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

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

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BACKGROUND: Robotic gastrectomy (RG) has emerged as a promising approach for gastric cancer (GC) treatment, offering advantages such as enhanced dexterity, improved visualization, and increased precision. However, its widespread adoption remains limited due to technical complexity, high costs, limited applications, and insufficient evidence. METHODS: We conducted a single-center, prospective study to evaluate the safety and feasibility of RG, including robotic total gastrectomy (RTG), robotic proximal gastrectomy (RPG), and robotic distal gastrectomy (RDG) with D1+ or D2 lymphadenectomy, in clinical stage I/II GC. The primary endpoint was the incidence of intraoperative and postoperative complications, while the secondary endpoints included surgical outcomes and long-term prognosis. RESULTS: Seven patients were enrolled. No intraoperative complications or conversions to open surgery occurred. The primary endpoint was met, with no major postoperative complications. RTG had a longer operative time and more lymph nodes dissected than RDG and RPG. The median postoperative hospital stay was 10 days. Recurrence was observed in two cases, one of which achieved long-term survival without chemotherapy. CONCLUSION: Our findings demonstrate the safety and feasibility of RG for early and advanced GC. Further multicenter studies with larger cohorts are needed to establish its oncological benefits and cost-effectiveness, facilitating broader clinical adoption.

DOI： 10.7759/cureus.79063

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Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and α-smooth muscle (α-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with α-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and α-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC.

DOI： 10.1038/s41598-025-88033-0

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BACKGROUND: The safety and feasibility of robotic pancreatoduodenectomy (RPD) in high-risk patients with postoperative pancreatic fistula (POPF) have rarely been investigated, although the rate of POPF is lower than in open pancreatoduodenectomy (OPD). This study aimed to examine the impact of robotic surgery on POPF in high-risk patients after pancreatoduodenectomy (PD). METHODS: This retrospective analysis included 204 patients who underwent RPD between January 2018 and June 2023. Of the 204 patients, 126 with high-risk POPF were included. The outcomes of RPD and OPD were compared. Multivariate analyses were conducted to identify risk factors associated with the development of clinically relevant POPF (CR-POPF) after surgery. RESULTS: Of the 126 patients, 50 underwent RPD and 76 underwent OPD. The incidence of CR-POPF was significantly lower in the RPD group than in the OPD group (6.0% vs. 38.2%, P < 0.001). Multivariate analyses identified OPD as an independent risk factor associated with CR-POPF (odds ratio [OR]: 7.87, 95% confidence interval [CI]: 2.11-29.4, P = 0.002). CONCLUSIONS: This study demonstrated the impact of robotic surgery on POPF in high-risk patients after PD. These results suggest that RPD may be significantly associated with a decreased incidence of CR-POPF in high-risk anastomoses.

DOI： 10.1159/000543737

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OBJECTIVE: Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil-lymphocyte ratio (NLR). METHODS: To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022. RESULTS: Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings (p = 0.0028). Among the participants, those with a high NLR had a shorter PFS (p = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p = 0.01) and absence of bevacizumab (HR = 4.25, p = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group (p = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group (p = 0.0036). CONCLUSION: Low NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups.

DOI： 10.1186/s12885-024-13370-8

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PURPOSE: Gastric cancer (GC) remains a major malignancy. Robotic gastrectomy (RG) has gained popularity due to various advantages. Despite those advantages, many hospitals lack the necessary equipment for RG and are still performing laparoscopic gastrectomy (LG) due to its established minimal invasiveness and safety. METHODS: This study assessed the effectiveness of the "Double-Surgeon Technique" (DST) for improving surgical education and proficiency with LG. The DST involves both a console-side surgeon and a patient-side surgeon working actively in RG, enhancing the skill acquisition needed for LG and potentially reducing surgical time. Assessment of this method was performed by surgical time, and cases were divided into three groups: first half (Phase 1: P1) and second half (P2) before the introduction of DST, and after the introduction of DST (P3). RESULTS: Two surgical trainees were trained using the DST. The learning curve in both reached a plateau in P2, but descended again in P3. For one trainee, surgical time for P3 was significantly reduced compared to P1 (p = 0.001) and P2 (p = 0.0027) despite the intervals between laparoscopic distal gastrectomy as the main surgeon in P3 being significantly longer than in P2 (p = 0.0094). Other surgical results in both trainees did not differ significantly. Further, no difference in induction phase results of RG were evident between surgeons and trainees with or without DST experience. CONCLUSION: Surgical education using the DST could be effective in the current context of the need for RG and LG.

DOI： 10.1007/s00423-024-03593-5

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Background: A high prognostic nutritional index (PNI) is associated with good prognosis in patients with esophageal cancer. However, nutritional status often decreases during neoadjuvant therapy. Functional tooth units (FTUs) provide an index for the status of posterior occlusal support. We have previously reported that low PNI is related to low FTUs. Objectives: The purpose of this study was to retrospectively examine whether the status of occlusal support relates to changes in PNI during neoadjuvant therapy in patients with esophageal cancer. Methods: This study included 34 patients who underwent neoadjuvant therapy before esophagectomy (32 men, 2 women; age, 36-82 years) in 2012 at Okayama University Hospital. Patients were divided into the good occlusal support group (FTUs ≥ 11, n = 18) or poor occlusal support group (FTUs < 11, n = 16), and changes in PNI during neoadjuvant therapy were investigated. Results: PNI decreased significantly after neoadjuvant therapy, particularly in the good occlusal support group, and became more dispersed after neoadjuvant therapy. Decreases in PNI after neoadjuvant therapy showed a significant positive correlation with good occlusal support by multiple regression analysis (p = 0.03). The proportions of patients provided with nutritional intervention (p = 0.02) or early dental intervention (p = 0.04) were lower in the good occlusal support group than in the poor occlusal support group. Conclusions: Even in patients with esophageal cancer with good occlusal support experienced significant declines in PNI during neoadjuvant therapy, potentially due to delayed nutritional and dental interventions. Early multidisciplinary interventions are thus recommended for all patients, regardless of preoperative dental or nutritional status.

DOI： 10.3390/nu16244383

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Work-life balance is often discussed in Japan. Yet surgeons find it challenging to take paternity leave because of their demanding surgical duties and a strong sense of responsibility. One Japanese male surgeon had his first paternity experience as a research fellow in the US. When he returned to Japan, he resumed his surgical training and started a research project to become an academic surgeon. When he and his wife were expecting their second child, they discussed his paternity participation before the delivery and decided on a sustainable paternity participation plan. By coordinating his responsibilities with his co-workers, he limited his attendance at work to daytime hours only for 1 month to manage paternity duties. This adjustment did not affect the number of main and assistant operations conducted that month and effective optimization of workflow processes decreased the extra workload for other team members. His experience suggests that the optimization of workflow processes can enhance personal life, including paternity participation. (150/150).

DOI： 10.1007/s00595-024-02959-y

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BACKGROUND: Pancreatectomies combined with arterial resection can be indicated for pancreatic cancer. In a pancreatectomy with arterial resection, intraoperative confirmation of blood flow through reconstructed vessels is crucial. This study highlights the usefulness of SPY laser fluorescence imaging during a pancreatoduodenectomy with common hepatic artery resection (PD-CHAR). PATIENT AND METHODS: A 55-year-old man with borderline resectable pancreatic head cancer underwent a PD-CHAR. After confirming tumor resectability, reconstruction of the CHA to the proper hepatic artery was performed. Subsequently, the superior mesenteric vein was reconstructed. RESULTS: SPY laser fluorescence imaging demonstrated arterial blood perfusion to the liver through the reconstructed hepatic artery, followed by perfusion from the portal vein. The operation lasted 493 min, with an estimated blood loss of 400 mL. The postoperative course was uneventful with good arterial blood flow. CONCLUSION: The SPY Portable Handheld Imager could be valuable for visualizing blood flow in reconstructed vessels and assessing tissue perfusion during a pancreatectomy combined with vascular reconstruction.

DOI： 10.1245/s10434-024-16659-x

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Rectal gastrointestinal stromal tumors (GISTs) are often asymptomatic and may be detected as giant tumors. This may require highly invasive surgery for radical resection. Here, we describe a 74-year-old man with a locally advanced non-metastatic GIST in the right anterolateral wall of the lower rectum. The tumor was giant (128 × 93 mm), and invasion into adjacent organs (right seminal vesicle and prostate gland) was suspected. Although neoadjuvant chemotherapy (NAC) with imatinib reduced the tumor size, it was still giant, 80 mm in diameter. Therefore, we performed super-low anterior resection using a robot-assisted laparoscopic approach with the transanal approach. The bi-directional approach enabled safe and precise surgery, is expected to increase the rate of anorectal preservation as well as R0 resection, and may prevent a decline in quality of life.

DOI： 10.7759/cureus.76352

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BACKGROUND/PURPOSE: This study clarifies the short- and long-term outcomes of liver resection with hepatic vein (HV) reconstruction for liver tumors and identifies the risk factors for poor outcome. METHODS: We contacted 263 specialized centers in Japan and collected data on this surgical procedure. Patient characteristics, surgical procedures, and outcomes were then analyzed. RESULTS: A total of 187 patients were enrolled from 36 institutions. Grade C post-hepatectomy liver failure (PHLF) and in-hospital mortality were 3.2% and 1.6%, respectively. The median overall survival (OS) and recurrence-free survival (RFS) were 49.9 and 9.8 months, respectively. Surgical outcomes, OS and RFS did not differ among three types of liver tumors, colorectal liver metastasis (CRLM) (n = 127), hepatocellular carcinoma (n = 27), and intrahepatic cholangiocarcinoma (n = 27). Patients with CRLM and seven or more courses of preoperative chemotherapy had significantly worse OS. Compared with HV reconstruction for securing liver remnant (LR) function (n = 148), reconstruction of the only main HV remaining in the LR (n = 39) had significantly worse short-term outcomes, but did not result in increased mortality, and showed equivalent OS and RFS. CONCLUSIONS: Liver resection with HV reconstruction can be achieved safely and contributes to a relatively good long-term outcome for patients with advanced liver malignancies.

DOI： 10.1002/jhbp.12077

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INTRODUCTION: Pancreatoduodenectomy (PD) is a complex procedure with a high morbidity rate. Internal hernia following PD is a rare but potentially life-threatening complication. Herein, we describe a rare case of internal hernia after PD. PRESENTATION OF CASE: A 76-year-old man who underwent subtotal stomach-preserving PD 7 years ago presented with vomiting and abdominal pain. Abdominal computed tomography revealed an internal hernia. Because conservative treatment failed, surgical intervention was performed. Intraoperative findings revealed efferent loop herniation in the space between the afferent loop near the Braun anastomosis and transverse mesocolon. The hernia was repositioned and the mesenteric defect was closed. DISCUSSION: This is an extremely rare case of an internal hernia that developed 7 years after PD. As conservative management provides a little chance for improvement, precise diagnosis and prompt re-intervention are essential for the management of internal hernia. In this case, the hernial orifice developed in the space between the afferent and efferent loops and the transverse mesocolon. Internal hernia could be a differential diagnosis in patients with ileus after PD. CONCLUSION: This study provided a detailed description of an extremely rare case of internal hernia following PD. Therefore, internal hernias should be considered in patients undergoing PD.

DOI： 10.1016/j.ijscr.2024.110673

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PURPOSE: Our perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older. METHODS: This was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined. RESULTS: The median age of the 71 patients (34 males, 37 females) was 78 (75-92) years, and their median body mass index (BMI) was 22.3 (13.4-31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15). CONCLUSION: The SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use.

DOI： 10.1007/s00423-024-03548-w

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BACKGROUND: Open pancreaticoduodenectomy (OPD) is an essential surgical procedure for expert hepato-biliary-pancreatic (HBP) surgeons. However, there is no standard for how many surgeries must be performed by a surgeon in training before they are considered to have enough experience to ensure surgical safety. METHODS: Cumulative Sum (CUSUM) analysis was performed using the surgical data of OPDs performed during the training period of board-certified expert surgeons of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. RESULTS: Fourteen HBP surgeons participated in this study and performed 334 OPDs during their training period. The median (interquartile range) values for operative time, blood loss, and length of hospital stay were 455 (397-519) minutes, 450 (234--716) ml, and 28 (21-38) days, respectively. CUSUM analysis showed inflection points at 20 surgeries performed for operative time. After 20 procedures, operative time was significantly shorter (461 min vs. 425 min, p = 0.021) and blood loss was significantly lower (470 ml vs. 340 ml, p = 0.038). No significant differences between within 20 and after 21 procedures were found in the complication rate (53% vs. 48%, p = 0.424) and rate of in-hospital deaths (1.5% vs.1.4%. p = 0.945). Up to 20 surgeries, PDAC and another malignant tumor had longer operative time than benign/low malignant diseases (486 min vs. 472 min vs. 429 min, p < 0.001), and higher blood loss (500 ml vs. 502 ml vs. 355 ml, p < 0.001). Mortality rate was higher at PDAC cases (5% vs. 0% vs. 0%, p = 0.01). After the 21 procedures, these outcomes were improved and no differences in by primary disease were observed. Multivariable analysis showed that within 20 surgeries were independent risk factors of longer operative time (HR2.6, p = 0.013) and higher blood loss (HR2.0, p = 0.049). CONCLUSIONS: To stabilize the surgical outcome of OPD for malignant disease, at least 20 surgeries should be performed at a certified institution during surgeon training. TRIAL REGISTRATION: Clinical trial number: Not applicable.

DOI： 10.1186/s12893-024-02677-9

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INTRODUCTION: Oesophageal duplication cyst is a congenital malformation and rare tumour, clinically manifesting as dysphagia, epigastric pain, or respiratory distress. Duplicate cysts associated with abscess formation or mediastinal penetration and malignancies have been reported, necessitating surgical resection. PRESENTATION OF CASE: A 55-year-old woman had chest discomfort for 1 year. Preoperative imaging, including computed tomography (CT), upper gastrointestinal endoscopy, and endoscopic ultrasound, revealed a tumour extending from the anterior wall to the lesser curvature of the near the oesophagogastric junction (OGJ) and a suspected mural nodule within the tumour. Contrast-enhanced CT revealed a cystic nodule on the wall of the lesser curvature of the OGJ, with an unclear boundary between the cystic nodule and the oesophageal wall. Magnetic resonance imaging showed an isointense signal on T1-weighted imaging and hyperintensity on T2-weighted imaging. Laparoscopic lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed to the confirm mucinous cyst. Pathological findings revealed a cystic lesion in the muscularis propria of the OGJ filled with mucinous components and lined with multilayered columnar epithelial cells. The cyst was diagnosed as a duplicate without malignancy. DISCUSSION: Since the border between the cyst and the oesophageal walls was unclear, and the cyst potentially contained a malignant component, instead of cystectomy, lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed with oesophagogastric anastomosis using the double-flap technique, tailored specifically for OGJ cancer. CONCLUSIONS: Oesophageal duplication cysts are rare. Lower oesophagectomy and proximal gastrectomy are selective surgical approaches for cyst duplication at the OGJ.

DOI： 10.1016/j.ijscr.2024.110572

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Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect.

DOI： 10.1007/s00262-024-03849-5

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BACKGROUND: Gastro-tracheal fistula is a rare but serious complication after esophageal surgery, often requiring long-term treatment and invasive procedures. Gastro-tracheal fistula usually occurs through the posterior mediastinal route and rarely through the retrosternal route. No previous reports have described gastro-tracheal fistula after retrosternal route reconstruction was cured by conservative treatment. CASE PRESENTATION: A 70-year-old man with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy in the prone position and gastric tube reconstruction through the retrosternal route with neck anastomosis after neoadjuvant chemotherapy. Despite anastomotic leakage on postoperative day 10, his general condition was stable, and he was managed conservatively with antibiotics and gastric tube decompression. On day 29, he presented with high fever and a gastro-tracheal fistula was observed by esophagography. Conservative management was continued because the patient remained stable. On day 48, esophagography showed that the fistula was undetectable. The patient was able to take fluids orally. He progressed well on an oral diet and was transferred to a different hospital. CONCLUSIONS: A gastro-tracheal fistula, although rare, can occur after retrosternal route reconstruction. When a patient is stable, gastro-tracheal fistula after retrosternal route reconstruction may be cured by conservative treatment.

DOI： 10.1186/s40792-024-02052-z

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AIM: Although hepatectomy is a complex surgical procedure, its incidence among older patients has increased due to global aging. However, few studies have focused on the association between age and failure to rescue (FTR) posthepatectomy. This study aimed to investigate the association between age and FTR and develop a risk model for FTR following hepatectomy. METHODS: We analyzed a total of 1371 consecutive patients who underwent primary hepatectomy between July 2003 and September 2022. The patients were divided into three groups according to their age: young-old (<65 years), pre-old (65-74 years), and old group (≥75 years). Additionally, the associations among age, FTR, and risk factors for FTR were investigated. Subsequently, a risk model was developed to predict the FTR. RESULTS: Of the 1371 patients, 373 (27.2%) experienced major complications, and FTR occurred in 15 patients. The older group showed a higher FTR rate (8.4%) than the young-old (1.3%) and pre-old (4.3%) groups (p = 0.03). Multivariate analyses indicated that older age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.00-1.15; p = 0.045) and American Society of Anesthesiologists Physical Status score ≥3 (OR 4.35; 95% CI 1.24-15.2; p = 0.02) were independent predictive factors for FTR. The risk model exhibited an accuracy with an area under the curve of 0.80 (95% CI 0.69-0.92). Calibration plots of the model revealed a concordance index of 0.73. CONCLUSIONS: This study identified an association between age, FTR, and risk factors for FTR posthepatectomy. Together, our risk model is a clinically relevant, internally validated, and useful tool for predicting FTR posthepatectomy.

DOI： 10.1111/hepr.14134

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BACKGROUND: Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement. CASE REPRESENTATION: A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital. CONCLUSIONS: Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical.

DOI： 10.1186/s40792-024-02030-5

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Anastomotic leakage and subsequent pelvic sepsis are serious complications after surgery for pelvic malignancies, particularly challenging due to the large pelvic cavity dead space post-exenteration. We report a 47-year-old man treated for a severely infected pelvic hematoma and sepsis following anastomotic leakage after anterior pelvic exenteration. Post robot-assisted exenteration for locally advanced sigmoid colon cancer treated with neoadjuvant chemotherapy, a pelvic abscess from anastomotic dehiscence was identified. Initial CT-guided drainage and subsequent laparoscopic drainage were performed. On postoperative day 22, a bleeding left internal iliac pseudoaneurysm required embolization. Despite these efforts, the sepsis worsened due to an enlarged, infected hematoma. Endoscopic lavage, in collaboration with skilled endoscopists, successfully removed the hematoma, leading to an improved inflammatory response, and the patient was discharged. Endoscopic lavage proved to be the safest and most effective treatment for pelvic sepsis with an infected hematoma after various attempted interventions.

DOI： 10.1111/ases.13384

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

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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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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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Dendritic cell(DC)vaccine therapy has been widely studied as cancer immunotherapy that potently induces cytotoxic T lymphocytes. However, their efficacy in clinical practice has not yet been established. We have developed an oncolytic adenovirus OBP-702 carrying the tumor suppressor gene p53 and have demonstrated its therapeutic potential to induce cytopathic effect and activate antitumor immunity via p53 induction. In this study, we investigated the combined effect of p53-transduced DC vaccine and OBP-702 in colorectal cancer.

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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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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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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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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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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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BACKGROUND: The superior mesenteric artery (SMA)-first approach for pancreatic cancer (PC) is common surgical technique in pancreaticoduodenectomy. To date, few studies have reported SMA-first approach in robot-assisted pancreaticoduodenectomy (RPD). Herein, we present the anterior SMA-first approach for PC during RPD. PATIENT AND METHOD: A 75-year-old man with resectable PC underwent RPD after neoadjuvant chemotherapy. As pancreatic head tumor contacted with the superior mesenteric vein (SMV), the anterior SMA approach was applied. After the mesenteric Kocher maneuver, the jejunum was divided and the left side of the SMA was dissected. Subsequently, the anterior plane of the SMA was dissected. Following the division of branches from the mesenteric vessels, the SMA was taped, and the circumferential dissection around the SMA was performed to detach the pancreatic neck from the SMA completely. Finally, the dissection between the SMV and the tumor was performed under vascular control to remove the specimen. CONCLUSIONS: The anterior SMA-first approach can be optional in patients with PC undergoing RPD. This unique approach allows for the circumferential dissection around the SMA during RPD.

DOI： 10.1245/s10434-024-16305-6

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Background: A difficulty scoring system was developed to estimate the surgical outcomes of laparoscopic liver surgery (LLS); however, the effect of the liver transection area (LTA) on LLS outcomes have not been previously examined. Therefore, this study investigated the predictive significance of the LTA for LLS. Methods: This retrospective study included 106 patients who underwent LLS in our hospital between January 2012 and December 2023. The association of the LTA with the surgical difficulty level and operative time was investigated. Multivariate analyses were performed to identify factors predicting surgical difficulty in LLS. Results: The median LTA and operative time were 62.5 (IQR, 36.0-91.8) cm2 and 250 (IQR, 195-310) minutes, respectively. The LTA was significantly associated with surgical difficulty as evaluated using the IWATE Criteria. Moreover, the LTA significantly correlated with operative time (r2 = 0.19, p < 0.001). The multivariable analyses found that the LTA (≥59 cm2) (odds ratio [OR], 6.07; 95% confidence interval [CI], 2.38-16.6; p < 0.001) and the type of LLS (≥segmentectomy) (OR, 3.79; 95% CI, 1.35-11.4; p = 0.01) were significant factors associated with surgical difficulty. Conclusions: The LTA is a useful parameter that reflects the difficulty of LLS.

DOI： 10.3390/jcm13195686

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Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

DOI： 10.1016/j.omton.2024.200845

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BACKGROUND: There are several reports on the safety and feasibility of pancreatoduodenectomy (PD) without reconstruction of the small remnant pancreas. However, a few studies have explored central pancreatectomy (CP) for non-reconstructed small remnant pancreases after PD. This study presents a case of CP without pancreatic reconstruction after PD. CASE PRESENTATION: A 58-year-old man with cerebral palsy underwent PD for distal cholangiocarcinoma. Three years postoperatively, a 12-mm tumor was detected in the remnant pancreatic body and diagnosed as a pancreatic neuroendocrine neoplasm. Surgical resection was performed, because the tumor was enlarged and chemotherapy resistant. The afferent loop with pancreatojejunostomy anastomosis was dissected, and CP, including pancreatojejunostomy anastomosis, was performed. Given the remnant pancreas was hard and atrophic, the pancreatic tail was transected using a stapler without reconstructing the small remnant pancreas. The patient experienced no postoperative complications including postoperative pancreatic fistula, and the endocrine function of the pancreas was preserved. CONCLUSIONS: We present a case of remnant pancreatic CP that did not require reconstruction after PD. Preservation of the small remnant pancreas without reconstruction during CP may be feasible to maintain endocrine function in select patients after PD.

DOI： 10.1186/s40792-024-02018-1

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The present study investigated the role of ramucirumab (RAM) in treating liver metastases (LMs) as a second-line or salvage treatment in patients with advanced CRC. Of the 36 patients, 21 (58%) received RAM plus folinic acid, fluorouracil and irinotecan (FOLFIRI) as second-line treatment, whereas 15 (42%) received it in a salvage setting. The median overall survival time was 23 months [95% confidence interval (CI), 12-34 months] for those in the second-line treatment group and 8 months (95% CI, 5-19 months) for those in the salvage treatment group. Of the 36 patients, 14 (39%) underwent surgical resection of LMs during chemotherapy. A total of 6 patients underwent surgical resection for LMs for the first time during second-line RAM plus FOLFIRI (RAM-LM); of the remaining 8 patients, 6 underwent resection of LMs during first-line bevacizumab (BEV)-based chemotherapy (BEV-LM). Immunohistochemical analysis of CD42b showed that the platelet aggregation score (CD42b score), which ranges from 0 (absence of deposition) to 3 (presence of linear deposition), tended to decrease with the increasing duration of treatment with both RAM and BEV. Although there was no significant difference in the mean duration of anti-VEGF antibody treatment between the BEV-LM and RAM-LM groups, the median CD42b score was higher in the RAM-LM group (median CD42b score, 3; range, 0-3) compared with that in the BEV-LM group (median CD42b score, 1; range, 0-3; P=0.01), suggesting that RAM induces a different degree of platelet aggregation in liver sinusoids compared to BEV.

DOI： 10.3892/ol.2024.14572

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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：(株)癌と化学療法社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00296&link_issn=&doc_id=20240920170003&doc_link_id=%2Fab8gtkrc%2F2024%2F005109%2F003%2F0865-0868%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2024%2F005109%2F003%2F0865-0868%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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DOI： 10.21037/gs-24-182

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Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.

DOI： 10.1111/cas.16298

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

DOI： 10.1016/j.jgo.2024.101837

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Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line-derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer.

DOI： 10.1158/1535-7163.MCT-23-0527

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BRAF-mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF-mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations.

DOI： 10.1007/s13691-024-00678-2

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A 68-year-old woman was referred to our hospital for rectal surgery after a pathological diagnosis of rectal carcinoid with venous invasion following endoscopic submucosal dissection of a 5 mm-sized submucosal tumor in the lower rectum. Chest CT showed nodules in the left upper lobe and right lower lobe, but positron emission tomography and somatostatin receptor scintigraphy showed no hyperaccumulation in the lung nodules. CT-guided needle biopsy was performed on the nodular lesion in the left upper lobe, which showed focal growth of tumor cells with a high N/C ratio and positive synaptophysin, leading to a diagnosis of pulmonary metastasis of rectal carcinoid. Since the patient was asymptomatic and did not wish to undergo surgery or chemotherapy, she was followed up strictly with sufficient informed consent. Three years have passed since the diagnosis, and there is no tendency for the lung metastasis to increase, and no other new lesions have been observed. The disease had not progressed and remained stable. Therefore, immunohistological analysis of the lung biopsy specimen was performed again, which was positive for TTF-1 and negative for CDX2. Consequently, the diagnosis was changed to primary lung carcinoid tumors, and the patient remains under follow-up with no disease progression.

DOI： 10.1002/jgh3.70003

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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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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：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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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：English   Publishing type：Research paper (scientific journal)  

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53-loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8+ lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8+ lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM toward a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.

DOI： 10.1016/j.omton.2024.200806

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BACKGROUND/AIM: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. MATERIALS AND METHODS: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α-smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. RESULTS: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor-β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. CONCLUSION: sCAFs promote peritoneal metastasis of DGC via IL-8-mediated crosstalk.

DOI： 10.21873/anticanres.17056

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Language：Japanese   Publisher：(株)ニュー・サイエンス社  

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Language：Japanese   Publisher：(株)ニュー・サイエンス社  

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Language：Japanese   Publisher：日本がん免疫学会・日本バイオセラピィ学会  

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BACKGROUND: Pancreatoduodenectomy and subtotal esophagectomy are widely considered the most invasive and difficult surgical procedures in gastrointestinal surgery. Subtotal esophagectomy after pancreatoduodenectomy is expected to be extremely difficult due to complicated anatomical changes, and selecting an appropriate intestinal reconstruction method will also be a difficult task. Therefore, perhaps because the method is considered impossible, there have been few reports of subtotal esophagectomy after pancreatoduodenectomy. CASE PRESENTATION: A 73-year-old man with a history of pancreatoduodenectomy was diagnosed with superficial thoracic esophageal squamous cell carcinoma. Definitive chemoradiation therapy was recommended at another hospital; however, he visited our department to undergo surgery. We performed the robot-assisted thoracoscopic subtotal esophagectomy. There were some difficulties with the reconstruction: the gastric tube could not be used, the reconstruction was long, and the organs reconstructed in the previous surgery had to be preserved. However, the concurrent reconstruction was achieved with the help of a free jejunal flap and vascular reconstruction. All reconstructions from the previous surgery, including the remnant stomach, were preserved via regional abdominal lymph node dissection. After reconstruction, intravenous indocyanine green showed that circulation in the reconstructed intestines was preserved. On postoperative day 1, no recurrent nerve paralysis was observed during laryngoscopy. The patient could start oral intake smoothly 2 weeks after surgery and did not exhibit any postoperative complications related to the reconstruction. The patient was transferred to another hospital on postoperative day 21. CONCLUSIONS: Owing to the free jejunal flap interposition method, we safely performed one stage subtotal esophagectomy and concurrent reconstruction, preservation of the remnant stomach, and pancreaticobiliary reconstruction in patients with a history of pancreatoduodenectomy. We believe that this method is acceptable and useful for patients undergoing complicated reconstruction.

DOI： 10.1186/s40792-024-01919-5

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Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

DOI： 10.1016/j.biomaterials.2024.122605

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DOI： 10.1016/j.asjsur.2024.04.155

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BACKGROUND: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. METHODS: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. RESULTS: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). CONCLUSION: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

DOI： 10.1002/ags3.12783

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Language：Japanese   Publisher：(株)アークメディア  

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

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Language：Japanese   Publisher：日本外科系連合学会  

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Language：Japanese   Publisher：日本外科系連合学会  

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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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Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.

DOI： 10.18926/AMO/66924

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

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A 90-year-old Japanese woman who had been aware of a subcutaneous mass on the right perineal region for 5 years was referred to our hospital for further examination and treatment because of the rapid growth of the mass and bleeding that began 3 months earlier. A biopsy of the mass revealed a diagnosis of well-differentiated squamous cell carcinoma. On preoperative examination, the tumor was 90×40 mm in size and was suspected to have partially invaded the levator ani muscle and external sphincter. Since a preoperative cardiac evaluation indicated severe aortic stenosis, we performed transcatheter aortic valve implantation. A radical resection was then performed with general anesthesia. The skin and subcutaneous tissue defects were reconstructed with a posterior gluteal-thigh propeller flap, and a sigmoid colostomy was created. The patient had a good postoperative course and was transferred to a rehabilitation facility 28 days after the surgery. Epidermal cysts are a common benign tumor, and clinicians should keep in mind that these cysts can become malignant.

DOI： 10.18926/AMO/66930

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Tailgut cyst is a rare cystic disease of the anterior sacral surface and the remains of an embryonic tail gut. Tailgut cysts have a potential for malignancy, and complete resection with an adequate surgical margin is necessary. Even if incomplete resection does not result in recurrence of malignant disease, there is a risk of local infection leading to refractory fistulas. The optimal treatment for such refractory recurrent lesions has not been reported. We describe a case in which the combination of laparoscopic and transsacral approaches was effective for resecting a recurrent refractory fistula after incomplete resection of a tail gut cyst.

DOI： 10.18926/AMO/66928

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A 52-year-old, Japanese man presented to the hospital with a complaint of anal bleeding, and detailed examination resulted in a diagnosis of locally advanced rectal cancer. The patient underwent total neoadjuvant therapy followed by short-course radiation therapy and consolidation chemotherapy, which provided a partial response. After preoperative contrast-enhanced computed tomography showed a horseshoe kidney, robot-assisted, precise, laparoscopic, low anterior resection with D3 dissection and ileostomy construction was performed. The horseshoe renal isthmus was elevated surrounding the inferior mesenteric artery, and the left ureter and seminal vessels ran in front of the kidney. The hypogastric nerve traveled ventral to the horseshoe kidney. With robotic surgery, it was possible to perform more precise surgery while recognizing vascular and nerve anatomy in a rectal cancer patient with a horseshoe kidney due to good three-dimensional visibility and articulated forceps manipulation.

DOI： 10.1111/ases.13296

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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)日本大腸肛門病学会  

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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)日本大腸肛門病学会  

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Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijscr.2024.109565

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BACKGROUND: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). METHODS: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). RESULTS: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. CONCLUSION: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.

DOI： 10.1038/s41416-024-02583-0

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

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Language：Japanese   Publisher：(株)南江堂  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00393&link_issn=&doc_id=20240416110010&doc_link_id=10.15106%2Fj_geka86_347&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka86_347&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a critical role in tumor immunosuppression. However, targeted depletion of CAFs is difficult due to their diverse cells of origin and the resulting lack of specific surface markers. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that leads to rapid cell membrane damage. METHODS: In this study, we used anti-mouse fibroblast activation protein (FAP) antibody to target FAP+ CAFs (FAP-targeted NIR-PIT) and investigated whether this therapy could suppress tumor progression and improve tumor immunity. RESULTS: FAP-targeted NIR-PIT induced specific cell death in CAFs without damaging adjacent normal cells. Furthermore, FAP-targeted NIR-PIT treated mice showed significant tumor regression in the CAF-rich tumor model accompanied by an increase in CD8+ tumor infiltrating lymphocytes (TILs). Moreover, treated tumors showed increased levels of IFN-γ, TNF-α, and IL-2 in CD8+ TILs compared with non-treated tumors, suggesting enhanced antitumor immunity. CONCLUSIONS: Cancers with FAP-positive CAFs in their TME grow rapidly and FAP-targeted NIR-PIT not only suppresses their growth but improves tumor immunosuppression. Thus, FAP-targeted NIR-PIT is a potential therapeutic strategy for selectively targeting the TME of CAF+ tumors.

DOI： 10.1038/s41416-024-02639-1

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

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

BACKGROUND: Although the current trend in pancreatoduodenectomy (PD) has shifted from open surgery to minimally invasive surgery (MIS), evidence on the role of MIS as an element of Enhanced Recovery After Surgery (ERAS) in PD is limited. This study aimed to investigate the effect of robotic surgery using the ERAS protocol on the outcomes of patients undergoing PD. METHODS: This retrospective study included 252 patients who underwent open PD (OPD) or robotic PD (RPD) managed using the ERAS protocol between January 2017 and March 2023. Outcomes stratified by the surgical approach were compared. Multivariable analyses were performed to evaluate the effect of ERAS items, including robotic surgery, on outcomes after PD. RESULTS: Of 252 patients, 202 (80.2%) underwent OPD, and 50 (19.2%) underwent RPD. Multivariable analyses demonstrated that perioperative management center support (odds ratio [OR], 2.85; 95% CI, 1.14-7.72; P = .025), robotic surgery (OR, 6.40; 95% CI, 1.94-26.1; P = .002), early solid intake (OR, 2.84; 95% CI, 1.46-5.63; P = .002), and early drain removal (OR, 3.77; 95% CI, 2.04-7.06; P < .001) were significant ERAS items related to early discharge after PD. CONCLUSION: Our study demonstrated that employing the ERAS protocol for OPD and RPD is feasible and safe. Moreover, our results suggested the role of robotic surgery as an element of the ERAS protocol for PD. A combination of ERAS protocols and MIS may be safe and feasible for accelerating postoperative recovery after PD.

DOI： 10.1016/j.gassur.2023.12.017

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

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Language：Japanese   Publisher：金原出版(株)  

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

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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)日本胃癌学会  

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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This study investigates methylation patterns in circulating cell-free DNA (ccfDNA) for their potential role in colorectal cancer (CRC) detection and the monitoring of treatment response. Through methylation microarrays and quantitative PCR assays, we analyzed 440 samples from The Cancer Genome Atlas (TCGA) and an additional 949 CRC samples. We detected partial or extensive methylation in over 85% of cases within three biomarkers: EFEMP1, SFRP2, and UNC5C. A methylation score for at least one of the six candidate regions within these genes' promoters was present in over 95% of CRC cases, suggesting a viable detection method. In evaluating ccfDNA from 97 CRC patients and 62 control subjects, a difference in methylation and recovery signatures was observed. The combined score, integrating both methylation and recovery metrics, showed high diagnostic accuracy, evidenced by an area under the ROC curve of 0.90 (95% CI = 0.86 to 0.94). While correlating with tumor burden, this score gave early insight into disease progression in a small patient cohort. Our results suggest that DNA methylation in ccfDNA could serve as a sensitive biomarker for CRC, offering a less invasive and potentially more cost-effective approach to augment existing cancer detection and monitoring modalities, possibly supporting comprehensive genetic mutation profiling.

DOI： 10.1186/s12943-023-01910-y

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BACKGROUND: Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG. METHODS: In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia. RESULTS: Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event. CONCLUSIONS: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG.Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm).

DOI： 10.1093/bjsopen/zrad161

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Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

DOI： 10.1371/journal.pone.0298292

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Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (-7.98% vs. -12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.

DOI： 10.1080/01635581.2024.2340782

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DOI： 10.1245/s10434-023-14778-5

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

BACKGROUND: Sufficient knowledge and surgical management of portal annular pancreas (PAP) are essential for pancreatic surgery. As PAP is a relatively rare pancreatic anomaly, few studies have described surgical techniques for patients with PAP undergoing robotic pancreatoduodenectomy (RPD). PATIENTS AND METHODS: An 82-year-old female patient who underwent RPD presented with distal cholangiocarcinoma and type III PAP (the fusion of the uncinate process with the anteportal main pancreatic duct). After the Kocher maneuver and stomach transection, the pancreas was transected into the neck of the anteportal portion. The retroportal portion was dissected, encircled with hanging tape, and compressed. Blood supply from the mesenteric vessels was confirmed using indocyanine green (ICG) fluorescence imaging. Subsequently, the retroportal portion was stapled. CONCLUSIONS: This study demonstrates a unique surgical technique for type III PAP using the hanging maneuver with ICG fluorescence imaging. Surgeons should decide on the surgical strategy on the basis of the fusion and ductal anatomy of the pancreas.

DOI： 10.1245/s10434-023-14685-9

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

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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

BACKGROUND/AIM: The aim of the present study was to clarify the clinical impact of prehabilitation by the perioperative management center (PERIO) at our hospital in severely frail octogenarians with colorectal cancer. PATIENTS AND METHODS: We compared the clinicopathological characteristics of octogenarians who underwent surgery for colorectal cancer before the establishment of PERIO intervention (Control group) with those who received prehabilitation (PERIO group). All patients were classified as American Society of Anesthesiologists (ASA) class 3 or higher. The primary outcome was the incidence of postoperative complications. RESULTS: There were 21 patients in the Control group and 19 patients in the PERIO group. Operative time was significantly longer in the PERIO group (Control group, 200 min vs. PERIO group, 230 min; p=0.03) and blood loss was significantly higher in the PERIO group (Control group, 5 ml vs. PERIO group, 30 ml; p=0.02). Postoperative complications occurred in 10 patients (47.6%) in the Control group and 3 patients (15.8%) in the PERIO group and were significantly lower in the PERIO group (p=0.03). Postoperative hospital stay was 13 days (range=7-31 days) in the Control group and 11 days (range=8-70 days) in the PERIO group (p=0.39). The rate of discharge directly to home was 81% in the Control group and 93.3% in the PERIO group (p=0.29). CONCLUSION: In frail octogenarians with colorectal cancer of ASA class 3 or higher, the incidence of postoperative complications was significantly lower after PERIO intervention.

DOI： 10.21873/anticanres.16762

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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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)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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

Near-infrared photoimmunotherapy(NIR-PIT)is a novel cancer treatment modality that employs antibody-IRDye700DX (IR700)conjugates. Recently, the clinical application of NIR-PIT has received approval in Japan for patients with inoperable head and neck cancer, specifically targeting the human epidermal growth factor receptor(hEGFR). Furthermore, NIR-PIT extends beyond the scope of tumor antigens and can be employed to eliminate specific host cells that contribute to the creation of immune-permissive environments supporting tumor growth. One of the distinguishing features of NIR-PIT is its ability to selectively eliminate various cell types within the tumor microenvironment(TME)by specifically targeting distinct antigens. By employing podoplanin(PDPN)-targeted NIR-PIT, PDPN-expressing fibroblasts were selectively eradicated, resulting in the suppression of tumor progression and a notable extension of overall survival. Additionally, we investigated the efficacy of depleting myeloid-derived suppressor cells(MDSCs)using NIR-PIT. This approach led to the selective elimination of MDSCs within tumors, and remarkable abscopal effects were observed in bilateral tumor models. Hence, NIR-PIT holds immense promise for the treatment of diverse cancer types by precisely targeting tumor cells, fibroblasts, and immune cells.

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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

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

BACKGROUND/AIM: Diffuse-type gastric cancer (GC) frequently exhibits peritoneal metastasis, leading to poor prognosis. However, efforts to develop antitumor strategies for preventing the peritoneal metastasis of GC have been unsuccessful. As diffuse-type GC cells often carry a genetic alteration in the tumor suppressor p53 gene, p53 restoration may be a potent strategy for preventing peritoneal metastasis of GC. In this study, we investigated the therapeutic potential of p53-expressing adenoviral vectors against peritoneal metastasis of diffuse-type GC cells. MATERIALS AND METHODS: Three diffuse-type human GC cell types with different p53 statuses (p53-wild type NUGC-4, p53-mutant type GCIY, and p53-null type KATOIII) were used to evaluate the therapeutic potential of p53 activation induced by the p53-expressing, replication-deficient adenovirus Ad-p53 and oncolytic adenovirus OBP-702. Viability, apoptosis, and autophagy of virus-treated GC cells were analyzed under normal and sphere-forming culture conditions using the XTT assay and western blot analysis. The in vivo antitumor effects of OBP-702 and Ad-p53 were assessed using xenograft tumor models involving peritoneal metastasis of NUGC-4 and GCIY cells. RESULTS: Under normal and sphere-forming culture conditions, OBP-702 induced a significantly greater antitumor effect in GC cells compared with Ad-p53 by strongly inducing p53-mediated apoptosis and autophagy and receptor tyrosine kinase suppression. In vivo experiments demonstrated that intraperitoneal administration of OBP-702 significantly suppressed the peritoneal metastasis of NUGC-4 and GCIY cells compared with Ad-p53, leading to prolonged survival of mice. CONCLUSION: Intraperitoneal administration of OBP-702 inhibits the peritoneal metastasis of GC cells by inducing p53-mediated cytopathic activity.

DOI： 10.21873/anticanres.16678

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

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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：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Although proximal gastrectomy (PG) is commonly used in patients with upper gastric cancer (GC) and esophagogastric junction (EGJ) cancer, long-term prognostic factors in these patients are poorly understood. The double-flap technique (DFT) is an esophagogastrostomy with anti-reflux mechanism after PG; we previously conducted a multicenter retrospective study (rD-FLAP) to evaluate the short-term outcomes of DFT reconstruction. Here, we evaluated the long-term prognostic factors in patients with upper GC and EGJ cancer. METHODS: The study was conducted as a secondary analysis of the rD-FLAP Study, which enrolled patients who underwent PG with DFT reconstruction, irrespective of disease type, between January 1996 and December 2015. RESULTS: A total of 509 GC and EGJ cancer patients were enrolled. Univariate and multivariate analyses of overall survival demonstrated that a preoperative prognostic nutritional index (PNI) < 45 (p < 0.001, hazard ratio [HR]: 3.59, 95% confidential interval [CI]: 1.93-6.67) was an independent poor prognostic factor alongside pathological T factor ([pT] ≥2) (p = 0.010, HR: 2.29, 95% CI: 1.22-4.30) and pathological N factor ([pN] ≥1) (p = 0.001, HR: 3.27, 95% CI: 1.66-6.46). In patients with preoperative PNI ≥45, PNI change (<90%) at 1-year follow-up (p = 0.019, HR: 2.54, 95%CI: 1.16-5.54) was an independent poor prognostic factor, for which operation time (≥300 min) and blood loss (≥200 mL) were independent risk factors. No independent prognostic factors were identified in patients with preoperative PNI <45. CONCLUSIONS: PNI is a prognostic factor in upper GC and EGJ cancer patients. Preoperative nutritional enhancement and postoperative nutritional maintenance are important for prognostic improvement in these patients.

DOI： 10.1016/j.suronc.2023.101990

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

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

Pancreatic ductal adenocarcinoma(PDAC)is lethal malignancy with abundant stroma. Cancer-associated fibroblasts (CAFs) exist in the PDAC stroma and contribute to progression of malignant transformation, treatment resistance, and recurrence. However, effective treatment to control PDAC stroma has not been established. We have developed tumor suppressor gene p53-armed oncolytic adenovirus(OBP-702), and have clarified therapeutic effects on PDAC cells. In this study, we investigate the therapeutic effect of OBP-702 on PDAC CAF.

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Language：Japanese   Publisher：(一社)日本胸部外科学会  

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Language：Japanese   Publisher：(一社)日本胸部外科学会  

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Language：Japanese   Publisher：(一社)日本胸部外科学会  

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Language：Japanese   Publisher：(一社)日本胸部外科学会  

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Language：Japanese   Publisher：(一社)日本胸部外科学会  

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Language：Japanese   Publisher：(一社)日本胸部外科学会  

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

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INTRODUCTION: Exosomes are cell-derived nanovesicles involved in cell-to-cell communications. These nanovesicles are generally considered to contain important carriers of information such as DNA and RNA, and show specific tropism. AREAS COVERED: The combination of existing therapeutic agents with exosomes enhances therapeutic effects by increasing uptake into the tumor. Induction of immunogenic cell death (ICD) may also be triggered more strongly than with the drug alone. Oncolytic viruses (OVs) are even more effective as a drug in combination with exosomes. Although OVs are more likely to cause immune activity, combination with exosomes can exert synergistic effects. OVs have potent anti-tumor effects, but many limitations, such as being limited to local administration and vulnerability to attack by antibodies. Incorporation into exosomes can overcome these limitations and may allow effects against distant tumors. EXPERT OPINION: Novel therapies using exosomes are very attractive in terms of enhancing therapeutic efficacy and reducing side effects. This approach also contains elements overcoming disadvantages in OVs, which have not been used clinically until now, and may usher in a new era of cancer treatments.

DOI： 10.1080/14728222.2023.2259102

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

DOI： 10.1007/s00540-023-03256-7

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Other Link： https://link.springer.com/article/10.1007/s00540-023-03256-7/fulltext.html

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

The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.

DOI： 10.1007/s00262-023-03531-2

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

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

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

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Language：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：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：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：(一社)日本大腸肛門病学会  

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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：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=2023&ichushi_jid=J05229&link_issn=&doc_id=20231002360024&doc_link_id=10.34410%2Fjspbm.46.0_43&url=https%3A%2F%2Fdoi.org%2F10.34410%2Fjspbm.46.0_43&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

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DOI： 10.1007/s11605-023-05806-6

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

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J03156&link_issn=&doc_id=20230907150026&doc_link_id=10.3919%2Fjjsa.84.1301&url=https%3A%2F%2Fdoi.org%2F10.3919%2Fjjsa.84.1301&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(株)メディカ出版  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07192&link_issn=&doc_id=20230726070012&doc_link_id=issn%3D2434-4575%26volume%3D28%26issue%3D8%26spage%3D788&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D2434-4575%26volume%3D28%26issue%3D8%26spage%3D788&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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

The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy.

DOI： 10.1016/j.canlet.2023.216260

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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：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis. CASE PRESENTATION: A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months. CONCLUSIONS: Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM.

DOI： 10.1186/s40792-023-01707-7

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Language：Japanese   Publisher：金原出版(株)  

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

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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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Navigation surgery using indocyanine green (ICG) fluorescence imaging has been used in thoracoabdominal surgery, and its usefulness has been reported in many cases. In this study, laparoscopic lateral lymph node dissection was performed using ICG fluorescence imaging in a patient with left femoral spinous cell carcinoma with inguinal and external iliac lymph node metastases. Spinous cell carcinoma is classified as a rare cancer in Japan, and there is a scarcity of evidence for pelvic lymph node dissection, as well as a lack of studies that mention the dissection area. We hypothesized that visualization of lymph nodes and lymph flow using intraoperative ICG fluorescence imaging would indicate the area of dissection and lead to more efficient dissection. In conclusion, intraoperative ICG fluorescence imaging may be useful in this area where there is limited evidence, although there are some limitations.

DOI： 10.1111/ases.13159

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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)日本膵臓学会  

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

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Language：English  

Salvage surgery for esophageal cancer after definitive chemoradiotherapy (dCRT) is effective, but it is associated with a high rate of perioperative complications. The indications for robot-assisted minimally invasive esophagectomy (RAMIE) are expanding. However, there are few reports of salvage RAMIE. A 73-year-old man was referred to our hospital for residual esophageal cancer with a mediastinal fistula after dCRT. The perioperative diagnosis was T3N1M0-Stage III, and the salvage RAMIE was performed. Although the dissection was difficult due to fibrosis caused by dCRT and the esophageal mediastinal fistula, RAMIE was performed safely with no complications. Multiple features of RAMIE contributed to stable surgery. The monopolar dissection is effective for hard scar tissue caused by CRT and inflammation.

DOI： 10.1111/ases.13155

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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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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：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT. CASE PRESENTATION: A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment. CONCLUSION: A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation.

DOI： 10.1186/s40792-023-01692-x

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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

Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors.

DOI： 10.3390/cancers15112971

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

BACKGROUND: Patient fitness is important for guiding treatment. Muscle mass, as a reflection thereof, can be objectively measured. However, the role of east-west differences remains unclear. Therefore, we compared the impact of muscle mass on clinical outcomes after liver resection for HCC in a Dutch (NL) and Japanese (JP) setting and evaluated the predictive performance of different cut-off values for sarcopenia. METHOD: In this multicenter retrospective cohort study patients with hepatocellular carcinoma (HCC) undergoing liver resection were included. The skeletal muscle mass index (SMI) was determined on CT scans obtained within 3 months before surgery. The primary outcome measure was overall survival (OS). Secondary outcome measures were: 90-day mortality, severe complications, length of stay, and recurrence free survival. The predictive performance of several sarcopenia cut-off values was studied using the c-index and area under the curve. Interaction terms were used to study geographic effect modification of muscle mass. RESULTS: Demographics differed between NL and JP. Gender, age, and body mass index were associated with SMI. Significant effect modification between NL and JP was found for BMI. The predictive performance of sarcopenia for both short- and long-term outcomes was higher in JP compared to NL (max c-index: 0.58 vs 0.55, respectively). However, differences between cut-off values were small. For the association between sarcopenia and OS, a strong association was found in JP (Hazard ratio (HR) 2.00 95%CI[1.230 ; 3.08], P=0.002), where this was not found in NL (0.76 [0.42 ; 1.36], P=0.351). The interaction term confirmed that this difference was significant (HR 0.37 95%CI[0.19 ; 0.73], P=0.005). CONCLUSIONS: The impact of sarcopenia on survival differs between the east and west. Clinical trials and treatment guidelines using sarcopenia for risk stratification should be validated in race-dependent populations prior to clinical adoption.

DOI： 10.1097/JS9.0000000000000458

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AIMS: Lymph node metastases (LNM) are associated with lethal prognosis in intrahepatic cholangiocarcinoma (ICC). Lymphadenectomy is crucial for accurate staging and hopes of possible oncological treatment. However, the therapeutic implications and optimal extent of lymphadenectomy remain contentious. METHODS: To clarify the prognostic value and optimal extent of lymphadenectomy, the therapeutic index (TI) for each lymph node was analyzed for 279 cases that had undergone lymphadenectomy in a multi-institutional database. Tumor localization was divided into hilar lesions (n = 130), right peripheral lesions (n = 60), and left peripheral lesions (n = 89). In addition, the lymph node station was classified as Level 1 (LV1: hepatoduodenal ligament node), Level 2 (LV2: postpancreatic or common hepatic artery nodes), or Level 3 (LV3: gastrocardiac, left gastric artery, or celiac artery nodes). RESULTS: Lymph node metastases were confirmed in 109 patients (39%). Five-y survival rates were 45.3% for N0 disease, 27.1% for LV1-LNM, 22.9% for LV2-LNM, and 7.3% for LV3-LNM (P < 0.001). LV3-LNM were the most frequent and earliest recurrence outcome, including multisite recurrence, followed by LV2, LV1, and N0 disease. The 5-year TI (5year-TI) for lymphadenectomy was 7.2 for LV1, 5.5 for LV2, and 1.9 for LV3. Regarding tumor location, hilar lesions showed 5-year TI >5.0 in LV1 and LV2, whereas bilateral peripheral lesions showed 5-year TI > 5.0 in LV1. CONCLUSION: The implications and extent of lymphadenectomy for ICC appear to rely on tumor location. In the peripheral type, the benefit of lymphadenectomy would be limited and dissection beyond LV1 should be avoided, while in the hilar type, lymphadenectomy up to LV2 could be recommended.

DOI： 10.1002/ags3.12642

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：(株)南江堂  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00393&link_issn=&doc_id=20230414270006&doc_link_id=10.15106%2Fj_geka85_345&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka85_345&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English  

A 70-year-old male with anal pain and fever was diagnosed with rectal cancer perforation and abscess in the right gluteus maximus (GM) muscle. He underwent a transverse colon colostomy followed by preoperative capecitabine+oxaliplatin. Some local control was achieved but a residual abscess was observed in the right GM muscle. To secure circumferential resection margin by tumor reduction, he received chemoradiotherapy as total neoadjuvant therapy (TNT) and underwent laparoscopic abdominoperineal resection, D3 lymph node dissection, combined coccyx resection, and partial resection of the right GM muscle. The skin defect and pelvic dead space were filled with a right lateral vastus lateral great muscle flap. Histopathologically, the resected specimen showed no tumor cells in the primary tumor or lymph nodes, indicating a pathological complete response (pCR). This case suggests that TNT might improve the R0 resection and pCR rates and overall survival.

DOI： 10.18926/AMO/65152

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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：医歯薬出版(株)  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00060&link_issn=&doc_id=20230502010024&doc_link_id=issn%3D0039-2359%26volume%3D285%26issue%3D5%26spage%3D446&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0039-2359%26volume%3D285%26issue%3D5%26spage%3D446&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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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The usefulness of laparoscopic and endoscopic cooperative surgery (LECS) for gastric submucosal tumors in the cardiac region has been reported in recent years. However, LECS for submucosal tumors at the esophagogastric junction with hiatal sliding esophageal hernia has not been reported, and its validity as a treatment method is unknown. The patient was a 51-year-old man with a growing submucosal tumor in the cardiac region. Surgical resection was indicated because a definitive diagnosis of the tumor was not determined. The lesion was a luminal protrusion tumor, located on the posterior wall of the stomach 20 mm from the esophagogastric junction, and had a maximum diameter of 16.3 mm on endoscopic ultrasound examination. Because of the hiatal hernia, the lesion could not be detected from the gastric side by endoscopy. Local resection was considered to be feasible because the resection line did not extend into the esophageal mucosa and the resection site could be less than half the circumference of the lumen. The submucosal tumor was resected completely and safely by LECS. The tumor was diagnosed as a gastric smooth muscle tumor finally. Nine months after surgery, a follow-up endoscopy showed reflux esophagitis. LECS was a useful technique for submucosal tumors of the cardiac region with hiatal hernia, but fundoplication might be considered for preventing backflow of gastric acid.

DOI： 10.7759/cureus.37902

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

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

DOI： 10.1007/s11605-023-05600-4

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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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Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a central role in tumor progression. Previously, we reported that CAFs might induce tumor immunosuppression via interleukin-6 (IL-6) and promote tumor progression by blocking local IL-6 in the tumor microenvironment with neutralizing antibody. Here, we explore whether an anti-IL-6 receptor antibody could be used as systemic therapy to treat cancer, and further investigate the mechanisms by which IL-6 induces tumor immunosuppression. In clinical samples, IL-6 expression was significantly correlated with α-smooth muscle actin expression, and high IL-6 cases showed tumor immunosuppression. Multivariate analysis showed that IL-6 expression was an independent prognostic factor. In vitro, IL-6 contributed to cell proliferation and differentiation into CAFs. Moreover, IL-6 increased hypoxia-inducible factor 1α (HIF1α) expression and induced tumor immunosuppression by enhancing glucose uptake by cancer cells and competing for glucose with immune cells. MR16-1, a rodent analog of anti-IL-6 receptor antibody, overcame CAF-induced immunosuppression and suppressed tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo. The anti-IL-6 receptor antibody could be systemically employed to overcome tumor immunosuppression and improve patient survival with various cancers. Furthermore, the tumor immunosuppression was suggested to be induced by IL-6 via HIF1α activation.

DOI： 10.1007/s00262-023-03378-7

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

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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Language：Japanese   Publisher：(一社)日本肝臓学会  

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An annular pancreas is a rare anomaly of the pancreas, defined as pancreatic tissue that totally or partly encircles the duodenum, usually the descending portion. A 76-year-old man who was diagnosed with gastric cancer cT3N0M0 Stage IIB underwent laparoscopic distal gastrectomy with D2 lymph node dissection. Intraoperatively, the dorsal half of the duodenal bulb was seen to be half surrounded by the pancreas, and a non-typical annular pancreas was diagnosed. Because of the risk to the pancreas, it was considered impossible to perform anastomosis by a linear stapler as in the usual laparoscopic procedure. Therefore, we performed laparoscopically assisted distal gastrectomy and Billroth-I reconstruction using a circular stapler, and the surgery was completed without difficulties. His postoperative course was good despite the development of a pancreatic fistula, which was an International Study Group for Pancreas Fistula biochemical leak. Some APs can be diagnosed preoperatively, but the rarer subtypes such as ours are more difficult to visualize on imaging. In gastrectomy, it is both oncologically important and technically challenging to perform lymph node dissection around the pancreas. In this case with an especially proximal pancreas, a circular stapler was considered better suited for gastroduodenal anastomosis and required a broader field than that afforded by laparoscopy. A case of non-typical annular pancreas diagnosed during laparoscopic gastric surgery is described.

DOI： 10.18926/AMO/64368

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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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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01117&link_issn=&doc_id=20230308270006&doc_link_id=10.5833%2Fjjgs.2022.0036&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2022.0036&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：金原出版(株)  

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

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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/AIM: It has recently been recognized that preoperative sarcopenia contributes to postoperative complications and overall survival in gastric cancer (GC). However, few studies have investigated the relationship between postoperative skeletal muscle loss (SML) and survival in GC, despite the inevitability of body weight loss after gastrectomy in most GC patients. Herein, we studied the impact of postoperative SML on GC prognosis. PATIENTS AND METHODS: A total of 370 patients with GC who underwent curative gastrectomy were retrospectively evaluated in this study. Postoperative SML was assessed on computed tomography (CT) images taken before surgery and 1 year after surgery. The impact of postoperative SML on survival was evaluated. RESULTS: Postoperative severe SML was significantly associated with presence of comorbidities, higher tumor stage, higher postoperative complication rate and longer hospital stay. Univariate and multivariate analyses of prognostic factors for overall survival revealed that SML was an independent indicator of poor prognosis, along with age, tumor stage, preoperative sarcopenia, and operation time (hazard ratio, 2.65; 95% confidence interval, 1.68-4.20, p<0.0001). There was a strong association of severe postoperative SML with decreased overall survival in patients with preoperative sarcopenia. CONCLUSION: To improve the prognosis of GC patients after surgery, it is important to prevent postoperative SML as well as preoperative sarcopenia. Perioperative multimodal interventions including nutritional counseling, oral nutritional supplements, and exercise are required to prevent SML after gastrectomy.

DOI： 10.21873/anticanres.16153

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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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Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis.

DOI： 10.1371/journal.pone.0294491

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Language：Japanese   Publisher：日本外科代謝栄養学会  

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BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

DOI： 10.1093/ecco-jcc/jjac186

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Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adenocarcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telomerase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracellular adenosine triphosphate and high-mobility group box protein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpression augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.

DOI： 10.1016/j.omto.2022.09.003

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We evaluated the usefulness of an oncolytic virus (Suratadenoturev; OBP-301) against radioresistant oral squamous cell carcinoma. We confirmed the expression of human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor in cell lines. Also, we examined the potential presence in a patient who has received existing therapy that is amenable to treatment with OBP-301. We evaluated: (1) the antitumor effects of OBP-301 alone and in combination with radiotherapy on radioresistant cell lines, (2) the molecular mechanism underlying the radiosensitizing effect and cell death increased by the combination therapy, and (3) the antitumor effect of the combination therapy in vivo using xenograft models (a radioresistant cell line-derived xenograft in mouse and a patient-derived xenograft). Human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor were expressed in all cell lines. OBP-301 decreased the proliferative activity of these cell lines in a concentration-dependent manner, and significantly enhanced the antitumor effect of irradiation. Phosphorylated STAT3 and its downstream molecules, which correlated with apoptosis and autophagy, showed significant changes in expression after treatment with OBP-301. The combination therapy exerted a significant antitumor effect versus radiotherapy alone in both xenograft models. Combination of OBP-301 with radiotherapy exerts a synergistic effect and may represent a promising treatment for radioresistant oral squamous cell carcinoma.

DOI： 10.1016/j.omto.2022.10.001

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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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)日本内視鏡外科学会  

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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：(一社)日本内視鏡外科学会  

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BACKGROUND: Remnant gastric cancer (RGC) has been increasing for various reasons such as a longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the oncological features of RGC. METHODS: Between January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis. RESULTS: On univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with poor overall survival (p=0.014, 0.0061, and 0.016, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.014, hazard ratio: 4.2, 95% confidence interval: 1.3-13.0). In addition, tumor-infiltrating CD8+ T cells expression was higher in the benign disease group than in the malignant group (p=0.046). CONCLUSIONS: Initial gastrectomy caused by malignant disease was an independent poor prognostic factor of RGC, and as one of the causes, lower level of tumor-infiltrating CD8+ T cells in RGC may involve in.

DOI： 10.1186/s12957-022-02853-2

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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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Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.

DOI： 10.1007/s00262-022-03334-x

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Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment.

DOI： 10.1038/s41598-022-24313-3

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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

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DOI： 10.1245/s10434-022-12645-3

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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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BACKGROUND: The number of gastric cancer (GC) patients with other diseases is increasing due to the aging of the population. In particular, in stage IA GC patients who have multiple diseases, surgical indications should be considered after identifying prognostic factors. We therefore investigated prognostic factors for stage IA GC in the elderly. METHODS: Patient characteristics were collected and analyzed retrospectively for elderly patients with stage IA GC who underwent curative surgical treatment at Okayama University Hospital between 2010 and 2015, and an elderly group (EG; 75-79 years old) and very elderly group (VEG; ≥80 years old) were compared. RESULTS: Fifty-three patient in the EG and 31 patients in the VEG were compared. No factors associated with clinicopathological characteristics or surgical or postoperative short-term outcomes differed significantly between groups. Although no factors in the EG appeared significantly associated with poor overall survival (OS), severe comorbidity [Charlson Comorbidity Index (CCI) ≥2; P=0.019], open gastrectomy (P=0.012), high volume of blood loss (≥300 mL; P=0.013) and long postoperative hospital stay (≥14 days; P=0.041) were significantly associated with poor OS. Furthermore, only CCI ≥2 [hazard ratio (HR) =9.2; 95% confidence interval (CI): 1.2-68.9; P=0.032] was an independent prognostic factor associated with poor OS. Five-year OS was 88.9% for CCI 0/1 patients and 62.3% for CCI ≥2 patients, representing very impressive results. CONCLUSIONS: CCI ≥2 is an important prognostic factor in clinical decisions in stage IA GC patients ≥2, so careful determination of surgical indications is desirable.

DOI： 10.21037/jgo-22-527

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

Pancreatic cancer has poor prognosis despite the various developed multimodal treatment strategies. Currently, neoadjuvant chemotherapy and immunotherapy have attracted substantial attention as effective treatment strategies. However, amplifying immune response with existing treatments is difficult. We developed telomerase-specific oncolytic adenoviruses (OAs), including OBP-301 that is currently tested in a clinical trial of combined anti-PD-1 antibody and p53-armed OBP- 301 variant(OBP-702). OAs have immune-modulation functions and induce CD8+ T cells into tumors by releasing immunogenic cell death markers, such as extracellular adenosine triphosphate. Here, we investigated the effectiveness of OBP- 702 in pancreatic cancer treatments, focusing on the influence on CD8+ memory T cells.

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

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BACKGROUND: The standard treatment for locally advanced esophageal cancer is preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), followed by surgery. Although docetaxel plus cisplatin and 5-fluorouracil (DCF) has been reported to have favorable outcomes, no study has compared its therapeutic efficacy to that of standard treatment. This study aimed to compare the therapeutic effects of CF and DCF in the real world by matching patient background factors using propensity scores. METHODS: We retrospectively reviewed the data of 237 patients with esophageal squamous cell carcinoma who underwent esophagectomy between January 2008 and December 2018. Patients were divided into two groups based on the preoperative chemotherapy regimens of CF (79 patients) or DCF (158 patients), and 49 matched pairs were finally analyzed using propensity score matching. Short- and long-term outcomes were compared between groups. RESULTS: After matching, although no significant differences in survival were observed among the groups, patients receiving DCF showed a significantly high histological response (P < 0.001). Subgroup analyses demonstrated that DCF therapy had better overall survival (P = 0.046) and relapse-free survival (P = 0.010) among pathological T3 and T4 cases. Whereas, adverse effects of chemotherapy were more frequent in the DCF group. CONCLUSIONS: Patients receiving DCF had higher pathological response and better survival than those receiving CF, especially in pathological T3 and T4 cases matched using propensity scores. Thus, the DCF regimen might be an effective treatment for locally advanced esophageal cancer. However, the adverse side effects of chemotherapy remain high and should be handled appropriately.

DOI： 10.1007/s10388-022-00934-5

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An 84-year-old female underwent open right hemicolectomy with D3 lymph node dissection for cecal cancer, pathologically identified as pT4aN2M0 Stage IIIc and BRAF mutation-positive. Due to early recurrence of abdominal wall and right lateral lymph nodes, the patient was treated with FOLFOXIRI+Bevacizumab. Imaging after 5 courses of chemotherapy found tumor shrinkage and no new metastases. The patient did not tolerate chemotherapy well, and tumor resection was performed. Microsatellite instability (MSI) testing using multiplex polymerase chain reaction (PCR) fragment analysis revealed MSI-high status. The patient is currently recurrence-free without chemotherapy at 1 year postoperatively. BRAF-mutated colorectal cancer has a poor prognosis, and may require resection of the metastatic or recurrent tumor after comprehensive evaluation.

DOI： 10.18926/AMO/64043

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

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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：Japanese   Publisher：(株)癌と化学療法社  

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