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AKITA MasayukiUniversity Hospital / Hepato-Biliary-Pancreatic SurgeryAssistant Professor
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■ Paper- Double gallbladder is a rare congenital anomaly of the biliary system. In this study, we present an extremely rare case of a double gallbladder with an accessory cystic duct draining into the main pancreatic duct. The patient was a 14-year-old boy with recurrent acute pancreatitis. Endoscopic retrograde cholangiopancreatography revealed an accessory gallbladder draining into the main pancreatic duct, along with a filling defect suggestive of a stone within the accessory cystic duct. These findings did not suggest pancreaticobiliary maljunction. We safely performed laparoscopic resection of the gallbladder and accessory gallbladder, as well as accessory cystic duct stone removal, using intraoperative cholangiography. Biochemical analysis revealed elevated amylase levels in the gallbladder bile and elevated bilirubin levels in the accessory gallbladder fluid, suggesting bidirectional reflux of pancreatic juice and bile. Given the potential risk of malignancy, careful long-term follow-up is required. In this case report, we reviewed existing classifications of multiple gallbladders and reorganized them based on previously reported cases.Nov. 2025, Clinical journal of gastroenterology, English, Domestic magazineScientific journal
- BackgroundThis study aimed to evaluate the impact of postoperative complications on early recurrence (ER) after pancreaticoduodenectomy (PD) for biliary tract cancer (BTC).MethodsPatients who underwent PD for BTC between 2009 and 2022 were enrolled in this study. Postoperative complications were assessed using the comprehensive complication index (CCI), calculated by summing all the complications. The optimal CCI cutoff value for predicting ER was selected based on the minimum P value from the chi-square test. ER was defined as recurrence within 12 months of resection. Risk factors for ER were identified using multivariate analysis.ResultsA total of 118 patients were analyzed. ER was observed in 34 (28.8 %) patients, indicating a significantly poorer prognosis than those without ER (log-rank, P < .001). No significant differences were observed in the primary tumor site or pathological features between the low CCI (<42.6) and high CCI (≥42.6) groups. The incidence of ER was significantly higher in the high CCI group than in the low CCI group (50.0% vs 24.0%, P = .015). Multivariate analysis revealed that high CCI (odds ratio [OR] 4.43, 95% confidence interval [CI] 1.41-13.97, P = .011) and R1 resection (OR 4.88, 95% CI 1.43-16.70, P = .012) were independent risk factors for ER.DiscussionPostoperative complications after PD for BTC were found to be independent risk factors for ER.Aug. 2025, The American surgeon, 31348251368282 - 31348251368282, English, International magazineScientific journal
- PURPOSE: The Global Leadership Initiative on Malnutrition (GLIM) criteria, proposed in 2018, provide universal diagnostic standards for malnutrition, a known risk factor for postoperative complications in patients with various cancers. However, its impact on surgery for biliary tract cancer (BTC) remains unclear. This study evaluates the relationship between GLIM-defined malnutrition and postoperative complications after resection for BTC. METHODS: The subjects of this retrospective study were patients who underwent pancreaticoduodenectomy or major hepatectomy with extrahepatic bile duct resection for BTC between January, 2013 and December, 2021. The comprehensive complication index (CCI), an indicator of postoperative complications, was calculated based on the total number and severity of postoperative complications. RESULTS: GLIM-defined malnutrition was diagnosed in143 (71.1%) of the total 201 patients. The median CCI was significantly higher in the GLIM-defined malnutrition group than in the non-malnutrition group (37.2 vs. 28.3; P < 0.001). Multivariate logistic regression analysis revealed that GLIM-defined malnutrition (odds ratio 2.87 [95% confidence interval 1.38-5.96], P = 0.005) and intraoperative blood loss > 1,000 mL (odds ratio 3.77 [95% confidence interval 1.06-13.47], P = 0.041) were independent predictors of high morbidity (CCI ≥ 37.1). CONCLUSION: Preoperative GLIM-defined malnutrition was closely associated with increased postoperative complications in patients who underwent resection for BTC.May 2025, Surgery today, 55(11) (11), 1598 - 1608, English, Domestic magazineScientific journal
- Feb. 2025, Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 29(2) (2), 101926 - 101926, English, International magazineScientific journal
- BACKGROUND/AIM: Biliary tract cancers (BTCs) have poor prognoses, with limited curative options beyond surgical resection. Adjuvant S-1 chemotherapy has shown survival benefits in Japanese patients undergoing resection for BTC. However, prognostic factors influencing survival in these patients remain uncertain. In this study, we aimed to investigate the efficacy of preoperative nutritional status using the Global Leadership Initiative on Malnutrition (GLIM) criteria as a prognostic factor in patients receiving adjuvant S-1 chemotherapy for BTC. PATIENTS AND METHODS: In this retrospective study, excluding intrahepatic cholangiocarcinoma, we evaluated 58 patients who underwent curative surgery for BTC at Kobe University from 2013 to 2022, followed by adjuvant S-1 chemotherapy. Nutritional status was classified by GLIM criteria into normal/moderate and severe malnutrition groups. Overall (OS) and recurrence-free (RFS) survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Of the 58 patients, 3.4% had no malnutrition, 72.5% had moderate malnutrition, and 24.1% had severe malnutrition. Patients with severe malnutrition had significantly worse 5-year OS (24.7% vs. 52.5%, p=0.0014) and RFS (34.3% vs. 52.0%, p=0.0066). Severe malnutrition was an independent prognostic factor for poorer OS (hazard ratio=3.40, 95% confidence interval=1.46-7.94; p=0.0047) and RFS (hazard ratio=2.48, 95% confidence interval=1.07-5.76; p=0.035). No significant difference in S-1 completion rates was observed. CONCLUSION: Severe malnutrition, as defined by GLIM criteria, is a poor prognostic factor in patients with BTCs undergoing adjuvant S-1 chemotherapy.2025, Cancer diagnosis & prognosis, 5(5) (5), 557 - 565, English, International magazineScientific journal
- Intrahepatic cholangiocarcinoma (iCCA) has been subclassified by its gross morphology into the mass-forming (MF), periductal-infiltrating (PI), and intraductal growth (IG) types and their combinations. This classification correlates well with clinical features; for example, MF-iCCA has less lymph-node metastasis and a better prognosis than PI-iCCA. According to the recently accumulated evidence from histological investigations, the WHO classification endorsed a subclassification scheme in which iCCA cases are classified into small- and large-duct types. Small-duct iCCA is considered to originate from septal or smaller bile ducts and is characterized by less frequent lymph-node metastasis, a favorable prognosis, and an MF appearance. Large-duct iCCA arises around the second branch of the biliary tree and has more aggressive biology and distinct genetic abnormalities. According to the practice guidelines for iCCA from the Liver Cancer Study Group of Japan and the National Comprehensive Cancer Network, upfront surgery is recommended for iCCA without distant metastasis regardless of the morphological subtype, based on clinical experience. In consideration of the biological heterogeneity of iCCA, the treatment strategy for iCCA needs to be reconsidered based on the WHO subtypes.Jan. 2025, Surgery today, 55(1) (1), 1 - 9, English, Domestic magazineScientific journal
- Dec. 2024, 癌と化学療法, 51(13) (13), 1633 - 1635, Japanese腹腔鏡補助下膵頭十二指腸切除術でR0切除となった胆管原発神経内分泌癌の1例Scientific journal
- Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.Nov. 2024, The American journal of surgical pathology, 48(11) (11), 1464 - 1471, English, International magazineScientific journal
- BACKGROUND: Preoperative recognition of the anatomy of caudate biliary branches is important for the safe and complete resection of perihilar cholangiocarcinoma (PHC). In the present study, we identified these branches using an endoscopic nasobiliary drainage tube (ENBD). METHODS: Between January 2012 and October 2022, 89 patients with suspected PHC underwent computed tomographic (CT) cholangiography through ENBD and caudate biliary branching patterns were examined. Multidetector raw CT (MDCT) scans on 85 patients with PHC without biliary drainage were also investigated. The caudate biliary branches detected by each modality were evaluated. RESULTS: ENBD-CT cholangiography detected 206 caudate branches (2.44 branches/patient), while MDCT identified 62 branches (0.78 branches/patient). ENBD-CT cholangiography showed that 89 caudate branches drained into the left hepatic duct (LHD), 87 into the posterior hepatic duct (Bpost), and 30 into the right hepatic duct. LHD and Bpost were the common roots of the caudate branches. Some branches (20%) joined the contralateral hepatic duct across the left-right border, but not the anterior hepatic duct or infraportal-type Bpost. CONCLUSIONS: ENBD-CT cholangiography clearly showed the caudate biliary branches in patients with PHC after biliary drainage.Nov. 2024, Journal of hepato-biliary-pancreatic sciences, 31(11) (11), 809 - 815, English, Domestic magazineScientific journal
- CONTEXT.—: Intraductal papillary neoplasm of the bile duct (IPNB) is classified into types 1 and 2 based on criteria proposed in 2019. Recent studies investigated the clinicopathologic and molecular features of IPNB, which contributed to a more detailed understanding of this undercharacterized neoplasm. OBJECTIVE.—: To summarize driver gene mutations, radiologic tumor evolution, and a potentially unique pattern of tumor progression in IPNB. DATA SOURCES.—: Data were derived from a literature review and personal clinical and research experiences. CONCLUSIONS.—: In contrast to de novo cholangiocarcinoma, type 1 IPNB often has mutations in APC, CTNNB1, STK11, and GNAS. These molecular features are shared with intraductal papillary mucinous neoplasm of the pancreas; however, the frequencies of individual gene abnormalities differ between these 2 neoplasms. A radiologic review of sequential images suggested that type 1 IPNB is a slow-growing neoplasm, with an ∼1-cm increase in size every 2 to 3 years, and remains in a noninvasive state for many years. A similar papillary neoplasm may develop in the biliary tree years after the complete surgical resection of IPNB. The second neoplasm has the same genetic abnormalities as the first neoplasm, indicating intrabiliary implantation rather than multifocal lesions. In contrast to type 1 IPNB, most cases of type 2 IPNB have invasive malignancy at the initial presentation. Type 2 IPNB shares many clinicopathologic and molecular features with de novo cholangiocarcinoma, questioning the distinctness of this tumor entity. The molecular mechanisms underlying malignant transformation in IPNB warrant further study.Sep. 2024, Archives of pathology & laboratory medicine, 148(9) (9), 989 - 996, English, International magazineScientific journal
- PURPOSE: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. METHODS: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. RESULTS: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. CONCLUSION: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. THE TRIAL REGISTRATION NUMBER: B230165 (approved at December 26, 2023).Aug. 2024, Langenbeck's archives of surgery, 409(1) (1), 243 - 243, English, International magazineScientific journal
- INTRODUCTION: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. METHODS: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. RESULTS: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. DISCUSSION: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.Jun. 2024, The American surgeon, 90(6) (6), 1279 - 1289, English, International magazineScientific journal
- BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of hepatectomy. The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding. Therefore, we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy. AIM: To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy. METHODS: The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed. Patients were divided into two groups according to whether or not they developed VTE after hepatectomy, as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities. Clinicopathological factors, including demographic data and perioperative D-dimer values, were compared between the two groups. Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value. Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors. RESULTS: In total, 234 patients who underwent hepatectomy were, of whom (5.6%) were diagnosed with VTE following hepatectomy. A comparison between the two groups showed significant differences in operative time (529 vs 403 min, P = 0.0274) and blood loss (530 vs 138 mL, P = 0.0067). The D-dimer levels on postoperative days (POD) 1, 3, 5, 7 were significantly higher in the VTE group than in the non-VTE group. In the multivariate analysis, intraoperative blood loss of > 275 mL [odds ratio (OR) = 5.32, 95% confidence interval (CI): 1.05-27.0, P = 0.044] and plasma D-dimer levels on POD 5 ≥ 21 μg/mL (OR = 10.1, 95%CI: 2.04-50.1, P = 0.0046) were independent risk factors for VTE after hepatectomy. CONCLUSION: Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.Jan. 2024, World journal of clinical cases, 12(2) (2), 276 - 284, English, International magazineScientific journal
- Dec. 2023, 癌と化学療法, 50(13) (13), 1534 - 1536, Japanese腹腔動脈起始部狭窄を伴う十二指腸乳頭部癌に対し膵頭十二指腸切除術および動脈血行再建を施行した1例Scientific journal
- UNLABELLED: Wnt signaling is known to maintain two cell states, hepatocyte differentiation and proliferation, in hepatocellular carcinoma (HCC). On the other hand, activation of Wnt signaling in colon cancer promotes uncontrollable stereotypic proliferation, whereas cells remain undifferentiated. To elucidate the unique mode of Wnt signaling in HCC, we comprehensively investigated HCC-specific Wnt pathway target genes and identified GREB1. Wnt signaling induced expression of GREB1 coupled with HNF4α and FOXA2, master transcription factors that maintain hepatic differentiation. Moreover, GREB1 was enriched at the regulatory region of atypical HNF4α target genes, including progrowth genes, thereby stimulating HCC proliferation. Therefore, GREB1 acts as a unique mediator of versatile Wnt signaling in HCC progression, bridging the roles of the Wnt pathway in differentiation and proliferation. SIGNIFICANCE: GREB1 is a liver cancer-specific Wnt signaling target gene that induces an oncogenic shift of HNF4α, a putative tumor suppressor, and may represent a therapeutic target in Wnt-activated hepatocellular carcinoma.Jul. 2023, Cancer research, 83(14) (14), 2312 - 2327, English, International magazineScientific journal
- BACKGROUND: Intracholecystic papillary neoplasm (ICPN) is one of the precursors of gallbladder cancer defined in the 2010 World Health Organization classification of tumors. We herein report ICPN with pancreaticobiliary maljunction (PBM), which is a high-risk factor for biliary cancer. CASE PRESENTATION: A 57-year-old female presented with abdominal pain. Computed tomography showed a swollen appendix and gallbladder nodules with bile duct dilatation. Endoscopic ultrasonography revealed a gallbladder tumor spreading into the cystic duct confluence accompanying PBM. Based on papillary tumors around the cystic duct detected using the SpyGlass DS II Direct Visualization System (SpyGlass DS), ICPN was suspected. We performed extended cholecystectomy, extrahepatic bile duct resection, and appendectomy with a diagnosis of ICPN and PBM. The pathological diagnosis was ICPN (90 × 50 mm) with high-grade dysplasia spreading into the common bile duct. The absence of residual cancer in the resected specimen was pathologically confirmed. P53 staining was totally negative in both the tumor and normal epithelium. The overexpression of CTNNB1 was not observed. CONCLUSIONS: We encountered a patient with a very rare gallbladder tumor, ICPN with PBM. SpyGlass DS contributed to a precise assessment of the extent of the tumor as well as a qualitative diagnosis.Jun. 2023, Clinical journal of gastroenterology, 16(3) (3), 476 - 481, English, Domestic magazineScientific journal
- Hepatocellular carcinoma (HCC) is the most prevalent malignant liver neoplasm. Despite the advances in diagnosis and treatment, the prognosis of HCC patients remains poor. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the glycosylated secretory protein Dickkopf-1 (DKK1), and the DKK1-CKAP4 axis is activated in pancreatic, lung, and esophageal cancer cells. Expression of DKK1 and CKAP4 has been examined in HCC in independent studies that yielded contradictory results. In this study, the relationship between the DKK1-CKAP4 axis and HCC was comprehensively examined. In 412 HCC cases, patients whose tumors were positive for both DKK1 and CKAP4 had a poor prognosis compared to those who were positive for only one of these markers or negative for both. Deletion of either DKK1 or CKAP4 inhibited HCC cell growth. In contrast to WT DKK1, DKK1 lacking the CKAP4 binding region did not rescue the phenotypes caused by DKK1 depletion, suggesting that binding of DKK1 to CKAP4 is required for HCC cell proliferation. Anti-CKAP4 Ab inhibited HCC growth, and its antitumor effect was clearly enhanced when combined with lenvatinib, a multikinase inhibitor. These results indicate that simultaneous expression of DKK1 and CKAP4 is involved in the aggressiveness of HCC, and that the combination of anti-CKAP4 Ab and other therapeutics including lenvatinib could represent a promising strategy for treating advanced HCC.May 2023, Cancer science, 114(5) (5), 2063 - 2077, English, International magazineScientific journal
- BACKGROUND/AIM: Recently, the Global Leadership Initiative on Malnutrition (GLIM), which includes the world's leading clinical nutrition societies, proposed the first global diagnostic criteria for malnutrition. However, the association between malnutrition diagnosed by the GLIM criteria and prognosis in patients with resected extrahepatic cholangiocarcinoma (ECC) remains unknown. This study aimed to investigate the predictive validity of the GLIM criteria for the prognosis of patients with resected ECC. PATIENTS AND METHODS: Between 2000 and 2020, 166 patients who underwent curative-intent resection for ECC were retrospectively analyzed. Prognostic significance of preoperative malnutrition diagnosed by the GLIM criteria was investigated using a multivariate Cox proportional hazards model. RESULTS: Eighty-five (51.2%) and 46 (27.7%) patients were diagnosed with moderate and severe malnutrition, respectively. Increased malnutrition severity tended to be correlated with increased lymph node metastasis rate (p-for-trend=0.0381). The severe malnutrition group had worse 1-, 3-, and 5-year overall survival rates than the normal (without malnutrition) group (82.2% vs. 91.2%, 45.6% vs. 65.1%, 29.3% vs. 61.5%, respectively, p=0.0159). In multivariate analysis, preoperative severe malnutrition was an independent predictor for poor prognosis (hazard ratio=1.68, 95% confidence interval=1.06-2.66, p=0.0282), along with intraoperative blood loss >1,000 ml, lymph node metastasis, perineural invasion, and curability. CONCLUSION: Severe preoperative malnutrition diagnosed by the GLIM criteria was associated with poor prognosis in patients who underwent curative-intent resection for ECC.May 2023, Anticancer research, 43(5) (5), 2299 - 2308, English, International magazineScientific journal
- A sebaceous carcinoma is rarely seen in extracutaneous sites. We present a 75-year-old man who was admitted with epigastralgia and melena. Endoscopic examination revealed an ulcer on the posterior wall of the gastric antrum, and distal gastrectomy was performed. Histopathological examination revealed thin to thick trabeculae of polygonal cells with scattered foci of foamy cells, whereas Sudan 3 staining showed lipid vacuoles. Immunohistochemistry was positive for both p40 and SALL4. After considering these findings, we suggest sebaceous differentiation as the diagnosis. To the best of our knowledge, this is the first case of gastric carcinoma with sebaceous differentiation.May 2023, ACG case reports journal, 10(5) (5), e01061, English, International magazineScientific journal
- Mar. 2023, 胆道, 37(1) (1), 130 - 133, Japanese胆嚢癌との鑑別に難渋した胆嚢結石症・慢性胆嚢炎[Refereed]Scientific journal
- Mar. 2023, 兵庫県外科医会会誌, 57, 13 - 15, Japanese横隔膜腹腔側に発生したsolitary fibrous tumorの1例Scientific journal
- Nov. 2022, 胆と膵, 43(11) (11), 1589 - 1592, Japanese術後遺残胆管癌の診断と治療Scientific journal
- PURPOSE: Gastric cancer patients with para-aortic lymph node metastases may achieve long-term survival with radical gastrectomy and para-aortic lymph nodal dissection (PAND) following neoadjuvant therapy. We introduced the Cattell-Braasch maneuver to facilitate safe and complete PAND for advanced gastric cancer with extensive lymph node metastases. METHODS: Between January 2014 and March 2020, 7 patients with highly advanced gastric cancer received preoperative chemotherapy followed by radical gastrectomy and PAND using the Cattell-Braasch maneuver. This maneuver consists of mobilization of the right hemi-colon and the total small intestine. RESULTS: Five patients received preoperative chemotherapy for para-aortic lymph node metastases and 2 for bulky lymph node metastases around the supra-pancreatic area. All patients received S-1 + cisplatin therapy, and one was additionally treated with paclitaxel chemotherapy followed by nivolumab. After chemotherapy, 2 patients with para-aortic lymph node metastases achieved down-staging on imaging tests. Total gastrectomy with PAND by the Cattell-Braasch maneuver was performed on all patients and was accompanied by splenectomy (n = 5) and distal pancreatectomy (n = 1). Pathological assessments revealed that 3 patients had para-aortic lymph node metastases, and the median number of retrieved para-aortic lymph nodes was 16. Three patients without para-aortic lymph node metastasis survived for more than 5 years without recurrence. CONCLUSION: The Cattell-Braasch maneuver provides a good surgical field and is useful for complete PAND for gastric cancer.Nov. 2022, Langenbeck's archives of surgery, 407(7) (7), 3141 - 3146, English, International magazineScientific journal
- Mutations in IDH1/2 and the epigenetic silencing of TET2 occur in leukaemia or glioma in a mutually exclusive manner. Although intrahepatic cholangiocarcinoma (iCCA) may harbour IDH1/2 mutations, the contribution of TET2 to carcinogenesis remains unknown. In the present study, the expression and promoter methylation of TET2 were investigated in iCCA. The expression of TET2 was assessed in 52 cases of iCCA (small-duct type, n = 33; large-duct type, n = 19) by quantitative PCR, immunohistochemistry (IHC) and a sequencing-based methylation assay, and its relationships with clinicopathological features and alterations in cancer-related genes (e.g., KRAS and IDH1) were investigated. In contrast to non-neoplastic bile ducts, which were negative for TET2 on IHC, 42 cases (81%) of iCCA showed the nuclear overexpression of TET2. Based on IHC scores (area × intensity), these cases were classified as TET2-high (n = 25) and TET2-low (n = 27). The histological type, tumour size, lymph node metastasis and frequency of mutations in cancer-related genes did not significantly differ between the two groups. Overall and recurrence-free survival were significantly worse in patients with TET2-high iCCA than in those with TET2-low iCCA. A multivariate analysis identified the high expression of TET2 as an independent prognostic factor (HR = 2.94; p = 0.007). The degree of methylation at two promoter CpG sites was significantly less in TET2-high iCCA than in TET2-low iCCA or non-cancer tissue. In conclusion, in contrast to other IDH-related neoplasms, TET2 overexpression is common in iCCA of both subtypes, and its high expression, potentially induced by promoter hypomethylation, is an independent poor prognostic factor.May 2022, Virchows Archiv : an international journal of pathology, 480(5) (5), 1077 - 1085, English, International magazineScientific journal
- BACKGROUND: Undifferentiated carcinoma of the biliary tree is extremely rare, and biliary undifferentiated carcinoma mostly originates from the gallbladder. We herein present a case of anaplastic undifferentiated carcinoma of the hilar bile duct and reviewed the literature. CASE PRESENTATION: The patient was an 81-year-old male with obstructive jaundice. Contrast-enhanced computed tomography (CT) showed a protruded tumor located at the hepatic hilum. Obstructive jaundice was relieved by endoscopic drainage. Endoscopic biopsy revealed carcinoma without glandular differentiation, and the patient was diagnosed with resectable hilar undifferentiated carcinoma. During the 5-week preoperative examination, the tumor increased in size from 23 to 45 mm. Left hemi-hepatectomy and extrahepatic bile duct resection were performed, and there were no postoperative complications. Histological findings demonstrated that the tumor was mainly composed of non-cohesive polygonal neoplasms with pleomorphic nuclei, and was diagnosed as anaplastic undifferentiated carcinoma of the common hepatic duct (T2a N0 M0 Stage II). One month after surgery, the patient was readmitted to our hospital with pyrexia due to cholangitis, and liver nodules suggestive of multiple liver metastases were detected by CT. Three months after surgery, the patient died of multiple liver metastases. CONCLUSIONS: This is the first case report of undifferentiated cholangiocarcinoma with anaplastic features. Anaplastic undifferentiated carcinoma of the hilar bile duct showed preoperative rapid growth and early relapse despite a cancer-negative surgical margin.Jan. 2022, Surgical case reports, 8(1) (1), 14 - 14, English, Domestic magazineScientific journal
- BACKGROUND: The aims of the present study were to demonstrate the anatomical change of superior mesenteric vein (SMV) branches and to show how the Cattell Braasch maneuver facilitates a safer ligation of these venous branches during a pancreatoduodenectomy (PD). METHODS: Between January 2010 and December 2019, 97 patients with peripancreatic tumors underwent pancreatectomy. We retrospectively reviewed preoperative triple-phase enhanced computed tomography (CT) images and analyzed variations in SMV branches. Anatomical changes in SMV branches after the Cattell Braasch technique were observed using our operation video and illustrations. RESULTS: The first jejunal vein (J1v) in 75% of patients ran posterior to the superior mesenteric artery (SMA), while the remainder (25%) ran anterior to it. The inferior pancreatoduodenal vein (IPDV) was preoperatively detected in 91% of patients. The IPDV drained into the J1v in 74% of patients and into the SMV in 37%. After the Cattell Braasch maneuver, the J1v which ran posterior to the SMA now was found to lie to the right anterolateral side the SMA and the visualization of both the J1v and the IPDV were much more clearly visualized. CONCLUSIONS: The most frequent venous variation was the IPDV draining into the J1v posterior to the SMA. After the Cattell Braasch maneuver, the IPDV was now located to the right anterolateral anterior aspect of the SMA which facilitates its visualization and should allow a safer ligation.Sep. 2021, BMC surgery, 21(1) (1), 341 - 341, English, International magazineScientific journal
- BACKGROUND: Gastrobronchial fistulas are rare, but life-threatening, complications of esophagectomy. They are caused by anastomotic leakage and mainly occur around anastomotic sites. In the present paper, we report a rare case of leakage from the staple line of a gastric tube after esophagectomy for esophageal cancer, which was successfully treated using an intercostal muscle flap and lung resection. CASE PRESENTATION: A 61-year-old male underwent subtotal esophagectomy with regional lymphadenectomy for esophageal cancer. The sutures along the staple line of the gastric tube failed 11 days after surgery, and a pulmonary abscess was also found on imaging. The abscess did not heal after conservative treatment; therefore, right lower lobectomy, gastrobronchial fistula resection, primary closure, and patching of the leaking portion of the gastric tube with an intercostal muscle flap were performed 9 months after the first operation. The patient's postoperative course was uneventful, and he was discharged on the 354th day. CONCLUSIONS: We experienced a case involving a gastrobronchial fistula caused by leakage from the staple line of a gastric tube and successfully treated it by performing right lower lobectomy and patching the leak with an intercostal muscle flap.Apr. 2021, Surgical case reports, 7(1) (1), 95 - 95, English, Domestic magazineScientific journal
- The gene mutation profiles of gastric neuroendocrine neoplasms are incompletely understood. The purpose of this study was to characterize the molecular pathology of poorly differentiated neuroendocrine carcinoma (NEC) and mixed neuroendocrine‒non-neuroendocrine neoplasm (MiNEN) of the stomach. Surgical cases of gastric NEC (n = 7) and MiNEN (n = 6) were examined by clinical review, immunohistochemistry, microsatellite instability (MSI) analysis and whole-exome sequencing. NEC cases consisted of small- (n = 2) and large-cell types (n = 4). All cases of MiNEN were histologically composed of large-cell type NEC and tubular adenocarcinoma. Whole-exome sequencing analysis detected recurrent mutations in TP53 in 8 cases (62%), and they were more frequently observed in MiNEN than in NEC (100% vs. 29%). Frameshift mutations of APC were observed in two cases of MiNEN. One case of large-cell type NEC had a frameshift mutation with loss of heterozygosity in RB1. The other mutated genes (e.g., ARID1 and KRAS) were detected in a single case each. A high level of MSI was confirmed in one case of MiNEN, which harbored mutations in two well-differentiated neuroendocrine tumor (NET)-related genes (MEN1 and ATRX1). In cases of MiNEN, two histological components shared mutations in TP53, APC and ZNF521, whereas alterations in CTNNB1, KMT2C, PTEN and SPEN were observed in neuroendocrine components only. In conclusion, TP53 is a single, frequently mutated gene in gastric NEC and MiNEN, and alterations in other genes are less common, resembling the mutation profiles of gastric adenocarcinomas. Gene mutations frequently observed in well-differentiated NET were uncommon but not entirely exclusive.Apr. 2021, Human pathology, 110, 1 - 10, English, International magazineScientific journal
- This study aimed to establish an immunohistochemical panel useful for subclassification of intrahepatic cholangiocarcinoma (iCCA) into small- and large-duct types. Fifty surgical cases of iCCA consisting of small- (n = 31) and large-duct types (n = 19) were examined. To imitate liver needle biopsies, tissue microarrays were constructed using three tissue cores (2 mm in diameter) obtained from one representative paraffin block of each case. Immunostaining for C-reactive protein (CRP), N-cadherin, tubulin beta-III (TUBB3), neural cell adhesion molecule (NCAM), and S100 calcium binding protein P (S100P) was conducted. Most cases of small-duct iCCA were immunoreactive to CRP and N-cadherin, whereas expressions of these markers were markedly less common in large-duct iCCA (CRP, 97% vs. 5%, P < 0.001; N-cadherin, 87% vs. 16%, P < 0.001). TUBB3 and NCAM were also more frequently expressed in small-duct iCCA (65% vs. 32%, P = 0.006; 58% vs. 5%, P < 0.001), but their sensitivities were lower than those of CRP and N-cadherin. S100P was more commonly expressed in large-duct iCCA than in small-duct iCCA (95% vs. 29%, P < 0.001), and diffuse expressions were observed in 17 of 19 cases of large-duct iCCA (90%). All cases with a CRP+/S100P- immunophenotype were of small-duct type, whereas all but one case with a CRP-/S100P+ immunophenotype were of large-duct type. Of 10 cases with a double-positive or double-negative immunophenotype, 7 were appropriately classified based on immunoreactivity to N-cadherin. In conclusion, CRP, N-cadherin, and S100P form a useful immunohistochemical panel for iCCA subclassification, and correct subclassification was possible in 92% of cases based on a proposed, simple algorithm.Mar. 2021, Human pathology, 109, 45 - 52, English, International magazineScientific journal
- Dec. 2020, Journal of surgical oncology, 122(8) (8), 1831 - 1831, English, International magazine
- Jun. 2020, Journal of surgical oncology, 121(7) (7), 1126 - 1131, English, International magazineScientific journal
- AIMS: Biliary intraductal tubular neoplasms that are non-mucinous and negative for mucin 5AC (MUC5AC) are called intraductal tubulopapillary neoplasms (ITPNs). Intraductal tubular neoplasms with mucinous cytoplasm and MUC5AC positivity also occur and their nature remains unclear, although some pathologists may classify these as 'intraductal papillary neoplasms of the bile duct (IPNBs) of gastric type'. This study aimed to elucidate genetic features of biliary intraductal tubular neoplasms. METHODS AND RESULTS: Six resected cases of biliary intraductal neoplasm with >70% tubular configuration were characterised by clinicopathological examination and whole exome sequencing, and the findings obtained were compared between MUC5AC-negative (n = 2) and -positive cases (n = 4). The intraductal tumours consisted of the pancreatobiliary-type epithelium with high-grade dysplasia arranged in back-to-back tubules. Both of the two MUC5AC-negative cases were non-invasive neoplasms and developed in the liver, whereas all MUC5AC-positive cases had invasive carcinoma and were present in the intrahepatic (n = 2), perihilar (n = 1) and distal bile ducts (n = 1). In an exome-sequencing study, MUC5AC-negative cases harboured mutations in CTNNB1, SF3B1, BAP1 and BRCA1 (one case each). KRAS mutations were observed in three of four MUC5AC-positive cases (75%) but none of the MUC5AC-negative neoplasms. Compared to published data, known driver genes of other intraductal neoplasms of the pancreatobiliary system (e.g. APC, CTNNB1, STK11, GNAS and PIK3CA) were wild-type in all but one MUC5AC-negative case with CTNNB1 mutation. Chromatin modifiers (ARID1A, BAP1 and KMT2C) were also altered in MUC5AC-positive cases, similar to usual cholangiocarcinomas. CONCLUSIONS: This exome-sequencing study suggested that MUC5AC-negative biliary ITPNs are genetically distinct from pancreatic ITPNs and IPNBs. They may also biologically differ from MUC5AC-positive tubular neoplasms despite morphological resemblance.Jun. 2020, Histopathology, 76(7) (7), 1005 - 1012, English, International magazineScientific journal
- BACKGROUND: Bochdalek hernia in an adult is very rare and often needs an immediate surgical repair for the herniation. Although its etiology and surgical techniques have frequently been reported, perioperative complications, especially cardiopulmonary problems, remain unknown. We reported two adults with Bochdalek hernia and reviewed the published literatures with a focus on these issues. CASE PRESENTATION: We experienced two adult cases of Bochdalek hernia with gastrointestinal strangulation. One case had massive herniation of the stomach, colon, spleen, and pancreas in the left chest, causing repeated vomiting. The other had a right-side hernia with strangulation of the colon. We successfully performed emergency repairs of these diaphragmatic hernias without any postoperative complications. CONCLUSIONS: Our literature review revealed that life-threatening cardiopulmonary complications, such as empyema or cardiac arrest caused by the tamponade effect of the herniated viscera, sometimes occurred in patients with Bochdalek hernia. These complications were found in Bochdalek hernia with gastrointestinal strangulation.Apr. 2020, Surgical case reports, 6(1) (1), 72 - 72, English, Domestic magazineScientific journal
- PURPOSES: Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer. METHODS: Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6 months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared. RESULTS: Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1 year, p < 0.01, respectively). Multivariate analysis showed that age > 75 years, serum CA19-9 > 1008 U/ml and perineural invasion were independent predictors of early recurrence. CONCLUSIONS: High serum CA19-9 values (> 1008 U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.Apr. 2020, Surgery today, 50(4) (4), 344 - 351, English, Domestic magazineScientific journal
- BACKGROUND: Pancreaticoduodenectomy (PD) is a standardized strategy for patients with middle and distal bile duct cancers. The aim of this study was to compare clinicopathological features of bile duct segmental resection (BDR) with PD in patients with extrahepatic cholangiocarcinoma. METHODS: Consecutive cases with extrahepatic cholangiocarcinoma who underwent BDR (n = 21) or PD (n = 84) with achievement of R0 or R1 resection in Kobe University Hospital between January 2000 and December 2016 were enrolled in the present study. RESULTS: Patients who underwent PD were significantly younger than those receiving BDR. The frequency of preoperative jaundice, biliary drainage and cholangitis was not significantly different between the two groups. The duration of surgery was longer and there was more intraoperative bleeding in the PD than in the BDR group (553 vs. 421 min, and 770 vs. 402 mL; both P<0.01). More major complications (>Clavien-Dindo IIIa) were observed in the PD group (46% vs. 10%, P<0.01). Postoperative hospital stay was also longer in that group (30 vs. 19 days, P = 0.02). Pathological assessment revealed that tumors were less advanced in the BDR group but the rate of lymph node metastasis was similar in both groups (33% in BDR and 48% in PD, P = 0.24). The rate of R0 resection was significantly higher in the PD group (80% vs. 38%, P<0.01). Adjuvant chemotherapy was more frequently administered to patients in the BDR group (62% vs. 38%, P = 0.04). Although 5-year overall survival rates were similar in both groups (44% for BDR and 51% for PD, P = 0.72), in patients with T1 and T2, the BDR group tended to have poorer prognosis (44% vs. 68% at 5-year, P = 0.09). CONCLUSIONS: BDR was comparable in prognosis to PD in middle bile duct cancer. Less invasiveness and lower morbidity of BDR justified this technique for selected patients in a poor general condition.Apr. 2020, Hepatobiliary & pancreatic diseases international : HBPD INT, 19(2) (2), 147 - 152, English, International magazineScientific journal
- Dec. 2019, 癌と化学療法, 46(13) (13), 2279 - 2281, Japanese-Scientific journal
- BACKGROUND: Acute cholecystitis (AC) after cardiovascular surgery (CS) tends to have a serious postoperative course; however, there are few reports of AC after CS. In this study, we investigated the clinical features of AC after CS. METHOD: Of 26 patients who underwent surgery for AC after CS between 2001 and 2018 were investigated. Of these patients, the severity of AC, onset time, surgical outcomes, and postoperative pathological findings were evaluated. RESULTS: Grade III accounted for 46% (12/26) of the AC after CS patients. Gallbladder drainage did not produce sufficient outcomes in all CS cases. The postoperative hospital days of AC after CS were extended (31/21 days, P = 0.07) and the postoperative pathologic findings revealed a higher rate of gangrenous cholecystitis (88/41%, P < 0.01) than the control group. With regard to the incidence of postoperative complications, there were no differences between CS and the control group (23/24%). The mortality rate of AC after CS was 12%. CONCLUSION: Because more than 80% of CS cases involved pathologically gangrenous cholecystitis, it may be necessary to perform early surgery for AC after CS, even when the severity of AC is Grade III.Nov. 2019, Journal of hepato-biliary-pancreatic sciences, 26(11) (11), 503 - 509, English, Domestic magazineScientific journal
- AIMS: To investigate whether genetic or inflammatory pro-oncogenic factors are relevant to the increased risk of gallbladder cancers in patients with pancreaticobiliary maljunction (PBM). METHODS AND RESULTS: Mutations in KRAS exon 2 were examined by a highly sensitive, droplet digital PCR platform using surgically resected specimens of PBM-associated (n = 31) and non-associated gallbladder cancers (n = 49). The tissue expression of IL-6 and IL-33, which are suspected to promote biliary carcinogenesis, was analysed by quantitative real-time PCR and in-situ hybridisation. The incidence of KRAS mutations was similarly low in PBM-associated (five of 32 cases; 16%) and non-associated cancers (four of 49 cases; 8%) (P = 0.272). The tissue expression of IL-33 mRNA, but not IL-6 mRNA, was significantly higher in PBM-associated gallbladder cancers than in gallbladder cancers without PBM (P = 0.004). A similar degree of IL-33 overexpression was also observed in the background non-cancerous mucosa in cases of PBM-associated gallbladder cancers, and was significantly greater than that in PBM cases with cholecystitis alone (P < 0.001). The results of in-situ hybridisation indicated that the source of IL-33 production in PBM-associated carcinomas was the endothelium, cancer cells and non-neoplastic biliary epithelium. In a combined PBM-associated and non-associated cohort, IL-33 overexpression in gallbladder cancers correlated with less aggressive features (e.g. a lower pT stage and longer overall survival), similar to recently reported findings on large-duct cholangiocarcinomas. CONCLUSIONS: KRAS mutations do not appear to be associated with a high risk of malignancy in PBM, while IL-33 overexpression may provide a pro-oncogenic microenvironment in the gallbladder mucosa of patients with PBM.Sep. 2019, Histopathology, 75(3) (3), 365 - 375, English, International magazineScientific journal
- AIMS: The present study aimed to systematically compare clinicopathological and genetic features between keratin 19 (K19)-expressing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHODS AND RESULTS: Consecutive cases of HCC (n = 430) were classified into K19+ and K19- using immunohistochemistry. ICCA cases were also separated into small-(S-iCCA; n = 36) and large-duct types (n = 22) based on recently proposed criteria, with the former being used in the present study. Mutational hot-spots in TERT, CTNNB1, KRAS and IDH1 were sequenced. Twenty-six cases (6%) of HCC expressed K19. K19+ HCC was more strongly associated with chronic hepatitis B than K19- HCC and S-iCCA (46% versus 17% and 6%; both P < 0.001). Lymph node metastasis was observed in K19+ HCC (8%) and S-iCCA (22%), but was exceptional in K19- HCC (1%). K19+ HCC had TERT promoter mutations less frequently than K19- HCC (31% versus 59%; P = 0.022), and lacked alterations in KRAS and IDH1. CTNNB1 mutations were similarly observed in K19+ and K19- HCC (23% and 19%, respectively), but rare in S-iCCA (3%). The postoperative survival curve of K19+ HCC was almost identical to that of S-iCCA in the first 5 years (approximately 50% at 5 years), and significantly worse than that of K19- HCC (P = 0.040). Extrahepatic recurrence was more common in K19+ HCC (50%) and S-iCCA (35%) than in K19- HCC (15%) (P = 0.001). CONCLUSIONS: Although K19+ HCC and S-iCCA showed similar biological behaviours, they did not share any driver gene mutations, suggesting the possible involvement of epigenetic alterations in the iCCA-like features of K19+ HCC.Sep. 2019, Histopathology, 75(3) (3), 385 - 393, English, International magazineScientific journal
- We recently experienced cases of pancreatobiliary-type intraductal papillary mucinous neoplasms (PB-IPMNs) with imaging features resembling pancreatic ductal adenocarcinomas (PDACs), and histologic appearance of purely pancreatobiliary morphology and highly distorted papillary growth, which led to the present study aiming to systematically investigate PB-IPMNs in comparison with PDACs. Surgical cases of PB-IPMNs (n = 31) and PDACs (n = 24) were examined. PB-IPMNs were classified into monotypic tumors (n = 12; 39%) consisting of entirely high-grade pancreatobiliary-type neoplastic cells and polytypic cases (n = 19; 61%) associated with components of low-grade dysplasia and/or other histologic types (eg, gastric, intestinal, or oncocytic types). Clinically, monotypic PB-IPMNs less commonly had dilatation of the ampullary orifice (0% versus 74%) and mucin hypersecretion (17% versus 89%) than did polytypic cases. In most cases of monotypic PB-IPMNs, cystic dilatation of the lesional ducts was less obvious on imaging; therefore, 33% were radiologically diagnosed as PDACs. Histologically, intraductal tumors in monotypic cases showed a highly complex papillary architecture with tubular/cribriform glands and irregular branching, and all these cases were associated with invasive malignancy. GNAS mutations were detected in polytypic PB-IPMNs (6/19; 32%), but there were no GNAS mutations in monotypic cases. The recurrence-free survival of patients with monotypic PB-IPMN or PDAC was similar and significantly worse than that of patients with polytypic PB-IPMN. In conclusion, some cases of monotypic PB-IPMNs lacked the classic characteristics of IPMNs and shared features with PDACs, raising the possibility that these cases may be better classified as a papillary variant of PDACs rather than IPMNs.Sep. 2019, Human pathology, 91, 26 - 35, English, International magazineScientific journal
- INTRODUCTION: Multimodal treatment prolongs the survival of patients with biliary tract cancer (BTC). However, the chemotherapy choices for this disease are few, and completing each chemotherapy session is important. Adjuvant chemotherapy has been attempted for BTC, but has only had a 75% completion rate. Body weight loss and cholangitis are reasons for the interruption of chemotherapy. Previous reports suggested that nutritional intervention with omega-3 fatty acids maintained body weight and improved the completion rate for chemotherapy. Moreover, omega-3 fatty acids have an anti-inflammatory effect. Therefore, we theorised that omega-3 fatty acids would improve the completion rate of adjuvant chemotherapy in patients with BTC. The aim of this study is thus to evaluate the effectiveness of omega-3 fatty acids for patients planning adjuvant chemotherapy for BTC. METHOD AND ANALYSIS: This study is a single-centre, open-label, single-arm, historically controlled study with a planned enrolment of 55 participants. Protocol treatment consists of four courses of S-1 adjuvant chemotherapy and an oral omega-3 fatty acid pharmaceutic adjuvant (LOTRIGA 2 g (Takeda Pharmaceutical Co.)), which includes 2 g of omega-3 fatty acids from day 1 until day 168 of the treatment period. The primary endpoint is the completion rate of four total courses of S-1. Secondary endpoints are postoperative cholangitis, time to recurrence or distant metastasis, changes in nutritional index, changes in the lymphocyte blast transformation test induced by phytohaemagglutinin, and concanavalin A and diamine oxidase serum activity during adjuvant chemotherapy. All adverse events will be evaluated. ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Board of Kobe University Hospital. The findings from this study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000031247.Aug. 2019, BMJ open, 9(8) (8), e029915, English, International magazineScientific journal
- BACKGROUND: Autoimmune pancreatitis (AIP) encompasses a heterogenous disease group that includes IgG4-related type 1 AIP and non-IgG4-related type 2 AIP. Clinically and on imaging, type 2 AIP mimics type 1 AIP, other forms of chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC); therefore, discriminatory markers may aid proper diagnosis. Herein, we examine the expression of PD-L1 and indoleamine 2,3-dioxygenase (IDO1) as a diagnostic tool to distinguish type 2 AIP from other forms of pancreatitis and PDAC. DESIGN: We evaluated 35 pancreatectomy specimens diagnosed with type 2 AIP and potential mimics of this disease including type 1 AIP (n=14), chronic pancreatitis-not otherwise specified (n=10), groove pancreatitis (n=14), and PDAC (n=278). We scored inflammatory infiltrates, fibrosis and atrophy and performed immunohistochemical staining for PD-L1 and IDO1. We validated our findings on a series of endoscopic ultrasound-guided biopsies from patients with suspected type 2 AIP and inflammatory and neoplastic mimics of this disease (n=37). RESULTS: The mean age of patients with type 2 AIP was 50 years with a F:M ratio of 1.2:1. Patients with type 2 AIP showed pancreatic ductal staining for PD-L1 and IDO1 in 69% (24/35) and 60% (15/25) of cases, respectively. PD-L1 reactivity was noted in 3% of patients with other forms of chronic pancreatitis and 3% of PDACs; notably, peritumoral ducts and acini were negative. Eight of 9 endoscopic ultrasound-guided biopsies with pancreatic ductal epithelium from patients with type 2 AIP were positive for PD-L1, while the inflammatory and neoplastic mimics were negative. Collectively, the sensitivity and specificity of PD-L1 as a marker of type 2 AIP was 70% and 99%, respectively. CONCLUSIONS: Ductal PD-L1 reactivity has the potential to distinguish type 2 AIP from other forms of pancreatitis and PDAC.Jul. 2019, The American journal of surgical pathology, 43(7) (7), 898 - 906, English, International magazineScientific journal
- Although intracholecystic papillary neoplasms (ICPNs) have been increasingly recognized, their features remain unclear because of the lack of standardized definition. This study aimed to elucidate clinicopathologic and genetic features of ICPNs using stringent diagnostic criteria. On the basis of the recently proposed criteria, gallbladder neoplasms showing delicate papillary growth were diagnosed as ICPNs, while polypoid papillary adenocarcinomas arranged in a complex architecture were categorized as papillary gallbladder cancers (GBCs). Clinicopathologic features were compared among ICPNs (n=7), papillary GBCs (n=24), and nonpapillary GBCs (n=44). Whole-exome and validation Sanger sequencing was also conducted. Gross mucin hypersecretion was detected in 3/7 ICPNs (43%), 1/24 papillary GBCs (4%), and 1/44 nonpapillary GBCs (2%) (P<0.001). All patients with ICPN lacked lymphovascular invasion and nodal metastasis, while these features were occasionally observed in patients with papillary or nonpapillary GBC (13% to 59%). ICPNs were less advanced than papillary and nonpapillary GBCs (P<0.001) with all cases of ICPNs being recurrence-free. Whole-exome and Sanger sequencing identified somatic mutations in STK11 (a causative gene of Peutz-Jegher syndrome; n=3), CTNNB1 (n=2), and APC (a gene of familial adenomatous polyposis; n=1) in ICPNs, while those alterations were exceptional in papillary and nonpapillary GBCs. ICPNs more commonly showed cytoplasmic and/or nuclear expressions of β-catenin than papillary and nonpapillary GBCs. In conclusion, the histology-based classification of gallbladder papillary neoplasms is useful for identifying ICPNs that share clinicopathologic features with the pancreatic counterpart. ICPNs meeting the criteria were genetically distinct from papillary and nonpapillary GBCs, with STK11, CTNNB1, and APC being identified as major driver genes for ICPNs.Jun. 2019, The American journal of surgical pathology, 43(6) (6), 783 - 791, English, International magazineScientific journal
- Apr. 2019, 癌と化学療法, 46(4) (4), 775 - 777, JapaneseConversion Surgeryを施行し得た高度進行胆嚢癌の1例Scientific journal
- This study aimed to elucidate the genetic landscape of biliary papillary neoplasms. Of 28 cases examined, 7 underwent whole exome sequencing, while the remaining 21 were used for validation studies with targeted sequencing. In the whole exome sequencing study, 4/7 cases had mutations in either APC or CTNNB1, both of which belong to the Wnt/β-catenin pathway. Somatic mutations were also identified in genes involved in RAS signaling (KRAS, BRAF), a cell cycle regulator (CDC27), histone methyltransferase (KMT2C, KMT2D), and DNA mismatch repair (MSH3, MSH6, PMS1). Combined with discovery and validation cohorts, mutations in APC or CTNNB1 were observed in 6/28 subjects (21%) and were mutually exclusive. When the cases were classified into intraductal papillary neoplasms of the bile duct (IPNBs, n=14) and papillary cholangiocarcinomas (n=14) based on the recently proposed classification criteria, mutations in APC and CTNNB1 appeared to be entirely restricted to IPNBs with 6/14 cases (43%) harboring mutations in either gene. These genetic alterations were detected across the 3 nonintestinal histologic types. In immunohistochemistry, the aberrant cytoplasmic and/or nuclear expression of β-catenin was found in not only 5/6 IPNBs with APC or CTNNB1 mutations, but also 6/8 cases with wild-type APC and CTNNB1 (total 79%). In addition, APC and CTNNB1 alterations were exceptional in nonpapillary cholangiocarcinomas (n=29) with a single case harboring CTNNB1 mutation (3%). This study demonstrated recurrent mutations in APC and CTNNB1 in nonintestinal-type IPNBs, suggesting that activation of the Wnt/β-catenin signaling pathway is relevant to the development and progression of IPNBs.Dec. 2018, The American journal of surgical pathology, 42(12) (12), 1674 - 1685, English, International magazineScientific journal
- Oct. 2018, 消化器内視鏡, 30(335) (335), 192 - 193, Japanese【胆膵疾患内視鏡アトラス】 胆嚢 ポリープ 2cmくらいまで 転移性腫瘍Scientific journal
- 日本消化器病学会近畿支部第124回例会, Jan. 2026, Japanese, Domestic conference-Others
- 第38回日本内視鏡外科学会総会, Dec. 2025, Japanese, Domestic conference-Oral presentation
- 第38回日本内視鏡外科学会総会, Dec. 2025, Japanese, Domestic conference-Oral presentation
- 第38回日本内視鏡外科学会総会, Dec. 2025, Japanese, Domestic conference-Oral presentation
- 第38回日本内視鏡外科学会総会, Dec. 2025, Japanese, Domestic conference-Oral presentation
- 第38回日本内視鏡外科学会総会, Dec. 2025, Japanese, Domestic conference-Public symposium
- 第23回日本消化器外科学会大会（JDDW2025）, Oct. 2025, Japanese, Domestic conference-Poster presentation
- 第23回日本消化器外科学会大会（JDDW2025）, Oct. 2025, Japanese, Domestic conference-Poster presentation
- 第23回日本消化器外科学会大会（JDDW2025）, Oct. 2025, Japanese, Domestic conference-Poster presentation
- 第61回日本移植学会総会, Oct. 2025, Japanese, Domestic conference-Oral presentation
- 第48回日本膵・胆管合流異常研究会, Sep. 2025, Japanese, Domestic conference-Oral presentation
- 第13回神戸肝胆膵外科ビデオクリニック, Aug. 2025, Japanese, Domestic conference-Oral presentation
- 第52回日本膵切研究会, Aug. 2025, Japanese, Domestic conference-Poster presentation
- 第52回日本膵切研究会, Aug. 2025, Japanese, Domestic conference-Oral presentation
- -, Jul. 2025, Japanese, Domestic conference-Oral presentation
- -, Jul. 2025, Japanese, Domestic conference-Oral presentation
- -, Jul. 2025, Japanese, Domestic conference-Public symposium
- The 15th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE2025), Jul. 2025, English, International conferenceImpact of Initial Hepatectomy With Hilar Manipulation on Short-Term Outcomes of Repeat Hepatectomy for Recurrent Liver CancerPoster presentation
- -, Jul. 2025, Japanese, Domestic conference-Keynote oral presentation
- -, Jul. 2025, Japanese, Domestic conference-Public symposium
- -, Jun. 2025, Japanese, Domestic conference-Oral presentation
- -, Jun. 2025, English, Domestic conferenceAcase of T1b ampullary adenocarcinoma with para-aortic lymph node metastasisPoster presentation
- -, Jun. 2025, English, Domestic conferenceAnomalous origin of the posterior superior pancreaticoduodenal artery (PSPDA): critical vascular variations in the field of hepato-pancreato-biliary surgeryPoster presentation
- -, Jun. 2025, English, Domestic conferenceAssociation between S-1 postoperative adjuvant chemotherapy and early postoperative recurrence in biliary tract cancerPoster presentation
- -, May 2025, Japanese, Domestic conference-Oral presentation
- -, May 2025, Japanese, Domestic conference-Oral presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Poster presentation
- -, Apr. 2025, Japanese, Domestic conference-Oral presentation
- -, Apr. 2025, Japanese, Domestic conference-Public symposium
- -, Mar. 2025, Japanese, Domestic conference-Oral presentation
- -, Mar. 2025, Japanese, Domestic conference-Oral presentation
- -, Mar. 2025, Japanese, Domestic conference-Oral presentation
- -, Feb. 2025, Japanese, Domestic conference-Oral presentation
- -, Feb. 2025, Japanese, Domestic conference-Public symposium
- -, Jan. 2025, Japanese, Domestic conference-Oral presentation
- APA/JPS/CAP/IAP 2024, Dec. 2024, English, International conferenceComprehensive analysis of altered lipid and amino acid metabolism in patients undergoing pancreatoduodenectomyOral presentation
- -, Oct. 2024, Japanese, Domestic conferencePostoperative complications assessed by the comprehensive complication index (CCI) are associated with early recurrence after curative resection for biliary tract cancerPoster presentation
- -, Oct. 2024, Japanese, Domestic conference-Poster presentation
- -, Oct. 2024, Japanese, Domestic conference-Poster presentation
- -, Oct. 2024, Japanese, Domestic conference-Poster presentation
- -, Oct. 2024, Japanese, Domestic conference-Poster presentation
- -, Oct. 2024, Japanese, Domestic conference-Poster presentation
- -, Oct. 2024, Japanese, Domestic conference-Poster presentation
- -, Oct. 2024, Japanese, Domestic conference-Oral presentation
- -, Sep. 2024, Japanese, Domestic conference-Oral presentation
- -, Jul. 2024, Japanese, Domestic conference-Public symposium
- -, Jul. 2024, Japanese, Domestic conference-Public symposium
- -, Jul. 2024, Japanese, Domestic conference-Poster presentation
- The 14th Asia-Pacific Primary Liver Cancer Expert Meeting 2024 (APPLE), Jul. 2024, English, International conferenceTextbook outcomes in initial liver resection for hepatocellular carcinoma: a study with malnutrition grade by the GLIM criteria.Poster presentation
- -, Jul. 2024, Japanese, Domestic conference-Oral presentation
- -, Jul. 2024, Japanese, Domestic conference-Oral presentation
- -, Jul. 2024, Japanese, Domestic conference-Oral presentation
- -, Jun. 2024, Japanese, Domestic conference-Oral presentation
- -, May 2024, Japanese, Domestic conference-Oral presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Poster presentation
- -, Apr. 2024, Japanese, Domestic conference-Oral presentation
- -, Apr. 2024, Japanese, Domestic conference-Oral presentation
- The 33rd Annual Meeting the Asian Pacific Association for the Study of the Liver (APASL2024), Mar. 2024, English, International conferenceThe Efficacy of Total Tumor Volume in Patients with Colorectal Liver MetastasesOral presentation
- -, Feb. 2024, Japanese, Domestic conference-Oral presentation
- -, Jan. 2024, Japanese, Domestic conference-Oral presentation
- -, Jan. 2024, Japanese, Domestic conference-Oral presentation
- -, Nov. 2023, Japanese, Domestic conference-Oral presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Nov. 2023, Japanese, Domestic conference-Poster presentation
- -, Sep. 2023, Japanese, Domestic conference-Others
- -, Sep. 2023, Japanese, Domestic conference-Oral presentation
- -, Sep. 2023, Japanese, Domestic conference-Poster presentation
- -, Sep. 2023, Japanese, Domestic conference-Poster presentation
- -, Sep. 2023, Japanese, Domestic conference-Poster presentation
- 4th World Congress of International Laparoscopic liver Society（ILLS2023）, Sep. 2023, English, International conferenceA comparative study of laparo-scopic liver resection for the segment 8 dorsal and ventral areaOral presentation
- 45th ESPEN Congress, Sep. 2023, English, International conferenceImpact of malnutrition diagnosed by the GLIM criteria on postoperative complications after pancreaticoduodenectomy for biliary tract cancerPoster presentation
- 45th ESPEN Congress, Sep. 2023, English, International conferenceImpact of malnutrition diagnosed by the GLIM criteria on outcome of elderly patients with hepatocellular carcinoma after liver resectionPoster presentation
- -, Sep. 2023, Japanese, Domestic conference-Oral presentation
- -, Sep. 2023, Japanese, Domestic conference-Oral presentation
- -, Jul. 2023, Japanese, Domestic conference-Public symposium
- -, Jul. 2023, Japanese, Domestic conference-Oral presentation
- -, Jul. 2023, Japanese, Domestic conference-Oral presentation
- -, Jul. 2023, Japanese, Domestic conference-Oral presentation
- -, Jul. 2023, Japanese, Domestic conference-Oral presentation
- -, Jun. 2023, Japanese, Domestic conferenceA study for infectious complication of hepatectomies in patients with preexisting bilioenteric anastomosisPoster presentation
- -, Jun. 2023, Japanese, Domestic conferenceIntracholecystic papillary neoplasm (ICPN) with pancreaticobiliary maljunction (PBM): Comparison with normal gallbladder cancer with PBMPoster presentation
- -, Jun. 2023, Japanese, Domestic conferenceSuccessful biliary drainage using hybrid EUS-BD for stricture of choledochojejunostomyPoster presentation
- -, Jun. 2023, Japanese, Domestic conferenceIntended destination for a board certified surgeon under 45Oral presentation
- -, Jun. 2023, Japanese, Domestic conferencePrognostic significance of malnutrition diagnosed by the GLIM criteria for resected extrahepatic cholangiocarcinoma: A single-center retrospective studyOral presentation
- -, Jun. 2023, Japanese, Domestic conferenceImprovement in stapler pancreatic transection to reduce pancreatic fistula after laparoscopic distal pancreatectomy: twelve-year experience at a single high-volume centerOral presentation
- -, Jun. 2023, Japanese, Domestic conferenceAnterior approach for open right hepatectomy for huge hepatocellular carcinomaPublic symposium
- -, Jun. 2023, Japanese, Domestic conferenceInvestigation of the relationship between complications after pancreaticoduodenectomy for distal cholangiocarcinoma and malnutrition diagnosed by the GLIM criteriaOral presentation
- -, Jun. 2023, Japanese, Domestic conference-Oral presentation
- -, Jun. 2023, Japanese, Domestic conference-Oral presentation
- -, Jun. 2023, Japanese, Domestic conference-Public symposium
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Poster presentation
- -, Apr. 2023, Japanese, Domestic conference-Oral presentation
- -, Apr. 2023, Japanese, Domestic conference-Oral presentation
- -, Apr. 2023, Japanese, Domestic conference-Public symposium
- -, Apr. 2023, Japanese, Domestic conference-Oral presentation
- -, Apr. 2023, Japanese, Domestic conference-Oral presentation
- -, Dec. 2022, Japanese, Domestic conference-Oral presentation
- -, Oct. 2022, Japanese, Domestic conference-Oral presentation
- -, Oct. 2022, Japanese, Domestic conference-Others
- -, Sep. 2022, Japanese, International conference-Poster presentation
- -, Sep. 2022, Japanese, Domestic conference-Oral presentation
- -, Jun. 2022, Japanese, Domestic conference-Public symposium