Published papers

Background: With recent advances in chemotherapy for unresectable pancreatic ductal adenocarcinoma (PDAC) with liver metastasis (LM), attempts have been made to resect the primary tumor in patients showing favorable responses to anti-cancer treatment (so-called “conversion surgery”; CS). This study aimed to clarify the outcomes of CS for PDAC with LM in a nationwide multicenter study. Methods: This retrospective, multicenter study was conducted as a project study of the Japan Pancreas Society and included patients with PDAC with LM at initial diagnosis, diagnosed radiologically or intraoperatively (occult LM), who underwent CS after at least 4 months of chemotherapy between 2010 and 2022. Survival outcomes and prognostic factors were analyzed. Results: 90 patients were enrolled from 31 Japanese institutions. Median duration of preoperative chemotherapy was 10.4 (range, 4.2–58.5) months, and gemcitabine plus nab-paclitaxel was the most common first-line regimen, followed by folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin. Liver metastasectomy was performed in 27 patients (30%). 82 patients (91.1%) initiated adjuvant chemotherapy, and 41 (45.6%) completed it. Overall survival (OS) from initial treatment was 53.1 (95% CI 41.6–65.7) months; OS after CS was 39.7 (95% CI 24.4–55.9) months, and disease-free survival was 14.7 (95% CI 9.3–23.4) months. Preoperative normalization of carbohydrate antigen 19-9 and pathologic negative lymph node metastasis were independent prognostic factors for OS. Conclusion: CS may provide a survival benefit for highly selected patients with PDAC and LM, including those with occult lesions, who respond well to multidisciplinary treatment.

Background: Although robotic pancreaticoduodenectomy (RPD) offers several technical advantages, prolonged operative time remains a major clinical challenge. Mesenteric Kocherization (MK) has recently been introduced as a technical modification for mobilizing the duodenum and pancreatic head during RPD. The present study evaluated the early clinical impact of MK on operative efficiency and perioperative outcomes. Methods: We retrospectively reviewed 56 consecutive patients who underwent totally robotic pancreaticoduodenectomy between July 2021 and June 2025. Conventional Kocherization (CK) was performed in 36 patients and MK in 20 patients. The primary outcome was total operative time. Secondary outcomes included console time, Kocherization time, estimated blood loss, transfusion, harvested lymph nodes, R0 resection rate, major postoperative complications (Clavien–Dindo ≥ IIIa), time to first oral intake, and 90-day unplanned readmission rate. To reduce selection bias, propensity score matching was performed using a 1:2 allocation (MK:CK). Results: In the full cohort, operative time tended to be shorter in the MK group than in the CK group (560 [516–598] vs. 592 [556–667] min; p = 0.057). Kocherization time was significantly shorter with MK (28 [27–36] vs. 50 [40–58] min; p < 0.001), while estimated blood loss was comparable (p = 0.875). After propensity score matching (MK n = 11; CK n = 22), MK was associated with significantly shorter total operative time (533 [511–575] vs. 580 [557–611] min; p = 0.031) and Kocherization time (28 [24–30] vs. 49 [43–55] min; p < 0.001). Blood loss, R0 resection rate, and major postoperative complications were comparable between groups. Conclusions: Mesenteric Kocherization was associated with improved operative efficiency in RPD, primarily through shortening the resection phase of the procedure while maintaining perioperative safety.

Background/Purpose: Surgical resection remains the only potentially curative treatment for advanced gallbladder cancer (GBC). However, preoperative diagnosis and staging are often challenging, and the indication for extended resection remains controversial. This study evaluated the feasibility of upfront resection for advanced GBC based on clinical T (cT) staging. Methods: Patients radiologically diagnosed with cT3 or cT4 GBC at six Japanese centers between 2010 and 2022 were retrospectively analyzed. Resection rate, benign lesions, perioperative outcomes, and overall survival (OS) were compared between the groups. Results: Among 300 patients (cT3, n = 182; cT4, n = 118), 260 (87%) underwent resection. Benign lesions were identified in 21 (8%) patients. Compared with cT3, cT4 tumors had higher rates of extended resection (75% vs. 40%, p < 0.001), exploratory laparotomy (24% vs. 7%, p < 0.001), and postoperative complications (59% vs. 29%, p < 0.001). Postoperative mortality tended to be higher in cT4 patients (7% vs. 3%, p = 0.197), and median OS was significantly shorter (22 vs. 44 months, p < 0.001). Conclusions: Clinical T staging helps guide treatment planning for advanced GBC. Upfront resection is feasible for cT3 GBC, whereas cT4 disease is associated with extensive surgery and poor outcomes.

Background/Purpose: The introduction of oligo-recurrence (OR) as a subtype of metastasis offered new hope, suggesting that local therapies may lead to prolonged survival/cure in selected cases. This study compared the genomic alterations between primary tumors and matched OR lesions in patients with pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA). Methods: Eight patients with OR of PDAC or CCA were eligible. Genomic DNA was extracted from the tissue samples of primary tumors and matched OR lesions. Comprehensive genomic profiling (CGP) was performed using a panel of 216 cancer-related genes. The genomic profiles of the two groups were compared. Results: Among 17 tumor samples from eight patients, 32 genomic mutations were identified in nine genes. A total of 48 copy number alterations were found across 31 distinct genes. Driver genomic mutations were concordant between the primary tumors and OR lesions in all cases, whereas differences in passenger mutations were observed in two cases. Five of the eight patients remained recurrence-free, including two pancreatic cancer cases who remained recurrence-free for > 4 years after surgery. Conclusions: The genomic mutation statuses of primary tumors and OR lesions were concordant, and patients' prognosis was significantly better than that of patients with other Stage IV cancers.

Background: Chemotherapeutic advances have increased opportunities for conversion surgery (CS) in unresectable locally advanced (UR-LA) pancreatic cancer (PC). However, the optimal indications for CS remain unclear. Sarcopenia has been associated with poor outcomes in PC, except UR-LA PC. Herein, we aimed to evaluate the impact of sarcopenia on the prognosis of patients with UR-LA PC. Methods: In this retrospective study, we reviewed consecutive patients with UR-LA PC who had received chemo(radio)therapy as an initial treatment between 2015 and 2023. We examined relevant clinical variables and CT findings at initial diagnosis and at 6 months after starting treatment. Results: Ten of the 41 patients had undergone CS. Tumor size at 6 months, clinical lymph node metastasis at diagnosis, and changes in sarcopenia over 6 months were associated with overall survival (OS) (multivariate analysis: hazard ratio = 3.25, 2.79, and 3.51, respectively). In the entire cohort, patients without any of these three factors had significantly better OS than those with one or more (median OS: 30.3 months vs. 17.3 months, p = 0.013). CS was associated with better OS among patients without these factors (not reached vs. 25.5 months, p = 0.039), but not in those with one or more. Conclusions: The impact of change in sarcopenia on prognosis was demonstrated in patients with UR-LA PC. Although, given the limited number of cases, CS might provide a survival benefit in carefully selected patients without prognostic factors such as tumor size at 6 months, clinical lymph node metastasis at diagnosis, and the rate of change of the psoas muscle mass index (PMI).

Background: Neoadjuvant chemotherapy (NAC) may improve outcomes in perihilar cholangiocarcinoma (PHC); however, its efficacy compared with upfront surgery (US) for resectable PHC remains unclear. We compared survival and clinicopathological characteristics between NAC and US in patients with technically resectable PHC, using propensity score matching (PSM). Methods: We retrospectively analyzed 261 patients with resectable PHC who underwent surgical treatment (2016–2024) across multiple institutions. Among them, 50 received NAC and 199 underwent US. The 38 patients receiving NAC were matched 1:1 with patients undergoing US using PSM. Overall survival (OS) and progression-free survival (PFS) were compared between groups. Pathological response to NAC and its association with chemotherapy doses were also evaluated. Results: Before PSM, OS and PFS did not differ significantly between the US and NAC groups. After PSM, OS did not differ significantly between groups, but PFS was significantly longer in the NAC group, where patients with a therapeutic-effect grade ≥1b had better PFS than those with US. Grade ≥1b response was associated with receiving ≥7 NAC doses. Discussion: NAC may improve PFS in selected patients with resectable PHC, especially those showing major pathological responses. Prospective studies should validate these findings and define optimal selection criteria and regimens.

Background/Purpose: A standardized liver parenchymal transection method in robotic-assisted liver resection has not yet been established, and the techniques used vary among institutions. We developed a novel transection technique for robotic-assisted liver resection termed “Trac & Pac,” which uses maryland bipolar forceps with a gentle stroking motion and strategic traction to progressively expose and dissect the liver parenchyma. Methods: We described the technical details of “Trac & Pac” and Evaluated its short-term outcomes (2022–2025), comparing them with those of conventional laparoscopic liver resection using the Cavitron Ultrasonic Surgical Aspirator (CUSA) (2018–2022). Results: The robotic-assisted liver resection group included 26 patients who underwent robotic left or right hepatectomy with the “Trac & Pac” technique, whereas the laparoscopic liver resection group comprised 34 patients who underwent laparoscopic left or right hepatectomy using the CUSA. The robotic group had a longer time from pneumoperitoneum to the start of intra-abdominal manipulation than the laparoscopic group (p < 0.001). Both groups had similar parenchymal transection times, blood loss, and postoperative complications. Conclusions: “Trac & Pac” is a safe and feasible robotic-assisted liver parenchymal transection technique that may provide a new solution for improving precision and exposure in minimally invasive liver surgery.

Background/objectives While adjuvant S-1 is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC) in Japan, the prognosis remains heterogeneous, with some patients facing poor outcomes. This study aimed to identify independent prognostic factors and develop a weighted scoring system for postoperative risk stratification after upfront surgery for resectable PDAC. Methods We retrospectively analyzed 173 patients who underwent upfront curative resection for resectable PDAC at a single institution (2015–2023). Among those receiving adjuvant chemotherapy, 97.2% were treated with S-1. Preoperative and pathological variables were evaluated using multivariable Cox regression to identify independent predictors of overall survival (OS), from which a weighted prognostic score was developed. Results The median OS was 53.5 months, with 3- and 5-year OS rates of 61.7% and 47.9%, respectively. Five independent prognostic factors were identified: CA19-9 ≥228 U/mL (HR 2.67), poorly differentiated histology (HR 2.60), low prognostic nutritional index (PNI <43.6; HR 2.12), tumor size >3 cm (HR 1.98), and R1 resection (HR 1.66). The model demonstrated robust predictive performance (optimism-corrected C-index: 0.743) and stratified patients into low-, intermediate-, and high-risk groups with 3-year OS rates of 92.2%, 58.3%, and 22.6%, respectively (p < 0.001). Conclusions Our weighted scoring system identifies high-risk patients who derive limited benefit from standard adjuvant S-1. Such individuals may be candidates for intensified postoperative strategies.

Background: CD44v6-positive extracellular vesicles (EVs) released by cancer cells drive tumor progression and liver metastasis. This study aimed to evaluate CD44v6-positive extracellular vesicles (EVs) as prognostic markers for pancreatic ductal adenocarcinoma (PDAC), a disease with poor prognosis. Methods: Plasma samples from 100 patients with hepatobiliary and pancreatic diseases were retrospectively analyzed. Non-pancreatic and unresectable pancreatic cancer cases were included as control groups for cross-sectional comparisons, whereas prognostic analysis using preoperative plasma samples was limited to resected PDAC. EVs were defined based on CD9, CD63, and CD81 membrane antigens, and the proportion of CD44v6-positive EVs was measured using nano-flow cytometry. CD44v6 expression in resected PDAC tissues was assessed using immunohistochemistry. Results: The proportion of CD44v6-positive EVs was significantly higher in patients with pancreatic cancer than in those without cancer (P = 0.0009). High CD44v6 expression in resected PDAC tissues correlated with elevated CD44v6-positive EVs in the plasma. Patients with CD44v6-positive EVs ≥ 31% had significantly poorer recurrence-free survival (P = 0.0008) and overall survival (P = 0.045) than those with < 31% EVs. Multivariate analysis confirmed CD44v6-positive EVs ≥ 31% were independent prognostic factors for recurrence-free (P = 0.005) and overall survival (P = 0.037), and a predictor of early liver metastasis (P = 0.001). Conclusions: These findings highlight the potential of preoperative quantification of CD44v6-positive EVs as a biomarker for risk stratification and treatment optimization in PDAC.

Objective: – To evaluate short- and long-term surgical outcomes in non-benchmark (non-BM) patients with perihilar cholangiocarcinoma (pCCA) using a multicenter cohort from Japan. Background: – Benchmark (BM) criteria have been proposed to standardize surgical outcomes in complex hepatopancreatobiliary procedures. However, BM studies typically exclude patients with significant medical comorbidities or those requiring technically demanding procedures. As a result, the majority of real-world pCCA cases, classified as non-BM, remain underrepresented in the literature, and their outcomes are insufficiently characterized. Methods: – Between 2014 and 2018, a total of 648 patients underwent curative intent resection for pCCA at six high volume centers in Japan. Among them, 412 patients (64%) were categorized as non-BM and 236 patients (36%) as BM according to established surgical and medical exclusion criteria. Perioperative and oncologic outcomes were analyzed and compared with benchmark thresholds previously reported in the literature. Non-BM cases were further stratified into surgical, medical, and dual subgroups for subgroup analysis. Results: – The median operative time (644 minutes), intraoperative blood loss (1185 mL), and postoperative hospital stay (31 d) exceeded BM thresholds. Nevertheless, most postoperative outcomes, including Grade B/C post-hepatectomy liver failure (16.7%), bile leakage (22.8%), and in-hospital mortality (2.9%), remained within benchmark reference values. The median overall survival was 46.0 months, with 1-, 3-, and 5-year survival rates of 85.8%, 55.0%, and 37.1%, respectively. Subgroup analysis revealed decreasing survival with increasing complexity: 5-year survival rates were 50.5% in medical, 34.1% in surgical, and 15.4% in dual non-BM patients. Notably, left trisectionectomy was associated with the highest mortality (9.5%) among all procedures. Conclusions: – Despite increased surgical complexity and patient-related risk factors, non-BM pCCA patients can achieve acceptable perioperative and long-term outcomes when treated at experienced, high-volume centers. Stratification by non-BM subgroup provides meaningful prognostic insight and may help guide surgical decision-making in complex pCCA cases.

Background: Perihilar cholangiocarcinoma (PHCC) presents a significant clinical challenge, often necessitating extensive hepatectomy in conjunction with extrahepatic bile duct resection (Hx + EBDR). The impact of preoperative chemotherapy on surgical outcomes remains uncertain. This multicenter retrospective cohort study aimed to assess the surgical and survival outcomes of patients with PHCC who received chemotherapy. Methods: We conducted a retrospective analysis of 563 patients who underwent extensive hepatectomy with extrahepatic bile duct resection for PHCC, including 81 patients who received preoperative chemotherapy. Propensity score matching was utilized to compare perioperative, pathological, and long-term outcomes between the two groups. Results: The morbidity and mortality rates in the chemotherapy group were 52% and 4%, respectively. The main postoperative complications were organ/space surgical site infection (27%), bile leakage (26%), and postoperative liver failure (21%), including duplicating occurrences, respectively. Following propensity score matching (n=80 per group), no significant differences were observed in operative time, intraoperative blood loss, morbidity, mortality, or pathological findings, including R0 resection rates. Across the entire cohort, the 5-year overall survival rates were 32.7% for the chemotherapy group and 30.9% for the control group (p=0.982). Conclusions: Preoperative chemotherapy for PHCC is associated with comparable surgical morbidity and mortality, despite longer operative times. Propensity score–matched analysis indicates that preoperative chemotherapy does not negatively affect surgical or pathological outcomes.

Hereditary breast and ovarian cancer (HBOC) syndrome, caused by pathogenic variants in BRCA1 or BRCA2, is associated with increased risks of breast, ovarian, pancreatic, and prostate cancers. Although long-term, multi-organ surveillance is recommended, real-world data on its implementation in Japan remain limited. We conducted a web-based cross-sectional survey among 274 individuals registered for a hybrid public lecture at Keio University Hospital in 2024; 121 responded (44.2%). Respondents included HBOC carriers, healthcare professionals, and the general public. Among 66 carriers, 57 were affected and 9 were unaffected. Although the sample size is small, surveillance uptake was high among affected carriers (89.5%). Approximately half of affected carriers undergoing surveillance reported satisfaction, while nearly half underwent surveillance at multiple institutions, suggesting fragmented care. Across all groups including healthcare professionals and the general public, the most acceptable annual cost was less than 50,000 yen. Healthcare professionals identified interdepartmental coordination and shortages of genetic specialists as major challenges. These exploratory findings suggest that affordability, convenience, interdepartmental and interfacility coordination, and the availability of genetic medicine professionals may be important considerations in efforts to develop sustainable HBOC surveillance systems in Japan.

Background: Anatomical segmentectomy 8 is challenging owing to the complex branching patterns and position of the Glissonean pedicle of segment 8 (G8) root. The hepatic vein-guided approach and extrahepatic Glissonean approach are essential for accurate G8 root identification. We evaluated the key anatomical factors for precise G8 root transection and proposed the hybrid Glissonean approach (HYBA) as a potential surgical strategy. Methods: Using high-quality multidetector-row computed tomography (CT) images from 73 living liver donor candidates, we assessed the position of the segment 8 portal vein (P8) root relative to the middle hepatic vein (MHV), intersegmental vein between segments 5 and 8 (IV5/8), and hepatic hilum. Distances from the MHV–IV5/8 confluence and alignment with the MHV/right hepatic vein (RHV) plane were also analyzed. Results: IV5/8 was not identified on CT in 9.6% of cases. In 61.6% of cases, the P8 root aligned with the MHV–RHV plane. Additionally, in 53.4% of cases, the shortest distance from the P8 root to the MHV matched the MHV–IV5/8 confluence. The distance from the MHV–IV5/8 confluence to the P8 root (5.8–32.5 mm), the first branch of the right anterior portal vein to the P8 root (3.9–39.4 mm), and the shortest distance from the MHV to the P8 root (5.1–28.9 mm) showed significant variation. Conclusions: This study highlights anatomical variations in the positional relationships of the G8 root with key landmarks (MHV, RHV, IV5/8, and hepatic hilum). Preoperative evaluation of these factors is crucial for selecting the optimal approach, and HYBA has been proposed as a viable option.

Purpose: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate the clinical characteristics of patients with PIAA with interventional drainage. Methods: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA. Results: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3–49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111 − 1.274; P < 0.001) was the only independent and significant predictive factor for PIAA. Conclusions: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy.

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research.

The symposium “New criteria of resectability for pancreatic cancer” was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice.

Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell–cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell–cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.

Hepatocellular carcinoma (HCC) in the caudate lobe presents surgical challenges due to the lack of distinct anatomical landmarks. This case report introduces a novel surgical approach combining Takasaki’s classification and indocyanine green negative counterstaining for precise anatomical caudate lobectomy. A 78-year-old patient with hepatocellular carcinoma in the caudate lobe underwent surgery following preoperative volumetric assessment. The method involved a glissonian approach for both left and right pedicles, coupled with meticulous dissection of hepatic pedicles of the caudate lobe guided by taping of left and right glissonian pedicles, followed by indocyanine green administration for improved visualization of caudate lobe boundaries. The procedure enabled complete tumor resection with minimal blood loss. At 50 months postsurgery, the patient maintains favorable liver function and performance status. This innovative approach offers a promising solution for precise resection of caudate lobe hepatocellular carcinoma, potentially improving surgical outcomes and long-term prognosis.