastrocolic ligament or retraction of the stomach. The present approach for robotic SPDP preserves splenic vessels, facilitating easy access to the pancreas with minimal dissection, and may be optional in selected patients, including those with low body mass index.

DOI： 10.1159/000527249

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BACKGROUND/AIM: Understanding different surgical approaches and anatomical landmarks adjacent to the splenic artery (SpA) is important for safe robotic distal pancreatectomy (RDP). Herein, we propose our standardized RDP techniques, focusing on these issues. PATIENTS AND METHODS: Between April 2021 and April 2022, 19 patients who underwent RDP at our Institution were reviewed. Anatomical patterns of the SpA were classified into three types: Type 1, no pancreatic parenchyma on the root of the SpA; type 2, any pancreatic parenchyma on the root of the SpA; and type 3, dorsal pancreatic artery around the bifurcation of the common hepatic artery and SpA. Next, the surgical strategy for approaching the SPA was determined according to the location of the pancreatic transection line: On the superior mesenteric vein (SMV) or on the left side of the root of the SpA. RESULTS: There were seven cases of type 1, nine cases of type 2, and three cases of type 3. When transecting the pancreas on the SMV, the SpA-first ligation technique was used for type 1 SpA anatomy, and the pancreas-first division technique was applied for types 2 and 3. In patients in whom the pancreas was transected at the left side of the root of the SpA, the SpA-first ligation technique was used. CONCLUSION: Our standardized surgical strategy based on anatomical landmarks and focusing on the approach to the SpA in RDP is demonstrated. Our strategy should help trainees approach the SpA and perform RDP safely.

DOI： 10.21873/anticanres.15947

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：日本分子腫瘍マーカー研究会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：日本分子腫瘍マーカー研究会  

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Most cases of colorectal cancers (CRCs) are microsatellite stable (MSS), which frequently demonstrate lower response rates to immune checkpoint inhibitors (ICIs). RNA editing produces neoantigens by altering amino acid sequences. In this study, RNA editing was induced artificially by chemoradiation therapy (CRT) to generate neoantigens in MSS CRCs. Altogether, 543 CRC specimens were systematically analyzed, and the expression pattern of ADAR1 was investigated. In vitro and in vivo experiments were also performed. The RNA editing enzyme ADAR1 was upregulated in microsatellite instability-high CRCs, leading to their high affinity for ICIs. Although ADAR1 expression was low in MSS CRC, CRT including oxaliplatin (OX) treatment upregulated RNA editing levels by inducing ADAR1. Immunohistochemistry analyses showed the upregulation of ADAR1 in patients with CRC treated with CAPOX (capecitabine + OX) radiation therapy relative to ADAR1 expression in patients with CRC treated only by surgery (p < 0.001). Compared with other regimens, CRT with OX effectively induced RNA editing in MSS CRC cell lines (HT29 and Caco2, p < 0.001) via the induction of type 1 interferon-triggered ADAR1 expression. CRT with OX promoted the RNA editing of cyclin I, a neoantigen candidate. Neoantigens can be artificially induced by RNA editing via an OX-CRT regimen. CRT can promote proteomic diversity via RNA editing.

DOI： 10.1038/s41598-022-17773-0

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: The optimal management for peritoneal dissemination in patients with hepatocellular carcinoma remains unclear. Although several reports have described the usefulness of surgical resection, the indications should be carefully considered. Herein, we report the case of a patient with hepatocellular carcinoma with peritoneal recurrence who underwent surgical resection using an indocyanine green fluorescence navigation system and achieved favorable disease control. CASE PRESENTATION: A 45-year-old Asian woman underwent left hemihepatectomy for a ruptured hepatocellular carcinoma. Seventeen months after the initial surgery, a single nodule near the cut surface of the liver was detected on computed tomography, along with elevation of tumor markers. The patient was diagnosed with peritoneal metastasis and underwent a surgical resection. Twelve months later, a single nodule on the dorsal side of the right hepatic lobe was detected on computed tomography, and we performed surgical resection. Indocyanine green (0.5 mg/kg) was intravenously administered 3 days before surgery, and the indocyanine green fluorescence imaging system revealed clear green fluorescence in the tumor, which helped us perform complete resection. Indocyanine green fluorescence enabled the detection of additional lesions that could not be identified by preoperative imaging, especially in the second metastasectomy. There was no further recurrence at 3 months postoperatively. CONCLUSION: When considering surgical intervention for peritoneal recurrence in patients with hepatocellular carcinoma, complete resection is mandatory. Given that disseminated nodules are sometimes too small to be detected by preoperative imaging studies, intraoperative indocyanine green fluorescence may be an essential tool for determining the indications for surgical resection.

DOI： 10.1186/s13256-022-03440-5

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BACKGROUND: Adenomatoid mesothelioma is a rare subtype of malignant mesothelioma that can be confused with adenomatoid tumors, which are classified as benign. The clinical features and optimal management of adenomatoid mesothelioma have not been elucidated in the literature. In this report, we present an extremely rare case of adenomatoid mesothelioma that developed on the peritoneal surface of the diaphragm as well as a literature review of adenomatoid mesothelioma in the abdominal cavity. CASE PRESENTATION: The patient was a 61-year-old Japanese woman who had undergone resection of a malignant peripheral nerve sheath tumor of the hand 18 years prior. She was diagnosed with clinical stage I lung adenocarcinoma on follow-up chest radiography. Simultaneously, a 20-mm enhancing nodule with slow growth on the right diaphragm was detected on contrast-enhanced computed tomography. She presented no specific clinical symptoms. At this point, the lesion was suspected to be a hypervascular tumor of borderline malignancy, such as a solitary fibrous tumor. After a left upper lobectomy for lung adenocarcinoma, she was referred to our department, and laparoscopic tumor resection was performed. Adenomatoid tumors were also considered based on the histopathological and immunohistochemical analyses, but we made the final diagnosis of adenomatoid mesothelioma using the results of the genetic profile. The patient remains alive, with no recurrence noted 6 months after surgery. CONCLUSION: We encountered a valuable case of adenomatoid mesothelioma of peritoneal origin. There are some previously reported cases of adenomatoid mesothelioma and adenomatoid tumors that may need to be recategorized according to the current classification. It is important to accumulate and share new findings to clarify the clinicopathological characteristics and genetic status of adenomatoid mesothelioma.

DOI： 10.1186/s13256-022-03420-9

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BACKGROUND: The international consensus guidelines for intraductal papillary mucinous neoplasm of the pancreas (IPMN) presented clinical features as indications for surgery. Whereas surveillance for recurrence, including de novo lesions, is essential, optimal surveillance protocols have not been established. AIM AND METHODS: This study aimed to assess the clinical features of recurrence at the remnant pancreas (Rem-Panc) and extra-pancreas (Ex-Panc) after surgery for IPMN. Ninety-one patients of IPMN that underwent detailed preoperative assessment and pancreatectomy were retrospectively analyzed, focusing especially on the type of recurrence. RESULTS: The IPMNs were finally diagnosed as low-grade dysplasia (LDA, n = 42), high-grade dysplasia (HAD, n = 19), and invasive carcinoma (IPMC, n = 30). Recurrence was observed in 26 patients (29%), of which recurrence was seen at Rem-Panc in 19 patients (21%) and Ex-Panc in 7 patients (8%). The frequency of Rem-Panc recurrence was 10% in LDA, 21% in HDA, and 37% in IPMC. On the other hand, Ex-Panc recurrence was observed only in IPMC (23%). Ex-Panc recurrence showed shorter median recurrence-free survival (RFS) and overall survival (OS) than Rem-Panc recurrence (median RFS 8 months vs. 35 months, p < 0.001; median OS 25 months vs. 72 months, p < 0.001). Regarding treatment for Rem-Panc recurrence, repeat pancreatectomy resulted in better OS than no repeat pancreatectomy (MST 36 months vs. 15.5 months, p = 0.033). On multivariate analysis, main duct stenosis or disruption as a preoperative feature (hazard ratio [HR] 10.6, p = 0.002) and positive surgical margin (HR 4.4, p = 0.018) were identified as risk factors for Rem-Panc recurrence. CONCLUSIONS: The risk factors for Rem-Panc and Ex-Panc recurrence differ. Therefore, optimal surveillance on these features is desirable to ensure that repeat pancreatectomy for Rem-Panc recurrence can be an appropriate surgical intervention.

DOI： 10.1186/s12885-022-09650-w

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BACKGROUND: Despite advances in perioperative management, recurrence after curative pancreatectomy is a critical issue in the treatment of pancreatic ductal adenocarcinoma (PDAC). The significance of local therapy for recurrent PDAC remains unclear. METHODS: We reviewed the medical records of patients with PDAC who underwent curative resection at our institution between January 2009 and December 2019. We examined the patterns of relapse and assessed the clinical outcomes of patients with recurrence who underwent local therapy, including surgical resection, radiotherapy, and radiofrequency ablation. RESULTS: A total of 246 patients with PDAC who underwent R0 or R1 resection were included in this study. The 3-year overall survival (OS) rate was 39.8%, and the 1-year recurrence-free survival rate was 51.2% for the entire population. Recurrence was observed in 172/246 (69.9%) patients, including multiple site recurrences in 50, liver metastasis in 41, locoregional recurrence in 34, and peritoneal dissemination in 27. Of the 172 patients, treatment was administered in 137 (79.7%), and 16 received local therapy, including surgical resection (n = 13), radiotherapy (n = 5), and RFA (n = 1). PS-matched analysis revealed that patients with recurrence who were treated with chemotherapy combined with local therapy showed better post-recurrence survival rates than those treated with chemotherapy alone (P = 0.016). Detailed clinical courses of these patients are presented in the main manuscript. CONCLUSIONS: Our results suggest that a multimodal approach may improve the clinical outcomes of patients with recurrent PDAC.

DOI： 10.1016/j.pan.2022.05.004

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BACKGROUND: Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC. METHODS: Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC. RESULTS: Using the Gene Expression Omnibus dataset 89749 and TCIA, we identified CD8+/forkhead box P3 (FoxP3)+ tumour-infiltrating lymphocytes (TILs), T-cell immunoglobulin and mucin domain 3 (TIM-3) and human leukocyte antigen-A (HLA-A) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3+ TILs correlated with CD8+ TILs (P = 0.045, Fisher's exact test) and that high FoxP3+/CD8+ ratio (FCR) was an important marker for poor survival (P < 0.001, log-rank test). Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases (P = 0.003, Mann-Whitney U test). CONCLUSIONS: FCR should be considered an important biomarker that represents the immune environment of ICC based on its potentially important role in tumour progression, especially lymph node metastasis.

DOI： 10.1038/s41416-022-01838-y

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BACKGROUND/AIM: Little is known regarding the impact of lymph node dissection on survival benefit after curative resection for pancreatic neuroendocrine tumor (PNET). This study aimed to evaluate the efficacy of lymph node dissection based on tumor location of PNET. PATIENTS AND METHODS: A retrospective study, including 50 patients with surgical resection for PNET between 2004 and 2020, was performed. The efficacy index (EI) was calculated by multiplication of the incidence of lymph node metastasis (LNM) at the station and the 5-year survival rate of patients with LNM at the station. RESULTS: In the pancreatic head tumors, the peri-pancreatic head and superior mesenteric artery lymph node stations had high EI of 13.3 and 25, respectively. In contrast, other stations, including stations 8 and 12, had zero EI. In the pancreatic body and tail tumors, only the splenic artery lymph node station had a survival benefit from lymph node dissection with an EI of 6.7. CONCLUSION: The extent of lymph node dissection for PNET should be decided based on the efficacy of lymph node dissection in accordance with tumor location. Our findings may be helpful in determining the extent of lymph node dissection required.

DOI： 10.21873/anticanres.15760

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Language：Japanese   Publisher：(一社)日本外科学会  

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BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. CASE PRESENTATION: Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. CONCLUSION: We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations.

DOI： 10.1186/s40792-022-01386-w

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Language：Japanese   Publisher：(一社)日本小児外科学会  

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BACKGROUND: Emerging data indicate that gastrointestinal disorders, in addition to pulmonary dysfunction, are also hallmarks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE PRESENTATION: A 42-year-old man with maintenance hemodialysis developed high fever and dyspnea. He was positive for SARS-CoV-2 and was diagnosed with pneumonia. After treatment for SARS-CoV-2, his respiratory condition improved. However, he developed right upper quadrant pain with elevated inflammatory markers (white blood cells, 21,160/μL; c-reactive protein, 163.9 mg/L) on the 13th day. Abdominal computed tomography revealed acute acalculous cholecystitis. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed together with antibiotic therapy, which resulted in improvement of symptoms. Laparoscopic cholecystectomy was performed 36 days after PTGBD. CONCLUSION: We report a rare case of acute acalculous cholecystitis (AAC) following pneumonia caused by SARS-CoV-2 infection. We also conducted a literature search to characterize SARS-CoV-2-related cholecystitis. Infection with SARS-CoV-2 is an important trigger for AAC, and appropriate therapeutic alternatives should be cautiously selected according to individual cases.

DOI： 10.1016/j.ijscr.2021.106731

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BACKGROUND/AIM: The optimal extent of lymph node dissection for ampullary carcinoma is controversial. The aim of this study was to investigate the efficacy of lymph node dissection for ampullary carcinoma. PATIENTS AND METHODS: Between 2000 and 2020, a total of 75 patients undergoing radical resection for ampullary carcinoma were included. The efficacy index (EI) was calculated by multiplication of the frequency of lymph node metastasis (LNM) at the station and the 5-year survival rate of patients with metastasis at the station. RESULTS: Out of 75 patients, 14 had LNM. The EI for the peri-pancreatic head (station 13 and 17) and superior mesenteric artery (station 14) lymph node were 4.4 and 3.5, respectively. Whereas the peri-gastric (station 5 and 6), common hepatic artery (station 8), and liver hilum (station 12) lymph node stations had zero EI. Although the number of patients with the station 16 dissected was small (9%), the para-aortic (station 16) lymph nodes had the highest EI of 14.3 despite being distant lymph nodes. CONCLUSION: We identified the distribution of LNM and survival benefit of lymph node dissection for ampullary carcinoma. Our results suggest that the optimal extent of lymph node dissection for ampullary carcinoma could be reconsidered.

DOI： 10.21873/invivo.12789

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Aim: To evaluate whether PCR-reverse sequence-specific oligonucleotide can examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. Materials & methods: We examined acquired mutations in chemoresistant lesions and blood obtained from four patients with RAS wild-type metastatic colorectal cancer who underwent treatment with anti-epidermal growth factor receptor antibodies. Results: In one patient, metastatic lesions harbored diverse acquired mutations in KRAS in all seven metastases; the two acquired mutations were detectable in blood collected after the patient acquired resistance. None of the other patients exhibited liquid biopsy mutations, except one, with a BRAF mutation confirmed in primary tumor and peritoneal dissemination. Conclusion: Liquid biopsy based on PCR-reverse sequence-specific oligonucleotide is a successful procedure for capturing acquired mutations with precise information on the RAS mutational spectrum.

DOI： 10.2144/fsoa-2021-0059

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Surgical intervention for hepatolithiasis following hepaticojejunostomy (HJ) has rarely been reported. Herein, we present a case of post-HJ multiple hepatolithiasis treated with left hemihepatectomy with double HJ reconstruction. A 72-year-old woman who had undergone HJ for iatrogenic bile duct injury developed repeated cholangitis due to complicated hepatolithiasis accompanied by an atrophied left hepatic lobe and HJ stricture. Since endoscopic intervention was unsuccessful, the patient underwent left hemihepatectomy with HJ re-anastomoses of the common hepatic duct and left hepatic duct (double HJ technique). The double HJ technique with hepatectomy can be a useful option for treating complicated hepatolithiasis following HJ.

DOI： 10.18926/AMO/62814

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Language：Japanese   Publisher：(株)へるす出版  

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BACKGROUND: To aid in the oncological management of multiple bilobar colorectal liver metastases (CRLMs), we describe a new surgical procedure, VEssel-Skeletonized PArenchyma-sparing Hepatectomy (VESPAH). STUDY DESIGN: Of 152 patients with CRLMs treated with hepatectomy, 33 patients had multiple bilobar liver metastases (≥8 liver metastases); their surgical procedures and clinical outcomes were retrospectively summarized and compared between those who underwent VESPAH and those who underwent major hepatectomy (Major Hx). RESULTS: Of the 33 patients, 20 patients were resected by VESPAH (the VESPAH group) and 13 patients by major hepatectomy (Major Hx group). The median number of CRLMs was 13 (range, 8-53) in the VESPAH group and 10 (range, 8-41) in the Major Hx group (P=0.511). No operative mortality nor severe morbidity was observed in either group. The VESPAH group showed earlier recovery of remnant liver function after surgery than the Major Hx group; the incidence of grade B/C post hepatectomy liver failure was 5% in the VESPAH group and 38% in the Major Hx group, P=0.048). Intrahepatic tumor recurrence was confirmed in 14 (70%) and 7 (54%) patients in the VESPAH and Major Hx groups, respectively (P=0.416). There was no significant difference in median overall survival (OS) after hepatectomy between the two groups; the median OS was 47 months in the VESPAH group and 33 months in the Major Hx group (P=0.481). The VESPAH group showed the higher induction rate of adjuvant chemotherapy within 2 months after surgery (P=0.002) and total number of repeat hepatectomy for intrahepatic recurrence (P=0.060) than the Major Hx group. CONCLUSIONS: VESPAH enables us to clear surgical navigation by hepatic vessel skeletonization and may enhance patient tolerability of not only adjuvant chemotherapy but also repeat hepatectomies during the patients' lifetimes.

DOI： 10.1007/s00423-021-02373-9

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The reconstruction of diaphragmatic defects after chondrosarcoma resection is challenging. In diaphragmatic reconstruction with chest wall defects, strong chest wall reconstruction and diaphragmatic flexibility are important to avoid interference with respiration. The artificial material, Gore-Tex, is used as the first choice, but it has infection-, exposure-, and durability-related drawbacks. As an alternative method using artificial material, we present our new alternative technique for diaphragmatic reconstruction using a reversed-combined pectoralis major and serratus anterior muscle flap.

DOI： 10.1016/j.athoracsur.2021.08.067

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Language：Japanese   Publisher：日本膵・胆管合流異常研究会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J05229&link_issn=&doc_id=20220308270016&doc_link_id=10.34410%2Fjspbm.44.0_42&url=https%3A%2F%2Fdoi.org%2F10.34410%2Fjspbm.44.0_42&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：日本膵・胆管合流異常研究会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J05229&link_issn=&doc_id=20220308270011&doc_link_id=10.34410%2Fjspbm.44.0_36&url=https%3A%2F%2Fdoi.org%2F10.34410%2Fjspbm.44.0_36&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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The outcomes of pancreatectomy with resection and reconstruction of the involved arteries for locally advanced pancreatic cancer following chemotherapy have improved in recent years. In pancreatic head cancers in which there is contact with the common and proper hepatic arteries, margin-negative resection requires pancreati-coduodenectomy, with the resection of these arteries and the restoration of hepatic arterial flow. Here, we describe a middle colic artery transposition technique in hepatic arterial reconstruction during pancreatoduo-denectomy for an initially unresectable locally advanced pancreatic cancer. This technique was effective and may provide a new option for hepatic artery reconstruction in such cases.

DOI： 10.18926/AMO/62410

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: Contrary to the increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), GEP-NETs of the accessory papilla of the duodenum are extremely rare. Furthermore, there have been no recommendations regarding the treatment strategy for GEP-NETs of the accessory papilla of the duodenum. We present a case of GEP-NET of the accessory papilla of the duodenum successfully treated with robotic pancreatoduodenectomy. CASE PRESENTATION: A case of a 70-year-old complaining of no symptoms was diagnosed with GEP-NET of the accessory papilla of the duodenum. A 8-mm tumor was located at the submucosal layer with a biopsy demonstrating a neuroendocrine tumor grade 1. The patient underwent robotic pancreatoduodenectomy as curative resection for the tumor. The total operative time was 406 min with an estimated blood loss of 150 mL. The histological examination revealed a well-differentiated neuroendocrine tumor with low Ki-67 index (< 1%). In the posterior areas of the pancreas, the lymph node metastases were detected. The patient was followed up for 6 months with no recurrence postoperatively. CONCLUSIONS: Considering the potential risks of the lymph node metastases, the standard treatment strategy for GEP-NETs of the accessory papilla of the duodenum should be radical resection with pancreatoduodenectomy. Minimally invasive approach can be the alternative to the conventional open surgery.

DOI： 10.1186/s40792-021-01241-4

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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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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本外科学会  

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BACKGROUND: Hemobilia occurs mainly due to iatrogenic factors such as impairment of the right hepatic or cystic artery, and/or common bile duct in hepatobiliary-pancreatic surgery. However, little or no cases with hemobilia from the intra-pancreatic remnant bile duct after bile duct resection (BDR) has been reported. Here, we report a case of massive hemobilia due to the perforation of psuedoaneurysm of the gastroduodenal artery (GDA) to the intra-pancreatic remnant bile duct after hepatectomy with BDR. CASE PRESENTATION: A 68-year-old male underwent extended right hepatectomy with BDR for gallbladder carcinoma. He presented with upper gastrointestinal bleeding 2 months after the initial surgery. Upper endoscopy identified a blood clot from the ampulla of Vater and simultaneous endoscopic balloon tamponade contributed to temporary hemostasis. Abdominal CT and angiography revealed a perforation of the psuedoaneurysm of the GDA to the intra-pancreatic remnant bile duct resulting in massive hemobilia. Subsequent selective embolization of the pseudoaneurysm with micro-coils could achieve complete hemostasis. He survived without any recurrence of cancer and bleeding. CONCLUSION: Hemobilia could occur in a patient with BDR due to perforation of the pseudoaneurysm derived from the GDA to the intra-pancreatic remnant bile duct. Endoscopic balloon tamponade was useful for a temporal hemostasis and a subsequent radiologic interventional approach.

DOI： 10.1186/s12893-020-00981-8

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BACKGROUND: Although perioperative outcomes following donor hepatectomy (DH) have been reported, little is known about the long-term outcomes in living donors of liver transplantation. The aim of this study was to investigate the short-term and long-term outcomes following DH. METHODS: A total of 408 living donors who underwent DH between 1996 and 2019 were analyzed in this retrospective study, focusing on short-term outcomes with respect to the operation period (era) and the graft type, as well as long-term outcomes. RESULTS: The overall incidence of postoperative complications was 40.4%. These included minor (30.4%), major (10.0%), and biliary (14.0%) complications. Short-term outcomes after DH slightly improved over time, and outcomes did not differ significantly between the graft types. With regards to long-term outcomes, the incidence of surgery-related complications such as keloids, incisional hernias, and mechanical bowel obstructions was 6.6% over a median follow-up of 7.2 years. In addition, some donors developed comorbidities such as lifestyle diseases and cancers during the follow-up period. CONCLUSIONS: Our study confirmed an improvement of perioperative outcomes in living donors. There was no significant association between the graft type and postoperative outcomes. Donors could develop various morbidities during long-term follow-up. Therefore, a careful perioperative management and long-term follow-up should be provided to living donors.

DOI： 10.1016/j.ijsu.2020.11.013

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INTRODUCTION: The liver hanging maneuver is an essential technique for controlling bleeding in hepatectomy, however it is often difficult in laparoscopic major hepatectomy. The present study describes a novel modified hanging maneuver in laparoscopic left hemihepatectomy. PRESENTATION OF CASE: A 29-year-old female underwent laparoscopic left hemihepatectomy for mucinous cystic neoplasm. After mobilizing the left lobe, the liver parenchyma was dissected along the demarcation line. For the hanging technique, the upper edge of the hanging tape was placed on the lateral side of the left hepatic vein, and fixed with the Falciform ligament. The lower edge of the tape was extracted outside the abdomen. Accordingly the hanging tape can be controlled extraperitoneally during the liver parenchyma dissection. DISCUSSION: This technique includes several advantages including no need of assistance using forceps, easy control of the hanging tape extraperitoneally, outflow control, better exposure of surgical field, and helpful guide of the liver dissection line toward the root of the left hepatic vein. CONCLUSION: Our novel modified hanging maneuver is easy and reproducible to use in laparoscopic left hemihepatectomy. Moreover, this technique can be applied to other laparoscopic hepatectomy.

DOI： 10.1016/j.ijscr.2020.10.002

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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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Because of the different forms of circulating miRNAs in plasma, Argonaute2 (Ago2)-miRNAs and extracellular vesicles (EV-miRNAs), we examined the two forms of extracellular miRNAs in vitro and developed a unique methodology to detect circulating Ago2-miRNAs in small volumes of plasma. We demonstrated that Ago2-miR-21 could be released into the extracellular fluid by active export from viable cancer cells and cytolysis in vitro. As miR-21 and miR-200c were abundantly expressed in both metastatic liver sites and primary lesions, we evaluated Ago2-miR-21 as a candidate biomarker of both active export and cytolysis while Ago2-miR-200c as a biomarker of cytolysis in plasma obtained from colorectal cancer (CRC) patients before treatment and in a series of plasma obtained from CRC patients with liver metastasis who received systemic chemotherapy. The measurement of Ago2-miR-21 allowed us to distinguish CRC patients from subjects without CRC. The trend in ΔCt values for Ago2-miR-21 and -200c during chemotherapy could predict tumor response to ongoing treatment. Thus, capturing circulating Ago2-miRNAs from active export can screen patients with tumor burdens, while capturing them from passive release by cytolysis can monitor tumor dynamics during chemotherapy treatment.

DOI： 10.1002/ijc.31960

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7-16 months] in BRAF-mutant and 34 months (95% CI: 22-58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21-25 months) in BRAF-mutant and 38 months (95% CI: 24-42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

DOI： 10.18632/oncotarget.24735

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Language：English   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：岡山医学会  

症例は46歳男性で、健診で便潜血陽性を指摘され、上下部内視鏡検査で大腸ポリープが散在するのみで腫瘍性病変は指摘できず、腹部CTで大動脈右側に14cm大の後腹膜腫瘍を認めた。血圧166/96mmHg、脈拍68回/分・整で、腫瘤は触れず、血液生化学検査・甲状腺機能に異常なかった。腫瘍マーカーはCEA 4.6ng/ml、CA19-9 9.2U/ml、AFP 7.8ng/ml、PIVKA-II 31AU/mlでいずれも正常範囲であった。血液中ノルアドレナリンは12.4ng/mlと上昇し、ドーパミン値も24.0ng/mlと高値、血液中アドレナリン値は0.04ng/mlと正常であった。腹部造影CTで右横隔膜下から右腎下極にかけ比較的境界明瞭な14×12×7cmの腫瘤が存在し、造影早期より強く濃染され、腫瘍内部は壊死像を呈した。下大静脈を右側に圧排し、膵臓を腹側に圧排していた。門脈は狭小化し、側副血行路が発達していた。131I-MIGBシンチグラフィーでCTで指摘された腫瘤に一致し集積が亢進していた。遠隔転移を疑う他部位への集積はみられなかった。異所性褐色細胞腫と診断し、根治切除について検討したが、肝臓や十二指腸、膵頭部上腸間膜動脈周囲、さらに右腎動脈などの合併切除を要する可能性があるため、根治切除は不可能と判断し、腫瘍の縮小による根治切除の可能性について検討し、131I-MIGB内照射療法を施行した。CTで軽度縮小効果は得られたが血中アドレナリン値上昇傾向であったため内照射療法を終了し化学療法(CVD療法)を行った。腫瘍の縮小に伴い血中カテコールアミン値も減少した。根治切除を目的に手術を施行した。右斜胸腹部切開で開腹し、腫瘍は肝十二指腸間膜や十二指腸下行脚を圧排して存在していた。術後経過は良好で術後23日目に退院し、術後10ヵ月、降圧薬を使用せず血圧は正常範囲で推移し、血液中ノルアドレナリン値も正常値に改善し再発なく経過している。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00175&link_issn=&doc_id=20151221140005&doc_link_id=10.4044%2Fjoma.127.213&url=https%3A%2F%2Fdoi.org%2F10.4044%2Fjoma.127.213&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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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：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本小児外科学会  

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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：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2017-5711

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

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Language：Japanese   Publisher：一般社団法人日本外科学会  

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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