Hepatobiliary & Pancreatic Diseases International最新文献

Background: Currently, there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreato-biliary surgery subsequent to experiencing breakthrough infection of coronavirus disease 2019 (COVID-19). This study aimed to find factors predicting postoperative complications and construct an innovative nomogram to pinpoint patients who were susceptible to developing severe complications following breakthrough infection of COVID-19 after undergoing elective hepato-pancreato-biliary surgery.

Methods: This multicenter retrospective cohort study included consecutive patients who underwent elective hepato-pancreato-biliary surgeries between January 3 and April 1, 2023 from four hospitals in China. All of these patients had experienced breakthrough infection of COVID-19 prior to their surgeries. Additionally, two groups of patients without preoperative COVID-19 infection were included as comparative controls. Surgical complications were meticulously documented and evaluated using the comprehensive complication index (CCI), which ranged from 0 (uneventful course) to 100 (death). A CCI value of 20.9 was identified as the threshold for defining severe complications.

Results: Among 2636 patients who were included in this study, 873 were included in the reference group I, 941 in the reference group II, 389 in the internal cohort, and 433 in the external validation cohort. Multivariate logistic regression analysis revealed that completing a full course of COVID-19 vaccination > 6 months before surgery, undergoing surgery within 4 weeks of diagnosis of COVID-19 breakthrough infection, operation duration of 4 h or longer, cancer-related surgery, and major surgical procedures were significantly linked to a CCI > 20.9. A nomogram model was constructed utilizing CCI > 20.9 in the training cohort [area under the curve (AUC): 0.919, 95% confidence interval (CI): 0.881-0.957], the internal validation cohort (AUC: 0.910, 95% CI: 0.847-0.973), and the external validation cohort (AUC: 0.841, 95% CI: 0.799-0.883). The calibration curve for the probability of CCI > 20.9 demonstrated good agreement between the predictions made by the nomogram and the actual observations.

Conclusions: The developed model holds significant potential in aiding clinicians with clinical decision-making and risk stratification for patients who have experienced breakthrough infection of COVID-19 prior to undergoing elective hepato-pancreato-biliary surgery.

Liver transplantation represents a complex surgical procedure and serves as a curative treatment for patients presenting an acute or chronic end-stage liver disease, or carefully selected liver malignancy. A significant gap still exists between the number of available donor organs and potential recipients. The use of an otherwise-wasted resected liver lobe from patients with benign liver tumors is a new, albeit small, option to alleviate the allograft shortage. This review provides evidence that resected liver lobes may be used successfully in liver transplantation.

Background: Cisplatin triggers Gasdermin E (GSDME) cleavage, causing membrane bubble formation, content release, and inflammation. Caspase-3 activation initiates GSDME cleavage, and thus inhibiting this pathway mitigates cisplatin-induced pyroptosis in hepatocytes. This study aimed to delve into how cisplatin induces liver injury via pyroptosis.

Methods: For animal experiments, C57BL/6J mice were divided into three groups: control, liver injury model group, and Ac-DMLD-CMK (caspase-3 inhibitor) intervention group. The liver histology was evaluated by hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and TUNEL staining. The mRNA and protein levels were detected by real-time polymerase chain reaction (PCR) and Western blot analysis. For in vitro experiments, HL-7702 cells were treated with cisplatin or GSDME siRNA. Cell pyroptosis was determined via cellular morphology, cytotoxicity and viability detection, flow cytometric assay, and Western blot detection for the expression of pyroptosis-related proteins.

Results: Cisplatin-induced distinct liver morphological changes, hepatocellular injury, and inflammation in mice, along with elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and increased pro-inflammatory cytokine expression. Heightened macrophage infiltration and hepatocellular death indicated cisplatin-induced hepatotoxicity. Cisplatin upregulated GSDME activation, along with Bax-mediated caspase-3 cleavage both in vivo and in vitro, implicating caspase-3/GSDME-dependent pyroptosis in liver injury. Treatment with Ac-DMLD-CMK ameliorated cisplatin-induced liver injury, reducing hepatocellular lesions, serum ALT and AST levels, cytokine expression, macrophage infiltration, and hepatocyte death. Ac-DMLD-CMK also attenuated GSDME-dependent pyroptosis post-cisplatin induction, as evidenced by decreased GSDME expression, Bax upregulation, and cleaved caspase-3 activation. For HL-7702 cells, GSDME siRNA transfection reduced GSDME expression, attenuated typical signs of cisplatin-induced pyroptosis, partially restored cell viability, and significantly inhibited cytotoxicity and a decrease in the proportion of propidium iodide-positive cells, indicating protection against cisplatin-induced hepatocyte pyroptosis.

Conclusion: Our study underscores the role of the caspase-3/GSDME signaling pathway in mediating cisplatin-induced hepatotoxicity, particularly in cases of excessive or cumulative cisplatin exposure. These findings suggest that targeting GSDME could represent a promising therapeutic approach to mitigate cisplatin-induced liver damage.

Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality. Liver resection (LR) is a curative treatment for early-stage HCC, but the prognosis of HCC patients after LR is unsatisfactory because of tumor recurrence. Prognostic prediction models with great performance are urgently needed. The present study aimed to establish a novel prognostic nomogram to predict tumor recurrence in HCC patients after LR.

Methods: We retrospectively analyzed 726 HCC patients who underwent LR between October 2011 and December 2016. Patients were randomly divided into the training cohort (n = 508) and the testing cohort (n = 218). The protein expression of 14 biomarkers in tumor tissues was assessed by immunohistochemistry. The nomogram predicting recurrence-free survival (RFS) was established by a multivariate Cox regression analysis model and was evaluated by calibration curves, Kaplan-Meier survival curves, time-dependent areas under the receiver operating characteristic (ROC) curves (AUCs), and decision curve analyses in both the training and testing cohorts.

Results: Alpha-fetoprotein [hazard ratio (HR) = 1.013, P = 0.002], portal vein tumor thrombosis (HR = 1.833, P < 0.001), ascites (HR = 2.024, P = 0.014), tumor diameter (HR = 1.075, P < 0.001), E-cadherin (HR = 0.859, P = 0.011), EMA (HR = 1.196, P = 0.022), and PCNA (HR = 1.174, P = 0.031) immunohistochemistry scores were found to be independent factors for RFS. The 1-year and 3-year AUCs of the nomogram for RFS were 0.813 and 0.739, respectively. The patients were divided into the high-risk group and the low-risk group by median value which was generated from the nomogram, and Kaplan-Meier analysis revealed that the high-risk group had a shorter RFS than the low-risk group in both the training (P < 0.001) and testing cohorts (P < 0.001).

Conclusions: Our newly developed nomogram integrated clinicopathological data and key gene expression data, and was verified to have high accuracy in predicting the RFS of HCC patients after LR. This model could be used for early identification of patients at high-risk of postoperative recurrence.

Background: Dorsal approach is the potentially effective strategy for minimally invasive liver resection. This study aimed to compare the outcomes between robot-assisted and laparoscopic hemihepatectomy through dorsal approach.

Methods: We compared the patients who underwent robot-assisted hemihepatectomy (Rob-HH) and who had laparoscopic hemihepatectomy (Lap-HH) through dorsal approach between January 2020 and December 2022. A 1:1 propensity score-matching (PSM) analysis was performed to minimize bias and confounding factors.

Results: Ninety-six patients were included, 41 with Rob-HH and 55 with Lap-HH. Among them, 58 underwent left hemihepatectomy (LHH) and 38 underwent right hemihepatectomy (RHH). Compared with Lap-HH group, patients with Rob-HH had less estimated blood loss (median: 100.0 vs. 300.0 mL, P = 0.016), lower blood transfusion rates (4.9% vs. 29.1%, P= 0.003) and postoperative complication rates (26.8% vs. 54.5%, P = 0.016). These significant differences consistently existed after PSM and in the LHH subgroups. Furthermore, robot-assisted LHH was associated with decreased Pringle duration (45 vs. 60 min, P = 0.047). RHH subgroup analysis showed that compared with Lap-RHH, Rob-RHH was associated with less estimated blood loss (200 vs. 400 mL, P = 0.013). No significant differences were found in other perioperative outcomes among pre- and post-PSM cohorts, such as Pringle duration, operative time, and hospital stay.

Conclusions: The dorsal approach was a safe and feasible strategy for hemi-hepatectomy with favorable outcomes under robot-assisted system in reducing intraoperative blood loss, transfusion, and postoperative complications.

With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, China that have enabled preoperative prognostication for judicious patient selection, downstaging therapy to definitive treatment, and postoperative therapies that have provided a growing role for liver transplantation in patients with more advanced hepatocellular carcinoma.