Surgical resection is considered the only potentially curative treatment for biliary tract cancer (BTC). However, for patients with locally advanced or metastatic BTC, systemic chemotherapy remains the primary therapeutic option. Historically, chemotherapies such as gemcitabine plus cisplatin (GC), gemcitabine plus S-1, and GC plus S-1 have been employed; however, the prognosis remains poor. Recently, combined therapy with immune checkpoint inhibitors (ICIs) has emerged as a promising therapeutic approach for unresectable BTC. In cases with long-term efficacy to systemic chemotherapy, sequential surgical resection, known as conversion surgery, has also shown potential to improve overall outcomes in unresectable BTC. This case report presents a case of advanced perihilar cholangiocarcinoma with histologically confirmed peritoneal dissemination that achieved a pathological complete response after combination therapy with GC and durvalumab, followed by conversion surgery. Achieving a pathological complete response in the presence of peritoneal dissemination is rare. This case provides valuable insights into treatment strategies for this aggressive malignancy, demonstrating that a pathological complete response is possible even in the presence of peritoneal dissemination.

Objective: Total pancreatectomy (TP) is an invasive surgery, resulting in pancreatic endocrine and exocrine dysfunction. With increasing indications for pancreatic neoplasms, including pancreatic ductal adenocarcinoma (PDAC), understanding long-term metabolic adaptation after TP is essential for survivorship care. Methods: We retrospectively analyzed 160 TP cases at Tohoku University Hospital between 2003 and 2024 and evaluated the prognosis. A subset of 20 long-term survivors (>10 years) underwent longitudinal assessment of nutritional parameters, body mass index (BMI), skeletal muscle index (SMI), and steatotic liver disease (SLD) preoperatively and at 3 to 6 months, 1, 5, and 10 years postoperatively. Results: PDAC patients (n = 87) had significantly worse survival than non-PDAC patients (n = 73) (10-year survival: 16.2% vs 70.7%; hazard ratio (HR), 6.92; P < .001). Serum albumin recovered within 3 to 6 months and remained stable for 10 years. BMI recovered in both sexes by 5 years, but muscle mass showed a striking sex disparity. Males regained preoperative SMI, while females suffered persistent loss (35.5-30.9 cm(2)/m(2) at 10 years). The new-onset SLD occurred far more frequently in females (37.5% at 3-6 months; 55.6% at 1 year) than males (0%-11.1%). Notably, the dramatic reduction of BMI and SMI was more frequently associated with the development of SLD after TP in females than in males. Conclusions: This is a pioneering study to describe the sex-specific long-term metabolic changes after TP. Females experienced persistent muscle loss and new-onset SLD after TP, highlighting the need for sex-specific long-term follow-up to improve quality of life and outcomes.

This study aimed to determine the risk factors for new-onset hepatic steatosis after total pancreatectomy (TP), focusing on muscle loss and sex. We retrospectively analyzed 100 patients who underwent TP between 2005 and 2024. Nutritional parameters, BMI, muscle volume, and liver status were evaluated. Logistic regression and subgroup analyses were performed to identify the risk factors for hepatic steatosis. The prevalence of hepatic steatosis increased from 3.0

BACKGROUND:Surgical resection is the only curative treatment for perihilar cholangiocarcinoma (pCCA); however, the majority of patients experience postoperative recurrence. While recurrence typically occurs within five years after surgery, recurrence after prolonged relapse-free survival has been occasionally observed. This study aimed to investigate the clinicopathological factors associated with late recurrence of pCCA. METHODS:Among the 258 consecutive patients who underwent radical hepatectomy with extrahepatic bile duct resection for pCCA at our institution between 1996 and 2019, 9 patients (3.4%) had postoperative recurrence more than five years after surgery. For this study, late recurrence was defined as recurrence occurring more than five years after surgery. Clinicopathological characteristics of late recurrence (beyond five years) were analyzed and compared with those of the patients who remained recurrence-free for over 12 years (no recurrence group, n=14). RESULTS:Among the nine cases of late recurrence, local recurrence was the most common, followed by liver metastasis. Chemotherapy was the primary treatment after recurrence, while surgical resection was performed in two cases. A comparison between the late recurrence and no recurrence group revealed similar demographics; however, the late recurrence group exhibited significantly higher cases with pathological perineural invasion (p=0.016), hepatopancreatoduodenectomy (HPD) (p=0.034) and neoadjuvant chemotherapy (NAC) (p=0.034) were performed significantly more frequently in the no recurrence group. Notably, all late recurrence cases demonstrated positive perineural invasion. CONCLUSIONS:The presence of pathological perineural invasion is significantly associated with late recurrence of pCCA. This finding provides significant insights for the long-term follow-up and managemant of pCCA patients.

BACKGROUND:Pancreatic cancer is characterized by a dense tumor microenvironment enriched with cancer-associated fibroblasts (CAFs), which display context-dependent tumor-promoting and tumor-restraining properties. However, the molecular basis of stromal heterogeneity remains incompletely understood. METHODS:We examined stromal responses of pancreatic stellate cells (PSCs), a major source of CAFs, using an orthotopic mouse co-implantation model, RNA sequencing, conditioned medium-based functional assays, and immunohistochemical analysis of resected pancreatic cancer specimens. RESULTS:Co-implantation of PSCs with pancreatic cancer cells was associated with smaller primary tumor volumes and selective activation of SMAD3 in PSCs. Cancer cell-derived conditioned medium activated SMAD3 signaling in PSCs but not in cancer cells, suggesting cell type-specific pathway activation. Transcriptomic analysis identified prostaglandin D2 receptor 2 (PTGDR2) as a gene upregulated in association with SMAD3 activation, and its expression decreased following SMAD3 inhibition. Functional assays showed that SMAD3 activation was associated with modulation of PTGDR2 and inflammatory gene expression in PSCs. In clinical samples, higher p-SMAD3 expression in CAFs correlated with favorable overall survival. CONCLUSIONS:SMAD3 activation in PSCs was observed in association with PTGDR2 expression, altered inflammatory profiles, and reduced tumor growth in vivo. These findings support the presence of distinct stromal phenotypes in pancreatic cancer and warrant further investigation into CAF modulation strategies.

Abstract Background: Biliary tract cancer (BTC) is an aggressive malignancy for which reliable prognostic biomarkers remain scarce. Although recent efforts have advanced the molecular characterization of intrahepatic cholangiocarcinoma (iCCA), the biology of extrahepatic CCA (eCCA) is still insufficiently understood. IQ motif-containing GTPase-activating protein 3 (IQGAP3) is a scaffold protein involved in cytoskeletal regulation, cell-cycle control, and epithelial junctional stability. Because epithelial-mesenchymal transition (EMT) drives invasion and metastasis in BTC, we hypothesized that IQGAP3 may influence epithelial identity and clinical behavior in eCCA. This study sought to clarify the clinicopathological significance of IQGAP3 and examine its biological role using integrated pathological and functional analyses. Methods: We retrospectively analyzed 100 patients who underwent curative resection for perihilar or distal CCA between 2016 and 2020. IQGAP3 expression was assessed by immunohistochemistry and quantified using QuPath-based H-scores; tumor regions were manually annotated in QuPath to ensure that H-scores reflected staining intensity exclusively in cancer cells. Associations with clinicopathological factors and overall survival (OS) were evaluated using standard statistical approaches. Functional studies were conducted in HuCCT1 and TFK-1 cells with shRNA-mediated IQGAP3 knockdown. RNA sequencing and gene set enrichment analysis (GSEA) were performed to identify transcriptional changes associated with IQGAP3 loss. Expression of epithelial markers, including E-cadherin (CDH1), was examined in cell models and resected tissues. Results: High IQGAP3 expression was associated with significantly longer OS than low expression (median 102.7 vs 40.2 months; hazard ratio 0.51; 95% CI 0.30-0.88; P = 0.017). Low IQGAP3 levels correlated with lymph-node metastasis, advanced stage, and positive resection margins. Functional assays showed that IQGAP3 knockdown activated EMT-related transcriptional programs in both cell lines (normalized enrichment score 1.43 and 1.44; P < 0.01; false discovery rate q < 0.25) and reduced CDH1 expression, suggesting impaired epithelial cohesion. In clinical samples, IQGAP3 and CDH1 mRNA levels demonstrated a strong positive correlation (r = 0.74), supporting a biological link between IQGAP3 loss and disruption of epithelial integrity. Conclusions: IQGAP3 plays a key role in maintaining epithelial identity in CCA. Its loss promotes EMT activation and is associated with more aggressive disease features, whereas high expression confers favorable prognosis in eCCA. IQGAP3 may serve as a practical biomarker for risk stratification and represents a potential target for strategies aimed at limiting EMT-driven tumor progression. Citation Format: Naoki Rikiyama, Daisuke Douchi, Ming Zhu, Keigo Murakami, Mitsuhiro Shimura, Takehiko Saijo, Shusuke Migita, Shuichiro Hayashi, Hideaki Sato, Koetsu Inoue, Shuichi Aoki, Masahiro Iseki, Takayuki Miura, Shimpei Maeda, Hideaki Karasawa, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Shinobu Ohnuma, Atsushi Masamune, Toru Furukawa, Michiaki Unno. IQGAP3 as a gatekeeper of epithelial integrity and prognostic biomarker in extrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3936.

To validate the prognostic value of histological treatment response, assessed using the Japan Pancreas Society (JPS) grading system, in patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemotherapy (NAC) followed by surgical resection. We analyzed, retrospectively, data from 117 consecutive patients who underwent NAC and curative-intent PDAC resection at Tohoku University Hospital between January 2010 and December 2022. Histological responses were graded using the JPS system. Survival analyses were conducted using Kaplan–Meier estimation and Cox proportional hazards modeling. Histological Grade 1a, 1b, 2, 3, and 4 responses were observed in 47 (40.2

We report the case of a 69-year-old man who was initially diagnosed with resectable distal cholangiocarcinoma, for which radical resection was planned. However, the disease was reclassified as an unresectable distal cholangiocarcinoma because peritoneal cytology was positive. After 8 courses of gemcitabine, cisplatin, and pembrolizumab (GCP) therapy, pancreaticoduodenectomy was performed as a conversion surgery because the peritoneal cytology was negative. During surgery, no non-curative factors were identified, and an R0 resection was achieved. On postoperative day 14, the patient developed a fever suspected of cholangitis, and the hyponatremia that appeared on day 20 became prolonged. Suspecting adrenal insufficiency, hydrocortisone replacement was initiated on day 27. The serum sodium levels gradually increased, which allowed tapering of the hydrocortisone dose. As only ACTH levels decreased among the anterior pituitary hormones examined, a diagnosis of isolated ACTH deficiency was made. Ten months postoperatively, the patient received S-1 as adjuvant chemotherapy, continued oral hydrocortisone, and is doing well without adverse events. Clinicians should be aware of irAEs during the perioperative period after ICI therapy. Serious complications can be prevented through multidisciplinary collaboration.

Peritoneal dissemination (PD) following endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is rare, particularly in pancreatic neuroendocrine neoplasms (PanNEN). Clinical indications for conversion surgery (CS) in PanNEN patients with PD remain poorly defined. A 65-year-old man was referred for evaluation of a pancreatic tail mass detected during bladder cancer treatment. EUS-FNB diagnosed PanNEN (G2). Laparoscopic distal pancreatectomy (LDP) was aborted after multiple PD nodules were identified within the lesser sac. Peritoneal cytology was negative, and no PD-suspected nodules were identified outside the lesser sac, raising suspicion of FNB‑related tumor seeding. Because lanreotide therapy maintained stable disease for 18 months without the development of distant metastasis, CS was planned. LDP with regional lymphadenectomy was successfully performed, achieving R0 resection. Pathology showed a well-demarcated pancreatic tail tumor and a white nodule with identical immunohistochemical profiles, suggesting a common origin. No evidence of recurrence has been observed at 4 months postoperatively. Given the rarity of PD and FNB-related tumor seeding in PanNEN, the present case provides valuable clinical insight into both the potential procedural risk and the feasibility of multimodal management incorporating systemic therapy, followed by curative-intent CS. CS may be a feasible option for selected PanNEN patients with PD after EUS-FNB.

BACKGROUND:Laparoscopic surgery is being increasingly used for pancreatic neuroendocrine neoplasms (PanNENs). Although laparoscopic regular pancreatectomy (LRP) is frequently performed, laparoscopic enucleation (LE), a parenchyma-sparing technique, may be better in preserving pancreatic endocrine function. However, limited evidence is available regarding the long-term oncological and endocrine outcomes of these two laparoscopic methods. This study aimed to compare the surgical and prognostic outcomes and endocrine function preservation in patients undergoing LE and LRP for well-differentiated, non-invasive PanNEN. METHODS:This retrospective cohort study included 67 consecutive patients who underwent laparoscopic surgery for small (< 2 cm) well-differentiated PanNEN at Tohoku University Hospital between January 2001 and December 2021. LE was performed for small tumors (< 2 cm) located away (> 3 mm) from the main pancreatic duct. Clinical characteristics, surgical details, tumor characteristics, postoperative complications, recurrence-free survival (RFS), overall survival (OS), and long-term endocrine function were retrospectively analyzed. Kaplan-Meier analysis, Cox regression, and the Mann-Whitney U test were used for statistical comparisons. RESULTS:The median follow-up was 78.1 months for LRP and 135.4 months for LE. No significant differences were observed between the two groups in terms of the operative time, blood loss, or postoperative complications. Five-year RFS was excellent and comparable in both groups (LE, 100%, LRP 96.0%; P = 0.313). Notably, LE was associated with a significantly reduced incidence of postoperative new-onset diabetes mellitus (NODM) compared to LRP (5-year cumulative incidence: 9.1% vs. 43.2%; P = 0.0181). Multivariate analysis identified LRP (hazard ratio [HR] = 7.71, 95% confidence interval [CI]:1.03-57.8; P = 0.0469), older age (> 60 years) (HR = 4.49, 95% CI 1.62-12.4; P = 0.0039), and non-functional tumor (HR = 2.78, 95% CI 1.08-7.19; P = 0.0342) as independent predictors of NODM. CONCLUSION:Given appropriate patient selection, LE of small well-differentiated PanNENs provides comparable oncological outcomes, perioperative safety, and superior long-term endocrine function preservation compared to LRP.

Surgical management of pancreatic head lesions complicated by chronic pancreatitis (CP) presents significant challenges, particularly in ensuring effective pancreatic duct drainage after resection. This report describes the detailed technique and key considerations for longitudinal pancreaticojejunostomy (LPJ) as a reconstructive method following pancreaticoduodenectomy (PD) in patients with CP. This approach aims to achieve wide-area drainage of the remnant pancreatic duct through a side-to-side anastomosis between the extensively opened pancreatic duct and jejunum. Conceptually derived from conventional drainage procedures such as the Frey and Partington procedures, this technique is particularly beneficial when significant ductal dilatation persists distal to the resection margin. Critical steps for successful LPJ include meticulous exposure of the pancreatic parenchyma, an adequate longitudinal incision of the main pancreatic duct, and precise anastomotic technique. We have successfully applied this procedure in three male patients (median age 68 years, range: 48-77), including one with CP complicated by duodenal bleeding and two with pancreatic head region malignancies complicated with CP. All patients had favorable postoperative outcomes with no clinically relevant postoperative pancreatic fistula (Grade B or C). Long-term follow-up showed significant symptom improvement without medication, and pancreatic function were relatively well preserved. Our preliminary experience suggests that LPJ provides safe and effective drainage of the pancreas following PD in patients with CP-complicated pancreatic head pathology and may represent a valuable reconstructive option, particularly in cases with marked pancreatic duct dilatation.

Purpose: Pancreaticoduodenectomy (PD) is one of the most invasive procedures in gastrointestinal surgery. However, the clinical significance of postoperative tube feeding remains unclear. This study investigated the impact of enteral nutrition (EN) on the postoperative nutritional status of patients undergoing PD.Methods: We retrospectively analyzed 129 patients who underwent PD at Tohoku University Hospital. Nutritional intake and status, evaluated using the Controlling Nutritional Status score, were compared between two groups: an EN group (97 patients) and a non-EN group (32 patients). Results: There were no significant differences between the two groups in age, sex, body mass index, underlying diseases, operative duration, blood loss, postoperative pancreatic fistula, postoperative complications, delayed gastric emptying, or length of hospital stay. Although the EN group showed improvements in nutritional status both at discharge and compared with preoperative values, none of these changes reached statistical significance. Oral caloric intake was significantly higher in the non-EN group (P=0.01). In contrast, total energy intake was higher in the EN group, but this difference did not reach statistical significance (P=0.07).Conclusion: Tube feeding after PD did not significantly influence postoperative nutritional status or overall nutritional intake. These findings suggest that EN offers no clear advantage over other approaches; however, further research is warranted to validate these results, refine existing guidelines, and optimize postoperative patient management.

BACKGROUND/OBJECTIVES:Positive peritoneal cytology (Cy+) is considered a form of microscopic dissemination and a poor prognostic factor in resected pancreatic cancer (PC). However, the clinical implications of equivocal categories such as atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) remain unclear. METHODS:We retrospectively analyzed patients with PC who underwent surgery at 13 high-volume centers between January 2009 and December 2018. Inclusion criteria were: 1) cytology results of AUS, SFM, or malignant (MAL); 2) resectable (R) or borderline resectable (BR); 3) no other macroscopic metastases; and 4) no preoperative therapy. RESULTS:A total of 239 cases were included (AUS: 58, SFM: 31, MAL: 150), with R/BR = 196/43. Survival curves for SFM closely resembled those for MAL but differed from AUS. Grouped analysis showed that SFM + MAL patients had significantly shorter median overall survival (OS) than AUS patients (19.6 vs. 28.0 months, HR 1.61, P < 0.01) and shorter recurrence-free survival (RFS: 8.0 vs. 12.7 months, HR 1.53, P = 0.01). This trend persisted in resectable cases (OS: 21.1 vs. 30.5 months, HR 1.74; RFS: 9.1 vs. 14.2 months, HR 1.57; all P < 0.01). CONCLUSIONS:The cytology of SFM in PC is associated with a prognosis comparable to that of MAL, suggesting the need for cautious clinical interpretation and potential reclassification.

OBJECTIVES:In patients with pancreatic ductal adenocarcinoma (PDAC) and portal vein/superior mesenteric vein (PV/SMV) contact, we can often separate the tumor from the PV/SMV and avoid PV/SMV resection (VR) owing to the favorable efficacy of neoadjuvant therapy (NAT). However, there is a risk that tumor cells may remain around the PV/SMV. This study aimed to elucidate whether separating a tumor from a PV/SMV is justified in the NAT setting. Methods: We reviewed patients with PDAC who underwent pancreaticoduodenectomies or total pancreatectomies between 2005 and 2019. We usually attempt the skeletonization of PV/SMV as long as possible. We explored recurrence patterns and overall survival (OS). Results: In total, 248 patients were enrolled and divided based on PV/SMV contact (PVC), NAT, and VR. In the NAT setting, local recurrence around PV the SMV occurred at almost the same rate among the three groups (8.1%, NAT+/PVC-; 11.8%, NAT+/PVC+/VR-; 13.6%, NAT+/PVC+/VR+), while the NAT-/PVC+/VR- had a higher local recurrence rate in upfront surgery (10.0%, NAT-/PVC-; 33.3%, NAT-/PVC+/VR-; 12.2%, NAT-/PVC+/VR+, P=0.021). In addition, the OS in the NAT+/PVC+/VR- was not inferior to that in the NAT+/PVC- (Median survival time: 46.6 months, NAT+/PVC-; 61.1, NAT+/PVC+/VR-; 33.0, NAT+/PVC+/VR+). Conclusions: Separation of the PV/SMV in NAT+/PVC+ patients did not enhance local recurrence or aggravate OS if PV/SMV invasion was not suspected intraoperatively. Therefore, an attempt to separate the PV/SMV is acceptable.

INTRODUCTION:Although several studies have highlighted the importance of recognizing gastroduodenal artery (GDA) anomalies during pancreaticoduodenectomy, their relevance during distal pancreatectomy has not been explored. Herein, we describe the safe performance of laparoscopic distal pancreatectomy in a patient with a rare vascular anomaly, specifically a GDA originating from the superior mesenteric artery (SMA). CASE PRESENTATION:A 63-year-old woman presented with recurrent pancreatitis due to a cystic lesion in the pancreatic body. Imaging suggested a branch-duct intraductal papillary mucinous neoplasm with substantial ductal stenosis. Multidetector CT (MDCT) revealed a rare anatomical variant: the GDA, arising from the SMA and traversing along the inferior border of the pancreas. Laparoscopic distal pancreatectomy was performed after placing an endoscopic nasopancreatic drainage tube. The aberrant GDA was successfully preserved through careful dissection and vessel loop isolation. Pancreatic transection was completed without vascular injury. A postoperative pancreatic fistula developed and was conservatively managed. Histopathological examination confirmed that the lesion was an intraductal papillary mucinous carcinoma without any invasive features. Follow-up MDCT revealed sustained patency and perfusion of the preserved GDA, right gastroepiploic artery, and anterior superior pancreaticoduodenal artery. CONCLUSIONS:Laparoscopic pancreatectomy can be safely performed in patients with SMA-derived GDA anomalies, when supported by detailed preoperative imaging and precise intraoperative techniques. These findings highlight the necessity of routine preoperative vascular assessment in patients undergoing minimally invasive pancreatic surgery, reinforcing the broader applicability of these approaches for patients with complicated vascular anatomy.

The importance of the microenvironment in cancer progression is widely recognized, and interactions between cancer cells and stromal cells play an important role in the progression of the disease. A major component of stromal cells are fibroblasts, known as cancer-associated fibroblasts (CAFs). CAFs are thought to enhance the malignant properties of cancer cells through various secreted proteins. It is also known that CAFs function as a leading cell in cancer invasion, and their migratory ability is involved in local cancer invasion. The aim of this study was to elucidate the function of CAF in gallbladder cancer, which is one of the gastrointestinal malignancies with the worst prognosis.CAFs were primarily cultured from surgical specimens of gallbladder cancer patients. We investigated the migration ability of established CAFs and the effects of conditioned medium obtained from CAFs on the growth and invasion ability of gallbladder cancer cell lines. Functional analysis showed that the migration ability of certain CAFs was enhanced compared to control, and that conditioned medium enhanced the migration and invasion of gallbladder cancer cell lines. Gene expression analysis of CAFs revealed that tenascin-C (TNC) and podoplanin (PDPN) were highly expressed in CAFs with the enhancing functions. Immunohistochemical staining of TNC and PDPN on surgical specimens was performed to investigate the relationship with the prognosis. Disease-free survival and overall survival were found to be reduced in patients with high expression of those genes. The results of this study indicate that CAFs expressing TNC and PDPN promote cancer progression in gallbladder cancer.

BACKGROUND:Hemihepatectomy with extrahepatic bile duct resection is considered the only curative treatment for perihilar cholangiocarcinoma. The aim of the study was to clarify the survival benefits in this invasive surgical procedure for elderly patients. METHODS:A total of 290 patients who underwent surgical resection for perihilar cholangiocarcinoma in our department from 2000 to 2020 were categorized into the E group (62 patients aged ≥75 years) and NE group (228 patients aged <74 years). RESULTS:The E group exhibited decreased pathological lymph node metastasis (p = .001) and had a shorter operative time (p = .021) and fewer cases of combined vascular resection (p = .002). We found no significant differences in postoperative mortality; however, disease-specific survival was significantly better in the E group (3-year survival: 75.6 vs. 60.3%, p = .031). After propensity score matching, overall survival and disease-specific survival did not differ between the two groups; nevertheless, the hospital mortality rate was significantly higher in the E group (11.5 vs. 1.6%, p = .020). In the E group, a high preoperative Glasgow prognostic score was the only factor associated with hospital mortality (odds ratio, 7.35; p = .026) and indicated worse prognosis. CONCLUSIONS:A high preoperative Glasgow prognostic score was associated with hospital mortality and poor prognosis in elderly patients with perihilar cholangiocarcinoma.

Pancreaticoduodenectomy is typically performed for patients with biliary and duodenal stenosis due to chronic pancreatitis. However, the procedure can be quite challenging in cases with severe inflammation and adhesions and may be too invasive for patients in poor general condition. We report two cases of triple bypass, a procedure that combines pancreatic duct drainage with biliary and gastric bypass, as an alternative to pancreaticoduodenectomy. Case 1 involves a 51-year-old man who underwent endoscopic pancreatic and biliary stenting for pancreatic and biliary stenosis caused by alcoholic chronic pancreatitis. Although coexistent duodenal stenosis was observed during upper gastrointestinal endoscopy, he was able to eat sufficiently at that time. Two years later, after self-interrupting treatment, he presented to our hospital with vomiting and jaundice. Due to the duodenal stenosis, endoscopic treatment was challenging, necessitating surgical intervention for the obstructed pancreatic and biliary stents. Triple bypass, including pancreaticojejunostomy, was performed instead of pancreaticoduodenectomy due to the patient's poor general condition and the development of collateral veins with superior mesenteric vein stenosis. Postoperatively, the patient experienced pancreatic fistula and fungal sepsis but was discharged from the hospital three months after surgery. Currently, his condition and nutritional status are good. Case 2 involves a 58-year-old man who was referred to our hospital due to pancreatic pseudocysts and pancreatic and biliary stenosis caused by alcoholic chronic pancreatitis. Endoscopic drainage for pancreatic pseudocysts and stenting for pancreatic and biliary stenosis were performed. After two years of follow-up, surgical treatment was performed due to the challenges posed by stenosis and multiple duodenal ulcers, which rendered endoscopic treatment difficult. Triple bypass, including longitudinal pancreaticojejunostomy with coring-out of the pancreatic head (Frey's procedure), was performed because pancreaticoduodenectomy was difficult due to severe inflammation and adhesions in the pancreatic head. His postoperative course was uneventful, and he was discharged 13 days after surgery. Triple bypass could serve as a viable alternative to pancreaticoduodenectomy in cases with poor general condition or a high risk of perioperative complications due to severe inflammation and adhesions.

Pancreaticobiliary maljunction (PBM) contributes to epithelial hyperplasia and, ultimately, the development of gallbladder cancer (GBC). Despite its clinical significance, the molecular and cellular mechanisms driving carcinogenesis in GBC with PBM remain poorly elucidated. This study investigated the oncogenic mechanisms, biomarkers, and performance associated with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-targeted therapies in GBC with PBM. Overall, 127 surgically treated patients were stratified as follows: Group A, normal gallbladder; Group B, PBM; Group C, GBC without PBM; and Group D, GBC with PBM. We performed whole-exome sequencing (WES) for Group D and human epidermal growth factor receptor 2 immunohistochemistry (HercepTest) for the entire cohort. Fluorescence in situ hybridization (FISH) was used to clarify human epidermal growth factor receptor 2 (HER2) expression in cases with equivocal HercepTest results. ERBB2 amplification was detected in 50