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Aim: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living‐donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients. Method: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT. Results: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles. Conclusion: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT. [ABSTRACT FROM AUTHOR]

Aim: There is limited evidence regarding the feasibility of living‐donor liver transplantation (LDLT) for patients aged over 70. The aims of this study were to assess postoperative outcomes in elderly recipients and to ascertain the potential feasibility and acceptability of LDLT. Methods: Data were collected from 762 recipients, including 26 in the elderly group (aged ≥70) and 736 in the younger group (aged <70), and reviewed even by propensity score matching (PSM). Results: No significant differences were observed in the frequency of postoperative complications between the two groups. Additionally, both groups exhibited a comparable 30‐day mortality rate after LDLT (3.9% in both) and similar hospital stays (36 days vs. 40 days). The 1‐, 3‐, and 5‐year graft survival rates in the elderly group were 92.0%, which was comparable to those in the younger group (p = 0.517), as confirmed by PSM. Notably, all donors for elderly patients were the children of the recipients, with an average age of 41.6 years, and grafts from donors aged ≥50 years were not utilized, signifying the use of high‐quality grafts. Our inclusion criterion for elderly recipients was strictly defined as an ECOG‐PS score of 0–2, which played a pivotal role in achieving favorable postoperative outcomes. Conclusion: LDLT can be performed safely for elderly patients aged 70 years or older, provided they have a preserved PS and receive high‐quality grafts from younger donors, inevitably all children of elderly recipients. This approach yields acceptable long‐term outcomes. Consequently, age alone should not serve as an absolute contraindication for LDLT. [ABSTRACT FROM AUTHOR]

Aim: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first‐line systemic therapy for unresectable hepatocellular carcinoma (u‐HCC). Methods: We enrolled 114 patients with u‐HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). Results: Twenty‐three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV‐eosinophil‐high group, which had better responses than the ATZ/BEV‐eosinophil‐low group (P = 0.0090). Kaplan–Meier curves revealed a trend toward significantly better progression‐free survival (PFS) in the ATZ/BEV‐eosinophil‐high group than the ATZ/BEV‐eosinophil‐low group (the median PFS: 4.7 months in the ATZ/BEV‐eosinophil‐low group vs 12.6 months in the ATZ/BEV‐eosinophil‐high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02–4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV‐eosinophil‐high group (P = 0.0285). The outcomes did not significantly differ between the LEN‐eosinophil‐high group and the LEN‐eosinophil‐low group. Conclusion: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u‐HCC and was associated with the incidence of AEs (≥ grade 3). [ABSTRACT FROM AUTHOR]

TP53‐induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron‐dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty‐two (24.4%) patients were categorized into TIGAR‐high and ‐low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease‐free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04–3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03–4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony‐forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD‐induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor‐suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the prognostic value of the preoperative albumin–lymphocyte–platelet–C‐reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2‐related factor 2 (p‐Nrf2) levels. Methods: Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross‐validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence‐free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p‐Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC. Results: A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha‐fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence‐free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p‐Nrf2 expression in HCC tumor cells. Conclusions: We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection. [ABSTRACT FROM AUTHOR]

Background: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)‐positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT). Methods: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin‐2 (Ang‐2) in VETC‐positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions. Results: Forty‐three of the 214 patients (20.1%) were VETC‐positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang‐2 expression was significantly higher in the mTOR‐positive than in the mTOR‐negative group (p = 0.037). Thirty‐four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC‐positive; five of these six patients also had VETC‐positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC‐positive lesions (p = 0.0018). Conclusions: We showed that mTOR expression was higher in the VETC‐positive primary and recurrent lesions than in the VETC‐negative ones. [ABSTRACT FROM AUTHOR]