Hepatic vagus activity regulates the inflammatory response of Kupffer cells via α7nAChR in NASH development.

Concomitant MVI was a strong prognostic factor in the setting of HCC with BDTT. Extended hepatectomy provided a good prognosis for the patients with BDTT alone without MVI.

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Background: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. Methods: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. Results: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). Conclusions: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.

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Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome‐wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.

Purpose: Few studies have investigated prognostic biomarkers in patients with intrahepatic cholangiocarcinoma (ICC). Nardilysin (NRDC), a metalloendopeptidase of the M16 family, has been suggested to play important roles in inflammation and several cancer types. We herein examined the clinical significance and biological function of NRDC in ICC. Experimental Design: We measured serum NRDC levels in 98 patients with ICC who underwent surgical resection in two independent cohorts to assess its prognostic impact. We also analyzed NRDC mRNA levels in cancerous tissue specimens from 43 patients with ICC. We investigated the roles of NRDC in cell proliferation, migration, gemcitabine sensitivity, and gene expression in ICC cell lines using gene silencing. Results: High serum NRDC levels were associated with shorter overall survival and disease-free survival in the primary (n ¼ 79) and validation (n ¼ 19) cohorts. A correlation was observed between serum protein levels and cancerous tissue mRNA levels of NRDC (Spearman r ¼ 0.413; P ¼ 0.006). The gene knockdown of NRDC in ICC cell lines attenuated cell proliferation, migration, and tumor growth in xenografts, and increased sensitivity to gemcitabine. The gene knockdown of NRDC was also accompanied by significant changes in the expression of several epithelial-mesenchymal transition (EMT)-related genes. Strong correlations were observed between the mRNA levels of NRDC and EMT-inducing transcription factors, ZEB1 and SNAI1, in surgical specimens from patients with ICC. Conclusions: Serum NRDC, a possible surrogate marker reflecting the EMT state in primary tumors, predicts the outcome of ICC after surgical resection.

The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients.