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Background/aim: The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for hepatocellular carcinoma (HCC). The present investigation demonstrated the expression profiles of ion channels in CSCs of HCC., Materials and Methods: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from HepG2 cells, a human HCC cell line, by fluorescence-activated cell sorting, and CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were investigated using microarray analysis., Results: Among HepG2 cells, ALDH1A1 messenger RNA level was higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels, such as calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The cytotoxicity of the CACNG4 inhibitor amlodipine was higher at lower concentrations in CSCs than in non-CSCs, and markedly decreased the number of tumorspheres. The cell population among HepG2 cells that highly expressed ALDH1A1 was also significantly reduced by this inhibitor., Conclusion: CACNG4 plays a role in maintaining CSCs, and its inhibitor, amlodipine, could potentially be a targeted therapeutic agent against HCC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery., Methods: We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I-IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction., Results: Forty-eight (13.3%) colorectal cancer patients (Stages I-IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P < 0.001). Univariate and multivariate analyses using Cox's proportional hazards model revealed that postoperative liver dysfunction independently was a poor prognostic factor (P = 0.001, Hazard ratio 2.75, 95% CI: 1.54-4.73)., Conclusions: Postoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction., (© 2023. The Author(s).)

Background: Primary liver cancer (PLC) is classified into hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular and intrahepatic cholangiocarcinoma (CHC). We investigated the genomic landscape of PLC according to the histological classification and established a cross-histological molecular subtyping for PLC by a multi-omics analysis., Methods: We analyzed 265 PLC cases with whole-exome sequencing and DNA copy number analyses and 251 cases with gene expression profiling., Results: The cohort included HCC (n = 223, 84%), ICC (n = 34, 13%), and CHC (n = 8, 3%). Mutation analyses identified histological type-specific driver genes, such as CTNNB1 in HCC and KRAS, IDH1, and PIK3CA in ICC, and ARID1A and KMT2C in CHC. The tumor suppressor gene TP53 mutation was detected in 21.1% of HCC, 16.1% of ICC, and 25.0% of CHC cases. Other well-characterized tumor suppressor genes included RB1, which was mutated in 2.8% of HCC and 3.2% of ICC; and PTEN, which was mutated in 1.4% of HCC, 3.2% of ICC, and 12.5% of CHC cases. DNA copy number analyses identified focal amplifications, with NUF2 (1q23.3) the most frequently detected as an amplified gene in all 3 types (HCC, 3.8%; CHC, 12.5%, ICC, 3.2%). Molecular subtyping for PLC based on the multi-omics analysis identified three subtypes, one of which was associated with recurrence after resection and amplified genes located at chromosome 8q., Conclusions: Our dataset serves as a fundamental resource for genomic medicine for PLC in Japan and identified amplified genes located at chromosome 8q as promising therapeutic targets for the subgroup with a poor prognosis., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Multiple mutation (MM) within a single gene has recently been reported as a mechanism involved in carcinogenesis. The present study investigated the clinical significance of MMs in hepatocellular carcinoma (HCC)., Methods: Two hundred twenty-three surgically resected HCCs were subjected to gene expression profiling and whole-exome sequencing., Results: MMs in individual genes were detected in 178 samples (MM tumors: 79.8%). The remaining samples all carried a single mutation (SM tumors: 20.2%). Recurrence-free survival in the MM group was significantly worse in comparison to the SM group (P = 0.012). A Cox proportional hazard analysis revealed that MM tumor was an independent predictor for worse a prognosis (hazard ratio, 1.72; 95% confidence interval, 1.01-3.17; P = 0.045). MMs were frequently observed across in various genes, especially MUC16 (15% of samples had at least one mutation in the gene) and CTNNB1 (14%). Although the MUC16 mRNA expression of MUC16 wild-type and MUC16 SM tumors did not differ to a statistically significant extent, the expression in MUC16 MM tumors was significantly enhanced in comparison to MUC16 SM tumors (P < 0.001). In MUC16, MMs were associated with viral hepatitis, higher tumor marker levels and vascular invasion. The MUC16 MMs group showed significantly worse recurrence-free survival in comparison to the MUC16 SM group (P = 0.022), while no significant difference was observed between the MUC16 SM group and the MUC16 wild-type group (P = 0.324)., Conclusions: MM was a relatively common event that may occur selectively in specific oncogenes and is involved in aggressive malignant behavior., (© 2022. The Author(s).)

As liver cancer (LC) is the sixth most commonly diagnosed malignancy, it is necessary to elucidate the molecular mechanisms responsible for LC progression. MicroRNAs (miRNAs/miRs) play crucial roles in tumor progression by regulating target gene expression. The present study assessed miRNA‑4730 expression and function in LC. The effects of miR‑4730 overexpression were examined in LC cell lines, and the target genes of miR‑4730 were evaluated using microarray analysis and TargetScan data. In addition, the association between miR‑4730 expression in tissue samples and the prognosis of 70 patients with LC was evaluated. miR‑4730 expression was suppressed in LC tissues and cell lines. miR‑4730 overexpression suppressed cell proliferation and cell cycle progression and promoted apoptosis. High mobility group A1 (HMGA1) was revealed as the direct target of miR‑4730 using luciferase reporter assay, and the inhibition of downstream integrin‑linked kinase (ILK) expression and Akt or glycogen synthase kinase 3β (GSK3β) phosphorylation was confirmed. The lower expression of miR‑4730 in tissue samples was significantly associated with a worse recurrence‑free survival of patients with LC. On the whole, miR‑4730 suppressed tumor progression by directly targeting HMGA1 and inhibiting the ILK/Akt/GSK3β pathway. miR‑4730 thus has potential for use as a prognostic marker and may prove to be a therapeutic target for miRNA‑based therapies.

Introduction: The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct-acting antivirals (DAA) or interferon (IFN) are still not fully understood., Methods: Sixty-nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole-exome sequencing., Results: Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV-positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV-SVR. According to the HCV treatment, 35 HCV-SVR HCCs were classified into two groups: eight tumors with DAA (HCV-SVR-DAA) and 24 tumors with interferon (HCV-SVR-IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV-SVR than in HCV-positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV-SVR samples than in HCV-positive samples (p = 0.048). Among the patients with HCV-SVR, the frequency of samples with TP53 mutations was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors (p = 0.030). TP53 inactivation scores in HCV-SVR-DAA tumors were found to be significantly enhanced in comparison to HCV-SVR-IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV-SVR-DAA tumors. HCV-SVR-DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV-SVR-IFN., Conclusion: Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV-SVR-DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV-positive tumors and HCV-SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate differences in the safety line of the future liver remnant plasma clearance rate of indocyanine green (RemK) necessary to prevent posthepatectomy liver failure (PHLF) associated with liver tumors and comorbidities., Methods: The subjects of this retrospective study were patients who underwent trisectionectomy, hemihepatectomy, or sectionectomy, other than left lateral sectionectomy, between 2011 and 2018, at the Shizuoka Cancer Center. We analyzed the risk factors for PHLF grades B and C and then evaluated the RemK in these groups, according to various risk factors., Results: A total of 463 patients were selected for the analyses. Among the patients with PHLF grades B and C, those with diabetes mellitus (DM), liver cirrhosis (LC), or hepatocellular carcinoma (HCC) had significantly higher RemK than those without these diseases. Multivariate analysis identified RemK ≤ 0.078, DM, and creatinine clearance rate < 60 mL/min as independent risk factors for PHLF grades B and C., Conclusions: Hepatectomy for patients with DM, HCC, or LC requires more functional hepatic reserve than that evaluated by RemK., (© 2021. Springer Nature Singapore Pte Ltd.)

Background: No study has clarified the clinical significance of albumin-bilirubin (ALBI) grade in a large cohort of pancreatic cancer patients., Methods: A total of 1006 consecutive patients diagnosed with pancreatic cancer and deemed eligible for surgical resection were analyzed. The ALBI score was calculated as: ALBI score = (log 10 bilirubin [µmol/L] × 0.66) + (albumin [g/L]  × - 0.0852). ALBI grade was assigned as grade 1, 2a, 2b, and 3. ALBI grade 1 was assigned to the ALBI low group (N = 566), and grades 2a, 2b, and 3 to the ALBI high group (N = 440)., Results: The primary lesion could not be resected in 129 patients. Among all patients, overall survival (OS) was significantly worse in the ALBI high group than in the ALBI low group (P = 0.024). Overall, 877 patients underwent pancreatectomy. In these patients, the ALBI high group was associated with high CA19-9 level (P < 0.001), lower morbidity rate (P < 0.001), and pancreatic head tumor (P = 0.001). Patients' OS after resection was significantly worse in the ALBI high group than in the ALBI low group (P < 0.001). Cox proportional hazard analysis revealed ALBI grade as an independent predictor for prognosis (hazard ratio, 1.33; P = 0.015). Even in the CA19-9 negative patients, OS was significantly worse in the ALBI high group than in the ALBI low group (P = 0.046)., Conclusions: The ALBI grade is a clinically useful predictor for prognosis in pancreatic cancer patients., (© 2021. Society of Surgical Oncology.)

Background: Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score., Methods: A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS., Results: Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p < .001). In the multivariate Cox model, a high OLGS was an independent predictor of 5-year OS (p < .001), and the hazard ratio (HR) of the OLGS-high group (HR = 7.171) was higher than that of the high clinical risk score group (HR = 4.337)., Conclusion: The OLGS, a simple and handy scoring system, better predicts the 5-year OS of patients with CRLMs after hepatectomy and warrants prospective validation., (© 2021 Wiley Periodicals LLC.)

Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescence probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a β-galactosidase (β-Gal)-activatable fluorescence probe SPiDER-βGal was examined. β-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-βGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, β-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-βGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-βGal. SPiDER-βGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-βGal would help surgeons detect tumours rapidly and achieve complete liver resection., (© 2021. The Author(s).)

Purpose: The aim of this study was to evaluate anatomical resection (AR) versus non-AR for primary solitary hepatocellular carcinoma (HCC) with predicted microscopic vessel invasion (MVI) and/or microscopic intrahepatic metastasis (MIM)., Methods: This retrospective study included 358 patients who underwent hepatectomy and had no evidence of MVI and/or MIM on preoperative imaging. The predictors of MVI and/or MIM were identified. The AR group (n = 222) and the non-AR group (n = 136) were classified by number of risk factor, and the survival rates were compared., Results: Microscopic vessel invasion and/or MIM were identified in 81 (22.6%) patients. A multivariate analysis showed that high des-gamma-carboxy prothrombin concentration [odds ratio (OR) 3.35], large tumor size (OR 3.16), and high aspartate aminotransferase concentration (OR 2.13) were significant predictors. The 5-year overall survival (OS) in the patients with zero, one, two, and three risk factors were 97.4%, 73.5%, 71.5%, and 65.5%, respectively. The OS of AR is superior to that of non-AR only in patients with one or two risk factors., Conclusion: The present findings suggest that AR should be performed for patients with one or two risk factors, and that AR may prevent recurrence, as these patients are at risk of having MVI and/or MIM., (© 2021. Springer Nature Singapore Pte Ltd.)

Background/aim: We attempted to stratify prognosis using the modified Journal of Hepato-Biliary-Pancreatic Sciences (mJHBPS) nomogram upon identification of colorectal liver metastasis (CRLM) and to investigate which strategy is better, surgery first (SF) or chemotherapy first (CF), in each risk group., Patients and Methods: A total of 137 patients with CRLM who underwent resection of the primary tumor were included. Patients with brain, bone, or perihilar lymph node metastases were excluded. Patients were scored using the mJHBPS nomogram upon identification of CRLM. Prognosis was investigated using event-free survival (EFS) and overall survival (OS)., Results: The nomogram allowed stratification of patients using EFS and OS: low-risk (0-6 score, n=38), medium-risk (7-11 score, n=42), and high-risk (12≥ score, n=57). In the low-risk group, the EFS and OS of the CF group were significantly poorer than those of the SF group (p=0.019 and p=0.014, respectively). CF was an independent prognostic factor for both EFS and OS., Conclusion: The mJHBPS nomogram can stratify CRLM patients with sufficient differences in EFS and OS. SF was recommended for patients in the low-risk group., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Biliary confluence is sometimes involved in colorectal liver metastasis (CRLM), and therefore bile duct resection (BDR) is occasionally necessary for complete resection. However, the utility of hepatectomy with combined BDR is unclear. The safety and survival outcome of hepatectomy with combined BDR for CRLM was assessed., Methods: Patients who underwent hepatectomy for CRLM between 2002 and 2017 were identified from a prospectively compiled database. Postoperative outcomes were compared between patients undergoing hepatectomy alone and with combined BDR for CRLM., Results: A total of 734 patients who underwent hepatectomy for CRLM were included. Hepatectomy with combined BDR was performed in 16 (2.1%) patients. The postoperative complications rate (Clavien-Dindo ≥ 3) of patients undergoing hepatectomy with BDR was 31.2%, which was higher than that without BDR (P = 0.001) for CRLM. The mortality rate of surgery for CRLM was 0%. The 5- and 10-year relapse-free survival (RFS) rates for hepatectomy with BDR were 45.0% and 30.0%, respectively. Patients undergoing hepatectomy with BDR had a similar RFS to those without BDR for CRLM (P = 0.351). The 5- and 10-year overall survival (OS) rates for hepatectomy with BDR were 62.6% and 62.6%, respectively. Patients undergoing hepatectomy with BDR had a similar OS to those without BDR for CRLM (P = 0.738)., Conclusions: In conclusion, hepatectomy with combined BDR was a potentially feasible treatment option that obtained favorable survival outcomes in patients with invasion of the biliary confluence by CRLM, although BDR with hepatectomy for CRLM was associated with a high rate of morbidity.

Purpose: There are many treatment choices for hepatocellular carcinoma (HCC), one of which is proton beam therapy (PBT). The purpose of this study was to compare surgical resection (SR) and PBT to clarify the prognostic factors for operable HCC based on a single institution's database., Methods: Patients with single primary nodular HCC ≤ 100 mm without vessel invasion on pretreatment imaging were divided into the SR group and PBT group. In the PBT group, the patients with unresectable HCC due to their liver function and/or performance status were excluded., Results: There were 314 and 31 patients who underwent SR and PBT, respectively. The median survival time in the SR group was significantly better than in the PBT group (104.1 vs. 64.6 months, p = 0.008). Regarding the relapse-free survival (RFS), there was no significant difference between the SR and PBT groups (33.8 vs. 14.0 months, p = 0.099)., Conclusion: The RFS was comparable between the PBT and SR groups. However, the PBT group had a significantly worse overall survival than the SR group. SR may therefore be favorable as an initial treatment for HCC compared to PBT.

Background: Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC). Achieving a sustained virological response (SVR) is associated with a reduced risk of recurrence. The recent introduction of direct acting antivirals (DAAs) has resulted in SVR rates of nearly 100% in treated patients. The purpose of the present study was to clarify the outcomes in patients who underwent antiviral therapy and patients without antiviral therapy., Methods: This retrospective study included 220 patients with primary HCV-related HCC who underwent hepatectomy. An SVR was defined as a serum HCV-RNA titer below the detection sensitivity limit at 6 months after the termination of antiviral therapy. Postoperative antiviral therapy was introduced after confirming that there was no early recurrence., Results: Eighty-eight patients received antiviral therapy. Among these, 58 patients (66%) obtained an SVR. With the exception of one patient, all patients who received DAAs obtained an SVR. The overall survival rate of the pre-operative SVR group was significantly better than that of the preoperative untreated group (P = 0.045). Moreover, there was no recurrence at 3 years after surgery in the pre-operative SVR group. The achievement of an SVR was an independent predictor of overall survival [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59-0.94, P = 0.011] and recurrence (HR 0.61, 95% CI 0.40-0.94, P = 0.024)., Conclusions: Obtaining an SVR either before or after surgery was associated with the suppression of HCC recurrence after hepatectomy in patients with primary HCV-related HCC.

Background: Postoperative complications affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM)., Methods: Between 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The clinicopathological parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS)., Results: One hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n = 49, 11.4%), bile leakage (n = 41, 9.6%), posthepatectomy liver failure (PHLF) (n = 26, 6.0%), and pulmonary complication (n = 20, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, ≥5 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P < 0.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive surgical margins, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year OS rates in patients with and without PHLF were 31% and 63%, respectively (P = 0.004)., Conclusions: Among the complications, only PHLF was associated with decreased long-term survival after hepatectomy for CRLM as well as tumor-specific prognostic factors., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The efficacy of infrahepatic inferior vena cava (IVC) semi-clamping for reducing blood loss during hepatic resection and its safety remain unclear. The aim of this study was to validate the effectiveness of IVC semi-clamping for reducing blood loss during hepatic resection and to confirm its safety., Methods: Patients who underwent anatomical hepatic resection between January 2011 and May 2018 were analysed by propensity score-matched and multivariate analyses., Results: Of 437 patients who underwent anatomical hepatic resection, IVC semi-clamping was performed in 196 patients (44.9%; clamping group). A propensity score-matched analysis demonstrated that even though there was no significant difference in the characteristics of the 141 patients in each group, IVC semi-clamping reduced the blood loss during hepatic resection (clamping group versus non-clamping group: 836 ± 123 vs. 1198 ± 124 ml, P = 0.04). Regarding post-operative complications, the multivariate analysis identified IVC semi-clamping as an independent risk factor for acute kidney injury on post-operative day 1 (P = 0.01, odds ratio = 9.23). A significant positive correlation was found between the duration of IVC semi-clamping and an increased level of serum creatinine (sCre) (P = 0.03), and a significant inverse correlation was found between the blood pressure after clamping and an increased level of sCre (P = 0.02). A receiver operating characteristic analysis revealed the duration and mean blood pressure after clamping that indicated a high risk of acute kidney injury to be 116 min and 65 mmHg, respectively., Conclusion: IVC semi-clamping can reduce blood loss during hepatic resection but still necessitates monitoring in order to avoid acute kidney injury.

Background and Aim: Previous studies have shown that microscopic vessel invasion (MVI) occurs in hepatocellular carcinoma (HCC) with a treatment history due to its poorer malignant behavior in comparison with primary HCC. The aim of the present study was to determine the predictors of MVI and overall survival in HCC patients with a treatment history., Methods: This retrospective study included 580 patients who underwent hepatectomy and whose preoperative imaging showed no evidence of macroscopic vessel invasion. The patients were classified into two groups: primary HCC (n = 425) and HCC with a treatment history (n = 155). MVI was defined as the presence of either microscopic portal vein invasion or venous invasion, which was invisible on preoperative imaging., Results: MVI was identified in 34 (21.9%) patients with a treatment history. A multivariate analysis showed that a high des-gamma-carboxy prothrombin (odds ratio [OR] 5.16, P = 0.002) and a large tumor diameter (OR 2.57, P = 0.030) were the significant predictor of MVI in HCC with a treatment history. Moreover, the presence of MVI (hazard ratio [HR] 2.27, P = 0.001) and tumor diameter >27 mm (HR 2.04, P = 0.006) remained significant predictors of the overall survival in HCC with a treatment history. The tumor diameter cutoff value for predicting MVI (27 mm) in HCC with a treatment history was smaller than in primary HCC (37 mm)., Conclusions: The presence of MVI was a significant predictor in the HCC patients with a treatment history. The tumor diameter is an important factor that can be used to predict the presence of MVI, especially in HCC with a treatment history.

Background/aim: This study aimed to investigate whether hypervascular intrahepatic cholangiocarcinoma (HICC) can be differentiated from hepatocellular carcinoma (HCC)., Materials and Methods: Among 100 patients with intrahepatic cholangiocarcinoma, 22 patients were diagnosed with HICC based on the computed tomography (CT) value in the late arterial phase as follows: the CT value of the tumor ≥ that of the liver parenchyma. The CT values of the HICC were compared to those of HCC cases (n=120)., Results: The CT value of HICC was lower in the unenhanced phase (UP) (p=0.016) and higher in the equilibrium phase (EP) (p<0.001) in comparison to HCC. The non-tumorous liver (odds ratio [OR]: 6.35, p=0.002) and an E/U ratio (the mean CT value of the tumor in the EP to that in the UP) of >2.3 (OR=13.1, p<0.001) were independent diagnostic factors for differentiating HICC from HCC., Conclusion: E/U ratio is useful for differentiating between HICC and HCC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The serum antibody to hepatitis B core antigen (HBcAb) is considered a risk factor of liver carcinogenesis. This study aimed to reveal whether HBcAb status is a prognostic factor after hepatectomy is performed for treating hepatocellular carcinoma (HCC)., Methods: This retrospective study enrolled 272 patients who underwent hepatectomy as the initial treatment for HCC and who were followed up over 5 years after surgery. The types of HCC were classified into the following 3 types according to the hepatitis virus infection status and the patients without hepatitis virus infection non-B non-C HCC (NBNC-HCC) were further classified into 2 groups., Results: There is no novel finding as a result of the comparison made among hepatitis virus status. Of 90 patients (33.1%) with NBNC-HCC, 10 patients were excluded because the preoperative HBcAb status was not measured. There were 51 patients (63.8%) who were HBcAb-positive and 29 patients (36.2%) who were HBcAb-negative. In multivariate analysis, the presence of HBcAb-negative (hazard ratio 2.10, 95% CI 1.09-4.03, p = 0.026) remained as significant independent risk factors for recurrence in NBNC-HCC., Conclusions: This study shows that the HBcAb-positive is rather a favorable predictor for recurrence after curative resection in NBNC-HCC., (© 2017 S. Karger AG, Basel.)

Background/aims: Several tumor factors seem to be related to the hepatocellular carcinoma (HCC) prognosis, but they are not definitive, except for major vascular invasion. We analyzed the impact of serosal invasion, which is histologically classified into four groups according to the definition of the Liver Cancer Study Group of Japan - S0: no tumor invasion of serosa, S1: tumor invasion of serosa, S2: tumor invasion of adjacent organs, S3: tumor rupture with intraperitoneal bleeding., Methods: This retrospective study included 421 consecutive patients who underwent hepatectomy as an initial treatment for HCC between September 2002 and December 2014., Results: Kaplan-Meier analysis and log-rank tests revealed that both recurrence-free survival (RFS) and disease-specific survival (DSS) worsened as the serosal invasion status advanced. Multivariate analyses showed that S2/S3 was independently correlated with RFS (hazard ratio [HR] 3.52; p  < 0.001) and DSS (HR 2.58; p  = 0.039). Another multivariate analysis showed that serosal invasion (S1-S3) was independently correlated with RFS (HR 1.70; p = 0.015) but not with DSS (HR 1.38; p = 0.27)., Conclusion: Invasion to adjacent organs and tumor rupture were crucial prognostic factors for both DSS and RFS. Serosal invasion was an independent prognostic factor only for RFS., (© 2017 S. Karger AG, Basel.)

Background: With aging populations increasing in developed countries, the prevalence of elderly patients with hepatocellular carcinoma (HCC) is expected to rise. The aim of this study was to determine the short- and long-term outcomes of HCC surgery in elderly patients (≥75 years) using propensity score matching., Methods: The study group included 421 patients who underwent hepatectomy as their initial treatment with curative intent. The patients were divided into elderly (n = 111) and non-elderly (n = 310) groups. We applied propensity score matching - taking into consideration patient background, blood examination, and tumor factors - to minimize the effect of potential confounders. We then compared the results before and after the propensity matching., Results: Before propensity matching, the elderly group included significantly more patients with a high American Society of Anesthesiologists physical status (p < 0.001). In addition, they were taking antihypertensive drugs or an anticoagulant (both p < 0.001). The severe postoperative complications and the overall survival rates for these elderly patients were significantly poorer than for the non-elderly patients (p = 0.015 and p = 0.030, respectively). We then chose 70 patients from each group for whom the preoperative confounding factors were balanced and compared the two groups. The factors identified before matching (severe complications and overall survival rates) were no longer relevant, i.e. there were no significant differences between the two groups., Conclusion: Hepatectomy for HCC in elderly patients is justified., (© 2018 S. Karger AG, Basel.)

Background/aim: Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent operation at our Institution. The aim of this study was to identify novel genes displaying altered gene expression related to the survival and early recurrence after hepatectomy for hepatocellular carcinoma (HCC) using the results of integrated GEP analysis., Materials and Methods: The present study included 92 patients. Genes with aberrant expression were selected by the difference of expression levels with ≥10-fold change between tumor and non-tumor tissues., Results: GEP analysis showed that down-regulation was frequently observed in the PRSS8 (64%), CYP3A4 (61%) and EPCAM (57%) genes. Multivariate analysis revealed tumor stage ≥II (p=0.008) and down-regulation of the CYP3A4 gene (p=0.036) as independent predictor for overall survival. Furthermore, multivariate analysis identified maximum tumor diameter ≥74mm (p=0.008), presence of intrahepatic-metastasis (p=0.020), and down-regulation of CYP3A4 gene (p=0.019) as independent predictors for early recurrence., Conclusion: CYP3A4 was identified as a novel tumor suppressor gene related to a poor prognosis in HCC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: It is difficult to identify patients at high risk of recurrence after pancreatectomy for pancreatic neuroendocrine tumor (PNET) using only the grading classification, especially the G2 category, which includes both benign and low- and high-grade malignant tumors., Methods: Forty-one patients with PNET who underwent pancreatectomy were enrolled in this study. We defined the computed tomography (CT) ratio as the CT value of the tumor divided by that of non-tumorous pancreatic parenchyma using the late arterial phase dynamic CT. The optimal cut-off values for CT ratio and tumor size were determined using p-values that were calculated using the log-rank test., Results: The optimal cut-off values of CT ratio and tumor size for dividing patients into groups according to the greatest difference in disease-free survival (DFS) were 0.85 (p < 0.001) and 3.0 cm (p < 0.001), respectively. In analysis using Spearman's correlation coefficient, CT ratio (p = 0.007) and tumor size (p = 0.003) were individually associated with the Ki-67 proliferative index. Cox proportional hazard analysis identified that a CT ratio <0.85 (n = 10, p = 0.006) and tumor size ≥3.0 cm (n = 13, p = 0.023) were independent prognostic factors associated with DFS. All patients in the CT ratio ≥0.85 and tumor size <3.0 cm group (n = 23, including seven patients with G2 disease) did not develop recurrence after surgery. On the other hand, 5-year DFS in the CT ratio <0.85 and tumor size ≥3.0 cm group (n = 5, including three patients with G2 disease) was zero., Conclusions: PNETs with a CT ratio <0.85 and tumor size ≥3.0 cm should be considered as having a high risk of recurrence after pancreatectomy.

Purpose: To establish the optimal cut-off value of the preoperative prognostic nutritional index (PNI) for prognosis according to the Tumor Node Metastasis (TNM) stage of hepatocellular carcinoma (HCC) after curative resection., Methods: This retrospective study reviewed the records of 375 patients. The optimal cut-off value of the PNI was established according to the TNM stage, and overall survival was compared between the low and high PNI groups., Results: The optimal cut-off value of the PNI decreased with increasing TNM stage, with 52, 47, and 43 patients having stage I, II, and III HCC, respectively. A low preoperative PNI predicted a poorer overall survival than did a high PNI for stage I (P < 0.001) and II (P = 0.002), but not stage III disease (P = 0.052). Multivariate analysis revealed that the preoperative PNI was an independent predictor of overall survival for stage I and II HCC (hazard ratios: 6.96 and 3.57, P = 0.001 and P = 0.001, respectively)., Conclusions: The findings of this study show that the optimal cut-off value for the PNI for prognosis differs among the TNM stages and that the preoperative PNI is a favorable prognostic factor for stage I HCC.

Background: Liver metastases (LMs) are sometimes diagnosed intraoperatively, even when multidetector-row computed tomography (MDCT) reveals no LM in the staging of pancreatic cancer (PC). Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MR imaging) may have a role to play in the detection of LM., Methods: The present study included a total of 201 patients who underwent an EOB-MR imaging examination before undergoing surgical resection for pancreatic cancer that was determined to be radiologically-resectable by MDCT. Intrahepatic lesions that were considered suspected to be liver metastases following an EOB-MR imaging examination were defined as possible lesions (PLs). All PLs were evaluated by a pathological examination or through close follow-up examinations. The diagnostic ability of EOB-MR imaging was assessed. The predictive factors for liver metastasis were evaluated., Results: Thirty-seven PLs were noted in 17 patients: 31 PLs were true LMs, and six were benign lesions (3 hemangiomas and 3 abscesses). Nine LMs were newly detected during surgery and were not detected by preoperative EOB-MR imaging. The diagnostic ability of EOB-MR imaging was as follows: sensitivity, 77.5%; specificity, 94.7%; positive predictive value, 83.8%; negative predictive value, 92.3%; and accuracy, 90.2%. A multivariate analysis revealed that the presence of PL on EOB-MR imaging was the only independent risk factor for intraoperative liver metastasis (P < 0.001)., Conclusion: EOB-MR imaging was useful in detecting tiny liver metastases from pancreatic cancer in cases that were determined to be radiologically resectable by MDCT., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Des-γ-carboxy prothrombin (DCP) is a representative tumor marker of hepatocellular carcinoma (HCC), and its values are occasionally very high in HCC cases. The current study aimed to clarify the postoperative half-life of DCP as a prognostic factor., Methods: This retrospective study enrolled 177 patients who had undergone liver resection as an initial treatment for HCC. Three DCP half-life groups were defined as follows: within the normal range, half-life shorter than 4 days, and half-life of 4 days or longer. The overall and recurrence-free survival rates were estimated and compared among the three groups., Results: There were 140 patients in the group with a DCP half-life in the normal range, 19 patients in the group with a DCP half-life shorter 4 days, and 18 patients in the group with a DCP half-life of 4 days or longer. A multivariate analysis showed that only a postoperative DCP half-life of 4 days or longer was an independent prognostic risk factor for overall and recurrence-free survival (respective hazard ratios of 2.92 and 4.19; P < 0.001). The group with a preoperative DCP value lower than 1400 mAU/mL, the median value of DCP in the current study, included no patients from the group with a half-life shorter than 4 days. The overall and recurrence-free survival rates in the group with a half-life of 4 days or longer were significantly poorer (P < 0.001) than in the group that had a half-life shorter than 4 days (P = 0.002) with a preoperative DCP status of 1400 mAU/mL or more., Conclusions: The current study showed for the first time that a prolonged half-life of DCP is an independent prognostic risk factor for survival and recurrence after liver resection with curative intent.

Background: Isolated anatomic total caudate lobectomy is indicated in patients who have liver tumors limited to the caudate lobe. However, isolated caudate lobe resection is a challenging surgical procedure that required safe and reliable techniques. All portal and hepatic veins that connect this area originate from the first branch of the portal vein or vena cava; therefore, the operator must be cautious of the potential for massive bleeding., Methods: The important points regarding the safety of our procedure include creating an optimal surgical view and preparing for accidental bleeding before parenchymal dissection. Sufficient mobilization and removal of Spiegel's lobe from the left to the right side of the vena cava allows the operator to perform parenchymal dissection under a right- or front-side view., Results: We have performed this technique in two patients with HCC and one patient with primary cystadenocarcinoma. The average operative time and amount of blood loss were 435 min and 1137 ml, respectively. No operative mortalities or postoperative complications were observed in any of the patients. Our three patients are currently doing well without any recurrence., Conclusion: Our modified high dorsal resection procedure can be used to safely remove the entire caudate lobe.

Purpose: The aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index were developed as a non-invasive parameter for predicting liver fibrosis. This study aimed to validate the APRI and FIB-4 indexes in patients treated with curative therapy for non-B non-C (NBNC) hepatocellular carcinoma (HCC)., Methods: Accumulated database comprising 399 patients who underwent hepatectomy was reviewed retrospectively. Analyses were performed to evaluate whether the APRI and FIB-4 indexes are predictors of liver cirrhosis and/or the prognosis in patients with NBNC-HCC. Forty-seven patients with NBNC-HCC who underwent curative radiofrequency ablation therapy (RFA) in the same period were enrolled as the validation set., Results: The APRI and FIB-4 indexes were significantly higher in the cirrhosis group than in the no-cirrhosis group (P = 0.001 and P < 0.001, respectively). A receiver operating characteristic curve analysis showed that the FIB-4 index was more accurate in predicting background liver cirrhosis than the APRI. According to a multivariate analysis, an FIB-4 index larger than 2.7 (hazard ratio 2.11 and 2.21, 95 % confidence interval 1.06-4.18 and 1.38-3.54, P = 0.033 and P = 0.001) remained significant independent predictors of overall and recurrence-free survival, respectively., Conclusions: The present findings showed that the FIB-4 index is a significant predictor of background liver cirrhosis and the prognosis after curative resection for NBNB-HCC.

Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma (HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC., (© 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: It is difficult to treat the American Joint Committee on Cancer (AJCC)/International Union against Cancer (UICC) T3 hepatocellular carcinoma (HCC), curatively., Patients and Methods: We compared the clinicopathology of T3 group (n=44: T3a 25, T3b 19) with that of the T1 (n=257) or T2 group (n=120) and evaluated favorable conditions of hepatectomy for T3 HCC patients., Results: The T3 group had significantly higher hepatitis B surface antigen (HBsAg)-positive rates and better liver function. Infiltrative large tumors located beyond one sub-segment with intrahepatic metastasis were significantly more common. Significantly, more non-curative large hepatectomies with transarterial embolization were performed. There was no significant difference between T3 and 2 groups in 5-year disease-free survival (DFS) and survival (S). Tumor size more than 55 mm and serum albumin less than 3.5 g/dl were risk factors of hepatectomy for T3 HCC patients by multivariate analysis., Conclusion: Surgeons should resect AJCC/UICC T3 HCC lesions if the patient is able to tolerate surgery., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To determine the best cut-off value between the early and late recurrence periods after the initial recurrence of hepatocellular carcinoma (HCC)., Methods: The clinical records of 404 patients who underwent macroscopic curative hepatectomy for HCC between 1980 and 2010 were retrospectively examined. We divided the 252 patients experienced a recurrence of HCC into two groups, the early and late recurrence groups using the "minimum P-value" approach. Factors for early recurrence were investigated using all 404 patients, and factors related to late recurrence were investigated in the patients who were confirmed to be recurrence free at the end of the early recurrence period., Results: For the 252 patients who experienced a recurrence, the optimal cut-off value for differentiating early and late recurrence based on the overall survival after initial recurrence was 17 mo (5-year overall survival after initial recurrence: 15.4% vs 36.3%, P=0.000018). Cox proportional hazard analysis identified early recurrence (P=0.003) as one of the independent prognostic factors associated with overall survival after initial recurrence. A logistic regression model showed that an alpha-fetoprotein level>100 ng/mL (P<0.001), multiple HCC (P<0.001), serosal invasion (P=0.031), and microvascular invasion (P=0.012) were independent factors associated with early recurrence, whereas the only independent factor related to late recurrence was liver cirrhosis (P=0.002)., Conclusion: Seventeen months after hepatectomy is a useful cut-off value between early and late recurrence of HCC based on the prognosis and different etiologies.

Aim: To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system., Methods: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system (7(th) edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein, vp2 as an invasion or tumor thrombus in the second branch of the portal vein, vp3 as an invasion or tumor thrombus in the first branch of the portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side., Results: The cumulative 5-year overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the 372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4 patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586, respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2-4), the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not (P = 0.747). There was a significant difference in the DFS between patients with stage I HCC and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P = 0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha-fetoprotein (AFP) > 100 mg/dL was independently associated with DFS., Conclusion: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.

A 78-year-old man presented with fever and jaundice. Computed tomography (CT) revealed a hepatocellular carcinoma in the hepatic left lobe as well as right-sided ligamentum teres (RSLT). Extended left hepatic lobetectomy was performed without division at the left Glissonian root in order to preserve the Glissonian branch at segment 8. No complications occurred during the post-operative course of 13 days. Pathologically, the tumor was diagnosed as a combined hepatocellular and cholangiocarcinoma. Additional congenital variations can exist in RSLT frequently; therefore, we must take care when performing hepatobiliary surgeries. Recently, advanced imaging modalities, such as multi-detector rowcomputed tomography (CT) and magnetic resonance imaging(MRI), help us obtain virtual images of vascular architecture and to plan the operative procedure.

Unlabelled: BACK GROUND/AIM: The purpose of the present study was to clarify the clinicopathological features of non-hepatitis B and -C (NBNC) hepatocellular carcinoma (HCC), the incidence of which has been increasing., Patients and Methods: Two hundred and eighty-four patients with HCC were classified into three groups according to viral hepatitis status, namely NBNC, hepatitis B, and hepatitis C. We compared the three groups and studied related risk factors., Results: Patients without cirrhosis who had increased number of platelets and diabetes mellitus, and a serum alpha-feto-protein (AFP) level <100 ng/dl were more common in the NBNC group. The cumulative survival and disease-free survival were better in the NBNC group than in the other groups. The tumor size and hepatitis B or C viral status were found to be independent risk factors of disease-free survival and the presence of multiple lesions was the only independent risk factor of survival., Conclusion: Close follow-up of NBNC liver cirrhosis and early detection of NBNC-HCC can improve the prognosis after surgery., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: This study aimed to clarify the efficacy of anatomical resection (AR) for the treatment of hepatocellular carcinoma (HCC) compared with that of nonanatomical resection (NAR) based on the stratification of liver function (LF)., Methods: The clinical records of 174 patients with a single HCC, 2-5 cm in diameter and without macroscopic vascular invasion, were analyzed. AR was performed in 132 patients and NAR was performed in 42 patients. The indocyanine green retention rate at 15 min (ICGR15) of the 78 patients classified as the good-LF group was 10-20 % and the ICGR15 of the 54 patients classified as the poor-LF group was 20-40 %., Results: The 5-year overall survival (OS) and disease-free survival rates of the 174 patients were 67.6 and 33.4 %, respectively. Cox proportional hazard analysis identified ICGR15 ≥ 20 %, liver cirrhosis, α-fetoprotein ≥ 100 mg/dL, and infiltrating growth as independent prognostic factors. Liver cirrhosis was significantly less frequent in patients who underwent AR than in patients who underwent NAR (52 vs. 79 %, p = 0.002). In the subgroup analysis of the good-LF group, there were no significant differences in 5-year OS after AR and NAR (73.3 vs. 65.2 %, p = 0.857). By contrast, in the subgroup analysis of the poor-LF group, the 5-year OS after AR was significantly worse than after NAR (45.3 vs. 77.4 %, p = 0.044)., Conclusion: In patients with an ICGR15 ≥ 20 %, we recommend NAR rather than AR for the treatment of a solitary 2-5-cm-diameter HCC and without macroscopic vascular invasion.

Background: It is of great clinical concern to preoperatively predict the need for blood transfusions during hepatectomy for hepatocellular carcinoma (HCC)., Patients and Methods: A total of 168 consecutive patients undergoing elective hepatectomy for HCC were retrospectively reviewed. We investigated preoperative factors potentially influencing intraoperative blood transfusion and established a predictive scoring system for intraoperative blood transfusion., Results: Thirty-eight patients (22.6%) received red cell blood transfusion during surgery. A preoperative predicting scoring system for blood transfusion was constructed using the following four factors: platelet count <10×10(4)/mm(3) (2 points), α-fetoprotein ≥80 ng/ml (1 point), tumor size ≥4.0 cm (1 point), and major hepatectomy (1 point). The nomogram showed an area under the curve (AUC) of 0.760. This scoring system was highly predictive for blood transfusion (AUC=0.758). When the score was 0 points, the incidence of intraoperative blood transfusion was 3%. The rate increased to 10% and 38% when the score was 1 and 2 points, respectively, and reached 45% when the score was 3 points or more., Conclusion: This predictive scoring system would be useful for preoperatively assessing the need for intraoperative blood transfusions during hepatectomy for HCC.

Background: The aim of this study was to characterize changes in outcome following hepatectomy for hepatocellular carcinoma (HCC) over a 30-year period., Patients and Methods: The clinical records of 372 patients who underwent a macroscopic curative hepatectomy for treatment of HCC between 1980 and 2009 were retrospectively examined. Patients were divided into two groups: an early group (1980-2000) and a late group (2001-2009). The relationship between the chronological treatment period and the surgical outcomes was investigated., Results: The disease-free survival (DFS) was comparable between the early and late groups (at 5 years: 30.3% vs. 31.2%, p=0.526), however, the overall survival (OS) of the late group was significantly better than the one of the early group (at 5 years: 80.1% vs. 50.4%, p<0.001), with this being an independent prognostic factor. Among the 148 patients who underwent transarterial chemoembolization (TACE) for initial hepatic recurrence, the OS after initial recurrence of the late group was significantly better than that of the early group (p=0.002). The OS after initial recurrence was significantly better in patients who underwent repeat hepatectomy than in those who underwent TACE (p=0.044)., Conclusion: The results of hepatectomy for HCC have improved over time by use of various combination therapies after initial HCC recurrence. A repeat hepatectomy may be an acceptable treatment option for HCC recurrence in selected patients.

Background/aim: This study aimed to clarify the efficacy of anatomical hepatectomy in patients with preserved liver function., Patients and Methods: We compared the clinicopathology of the anatomical hepatectomy (AH) group (n=264) with that of the non-anatomical hepatectomy (NAH) group (n=85) and evaluated favorable conditions of anatomical hepatectomy for patients with HCC with an indocyanine green 15-minute retention rate of less than 30%., Results: There was no significant difference between the two groups in five-year disease-free survival. However, disease-free survival of the AH group was significantly better than that of the NAH group when patients had T1 tumors, tumors without intrahepatic metastasis, tumors located within one subsegment, or serum alpha feto-protein less than 100 ng/dl (p=0.015, p=0.009, p=0.046 and p=0.036, respectively). Anatomical hepatectomy was an independent favorable prognostic factor by multivariate analysis taking into consideration clinical factors, which could be clarified pre- or intraoperatively (p=0.003)., Conclusion: Anatomical hepatectomy should be performed for HCC patients with HCC with preserved liver function.

Purpose: This study was undertaken to elucidate the clinicopathological characteristics and surgical outcome of the periductal infiltrating (PI) type of intrahepatic cholangiocarcinoma (ICC), which is a distinct macroscopic type of ICC arising from the second-order of the intrahepatic bile ducts without apparent invasion of the surrounding liver parenchyma., Methods: All patients with the PI type of ICC were identified from a database of patients with intrahepatic cholangiocellular carcinoma that underwent surgical resection between 1983 and 2009. The clinicopathological data of these patients were analyzed retrospectively., Results: Sixteen of 203 patients (7.9%) had the PI type of ICC. The median survival was 7.7 years with 5-year survival rate of 62.1%. The PI type of ICC showed a significantly better survival than the mass-forming (MF) type (P = 0.0293) or MF plus PI type of ICC (P = 0.0001). Microscopic examinations showed intrahepatic metastasis to be absent in all the patients with PI type ICC. The incidence of intrahepatic metastases in patients with PI type was significantly lower in comparison to that of patients with MF type (P = 0.0030) and MF plus PI type (P = 0.0533), respectively., Conclusion: Surgery could therefore provide a favorable outcome in patients with the PI type of ICC, probably due to its lower incidence of intrahepatic metastases.

Background: Operative and nonoperative treatment for hepatocellular carcinoma (HCC) originating in the caudate lobe is regarded as challenging because of its deep location in the liver and possibly worse prognosis than HCC in other sites in the liver. The objective of this study is to investigate the clinicopathologic factors and survival of patients who underwent hepatectomy for solitary HCC originating in the caudate lobe., Methods: A retrospective review of 783 patients who underwent curative hepatectomy for solitary HCC between 1988 was performed. Clinicopathologic factors and survival rate of 46 (5.9%) patients with HCC originating in the caudate lobe were compared with those of 737 (94%) patients with HCC arising in other sites., Results: The clinical backgrounds of patients with HCC in the caudate lobe and in other sites were comparable. Hepatectomy for HCC in the caudate lobe was associated with greater operative time and blood loss than for HCC in other sites of the liver. Pathologically, HCC in the caudate lobe was associated with less frequent intrahepatic metastasis, lesser operative margins, and more frequent tumor exposure than HCC in other sites. Overall and disease-free 5-year survival rates of the 46 patients with solitary HCC in the caudate lobe were 76% and 45%, respectively; no significant difference was observed in the overall or disease-free survival rates between the 2 groups (P = .07 and P = .77, respectively). Resection of HCC in the paracaval portion of the caudate lobe (n = 27) was associated with more frequent anatomic resection, greater operative time and blood loss, and a lesser operative margin than HCC in the Spiegel lobe or caudate process (n = 19)., Conclusion: Resection for HCC in the caudate lobe, especially in the paracaval portion, remains technically demanding. The prognosis of patients with solitary HCC in the caudate lobe, however, was as good as that of patients with solitary HCC in other sites in the liver., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Despite recent advances in surgical techniques, hepatectomies remain one of the most hemorrhagic procedures in abdominal surgery. It is important to identify preoperatively patients who are at high risk of suffering massive intraoperative blood loss., Methods: The clinical records of 251 patients who underwent an elective hepatectomy for liver tumors between September 2007 and December 2009 were reviewed retrospectively. A multivariate logistic regression analysis of preoperative factors potentially influencing intraoperative blood loss was performed. We set the cut-off value of the amount of blood loss for safe hepatectomy as less than 1,500 mL because no patients with blood loss of less than 1,500 mL received blood transfusion in this study. A scoring system to predict blood loss of more than 1,500 mL was constructed and validated in a cohort of 59 subsequent patients., Results: Intraoperative blood loss of more than 1,500 mL was recognized in 35 of 251 patients (13.9%). Prothrombin activity < 70%, nonperipheral location of the tumor, involvement of hepatic veins, body mass index ≥ 23.0, and major hepatectomy were independently associated with intraoperative blood loss of more than 1,500 mL. The score was calculated by assigning 1 point for each of the 5 risk factors. The area under the receiver operating characteristic curve (AUC) was 0.814 (95% CI 0.731-0.898). This scoring system was highly predictive in the subsequent validation group of 59 patients (AUC = 0.839, 95% CI 0.710-0.969)., Conclusion: This predictive scoring system is considered to be useful for identifying before hepatectomy those patients with a high risk of intraoperative blood loss of more than 1,500 mL., (© 2011 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

A 72-year-old man was found to have a 40 mm mass in liver segment VIII during follow-up abdominal ultrasonography for type C viral hepatitis. Abdominal ultrasound showed a well-defined mass containing a cystic component, and computed tomographic hepatic arteriography showed heterogeneous enhancement except for cystic necrosis. Under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC), partial resection of liver segment VIII was performed. The encapsulated tumor consisted of a peripheral solid component with a central necrotic area. Histologically, the solid component had a two-layer structure, an HCC component in the external area and a sarcomatous component with neoplastic osteoid formation in the internal area, showing histological transition. Immunohistochemically, the HCC component was positive for hepatocyte antigen and negative for vimentin. The Ki-67 labeling index was found to increase from 5% to 58% with increasing histologic atypia. The sarcomatous component was positive for vimentin and negative for pan-keratin and hepatocyte antigen, with a Ki-67 labeling index of >90%. These findings led to a diagnosis of primary hepatic carcinosarcoma. Although previously reported patients with hepatic carcinosarcoma showed early metastasis with a very poor outcome, this patient has remained free of recurrence for 30 months, which is the longest recurrence-free survival time recorded for this type of cancer. Since relatively early-stage hepatic carcinosarcoma rarely seems to present as a small tumor showing a concentric growth pattern, we report this case with a review of the literature.

We identified that microRNA expression changed dynamically during liver development and found that miR-500 is an oncofetal miRNA in liver cancer. miR-500 was abundantly expressed in several human liver cancer cell lines and 45% of human hepatocellular carcinoma (HCC) tissue. Most importantly, an increased amount of miR-500 was found in the sera of the HCC patients. In fact, miR-500 levels in sera of the HCC patients returned to normal after the surgical treatment in three HCC patients. Our findings reveal that diverse changes of miRNAs occur during liver development and, one of these, miR-500 is an oncofetal miRNA relevant to the diagnosis of human HCC.

Background: Surgical resection for pancreatic and hepatic cancer sometimes involves combined resection and reconstruction of the major veins using venous grafts. Autologous venous grafts made from the bilateral gonadal veins (BGVs) have never been utilized or discussed., Materials and Methods: We reconstructed the portal vein (PV), superior mesenteric vein (SMV), and middle hepatic vein (MHV) using cylindrical or patch grafts customized from the BGVs in two female patients and in one male patient. In order to assess the sexual difference in the availability of the cylindrical graft to replace these major veins, we measured the diameters of the BGVs, PV, SMV, and MHV on computed tomography in 50 male and 50 female patients, and estimated the diameter-ratios (DRs) of the cylindrical graft made from BGVs/PV, SMV, and MHV. We assumed that the cutoff value of the DR would be 0.8, for replacing of major veins using cylindrical grafts., Results: The reconstructed PV, SMV, and MHV presented sufficient patency, and the postoperative courses were uneventful. The DRs of BGVs graft/PV, graft/SMV, and graft/MHV were significantly larger in female patients than those in male patients (0.82 vs. 0.54, p < 0.01, 0.96 vs. 0.61, p < 0.01, 1.39 vs. 0.95; p < 0.01) and were larger than 0.8 in 50%, 70%, and 92% in female patients, respectively, and 0%, 8%, and 68% in male patients, respectively., Conclusions: The present newly customized cylindrical and patch grafts made from the BGVs showed sufficient feasibility. A cylindrical graft made from the BGVs would be better utilized in female patients than in male patients.

Introduction: Hepatocellular carcinoma (HCC) with major portal tumor thrombus has been considered to be a fatal disease. A thrombectomy remains the only therapeutic option that offer a chance of complete tumor removal avoiding acute portal vein obstruction. However, the efficacy of tumor thrombectomy in addition to hepatectomy has not been well evaluated., Methods: Of 979 patients who consecutively underwent initial HCC resection, 45 (4.6%) HCC patients with tumor invasion of the first branch of the portal vein (vp3) and tumor in the main portal trunk or the opposite-side portal branch (vp4) were retrospectively analyzed to evaluate the efficacy of hepatectomy and tumor thrombectomy., Results: Alpha-fetoprotein, serosal invasion, and intrahepatic metastases were independently significant prognostic factors in all the 45 patients with vp3 or vp4 HCC. The 3- and 5-year survival rates in vp3 and vp4 group were 35.3% and 41.8%, and 21.2% and 20.9%, respectively. There were longer operative times and more intraoperative bleeding in patients with vp4, but no significant difference in mortality, morbidity, and survival between patients with vp3 and vp4., Conclusion: Hepatectomy and thrombectomy for vp4 could not only avoid acute portal occlusion due to tumor thrombus but provide a comparable survival benefit with hepatectomy for vp3.