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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: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, and such early recurrence (ER) is associated with a poor prognosis. Predicting ER is useful for determining the optimal treatment. Methods: One hundred fifty-three patients who underwent pancreatectomy for PDAC were divided into an ER group (n = 54) and non-ER group (n = 99). Clinicopathological factors were compared between the groups, and the predictors of ER and prognosis after PDAC resection were examined. Results: The ER group had a higher platelet count, higher platelet-to-lymphocyte ratio (PLR), higher preoperative CA19-9 concentration, higher SPan-1 concentration, larger tumor diameter, and more lymph node metastasis. The receiver operating characteristic (ROC) curve analysis identified cut-off values for PLR, carbohydrate antigen 19–9 (CA19-9), SPan-1, and tumor diameter. In the multivariate analysis, a high PLR, high CA19-9, and tumor diameter of >3.1 cm were independent predictors of ER after resection (all p < 0.05). When the parameter exceeded the cut-off level, 1 point was given, and the total score of the three factors was defined as the ER prediction score. Next, our new ER prediction model using PLR, CA19-9 and tumor diameter (Logit(p) = 1.6 + 1.2 × high PLR + 0.7 × high CA19-9 + 0.5 × tumor diameter > 3.1cm) distinguished ER with an area under the curve of 0.763, a sensitivity of 85.2%, and a specificity of 55.6%. Conclusions: ER after resection of PDAC can be predicted by calculation of a score using the preoperative serum CA19-9 concentration, PLR, and tumor diameter. [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]

Background: There is limited published information about prognostic value of vessels that encapsulate tumor cluster (VETC) based on their involvement with immune cells in hepatocellular carcinoma (HCC). Our goal was to evaluate prognostic impact of VETC in patients who underwent living-donor liver transplantation (LDLT) for HCC, focusing on the involvement of VETC with immune status in tumor microenvironment (TME). Methods: Using a database of 150 patients who underwent LDLT for HCC, immunohistochemical staining of CD34 for VETC, angiopoietin-2 (Ang-2), CD3, and CD68, was reviewed with patients' clinicopathological factors. Results: A strong correlation between VETC pattern and malignant potential in HCC was observed; larger tumor size (P < 0.001), more numbers of tumors (P = 0.003), higher α-fetoprotein levels (P = 0.001), higher des-γ-carboxy prothrombin levels (P = 0.022), microvascular invasion (P < 0.001), and poor differentiation (P = 0.010). Overall survival (OS) of patients with VETC(+) was significantly lower than those with VETC(−) (P = 0.021; 5-year OS rates, 72.0% vs. 87.1%). Furthermore, the ratio of CD3(+) cells was significantly lower in VETC(+) group (P = 0.001), indicating that VETC activity may be strongly correlated with lymphocyte activity. Moreover, combination status of VETC(+)/CD3low was an independent risk factor for mortality (hazard ratio 2.760, 95% confidence interval 1.183–6.439, P = 0.019). Additionally, the combination of VETC expression with immune status (low CD3 levels) enabled further classification of patients based on their clinical outcome. Conclusions: Our results show the prognostic impact of VETC expression, tumor-infiltrating lymphocytes (TILs), and their combination in the setting of LDLT for HCC, which can be a novel prognostic biomarker for mortality after LDLT. [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]