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Abstract Aim The present study investigated the prognostic factors associated with actual 5‐y recurrence‐free survival (RFS) after upfront surgery for resectable pancreatic cancer (R‐PC) in patients who were deemed not to require neoadjuvant treatment. Methods Between 2007 and 2016, 316 patients who underwent pancreatectomy for radiologically R‐PC were retrospectively reviewed to evaluate the predictors of actual 5‐y RFS. Predictors were identified using logistic regression analysis of preoperative evaluable factors. The cutoff values for continuous variables were determined based on a minimum p‐value approach (model 1) or the value that maximized the rate of 5‐y RFS survivors (model 2). Results Fifty‐one patients (16.1%) achieved a 5‐y RFS. A tumor size ≤23 mm, the absence of serosal invasion on computed tomography (CT), and Neutrophil‐to‐Lymphocyte Ratio

Abstract Background Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. Methods This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. Trial registration This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Abstract In cancer genome analysis, identifying pathogenic alterations and assessing their effects on oncogenic processes is important. Although whole exome sequencing (WES) can effectively detect such changes, driver alterations could not be identified in 27.8% of the cases, according to a previous study. The objectives of the present study were to evaluate the utility of whole genome sequencing (WGS) and clarify its differences with WES in terms of driver alteration detection. For this purpose, WGS analysis was conducted on 177 driverless WES samples, selected from 5,480 fresh frozen samples derived from 5,140 Japanese patients with cancer. These samples were selected as primary tumor, both WES and transcriptome profiling were performed, estimated tumor content of ≥ 30%, and no driver alterations were identified by WES. WGS identified driver and likely driver alterations in 68.4 and 22.6% of the samples, respectively. The most frequent alteration type was oncogene amplification, followed by tumor suppressor gene deletion and small variants located outside the coding region. In the remaining 9.0% of samples, no such signals were identified; therefore, further investigations are required. The current study clearly demonstrated the role and utility of WGS in identifying genomic alterations that contribute to tumorigenesis.

Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Abstract Background Lymph node metastasis (LNM) is associated with poor prognosis in patients with duodenal cancer (DC). However, the efficacy and optimal extent of lymph node (LN) dissection have not been thoroughly discussed. Methods A total of 98 consecutive patients with DC who underwent surgical resection (pancreatoduodenectomy, n = 55; partial resection, n = 32; pancreas‐sparing total duodenectomy, n = 9) were retrospectively analyzed. The LN stations located upstream of the lymphatic flow were defined as Np stations according to tumor location, whereas the others were defined as Nd stations. The association between the dissection of each LN station and survival outcome was investigated using the efficacy index (EI; percentage of metastases to lymph nodes in each station multiplied by the 5‐year survival rate of metastatic cases). Results The survival of patients with LNM at the Nd stations (n = 6) was significantly worse than that of patients with LNM only at the Np stations (n = 20) (relapse‐free survival, median survival time [MST], 6.0 vs. 48.4 months, p

Abstract Background Suvorexant and ramelteon have been presented as useful for preventing postoperative delirium. Previous studies reported on the comparison with benzodiazepine hypnotics which have been known for the risk for inducing delirium, but the comparison with patients not taking any hypnotics has not been reported yet. Therefore, we assessed the incidence rates for postoperative delirium comparing cancer patients who received preoperative combined administration with suvorexant and ramelteon and those not taking any hypnotics. Methods Among 110 cancer patients who underwent surgeries at the Division of Hepato-Biliary-Pancreatic Surgery at the Shizuoka Cancer Center between April 1, 2017 and June 30, 2020, 50 patients who received combined administration with suvorexant and ramelteon from 7 days prior to their surgeries and 60 patients who did not take any hypnotics including suvorexant and ramelteon were classified. They were retrospectively observed during the 7 days from their surgeries onward to compare the cumulative incidence rates for postoperative delirium. Results The cumulative incidence rate for postoperative delirium during the 7 days in the combined-administration group was 14.0% (7/50), while that for the no-hypnotic group was 36.7% (22/60), which proved that the incidence rate for the former was significantly low (OR: 0.28, 95%CI: 0.11–0.73, P = 0.009). Conclusions The present study suggests that the preventive combined administration with suvorexant and ramelteon starting from the preoperative period for cancer patients can be effective in lowering the incidence rate for postoperative delirium. Trial registration Retrospectively registered.

Abstract Background Small bowel cancer (SBC) is a rare malignancy that is often diagnosed at an advanced stage. Palliative chemotherapy is the standard treatment for patients with metastatic SBC. The relevant literature on conversion surgery in patients who have responded favorably to chemotherapy is limited. Case presentation A 64-year-old man was diagnosed with jejunal carcinoma with multiple peritoneal metastases. After implanting an expandable metallic stent at the primary site, the patient underwent 6 months of FOLFOX therapy, resulting in a clinical complete response. Chemotherapy was continued, and four years after the initiation of therapy, the patient showed no evidence of disease progression. Nevertheless, anemia of continuous minor hemorrhages from the stent site and general malaise of chemotherapy got progressively worse during treatment. After confirming negative ascites cytology and the absence of peritoneal metastasis via staging laparoscopy, the patient underwent partial jejunectomy. Pathologically, no residual tumor was detected in the resected specimen. The postoperative course was uneventful, and the patient remained free of recurrence for 30 months after surgery without chemotherapy. Conclusion Although infrequent, conversion surgery may be a valid therapeutic option for selected cases of SBC with peritoneal metastasis.

Abstract Background Clostridium perfringens sepsis has been reported to have a rapid onset and severe clinical outcome. We herein report a case of C. perfringens sepsis associated with massive intravascular hemolysis after left hepatic trisectionectomy for perihilar cholangiocarcinoma. Case presentation A 72-year-old woman underwent left hepatic trisectionectomy for perihilar cholangiocarcinoma. Her postoperative course was uneventful except for bile leakage. She was discharged on postoperative day (POD) 35. On POD 54, she was readmitted because of abdominal pain with a high fever. Although her vital signs were stable on arrival at the hospital, a laboratory examination showed a severe inflammatory reaction and hemolysis, and she had developed disseminated intravascular coagulation. Abdominal contrast-enhanced computed tomography showed a 70-mm irregular shape and low-density containing air in liver segment 6, which suggested a liver abscess. The abscess was immediately drained of pus containing air. The pus showed multiple Gram-positive bacilli, and two blood cultures showed Gram-positive bacilli and hemolysis. Empirical antibiotic therapy with vancomycin and meropenem was started because C. perfringens was detected from the preoperative bile culture. Four hours after arrival, tachypnea and decreased oxygen saturation were observed. Her general condition deteriorated rapidly with significant hypoglycemia, progressive acidosis, anemia, and thrombocytopenia. Despite rapid drainage and empiric therapy, she died six hours after her arrival. At autopsy, the abscess consisted of coagulation necrosis of liver cells with inflammatory cell infiltration, and clusters of Gram-positive large bacilli were observed in the necrotic debris. C. perfringens was detected in the drainage fluid and blood culture. She was diagnosed with a liver abscess and severe sepsis caused by C. perfringens and treated promptly, but the disease progressed rapidly and led to her death. Conclusions Sepsis caused by C. perfringens can progress rapidly and lead to death in a few hours, so prompt treatment is needed. When patients who have undergone highly invasive hepatobiliary-pancreatic surgery show hemolysis and hepatic abscesses with gas, C. perfringens should be considered the most likely bacterium.

Abstract Background Small intestine carcinoma (SIC) cases in Japan have recently been treated with chemotherapy according to colorectal carcinoma classification, while papilla of Vater carcinoma (PVC) cases according to cholangiocarcinoma (CHC) classification. However, few research reports support the molecular genetic validity of these therapeutic choices. Patients and methods Here, we investigated the clinicopathological and molecular genetic factors of SIC and PVC. We used the data from the Japanese version of The Cancer Genome Atlas. Additionally, molecular genetic data on gastric adenocarcinoma (GAD), colorectal adenocarcinoma (CRAD), pancreatic ductal adenocarcinoma (PDAC), and CHC were also referred to. Results This study consisted of tumor samples from 12 patients of SIC and three patients of PVC treated from January 2014 to March 2019. Among them, six patients had pancreatic invasion. t‐Distributed stochastic neighbor embedding analysis showed that the gene expression pattern of SIC was similar not only to those of GAD and CRAD, but also to that of PDAC in the pancreatic invasion patients. In addition, PVC resembled the GAD, CRAD, and PDAC, rather than the CHC. The molecular genetic characteristics of the six patients with pancreatic invasion were: one had high microsatellite instability, two had a TP53 driver mutation, and three had tumor mutation burden values

Abstract Background Acquired hemophilia A (AHA) is a rare disease characterized by a prolonged activated partial thromboplastin time (aPTT) and the production of coagulation factor VIII inhibitors. We encountered two cases of AHA in the perioperative period of pancreatoduodenectomy (PD). Case presentation Case 1: A 76-year-old woman with intraductal papillary mucinous carcinoma developed acute cholecystitis 5 days before PD. Despite immediate improvement in her acute cholecystitis with biliary drainage and antibiotics, her aPTT level was prolonged (55.9 s). PD was performed as scheduled. On postoperative day (POD) 2, she developed intra-abdominal hemorrhaging that required reoperation. However, intra-abdominal bleeding and concomitant anemia persisted after reoperation. On POD 13, she was diagnosed with AHA based on the detection of an inhibitor of coagulation factor VIII. Despite hemostatic and immunosuppressive treatment, including massive blood transfusion, her general condition gradually worsened due to continuous bleeding and secondary infections. She ultimately died of multiple organ failure on POD 71. Case 2: An 82-year-old man received PD for distal cholangiocarcinoma. On POD 3, a small amount of blood via abdominal drainage was observed. On POD 4, his aPTT level was prolonged (61.5 s). On POD 8, subcutaneous hemorrhaging of the median wound was observed, and corticosteroids were administered under suspicion of AHA on POD 9. On POD 15, an inhibitor of FVIII was detected, and he was diagnosed with AHA. On POD 17, the aPTT level had normalized, and an inhibitor of FVIII was undetectable. On POD 41, he was discharged without any serious hemorrhagic events. Conclusions AHA may be more frequent than previously reported. When unexplained prolonged aPTT or bleeding symptoms are observed, it is important to keep AHA in mind during the perioperative period of invasive surgery.

Abstract Background Pancreatic cancer (PC) is one of the most aggressive cancers worldwide. Although many studies have investigated genomic alterations, the genomic landscape of Japanese PC patients has not been fully elucidated. Methods We used whole‐exome sequencing, cancer gene panel deep‐sequencing, and microarray gene expression profiling data derived from the Japanese version of the Cancer Genome Atlas (JCGA) in 93 PC cases. Results Somatic driver mutations were identified in 65.6% of samples in 19 genes. The median tumor mutation burden (TMB) value was 0.24 Muts/Mb (interquartile range, 0.15–0.64 Muts/Mb). The commonly mutated genes were KRAS (58%), TP53 (40%), CDKN2A (10%), SMAD4 (10%), FGFR2 (9%), and PKHD1 (9%). Frequent germline variation genes were BRCA1 (8%), CDH1 (5%), MET (5%), MSH6 (5%), and TEK (5%). Frequent chromosomal arm alterations included copy number gains in 2q (42%), 7q (24%), and 3q (24%), and copy number losses in 19p (62%), 19q (47%), 12q (34%), and 7q (30%). A prognostic analysis according to the presence of driver mutations showed that overall survival (OS) in the driver mutation‐positive group was significantly worse in comparison to that of the driver mutation‐negative group (median, 23.1 vs 46.7 mo; P = .010). A Cox proportional hazards analysis for OS identified driver mutation (hazard ratio [HR], 1.89; P = .025) and lymph node metastasis (HR, 3.27; P = .002) as independent prognostic factors. Conclusion The present results from the JCGA dataset constitute a fundamental resource for genomic medicine for PC patients, especially in Japan.

Abstract Aim This study was undertaken to evaluate the long‐term outcomes of staged liver resection for synchronous liver metastases (SLM) from colorectal cancer (CRC), and to elucidate the prognostic impact and predictors of early recurrence (ER), which was defined as recurrence within 6 mo. Methods Patients with SLM from CRC, except for initially unresectable SLM, from January 2013 to December 2020 were included. First, overall survival (OS) and relapse‐free survival (RFS) after staged liver resection were evaluated. Second, eligible patients were classified as follows: patients who were unresectable after resection of CRC (UR), patients with ER, and patients without ER (non‐ER), and their OS after resection of CRC were compared. In addition, risk factors for ER were identified. Results The 3‐y OS and RFS rates after resection of SLM were 78.8% and 30.8%, respectively. Next, the eligible patients were classified as follows: ER (N = 24), non‐ER (N = 56), and UR (N = 24). The non‐ER group had a significantly better OS than the ER (3‐y OS: 89.7% vs 48.0%, P = .001) and UR (3‐y OS: 89.7% vs 61.6%, P

Abstract In pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The TMB was classified as High (≥ 5.0), Low (

Abstract Background Budd–Chiari syndrome (BCS) is a rare vascular disorder of the liver, and acute and secondary BCS is even rarer. Case presentation A 62-year-old man with perihilar cholangiocarcinoma of Bismuth type IIIa underwent right hemi-hepatectomy with caudate lobectomy and pancreatoduodenectomy. Adjuvant chemoradiotherapy was performed due to a positive hepatic ductal margin. Subsequently, the disease passed without recurrence. The patient visited for acute onset abdominal pain at the 32nd postoperative month. Multidetector-row computed tomography (MDCT) showed stenosis of the left hepatic vein (LHV) root, which was the irradiated field, and thrombotic occlusion of the LHV. The patient was diagnosed with acute BCS caused by adjuvant radiotherapy. Although anticoagulation therapy was performed, the patient complained of sudden upper abdominal pain again. MDCT showed an enlarged LHV thrombus and hepatomegaly. The patient was diagnosed with exacerbated acute BCS, and stenting for the stenotic LHV root was performed with a bare stent. Although stenting for the LHV root was very effective, restenosis occurred twice due to thrombus in the existing stent, so re-stenting was performed twice. The subsequent clinical course was acceptable without recurrence or restenosis of the LHV root as of 6 months after the last stenting using a stent graft. Conclusion Although no case of BCS caused by radiotherapy has yet been reported, the present case showed that late side effect of radiotherapy can cause hepatic vein stenosis and secondary BCS.

Abstract Background The primary disease of Trousseau’s syndrome is often highly advanced cancer, and treatment of the primary disease after cerebral infarction is often difficult. We herein report a case of pancreatic head cancer with Trousseau’s syndrome treated with radical resection and anticoagulant therapy. Case presentation A 78-year-old man was admitted with dizziness and diagnosed with cerebral infarction. Abdominal contrast-enhanced computed tomography for a thorough checkup indicated borderline resectable pancreatic head cancer. Radical resection after neoadjuvant chemotherapy (NAC; gemcitabine plus nab-paclitaxel) was scheduled. During the second course of NAC, multiple cerebral infarctions recurred, and the patient was diagnosed with Trousseau’s syndrome. Continuous intravenous infusion of heparin was started for cerebral infarction. Since it was impossible to continue NAC and there was no worsening of imaging findings, radical resection was planned. Thereafter, he underwent pancreatoduodenectomy with superior mesenteric vein resection. The patient progressed well and was discharged on the 19th day after surgery. He continued subcutaneous injection of heparin at home and is alive without recurrence of cancer or cerebral infarction at more than 21 months after surgery. Conclusion Surgical treatment may be an option for pancreatic cancer with Trousseau’s syndrome under favorable conditions.

Abstract Background Multiple mutation (MM) within a single gene has recently been reported as a mechanism involved in carcinogenesis. The present study investigated the clinical significance of MMs in hepatocellular carcinoma (HCC). Methods Two hundred twenty-three surgically resected HCCs were subjected to gene expression profiling and whole-exome sequencing. Results MMs in individual genes were detected in 178 samples (MM tumors: 79.8%). The remaining samples all carried a single mutation (SM tumors: 20.2%). Recurrence-free survival in the MM group was significantly worse in comparison to the SM group (P = 0.012). A Cox proportional hazard analysis revealed that MM tumor was an independent predictor for worse a prognosis (hazard ratio, 1.72; 95% confidence interval, 1.01–3.17; P = 0.045). MMs were frequently observed across in various genes, especially MUC16 (15% of samples had at least one mutation in the gene) and CTNNB1 (14%). Although the MUC16 mRNA expression of MUC16 wild-type and MUC16 SM tumors did not differ to a statistically significant extent, the expression in MUC16 MM tumors was significantly enhanced in comparison to MUC16 SM tumors (P

Abstract Aim The appropriate extent of lymphadenectomy for pancreatic cancer of the body/tail has not been standardized worldwide. The present study evaluated the optimal extent of harvesting lymph nodes. Methods Patients who underwent distal pancreatectomy for invasive ductal carcinoma of the pancreas between 2007 and 2018 were retrospectively reviewed. Patients were subclassified into three groups depending on the tumor location: pancreatic body (Pb), proximal pancreatic tail (Ptp), and distal pancreatic tail (Ptd). The pancreatic tail was further divided into even sections of Ptp and Ptd. Patterns of lymph node metastasis and the impact of lymph node metastasis on the prognosis were examined. Results A total of 120 patients were evaluated. Fifty‐eight patients had a tumor in the Pb, 38 in the Ptp, and 24 in the Ptd. No patients with a Ptd tumor had metastasis beyond the peripancreatic and splenic hilar lymph nodes (LN‐PSH). All patients with metastasis to the lymph nodes along the common hepatic artery (LN‐CHA) or along the left lateral superior mesenteric artery (LN‐SMA) also had metastasis to the LN‐PSH. Recurrence after surgery occurred significantly earlier in this population. In a multivariate analysis, metastasis to the LN‐CHA or LN‐SMA (hazard ratio [HR] 3.3; P = .04) was an independent risk factor for overall survival. Furthermore, high levels of preoperative serum CA19‐9 (HR 10.9; P = .013) were a predictive factor for metastasis to the LN‐CHA or LN‐SMA. Conclusions Metastasis to the LN‐CHA or LN‐SMA was rare but a significant prognostic factor in patients with pancreatic body/tail cancer.

Summary: Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p

Abstract Introduction The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct‐acting antivirals (DAA) or interferon (IFN) are still not fully understood. Methods Sixty‐nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole‐exome sequencing. Results Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV‐positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV‐SVR. According to the HCV treatment, 35 HCV‐SVR HCCs were classified into two groups: eight tumors with DAA (HCV‐SVR‐DAA) and 24 tumors with interferon (HCV‐SVR‐IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV‐SVR than in HCV‐positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV‐SVR samples than in HCV‐positive samples (p = 0.048). Among the patients with HCV‐SVR, the frequency of samples with TP53 mutations was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors (p = 0.030). TP53 inactivation scores in HCV‐SVR‐DAA tumors were found to be significantly enhanced in comparison to HCV‐SVR‐IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV‐SVR‐DAA tumors. HCV‐SVR‐DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV‐SVR‐IFN. Conclusion Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV‐SVR‐DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV‐positive tumors and HCV‐SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors.

Abstract Aim The prognostic value of the perioperative carbohydrate antigen 19‐9 (CA19‐9) value and the prognostic relationship between the CA19‐9 value and the surgical margin in extrahepatic cholangiocarcinoma (EHCC) have not been fully discussed. Methods A total of 390 patients who underwent curative resection for EHCC between 2002 and 2018 were retrospectively analyzed. According to the perioperative CA19‐9 value, patients were divided into three groups: preoperative normal (Normal, n = 178), preoperative high and postoperative normal (Normalization, n = 155), and preoperative high and postoperative high (Nonnormalization, n = 57). Survival was analyzed according to the perioperative CA19‐9 value and surgical margin. Results The optimal cutoff value of CA19‐9 was 37 U/mL. Overall survival (OS) was significantly stratified according to the perioperative CA19‐9 value. The 5‐y OS rates in the Normal, Normalization, and Nonnormalization groups were 53%, 38%, and 23%, respectively (P

Abstract Background Conversion surgery for initially unresectable gallbladder cancer is rarely performed due to the low response rate for systemic chemotherapy, and a pathological complete response is seldom achieved. Case presentation A 67-year-old woman with jaundice was referred to our hospital and diagnosed with unresectable gallbladder cancer with extra-regional lymph node metastasis after examinations. After biliary decompression, gemcitabine plus cisplatin therapy was started. The tumor marker levels markedly decreased, and imaging studies revealed a reduction in the primary tumor and metastatic lymph nodes. The primary tumor and metastatic lymph node were still shrunk at 4 years after the start of gemcitabine plus cisplatin therapy, so we decided to perform conversion surgery. Gallbladder bed resection and lymph node dissection were performed. The pathological findings of the resected specimen showed only partial fibrosis in the gallbladder wall and no malignant findings in the dissected lymph nodes, indicating a pathological complete response. As of 24 months after the operation, she is alive without recurrence. Conclusion Although there have been only a few reports of conversion surgery for initially unresectable gallbladder cancer, it may be worthwhile to perform chemotherapy with the potential goal of subsequent conversion surgery.

Abstract Aim Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) in Japan. However, the cause and prognosis of HCC may be dramatically changed by direct acting antiviral agents (DAAs). Although the 2015 nationwide survey used a large cohort, its findings may be outdated. The present study therefore aimed to show the latest outcomes by patients’ hepatitis virus infection status. Methods We included 552 patients who underwent hepatectomy for primary HCC between 2002 and 2018 and compared clinical factors between those treated before 2014 (n = 380) and after 2014 (n = 172), when DAAs became available. Results Distribution of hepatitis virus infection status between the two groups differed significantly (P

Abstract The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI 22.5 U/mL (OR 6.64, 95% CI 1.73–25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.

Abstract Background Optimal treatment for patients with hepatic epithelioid hemangioendothelioma (HEHE) remains unclear. Laparoscopic repeat liver resection (LR) is a minimally invasive and potentially effective surgical option for multiple HEHEs. Case presentation A 42-year-old woman with no relevant history was admitted for multiple liver tumors. Six tumors were observed on T2-weighted magnetic resonance imaging (MRI) including one in S2, two in S3, two in S7, and one in S8. Pathological evaluation of percutaneous tumor biopsy tissue suggested a diagnosis of HEHE and laparoscopic LR was planned. The procedure began with partial resection of S7 and partial resection of S8 and left lateral sectionectomy were performed. Another tumor was found intraoperatively on the surface of S6, necessitating removal by partial resection. Pathological evaluation of the resected tumor tissue from all seven tumors concurred with that of the preoperative biopsy. The patient was discharged on postoperative day 6 without any complications. A follow-up MRI 15 months after the primary surgery revealed one tumor each in S4, S6, and S8. Laparoscopic repeat LR was performed. The patient was discharged on postoperative day 5 without any complications. All three recurrent tumors were pathologically confirmed as HEHEs. Conclusions We successfully treated primary and recurrent HEHEs with laparoscopic LR, which is a reasonable minimally invasive procedure considering the possibility of multiple courses of liver surgery in patients with HEHE.

Abstract Background Intraductal tubulopapillary neoplasm (ITPN) is a rare and newly described entity defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. Because of its rarity, the clinical and molecular aspects of ITPN have not been fully investigated. Case presentation A 73-year-old woman presented to a local hospital with epigastric discomfort and pain. Abdominal multidetector-row computed tomography (MDCT) revealed a 2.5-cm hypovascular tumor in the pancreatic body with distal pancreatic duct dilatation and a slightly low-density area spreading over the ventral side of the pancreatic body. Endoscopic ultrasonography and fine-needle biopsy of the tumor revealed adenocarcinoma of the pancreas. She was referred to our hospital 2 months later. MDCT performed at our hospital showed no significant change in the tumor size or pancreatic duct dilatation. However, the low-density area at the ventral side of the pancreas had shrunk; therefore, this finding was considered to have been an inflammatory change. Under a preoperative diagnosis of resectable pancreatic ductal adenocarcinoma, distal pancreatectomy was performed. The final diagnosis was ITPN with associated invasive carcinoma. Macroscopically and microscopically, the main pancreatic duct (MPD) had ruptured at the distal side of the tumor, and the fistula connected the MPD and extrapancreatic scar tissue. Conclusions ITPN with rupture of the pancreatic duct is extremely rare. In the present case, a sudden increase in the pancreatic duct internal pressure or acute inflammation likely caused the rupture of the MPD.

Abstract Aim This study evaluated the effects of postoperative adjuvant chemoradiotherapy (A‐CRT) for positive hepatic ductal margin (HM+) in extrahepatic cholangiocarcinoma (EHCC). Methods Patients with EHCC who underwent surgical resection between 2002 and 2014 were included in this retrospective study. For patients with HM+, A‐CRT was conducted. The clinical effect of A‐CRT for HM+ on the survival and recurrence and prognostic factors of EHCC was reviewed. Results Among 340 patients, the hepatic ductal margin was negative in 296 and positive in 44. Of the 44 patients with HM+, 22 received postoperative A‐CRT, and 22 did not. Hepatic stump recurrence occurred in 19 patients. The incidence was significantly higher in patients with HM+ (20%, 9/44) than in those with negative hepatic ductal margin (HM−) (3%, 10/296) (P

Abstract Background Bilateral ligamentum teres (BLT) hepatis is a very rare anomaly defined as the connection of the bilateral fetal umbilical veins to both sides of the paramedian trunk, and it has never been reported in the English literature. Case presentation A 72-year-old man who presented with obstructive jaundice was referred to our hospital. Contrast-enhanced computed tomography revealed that the patient had right-sided ligamentum teres (RSLT) and left-sided ligamentum teres (LSLT). The umbilical portion of the left portal vein, which the LSLT connected, became relatively atrophic in this patient. The RSLT attached to the tip of the right anterior pedicle and formed the umbilical portion of the right portal vein. The patient was diagnosed with perihilar cholangiocarcinoma which had invaded the root of the posterior branch of the bile duct, LHD, and intrapancreatic bile duct. The central bisectionectomy, in which the liver parenchyma was resected along the RHV on the right side and the LSLT on the left side, and caudate lobectomy combined with pancreatoduodenectomy were performed. The presence of the patient with BLT is important for ascertaining the mechanism of the development of RSLT. Two umbilical veins are present initially during the embryonic stage. In general, the right-sided vein disappears, and the atrophic left-sided vein remains connected to the left portal vein originating from the vitelline vein. Several papers on the mechanism of the development of RSLT have been published. Some authors have mentioned that a residue of the right umbilical vein and the disappearance of the left umbilical vein are the causes of RSLT. On the other hand, some authors have asserted that RSLT is the result of atrophy of the medial liver area. The presence of BLT in patients indicates that the mechanism of the development of RSLT is characterized by a residue of the right umbilical vein and the disappearance of the left umbilical vein. Conclusions The mechanism and origin of RSLT can be understood through cases of BLT, and surgeons must pay attention to anomalies of the portal and hepatic veins in patients with abnormal ligamentum teres.

Abstract Background When a postoperative hepatic artery pseudoaneurysm develops after massive hepatectomy, both an intervention for the pseudoaneurysm and patency of hepatic artery should be considered because occlusion of the residual hepatic artery results in critical liver failure. However, the treatment strategy for a pseudoaneurysm of the hepatic artery after hepatobiliary resection is not well established. Case presentation A 65-year-old woman underwent right hepatectomy, extrahepatic duct resection, and portal vein resection, for gallbladder cancer. Although the patient had an uneventful postoperative course, computed tomography on postoperative day 6 showed a 6-mm pseudoaneurysm of the hepatic artery. Angiography revealed the pseudoaneurysm located on the bifurcation of the left hepatic artery to the segment 2 artery plus the segment 3 artery and 4 artery. Stent placement in the left hepatic artery was not feasible because the artery was too narrow, and coiling of the pseudoaneurysm was associated with a risk of occluding the left hepatic artery and inducing critical liver failure. Therefore, portal vein arterialization constructed by anastomosing the ileocecal artery and vein was performed prior to embolization of the pseudoaneurysm to maintain the oxygen level of the remnant liver, even if the left hepatic artery was accidentally occluded. The pseudoaneurysm was selectively embolized without occlusion of the left hepatic artery, and the postoperative laboratory data were within normal limits. Although uncontrollable ascites due to portal hypertension occurred, embolization of the ileocolic shunt rapidly resolved it. The patient was discharged on postoperative day 45. Conclusion Portal vein arterialization prior to embolization of the aneurysm may be a feasible therapeutic strategy for a pseudoaneurysm that develops after hepatectomy for hepatobiliary malignancy to guarantee arterial inflow to the remnant liver. Early embolization of arterioportal shunting after confirmation of arterial inflow to the liver should be performed to prevent morbidity induced by portal hypertension.

Objectives:. To review our novel technique of hepatopancreatoduodenectomy (HPD) with delayed division of the pancreatic parenchyma (DDPP) for reducing postoperative pancreatic fistula (POPF). Background:. The high operative morbidity and mortality rates after HPD remains a major issue. One of the most troublesome complications is POPF, which might possibly be caused by peripancreatic saponification due to long interval between pancreas resection and reconstruction, as most surgeons prefer a caudocranial approach, performing pancreatoduodenectomy (PD) first and then hepatectomy (conventional HPD [C-HPD]). Methods:. A review of the patients undergoing C-HPD and HPD with DDPP was performed. Postoperative outcomes were compared. Multivariable analysis was conducted to evaluate the risk factors of POPF after HPD. Results:. One-hundred two patients comprised of 50 patients undergoing C-HPD and 52 patients undergoing HPD with DDPP. The interval between pancreas resection and reconstruction was significantly shorter in HPD with DDPP group than in C-HPD group (51 vs 263 minutes; P < 0.001). The incidence of POPF was significantly lower in HPD with DDPP group than in C-HPD group (32.7% vs 77.3%; P < 0.001). The postoperative hospital stay was shorter in patients undergoing HPD with DDPP than in those undergoing C-HPD (32 vs 45 days). A multivariate analysis revealed that body mass index >24 kg/m2 and conventional (PD first) procedure were significant risk factors for POPF after HPD. Conclusions:. A novel technique of HPD with DDPP is a simple procedure and the optimal treatment choice to reduce the risk of developing POPF after this extensive surgery.

Abstract Background A right-sided ligamentum teres (RSLT) is a rare congenital anomaly in which the fetal umbilical vein is connected to the right paramedian trunk. RSLT creates difficulty in liver resection with respect to decision-making regarding the resection line, deviation of the vasculobiliary architecture. We report a case in which laparoscopic left lateral sectionectomy (LLLS) was performed to treat colorectal liver metastasis (CRLM) in a patient with RSLT. Case presentation A 63-year-old man with a past history of rectal cancer presented to our institution due to liver metastasis in the left lateral section from rectal cancer. In this patient, an RSLT was diagnosed and LLLS was planned. The lateral superior branch of the portal vein (P2) branched off behind the bifurcation of the portal vein and running separately from the common branch of the lateral inferior branch (P3) and left paramedian branch (P4) so that stapling could not be performed for liver resection. Frequent intraoperative ultrasonography (IOUS) was necessary to identify the root of P2 and P3. The resection line was distant from the falciform ligament and was carefully decided. The lateral superior branch of Glisson (G2) and lateral inferior branch of Glisson (G3) were separately resected. The patient had a favorable clinical course without any complications. Conclusions The resection line of LLLS, which is distant from the falciform ligament, should be carefully identified using IOUS due to the deviation of the umbilical portion and falciform ligament. The recognition of portal vein and hepatic vein anomalies and clear identification of the lateral sectional branches are important to complete LLLS in patients with an RSLT.

Abstract Background No reports have so far described arteriovenous malformation (AVM) in the pancreas caused by a tumor. We herein report a case of pancreatoduodenectomy for a patient who developed duodenal hemorrhage due to AVM developed around serous cystic neoplasm (SCN) of the pancreas. Case presentation A 79-year-old man was referred to our hospital because of anemia (Hb 7.4 g/dl) and pancreatic head tumor. Computed tomography showed microcystic-type SCN, 87 mm in size, in the pancreatic head. Vascular hyperplasia had developed around the cystic lesion. Upper gastrointestinal endoscopy and colonoscopy did not reveal the cause of anemia, so the patient was followed closely without hemostatic therapy. Iron preparations had improved the anemia. Three months later, the patient developed anemia (Hb 5.8 g/dl) again. Gastrointestinal endoscopy showed oozing from the mucosa in the duodenum via the swollen vascular hyperplasia. He was diagnosed as duodenal hemorrhage from the blood vessels around SCN. Pancreatoduodenectomy was performed to control repeated duodenal bleeding. A histopathological examination revealed that the cystic lesion in the pancreatic head was SCN, and the AVM developed around SCN and duodenum, causing repeated duodenal hemorrhage. The patient was discharged on postoperative day 22. Nine months after surgery, the patient had no recurrence of anemia. Conclusions There have been no reports of duodenal hemorrhage due to acquired pancreatic AVM around pancreatic tumor, including SCN. We successfully treated a case of duodenal hemorrhage due to pancreatic AVM around SCN by pancreatoduodenectomy.

Abstract Background Surgeons sometimes must plan pancreatoduodenectomy (PD) for patients with a variant common hepatic artery (CHA) branching from the superior mesenteric artery (SMA) penetrating the pancreatic parenchyma, known as a transpancreatic CHA (tp-CHA). Case presentation A 67-year-old man was admitted to our hospital because of liver dysfunction. A duodenal tumor was identified by gastrointestinal endoscopy, and a biopsy revealed a neuroendocrine tumor. Computed tomography showed multiple metastases in the left three sections of the liver. As an anatomical variant, the CHA branched from the SMA and passed through the parenchyma of the pancreatic head, and all hepatic arteries branched from the CHA. Furthermore, the arcade between the left and right gastric artery (RGA) was detected, and the RGA branched from the root of the left hepatic artery. PD and left trisectionectomy of the liver were performed. The tp-CHA was resected with the pancreatic head, and the gastric arterial arcade was preserved to maintain the right posterior hepatic arterial flow. Postoperatively, there were no signs of hepatic ischemia. Conclusions When planning PD, including hepatopancreatoduodenectomy, for patients with a tp-CHA, surgeons should simulate various situations for maintaining the hepatic arterial flow. The preservation of the gastric arterial arcade is an option for maintaining the hepatic arterial flow to avoid arterial reconstruction.

Objective: To assess the correlation between recurrence-free survival (RFS) and overall survival (OS) in the hepatobiliary-pancreatic (HBP) surgical setting to validate RFS as a surrogate endpoint. Background: Reliable surrogate endpoints for OS are still limited in the field of HBP surgery. Methods: We analyzed patients who underwent curative resection for HBP disease [986 patients with pancreatic ductal adenocarcinoma (PDAC), 1168 with biliary tract cancer (BTC), 1043 with hepatocellular carcinoma, and 1071 with colorectal liver metastasis] from September 2002 to June 2022. We also conducted meta-analyses of randomized controlled trials of neoadjuvant or adjuvant therapy to validate the surrogacy in PDAC and BTC. Results: Correlation coefficients between RFS and OS were low for hepatocellular carcinoma (p = 0.67) and colorectal liver metastasis (p = 0.53) but strong for PDAC (p = 0.80) and BTC (p = 0.75). In a landmark analysis, the concordance rates between survival or death at 5 years postoperatively and the presence or absence of recurrence at each time point (1, 2, 3, and 4 years) were 50%, 70%, 74%, and 77% for PDAC and 54%, 67%, 73%, and 78% for BTC, respectively, both increasing and reaching a plateau at 3 years. In a meta-analysis, the correlation coefficients for the RFS hazard ratio and OS hazard ratio in PDAC and BTC were p = 0.88 (P < 0.001) and p = 0.87 (P < 0.001), respectively. Conclusions: Three-year RFS can be a reliable surrogate endpoint for OS in clinical trials of neoadjuvant or adjuvant therapy for PDAC and BTC. [ABSTRACT FROM AUTHOR]

Background/Aim: Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. Patients and Methods: Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. Results: Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. Conclusion: These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal downregulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors. [ABSTRACT FROM AUTHOR]