Hepatobiliary & Pancreatic Diseases International最新文献

Background: The analysis and prediction of pancreaticobiliary reflux (PBR) play a crucial role in planning surgical interventions for hepato-biliary-pancreatic diseases, considering the uncertain mechanism behind it. However, current practices are limited by fragmented clinical observations, making it challenging to visualize the complex phenomenon in the pancreaticobiliary junction (PBJ) through imaging and radiography experiments. This study aimed to comprehensively describe the retrograde flow characteristics in various PBR scenarios and assess the factors leading to PBR using simulations based on idealized geometry and boundary conditions.

Methods: By Cadence Pointwise, we developed a computational fluid dynamics (CFD) model using an idealized PBJ system. Standard parameters such as pressure and viscosity were applied, along with typical assumptions relevant to fluid dynamic modeling. Subsequently, based on the aforementioned basic idealized model, we analyzed 8 hypothetical PBR conditions, covering a range of high (shorter) and low (longer) values or different positions for each specific parameter, at a representative stage of a peristaltic propagation cycle of the Oddi's sphincter.

Results: We modeled a two-dimensional PBJ with the propagation of a peristaltic wave. These findings demonstrated that the shortened septum, the extended ampulla, the increased wavelength and enhanced amplitude of the Oddi's sphincterial peristalsis, the widened diameter difference and the increased pressure difference between the common bile duct (CBD) and the main pancreatic duct (MPD), as well as the gravitational effect (position), strongly impacted PBR, while the viscosity of bile and pancreatic juice had a weaker influence. Additionally, an inequality incorporating these risk factors was developed for the evaluation of whether reflux occurs.

Conclusions: Numerical simulation can be used to describe the reflux flow field, offering the possibility to visualize and analyze PBR, which has the potential to significantly revolutionize the understanding of PBR and improve clinical decision-making. Future work should focus on bridging the gap between CFD and clinical practice.

Background: Immune checkpoint inhibitors (ICIs) have transformed systemic therapy for hepatocellular carcinoma (HCC), leading to growing interest in their integration into liver transplantation (LT) protocols. Their use in the neoadjuvant and adjuvant settings aims to expand transplant eligibility, improve downstaging and/or bridging options, and reduce tumor recurrence. However, the balance between oncologic benefit and immunologic risk, particularly graft rejection, remains a critical challenge.

Data sources: A literature search was conducted on PubMed for articles published up to August 2025. The search keywords included "hepatocellular carcinoma", "liver transplantation", "immune checkpoint inhibitor", "immunotherapy", "neoadjuvant", "adjuvant", "bridging", "downstaging", "immunosuppression", and "washout". Relevant clinical trials, cohort studies, meta-analyses, and case series were included.

Results: Early-phase trials and multicenter cohorts show that pre-LT ICIs achieved downstaging in ∼75%-82%, with radiologic responses up to 94% and pathologic responses 35%-88%. One- and three-year survival after ICI bridging reached ∼95% and 70%-80%, while post-LT survival remained above 85% in 3 years. Rejection risk is substantial: 16%-28% across large series, highest with washouts < 90 days, but largely mitigated with longer intervals. An individual patient data meta-analysis confirmed a 26.4% rejection rate and highlighted washout duration as the key determinant. Adjuvant ICI use post-LT remains limited to case reports, with rejection in ∼25% and mortality in 10%-12%. Novel strategies such as natural killer cell therapy and atezolizumab/bevacizumab combinations show early promise, with recurrence-free survival up to 82% and post-LT survival near 90% in 3 years.

Conclusions: ICIs represent a powerful tool to extend transplant eligibility and improve outcomes in HCC, but their role before and after LT is not yet standardized. Current evidence highlights the importance of patient selection, timing of therapy, and careful management of immunosuppression. Until prospective randomized trials define optimal strategies, ICI integration into transplant practice should remain individualized, multidisciplinary, and confined to experienced transplant centers.

Organ transplantation faces a persistent mismatch between the number of available donor organs and the growing demand for transplants. Conventional preservation techniques primarily focus on delaying deterioration rather than actively restoring organ function, especially at the mitochondrial level, a key site of injury during ischemia-reperfusion. Mitochondrial transplantation, a novel regenerative strategy, offers a compelling solution by delivering viable mitochondria to damaged tissues ex vivo, particularly during machine perfusion. This approach not only improves bioenergetic recovery and reduces oxidative stress but also reconditions marginal organs to meet transplantation standards. Preclinical studies across heart, lung, and kidney models demonstrate the potential of mitochondrial transplantation to bridge preservation and repair, expanding the transplantable organ pool. This review highlights mitochondrial transplantation as a transformative intervention poised to reshape the future of organ preservation and transplant viability.