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Aim: This study was performed to investigate the relationship between the preoperative cachexia index (CXI) and long‐term outcomes in patients who have undergone radical resection of pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 144 patients who underwent pancreatic resection for treatment of PDAC were retrospectively analyzed. The relationship between the CXI and the patients' long‐term outcomes after PDAC resection was investigated. The CXI was calculated based on the preoperative skeletal muscle index, serum albumin level, and neutrophil‐to‐lymphocyte ratio. After propensity‐score matching, we compared clinicopathological features and outcomes. Results: The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.16–3.23; P = 0.0118), R1 resection (HR, 57.20; 95% CI, 9.39–348.30; P < 0.0001), and a low CXI (HR, 2.10; 95% CI, 1.27–3.46; P = 0.0038) were independent and significant predictors of disease‐free survival (DFS) after PDAC resection. Moreover, a low CXI (HR, 3.14; 95% CI, 1.71–5.75; P = 0.0002) was an independent and significant predictor of overall survival (OS) after PDAC resection. After propensity‐score matching, the low CXI group had a significantly worse prognosis than the high CXI group for both DFS and OS. Conclusion: The CXI can be a useful prognostic factor for DFS and OS after pancreatic resection for treatment of PDAC. [ABSTRACT FROM AUTHOR]

Background and Aim: The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. Methods: Whole‐genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. Results: The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non‐tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. Conclusion: This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence. [ABSTRACT FROM AUTHOR]

Aim: Oxaliplatin, an anticancer drug for advanced colorectal cancer, causes liver sinusoidal damage, sometimes with portal hypertension. We conducted a retrospective comparative study of the relationship of liver sinusoidal disorders and liver function with the prognosis in patients who underwent hepatectomy for colorectal liver metastasis (CRLM). Methods: In total, 158 patients who underwent hepatectomy for CRLM were included in the study, and the effect of chemotherapy‐associated liver damage on the prognosis was examined. Results: Preoperative oxaliplatin was used in 75 of 158 patients; of these 75 patients, 26 had intraoperative blue liver (BL). In a comparison of the BL group (n = 26) and non‐BL group (n = 132), patients in the BL group had a significantly lower serum albumin concentration and a significantly higher indocyanine green test result, aspartate aminotransferase‐to‐platelet ratio index (APRI), and FIB‐4 score. Operative morbidities were not significantly different between the two groups. The overall survival rate after hepatectomy was significantly worse in the BL group than in the non‐BL group. In the univariate analysis, the serum albumin concentration, indocyanine green test, a high tumor burden score (TBS), and the APRI were statistically significant poor prognostic factors. In the multivariate analysis, the APRI and a high TBS were independent poor prognostic factors. Conclusion: The APRI and TBS in patients with CRLM are prognostic predictors after hepatectomy for metastatic liver cancer. This study indicated that liver damage in patients treated with preoperative oxaliplatin has an effect on the prognosis. [ABSTRACT FROM AUTHOR]

Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High‐mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage‐associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor‐α and interleukin‐6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1. [ABSTRACT FROM AUTHOR]

Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis. We analyzed 25 advanced HCC patients and prospectively evaluated TEMs before (Pre TEMs) and at 1 month after initial therapy (T1m TEMs). The radiologic response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Median survival time (MST) was significantly longer in the partial response/stable disease (PR/SD) group (21.8 months) than in the PD group (8.7 months). ΔTEMs (changes of T1m TEMs compared to Pre TEMs) were significantly lower in the PR/SD group than in the PD group. MST of the ΔTEMs low group (14.2 months) was significantly longer than that of the high group (8.7 months). Univariate and multivariate Cox regression analyses showed that ΔTEMs [hazard ratio (HR) = 8.53, 95% confidence interval (CI) = 1.51-48.16, p = 0.015] and Child-Pugh class (HR = 5.59, 95% CI = 1.06-29.63, p = 0.043) were independently associated with overall survival. Our results suggest that ΔTEMs could serve as a biomarker for predicting radiologic response and overall survival in sorafenib-treated patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Acoustic radiation force impulse ( ARFI) imaging is an ultrasound-based modality to evaluate tissue stiffness using short-duration acoustic pulses in the region of interest. Virtual touch tissue quantification ( VTTQ), which is an implementation of ARFI, allows quantitative assessment of tissue stiffness. Twenty recipients who underwent living donor liver transplantation ( LDLT) for chronic liver diseases were enrolled. Graft types included left lobes with the middle hepatic vein and caudate lobes (n = 11), right lobes (n = 7), and right posterior segments (n = 2). They underwent measurement of graft VTTQ during the early post- LDLT period. The VTTQ value level rose after LDLT, reaching a maximum level on postoperative day 4. There were no significant differences in the VTTQ values between the left and right lobe graft types. Significant correlations were observed between the postoperative maximum value of VTTQ and graft volume-to-recipient standard liver volume ratio, portal venous flow to graft volume ratio, and post- LDLT portal venous pressure. The postoperative maximum serum alanine aminotransferase level and ascites fluid production were also significantly correlated with VTTQ. ARFI may be a useful diagnostic tool for the noninvasive and quantitative evaluation of the severity of graft dysfunction after LDLT. [ABSTRACT FROM AUTHOR]

Aim Hepatocellular carcinoma ( HCC) is primarily treated with hepatic resection and/or locoregional therapy. When HCC recurs and further treatment is no longer possible owing to poor liver function, liver transplantation ( LT) or living-donor LT ( LDLT) is considered. The aim of this study was to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. Methods The study comprised 104 patients who had undergone LDLT because of end-stage liver disease with recurrent HCC. The recurrence-free survival rates after the LDLT were calculated. Risk factors for tumor recurrence were identified. Results The 1-, 3- and 5-year recurrence-free survival rates were 89.6%, 80.3% and 78.4%, respectively. By univariate analysis, the factors affecting recurrence-free survival were the sum of the largest tumor size and number of tumors of 8 or more ( P < 0.0001), des-γ-carboxy prothrombin of more than 300 mAU/mL ( P = 0.0001), and a neutrophil-to-lymphocyte ratio ( NLR) of 4 or more ( P = 0.0002), α-fetoprotein of more than 400 ng/mL ( P = 0.0001) and bilobar tumor distribution ( P = 0.046). A multivariate analysis identified independent risk factors for post- LDLT tumor recurrence including the sum of tumor size and number of tumors of 8 or more ( P = 0.0004) and an NLR of 4 or more ( P = 0.01). The 1- and 3- year recurrence-free survival rates in the recipients who had both risk factors were 30.0% and 15.0%, respectively. Conclusion LDLT should not be performed for patients who have both independent risk factors after any treatments for HCC. [ABSTRACT FROM AUTHOR]

Background: Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas. Methods: The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011. Results: Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure. Conclusions: Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors. [ABSTRACT FROM AUTHOR]

Aim: A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. Methods: Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/RBV therapy were enrolled. The rs1127354 was determined for each individual. Results: There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n = 43) and those carrying the CA allele (CA group, n = 20). The incidence of hemoglobin (Hb) decline >3 g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels <10 g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels <10 g/dL at 4 weeks ( P = 0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels <10 g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). Conclusion: The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype. [ABSTRACT FROM AUTHOR]