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Background/aim: Sarcopenia is diagnosed based on grip strength and skeletal muscle mass. Although decreased skeletal muscle mass has been reported to be associated with poor outcomes after hepatectomy, a few studies have included data on grip strength in hepatectomy candidates. This multicenter study investigated the clinical factors and postoperative complications associated with sarcopenia by assessing the grip strength and skeletal muscle mass in patients undergoing hepatectomy for hepatocellular carcinoma (HCC)., Patients and Methods: Data from patients who underwent hepatectomy for HCC between January 2020 and March 2022 were retrospectively collected from multi-institutional databases. Sarcopenia was defined as reduced grip strength and skeletal muscle mass. The patients were categorized into the sarcopenia and non-sarcopenia groups, and baseline characteristics and short term outcomes were compared between the two groups., Results: Overall, 253 patients were included, among which 36 (14.2%) had sarcopenia. The sarcopenia group was significantly associated with older age, low body mass index, comorbid heart or chronic pulmonary disease, cerebrovascular accident history, and overall and major postoperative complications compared to the non-sarcopenia group. Among major postoperative complications [Clavien-Dindo classification (CDC) ≥III], the incidence of bile leakage and intra-abdominal abscess were higher in the sarcopenia group than in the non-sarcopenia group. Multivariate analysis revealed that sarcopenia was an independent risk factor for overall and major postoperative complications (CDC ≥III)., Conclusion: Sarcopenia, defined by grip strength and skeletal muscle mass, is a predictor of overall and major complications after hepatectomy for HCC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion., Methods: A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests., Results: LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy., Conclusion: LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Purpose: Factors affecting the prognosis of repeat hepatectomy for transplantable hepatocellular carcinoma (HCC) recurrence after hepatectomy remain unclear. We aimed to clarify the prognostic factors for transplantable hepatocellular carcinoma recurrence after hepatectomy., Methods: We included 1758 primary and 486 repeat hepatectomies out of 2244 for HCC performed between 2006 and 2017 using the Hiroshima Study Group for Clinical Oncology and Surgery database. We first compared survival rates of primary and repeat hepatectomy patients. Subsequently, prognostic factors were analyzed in patients who underwent a repeat hepatectomy for transplantable hepatocellular carcinoma recurrence after hepatectomy (defined as age < 70 years at the time of recurrence and recurrent tumor morphology that meets the Milan criteria)., Results: The 5-year overall survival rate (OS) after repeat hepatectomy was 63.2%, while the 5-year recurrence-free survival rate (RFS) was 23.7%. RFS demonstrated significant inferiority in the repeat hepatectomy group than in the primary hepatectomy group; however, OS did not present a notable difference between the two cohorts. In the transplantable recurrence group, mALBI grade 2b, max tumor size > 20 mm, and multiple tumors were independent prognostic risk factors for overall survival. Patients with two or more risk factors had a significantly lower survival rate (only 30.6% at 5 years) compared to those with one or fewer risk factors (81.8% at 5 years)., Conclusions: We identified the risk factors involved in post-hepatectomy survival for patients with transplantable recurrence after hepatectomy. The results are a potential indicator of whether salvage liver transplantation should be considered during repeat hepatectomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The importance of a nutrition scoring system, including the geriatric nutritional risk index (GNRI), was reported as an objective tool widely used to assess nutritional status in patients with inflammatory disease, chronic heart failure, and chronic liver disease. However, studies on the relationship between GNRI and the prognosis in patients who have undergone initial hepatectomy have been limited. Thus, we conducted a multi-institutional cohort study to clarify the relationship between GNRI and long-term outcomes for hepatocellular carcinoma (HCC) patients after such a procedure., Methods: Data from 1,494 patients who underwent initial hepatectomy for HCC between 2009 and 2018 was retrospectively collected from a multi-institutional database. The patients were divided into two groups according to GNRI grade (cutoff: 92), and their clinicopathological characteristics and long-term results were compared., Results: Of the 1,494 patients, the low-risk group (≥ 92; N = 1,270) was defined as having a normal nutritional status. Meanwhile, low GNRI (< 92; N = 224) were divided into malnutrition as the high-risk group. Multivariate analysis identified seven prognostic factors of poor overall survival (higher tumor markers; α-fetoprotein (AFP) and des-γ-carboxy protein [DCP], higher ICG-R15 levels, larger tumor size, multiple tumors, vascular invasion, and lower GNRI and eight prognostic factors of high recurrence (HCV antibody positive, higher ICG-R15 levels, higher tumor markers such as AFP and DCP, greater bleeding, multiple tumors, vascular invasion, and lower GNRI)., Conclusions: In patients with HCC, preoperative GNRI predicts poorer overall survival and high recurrence., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy., Methods: This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test., Results: Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( P < .001), and preoperative hemoglobin level ( P = .007) were related to HCC development, and the presence of HCC history ( P = .002) and preoperative hemoglobin level ( P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011)., Discussion: The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

Background/purpose: The incidence of bile leakage after liver resection for hepatocellular carcinoma (HCC) remains a cause for concern. There are limited reports on the impacts of postoperative bile leakage on long-term clinical outcomes. This study aims to evaluate the effects of postoperative bile leakage on recurrence-free survival (RFS) and overall survival (OS)., Methods: A total of 1,178 patients who underwent curative liver resection for HCC between 1986 and 2012 were included in the present study. Postoperative bile leakage was defined using the International Study Group of Liver Surgery definition, and the primary end points of the study were OS and RFS at 5 years., Results: Forty-three (3.7%) patients had bile leakage following liver resection. The median follow-up was 5 years. A follow-up analysis revealed that patients with bile leakage had poor 5-year rates of OS (41.0% vs 56.4%, P = .013) and RFS (14.6% vs 28.7%, P < .001). Additionally, bile leakage was an independent factor for both OS [hazard ratio (HR) 1.559, P = .022] and RFS (HR 1.517, P = .024). Furthermore, bile leakage was the only factor affecting prognosis among postoperative complications., Conclusions: Postoperative bile leakage worsens long-term clinical outcomes following liver resection in HCC patients., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: This study examined whether single nucleotide polymorphism (SNP) in programmed cell death protein (PD)-1 is related to the postoperative prognosis of patients with hepatocellular carcinoma (HCC). The immune checkpoint protein PD-1 is an important inhibitor of T cell responses. SNP in the promoter region of PD-1 -606 G/A has been reported to result in high activation and expression of PD-1 associated with cancer risk., Materials and Methods: We analyzed 321 patients with HCC who underwent hepatectomy between 2010 and 2015. PD-1 SNP was analyzed by polymerase chain reaction, and the prognosis after surgical treatment of patients with HCC was analyzed., Results: The PD-1 SNP statuses were as follows: 90 AA (28.1%), 163 GA (50.8%), 68 GG (21.2%). The baseline parameters did not statistically differ between the three groups. The overall survival (OS) of patients with the GG genotype was significantly lower than that of those with the other genotypes (P = 0.031). The GG genotype was an independent risk factor for OS (P = 0.009; HR 2.201). There was no significant difference between the GG genotype and other genotypes in recurrent-free survival. The extrahepatic recurrence (EHR) rate of those with the GG genotype was significantly higher than that of those with the other genotypes (P = 0.036). The GG genotype was an independent risk factor for EHR (P = 0.008; HR 2.037)., Conclusions: The PD-1 SNP GG genotype is associated with poor survival and increased EHR in HCC. Furthermore, the GG genotype is an independent predictive factor for OS and EHR., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

The utility of glypican-3 (GPC3) expression for the detection of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) patients has not been elucidated. The aim of this study was to identify associations between the presence of GPC3-positive CTCs and clinicopathological factors of these patients, furthermore, to evaluate whether CTC can predict microscopic portal vein invasion (mPVI). This study was done on 85 patients who underwent hepatectomy as the first-line treatment and whose preoperative imaging showed no evidence of macroscopic PVI and distant metastases. Peripheral blood was collected from all patients immediately before surgery. Cells were purified initially by density gradient centrifugation followed by immunomagnetic positive enrichment based upon the expression of GPC3. The numbers of CTCs contained in the enriched samples were enumerated via flow cytometry. Protocol validation using HepG2 cells spiked into 8.0 mL of blood from a healthy volunteer indicated that we were able to recover 12.1% of the tumor cells. A median number of 3 CTCs (range: 0-27) was detected in the 8.0 mL of peripheral blood of the 85 analyzed HCC patients. Thirty-three patients had CTCs ≥5, and these patients had a higher incidence of mPVI (p < 0.001), a lower disease-free survival (p = 0.015), and a lower overall survival (p = 0.047) than those with CTCs <5. Multivariate analysis identified CTCs ≥5 as an independent predictor of mPVI (p < 0.001). In conclusion, preoperative GPC3-positive CTCs ≥5 was a risk factor of mPVI and poor prognosis, and therefore may be a useful biomarker for HCC patient outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Bile leakage is a major cause of morbidity after hepatectomy. This study aimed to identify the predictive factors for bile leakage after hepatectomy., Materials and Methods: Between January 2011 and December 2016, 556 patients underwent a liver resection for hepatocellular carcinoma with curative intent, and were enrolled to participate in this study. The incidence of postoperative bile leakage (POBL) was determined and the predictive factors for POBL were identified using univariate and multivariate analysis., Results: POBLs occurred in 28 patients (5.0%). The multivariate analysis identified a history of stereotactic body radiotherapy, a body mass index <20 kg/m 2 , Child-Pugh class B cirrhosis, a central hepatectomy, and an operation time ≥375 min as risk factors that were associated with POBL. When the study cohort was grouped according to the number of the predictive factors present, the incidence of POBL increased as the number of the extant independent predictive factors increased. The POBL rate was 45.0% in patients with ≥3 predictive factors., Conclusion: We determined that POBL was associated with operative mortality and identified five independent predictive factors associated with POBL. Risk stratification using these predictive factors may be useful for identifying patients at a high risk of POBL., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: Although obesity is associated with hepatocellular carcinoma (HCC) development, its impact on the surgical outcomes of patients with hepatitis B virus (HBV)-and hepatitis C virus (HCV)-related HCC remains unclear., Methods: We retrospectively analyzed 714 patients with HCC who underwent curative hepatectomy. Among them, the HBV-related HCC group (n = 125) and HCV-related HCC group (n = 426) were subdivided according to the presence of body mass index (BMI) ≥ 25 kg/m 2 . The surgical outcomes were compared., Results: The 5-year overall survival rate after hepatectomy in the HBV-related HCC group was significantly better than that in the HCV-related HCC group. The 5-year overall survival rates of the HBV-related HCC with and without BMI ≥ 25 kg/m 2 groups were 65 and 85%, respectively. The 5-year overall survival rates in the HCV-related HCC with and without BMI ≥ 25 kg/m 2 groups were 75 and 65%, respectively. The HBV-related HCC with BMI ≥ 25 kg/m 2 groups had a significantly worse prognosis than the HBV-related HCC without BMI ≥ 25 kg/m 2 groups, while the HCV-related HCC with BMI ≥ 25 kg/m 2 groups had a significantly better prognosis than the HCV-related HCC without BMI ≥ 25 kg/m 2 groups. Multivariate analysis revealed that BMI ≥ 25 kg/m 2 was the positive and negative prognostic factor for the surgical outcomes of patients with HBV- and HCV-related HCC, respectively., Conclusions: BMI ≥ 25 kg/m 2 negatively affected the surgical outcomes of patients with HBV-related HCC and positively affected those of patients with HCV-related HCC.

Background: This study evaluates the survival benefit and safety of hepatectomy after down-staging by 3-dimensional conformal radiation therapy (3D-CRT) for major portal vein tumor thrombus (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC)., Methods: Fifty-two patients with unresectable advanced HCC treated with HAIC combined with 3D-CRT for PVTT, from January 2002 to March 2015, were analyzed in this retrospective study. Hepatectomy was offered to patients if, based on radiologic findings, all gross lesions were considered resectable. The safety of hepatectomy was investigated and overall survival (OS) was compared between the resection group (n = 7) and non-resection group (n = 43)., Results: OS was significantly higher in the resection group than in the non-resection group. Results of multivariate analysis identified conversion to surgery (hazard ratio, 0.35; 95% confidence interval, 0.10-0.99; P = 0.048) as an independent factor influencing OS. There were no serious postoperative complications and no case of mortality in patients who underwent hepatectomy., Conclusions: Our findings suggest that hepatectomy after down-staging by 3D-CRT for PVTT combined with HAIC for advanced HCC is safe and results in good long term outcome., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to investigate the prognostic factors associated with extrahepatic metastasis of primary hepatocellular carcinoma (HCC)., Patients and Methods: We retrospectively analyzed 559 patients with HCC who underwent curative hepatectomy. We divided the patients into no recurrence (NoR), intrahepatic early recurrence (IHER), intrahepatic late recurrence (IHLR), and extrahepatic recurrence (EHR) groups. We compared the non-metastatic group (IHLR and NoR) with the metastatic group (IHER and EHR) and also compared IHER with EHR to determine risk factors for EHR., Results: There were 252, 163, 109, and 35 patients with NoR, IHER, IHLR, and EHR, respectively. For the EHR group, the independent risk factor was vascular invasion. The EHR group had better liver function and worse tumor factors., Conclusion: Vascular invasion is predictive of extrahepatic metastasis of HCC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The number of patients with hepatocellular carcinoma (HCC) negative for both hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) has increased recently. The purpose of the present study was to investigate the clinical characteristics and prognoses of non-B non-C HCC (NBNC-HCC) patients., Materials and Methods: From January 2000 to December 2013, 154 patients with NBNC-HCC and 560 patients with HBsAg or HCVAb positive (BC)-HCC who underwent curative resection were analyzed retrospectively. The clinical features of NBNC-HCC and BC-HCC were compared, and the prognoses of NBNC-HCC patients were analyzed., Results: In comparison to patients with BC-HCC, patients with NBNC-HCC had better liver function but higher pathological tumor stages. The disease-free survival (DFS) duration was significantly higher in patients with NBNC-HCC than it was in those with BC-HCC. In patients with NBNC-HCC, aspartate aminotransferase ≥40 IU/L, albumin level <3.5 g/dL, and multiple tumors were independent risk factors of overall survival; and male sex and multiple tumors were independent risk factors of DFS., Conclusion: Patients with NBNC-HCC had significantly longer DFS durations than those with BC-HCC. The patient sex had an impact on the postsurgical outcomes of patients with NBNC-HCC in DFS., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The risk factors of postoperative complications and prognostic factors of hepatocellular carcinoma in patients aged ≥80 years have not yet been defined. We aimed to identify these factors in this patient population., Methods: This single-center, retrospective cohort study included 625 patients who underwent curative hepatectomy from January 2004 to December 2013. Elderly patients were defined as those aged ≥80 years. Clinicopathological data and outcomes after hepatectomy for 60 elderly patients and 565 non-elderly patients were compared., Results: The elderly group had more comorbidities than the non-elderly group. Liver function, surgical data, tumor factors, the incidence of postoperative complications, disease-free survival rate, and overall survival rate did not differ significantly between the two groups. Results of multivariate analysis showed that the levels of cholinesterase, total cholesterol, and hemoglobin A1c were predictors of complications in the elderly group. The Child-Pugh grade, protein induced in vitamin K absence or antagonists-II level, and multiple tumors were significantly associated with disease-free survival., Conclusions: Although elderly patients had more comorbidities, their postoperative complications and prognosis were comparable to those of the non-elderly patients. Hepatectomy may be justified for elderly patients, but it is important to evaluate levels of cholinesterase, total cholesterol, and hemoglobin A1c preoperatively., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)