Journal of Hepato‐Biliary‐Pancreatic Sciences最新文献

Background: Although several prophylactic strategies have been developed for postoperative pancreatic fistula (POPF), research on its severe form is few. Recently, it has been reported that severe POPF can be caused by intraabdominal lipolysis. This study aimed to establish a rat model of severe POPF by combining pancreatic juice leakage and lipolysis and to develop a prophylactic strategy for POPF.

Methods: Sprague-Dawley rats were subjected to pancreatic transection to induce pancreatic juice leakage (PT group). Autologous fat tissue was thermally treated to prepare a fat solution, which was intraperitoneally administered to the rats in the PT group (PT + F group). A water-solubilized lipase inhibitor (cetilistat) was administered intraperitoneally to the rats in the PT + F group. A polyethylene glycol-based hydrogel (PEG-HG) formulation of water-solubilized cetilistat was equally administered. Ascitic and serum biochemical tests, including free fatty acids (FFA) levels, macroscopic or microscopic examinations, and survival analyses, were performed.

Results: In the PT + F group, significantly elevated ascitic and serum FFA levels and serum inflammatory cytokine levels were observed 24 h postoperatively (p < .001), and the survival rate was significantly exacerbated (p < .0001). Intraperitoneal administration of water-solubilized cetilistat resulted in reduced inflammation and improved outcomes. Although PEG hydrogel itself did not improve blood parameters or survival outcomes, the incorporation of water-solubilized cetilistat into the PEG-HG enabled similar improvement.

Conclusion: Intraperitoneal administration of water-solubilized cetilistat prevented severe inflammation and multiple failures associated with severe POPF. The incorporation of water-solubilized cetilistat into the PEG-HG is a promising delivery system for clinical application.

Background: Although animal studies have indicated that the periportal lymphatic system is an important intrahepatic lymphatic route, detailed human studies are scarce. We studied the lymphatic pathways and dynamics around Glisson's capsule in human livers.

Methods: We performed whole-mount immunostaining for the liver using podoplanin and CD-31 to elucidate the lymphatic vessel distribution around the hepatic triad (HT). Next, 5 mL of India ink was injected into the liver parenchyma to observe the lymph fluid dynamics around Glisson's capsule. Lastly, immunohistochemical staining for CCL21, a chemokine important for lymphocyte migration, and its receptor CCR7 was performed to observe the lymphocyte dynamics within Glisson's capsule.

Results: Lymphatic vessels with blind-ended structures were observed around the peripheral HT. These vessels ran longitudinally, forming a network with numerous blind ends around HT. Ink distribution was observed within gaps and capillary lymphatic vessels in Glisson's capsule. These gaps were CCL21-positive, and a concentration gradient was observed toward the capillary lymphatic vessels.

Conclusions: The intrahepatic lymphatic fluid enters the capillary lymphatic vessels via the extravascular pathway, and lymphocyte components enter the capillary lymphatic vessels through the CCR7/CCL21 transport system in the extravascular pathway. This is the first study to elucidate the human intrahepatic periportal lymphatic system.

Background: The long-term effects of cholecystectomy on mortality and cardiovascular disease (CVD) in patients with diabetes have not been evaluated. In the present study, we investigated the longitudinal effects of cholecystectomy on mortality and CVD in a population-based cohort with type 2 diabetes (T2D).

Methods: In total, 2 216 930 national health examination participants with T2D, including 19 258 patients with cholecystectomy, were followed up for a median of 7.9 years. The adjusted hazard ratios (aHRs) were calculated for all-cause mortality and CVD (myocardial infarction or ischemic stroke) in the cholecystectomy group compared with the nonoperative controls.

Results: The cholecystectomy group had a significantly higher risk of mortality than controls (aHR 1.10, 95% confidence interval [CI]: 1.06-1.14), which was more pronounced in younger participants (aHR 1.67 [1.38-2.03], 1.22 [1.13-1.31], and 1.05 [1.00-1.10] for those aged <50, 50-64, and ≥65 years) and participants with less advanced diabetes treatment. The risk of CVD was increased with cholecystectomy only in those aged <50 years (aHR 1.24 [1.01-1.52]).

Conclusions: Cholecystectomy in patients with T2D is associated with an increased risk of all-cause mortality, particularly in younger patients without diabetes medication. Only patients aged <50 years have a higher risk of developing CVD after cholecystectomy.

Background: With the evolving treatment paradigms for pancreatic cancer, there is an increasing need for reliable markers to evaluate the effectiveness of preoperative chemotherapy. Due to the limitations of current indicators, this study aimed to evaluate the prognostic value of metabolic response based on the changes in the maximum standardized uptake value (SUV_max) on fluorine-18-fluorodeoxyglucose positron emission tomography.

Methods: This study included 210 patients with pancreatic cancer who underwent post-chemotherapy curative surgery between 2013 and 2022. Using maximally selected rank statistics for survival, the metabolic response was defined as follows: metabolic responder (%ΔSUV_max >75%), metabolic stable disease (15%-75%), and metabolic non-responder (≤15%).

Results: Among patients, 15.7%, 66.7%, and 11.6% were categorized into the metabolic responder, metabolic stable disease, and metabolic non-responder groups. The metabolic responder group (83.0 months) had longer median overall survival than the metabolic stable disease (51.0 months, p = .013) and metabolic non-responder (32.0 months, p = .002) groups. In addition, being metabolic responders (vs. non-responders) was an independent predictor of low recurrence rates (hazard ratio [95% confidence interval]: 0.46 [0.23-0.91]; p = .026) and achieving pathologic complete response (odds ratio [95% confidence interval]: 13.39 [1.61-300.77]; p = .035).

Conclusions: Metabolic response during preoperative chemotherapy has predictive power for post-resection prognosis and residual tumor status.

Purpose: This study aimed to identify the significant factors associated with liver transplant-free survival time in Japanese patients with large-duct primary sclerosing cholangitis (PSC) by evaluating the association between various parameters and clinical scores at PSC diagnosis.

Methods: This single-center retrospective study investigated factors influencing liver transplant-free survival in Japanese large-duct PSC patients. Univariate analysis using log-rank tests identified significant clinical parameters and scoring systems, which were further analyzed with multivariate Cox proportional hazards models to determine independent predictors of liver transplant-free survival.

Results: A total of 77 patients with large-duct PSC were included. The univariate analysis identified that age (p < .001), serum albumin level (p = .024), Child-Pugh score (p = .0012), albumin-bilirubin score (p = .0083), Amsterdam-Oxford PSC score (p < .001), and revised Mayo risk score (p < .001) were significant predictors of liver transplant-free survival time. However, the multivariate analysis revealed that only the Amsterdam-Oxford PSC score remained as an independent factor significantly associated with liver transplant-free survival time (hazard ratio: 12.90, 95% confidence interval: 2.78-59.81, p = .0011).

Conclusions: This study underscored the importance of utilizing the Amsterdam-Oxford PSC score in clinical practice to assess disease prognosis and guide patient management in Japanese patients with large-duct PSC.

Background: The prognosis for unresectable perihilar cholangiocarcinoma (phCCA) is extremely poor. Liver transplantation in combination with neoadjuvant chemoradiation therapy has become the treatment of choice for unresectable phCCA in the USA. In 2018, we launched a prospective study to evaluate the safety and efficacy of living donor liver transplantation (LDLT) for unresectable phCCA.

Methods: A total of 10 patients were enrolled in this study between 2018 and 2024. Finally, five patients with unresectable phCCA underwent LDLT after neoadjuvant chemotherapy, radiation, and staging laparotomy, while the other five patients dropped out of the protocol.

Results: The median follow-up period was 23.7 months. The overall survival rate for the five patients who underwent LDLT was 100% after one year. Hepatic artery thrombosis and delayed gastric emptying occurred in two and three cases, respectively. The histological efficacy of preoperative treatment was grade IIb and III, according to the Evans classification, in all five patients. All surgical margins and dissected lymph nodes were negative. Four patients were alive with no evidence of disease recurrence while one patient had recurrence 10 months after LDLT.

Conclusions: LDLT is feasible and may be a last-resort treatment option for unresectable phCCA, although the long-term outcomes need to be carefully monitored.

Clinical trial register and clinical registration number: The UMIN registration number for this study is 000033348.

Background: Nuclear expression of CTNNB1 is occasionally negative in solid-pseudopapillary neoplasm (SPN) of the pancreas, leading to a missed diagnosis. In the present study, we aimed to investigate the clinical significance of CTNNB1 mutation detection for diagnosing SPN and explore the difference in clinicopathological characteristics at different ages and sex.

Methods: Patients who underwent surgery for a pathologically confirmed SPN in our institution between 2011 and 2020 were collected. Their clinicopathological data were analyzed.

Results: The median age of the 179 patients was 31 years (6-64 years), including 34 pediatric patients (19.0%), and 32 patients were male (17.9%). We detected point mutations in exon 3 of CTNNB1 in 74.3% (133/179) of SPNs by Sanger sequencing. The main mutation sites were D32, S33, S37, G34 and T41. In the three SPNs without nuclear expression of CTNNB1, Sanger sequencing showed point mutations of CTNNB1. NGS did not detect any consistent mutation except CTNNB1 in the three cases. The tumor size, Ki-67 index, and the negative rates of CTNNB1 nuclear expression and synaptophysin expression in the pediatric group were higher than those in other groups (p < .05).

Conclusions: For atypical cases, testing for CTNNB1 mutations can help in the accurate diagnosis of SPN. Compared with adult patients, pediatrics with SPN may be more prone to recurrence, and their immunohistochemical phenotype is more complex, requiring additional care in the diagnosis and postoperative follow-up.

Background: A complete dissection around the superior mesenteric artery (SMA) with artery-first concept is crucial during pancreaticoduodenectomy for periampullary cancers. The left-posterior (LP) approach to the SMA may be effective during robot-assisted pancreaticoduodenectomy (RPD), but data on its technical feasibility and clinical outcomes are limited.

Methods: We retrospectively reviewed 83 RPD patients utilizing the LP approach, dividing them into early (n = 42) and late (n = 41) groups to assess procedural maturity. The LP approach was initiated at the first phase of resection to achieve circumferential SMA dissection from the left and posterior aspect and early vascular control through ligation of the inferior pancreaticoduodenal artery (IPDA). Postoperative short-term outcomes were compared between the two groups.

Results: The late group demonstrated significantly shorter operative times (518 vs. 626 min; p < .01) and higher rates of IPDA ligation (90% vs. 71%; p = .03). The median blood loss in the late group was 50 mL (65 mL in the early group; p = .39). Lymph node retrieval number was 17 in both (p = .81), and R0 resection was achieved in all late group cases (96% in the early group; p = .35).

Conclusions: With experience from approximately 80 cases, the LP approach for RPD has enabled precise SMA dissection and early vascular control. A stable and super-magnified caudal view provided by robotic surgery is particularly advantageous for this approach.