To determine if preoperative sarcopenia and prognostic nutritional index (PNI) could accurately predict the postoperative outcomes of patients with hepatocellular carcinoma (HCC) undergoing initial hepatectomy. Three hundred three patients who underwent curative hepatectomy for HCC between January 2010 and August 2021 were enrolled and their data were retrospectively analyzed. Sarcopenia was determined from computed tomography images obtained 3 weeks prior to surgery, and PNI was calculated from preoperative albumin and whole lymphocyte count data in receiver operating characteristic (ROC) curve analysis, with a cutoff value of 46.2 to categorize high and low groups. One hundred six (35%) patients had sarcopenia prior to surgery. Kaplan-Meier analysis revealed that sarcopenia and low PNI were associated with significantly worse overall survival (OS) compared with no sarcopenia and high PNI, respectively (P = 0.023 and P = 0.035, respectively). In addition, patients with sarcopenia had worse OS than those without sarcopenia in the high and low PNI groups (P = 0.058 and P = 0.038, respectively). Sarcopenia (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.00-2.76; P = 0.048) and PNI ≤46.2 (HR 1.96; 95% CI 1.17-3.27; P = 0.011) were independent prognostic factors on multivariate analysis, and combined sarcopenia and PNI had a higher AUC value (AUC = 0.722, P < 0.001) than either one alone in ROC analysis. Combined sarcopenia and PNI as a prognostic marker can better predict the postoperative prognostic outcomes of HCC patients following hepatectomy than either sarcopenia or PNI alone.

Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa‐2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine‐resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti‐apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1–heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis‐related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.

Introduction: Cirrhosis is deemed to be a contributing factor to the postoperative recurrence of hepatocellular carcinoma (HCC); however, the precise impact of liver fibrosis on both cancer-specific prognoses remains unclear. This investigation sought to elucidate the effect of liver fibrosis severity on the cancer-specific prognosis. Methods: A total of 524 consecutive patients were included. Recurrence-free survival (RFS) and disease-specific survival (DSS) were compared according to fibrosis stage. Moreover, postoperative outcomes were subjected to analysis in cohorts of patients with F0 and F1–3, as well as in those with F1–3 and F4, who were carefully matched for background factors. Results: The 5-year RFS exhibited a significantly worse outcome in the F4 group compared to other stages of fibrosis: 5-year RFS – F0 (46.6%), F1–3 (33.1%), and F4 (23.5%), p = 0.03 (F0 vs. F1–3) and p < 0.01 (F1–3 vs. F4). Additionally, the 5-year DSS also presented a significantly worse prognosis in the F4 group: 5-year DSS – F0 (82.9%), F1–3 (73.6%), and F4 (57.4%), p = 0.04 (F0 vs. F1–3) and p < 0.01 (F1–3 vs. F4). In multivariate analysis, fibrosis 1, 2, 3, and 4 stage (compared with F0) (HR: 1.70, 1.81, 1.89, and 3.99, 95% confidence interval: 1.10–1.99, 1.39–2.22, 1.41–2.55, and 2.25–5.01, p = 0.022, p = 0.008, p < 0.001, and p < 0.001, respectively) was independent risk factor for RFS. After matched analysis, both RFS and DSS exhibited significantly worse prognoses in the presence of more advanced fibrosis. There was a significantly higher incidence of multiple recurrences in the F4 group than the F1–3 group, and a number of recurrences were observed both in the same hepatic segment as the resected side and in the contralateral lobe in F4 group. Discussion/Conclusion: The hazard and recurrence pattern of HCC signifies that the prognosis could potentially be poor, as the hepatic fibrosis likely owing to a higher hepatocarcinogenic potential, even in the absence of progression to cirrhotic condition. The risk of de novo recurrence may also increase with the progression of this fibrosis.

Functional assessment of the future liver remnant (FLR) after major hepatectomy is essential but often difficult in patients with biliary malignancy, owing to obstructive jaundice and portal vein embolization. This study evaluated whether a novel index using gadoxetate disodium-enhanced MRI (EOB-MRI) could predict posthepatectomy liver failure (PHLF) after major hepatectomy for biliary malignancy. The remnant hepatocellular uptake index (rHUI) was calculated in patients undergoing EOB-MRI before major hepatectomy for biliary malignancy. Receiver operating characteristic (ROC) curve analyses were used to evaluate the accuracy of rHUI for predicting PHLF grade B or C, according to International Study Group of Liver Surgery criteria. Multivariable logistic regression analyses comprised stepwise selection of parameters, including rHUI and other conventional indices. This study included 67 patients. The rHUI accurately predicted PHLF (area under the curve (AUC) 0.896). A cut-off value for rHUI of less than 0.410 predicted all patients who developed grade B or C PHLF. In multivariable analysis, only rHUI was an independent risk factor for grade B or C PHLF (odds ratio 2.0 × 10³, 95 per cent c.i. 19.6 to 3.8 × 10⁷; P < 0.001). In patients who underwent preoperative portal vein embolization, rHUI accurately predicted PHLF (AUC 0.885), whereas other conventional indices, such as the plasma disappearance rate of indocyanine green of the FLR and FLR volume, did not. The rHUI is potentially a useful predictor of PHLF after major hepatectomy for biliary malignancy.