Chronic viral hepatitis patients, especially hepatitis C patients, often fall victim to liver cirrhosis and subsequent hepatocellular carcinoma (HCC). 1 It is now believed that the HCV infection in hepatocytes itself is not cytopathic whereas the cellular immune response to infected hepatocytes may indeed cause hepatocyte injury. 1 It has been suggested that nonspecific NK cell activation 1,2 and viral antigen-specific activation of either CD4 ϩ T cells or cytotoxic CD8 ϩ T cells may be responsible for hepatocyte injury. 1,3-6 Consistent with this hypothesis, it has also been reported that liver lymphocytes expressed T helper 1 cytokine, IFN-␥, and IL-2 messenger RNA, and the serum levels of these cytokines were elevated in the patients with HCV. 7,8 On the other hand, livers from mice and humans have recently been reported to contain not only a large population of NK cells but also of T cells with NK cell markers. 9-13 Namely, mouse NK1.1 antigen ϩ T (NKT) cells and human CD56 ϩ T cells are abundant in the livers. NKT cells in mice were activated by IL-12 and inhibited tumor metastases in the liver of mice 10,11,14-16 (for a review, see Seki et al.,16 ). Human peripheral blood CD56 ϩ T cells were also activated in vitro by IL-12 and thus acquired an antitumor cytotoxicity against NK-resistant tumors. 13 Furthermore, strongly activated mouse liver NKT cells destroyed the syngeneic hepatocytes. 17 Therefore, the possibility has been raised that human CD56 ϩ T cells may also play an important role in both hepatocyte injury in chronic viral hepatitis and antitumor immunity in the liver. In the present study, we show that human liver MNC activated by anti-CD3 Ab or a combination of IL-2 and IL-12 (or IL-2 alone) both produced IFN-␥ and killed tumors more effectively than did PBMC. Furthermore, human liver CD56 ϩ T cells and CD56 ϩ NK cells gradually decreased in parallel with the progress of the hepatitis C and diminished in livers with cirrhosis. These liver MNC from cirrhotic livers could not effectively produce IFN-␥ and could not effectively kill not only K562 cells and Raji cells but also a human HCC cell line, HuH-7 cells, thus suggesting that the decrease in CD56 ϩ T cells and NK cells may be one of the mechanisms explaining why HCC frequently originates from cirrhotic livers. PATIENTS AND METHODSPatients and Liver Specimens. Liver specimens were obtained during surgery from the patients listed in Table 1 after obtaining their informed consent. Liver specimens obtained from the anti-HCV Aband HBs antigen (Ag)-negative patients with cancers other than HCC and were regarded as the HCV (Ϫ) liver specimens. Other liver specimens were from anti-HCV Ab-positive patients with chronic hepatitis C or with liver cirrhosis. Peripheral blood samples were also obtained during surgery. All liver specimens were obtained from areas other than tumor nodules.Reagents. Anti-CD3 Ab (UCHT1, mouse IgG1) were purchased from PharMingen (San Diego, CA). Recombinant human IL-2 and IL-12 were purchased from PEPRO TECH EC (London, UK). ...

To identify differentially expressed genes in hepatocarcinogenesis, we performed differential display analysis using surgically resected hepatocellular carcinoma (HCC) and adjacent non-tumorous liver tissues. We identified four cDNA fragments upregulated in HCC samples, encoding antisecretory factor-1 (AF), gp96, DAD1 and CDC34. Northern blot analysis demonstrated that these mRNAs were expressed preferentially in HCCs compared with adjacent non-tumorous liver tissues or normal liver tissues from non-HCC patients. The expression of these mRNAs was increased along with the histological grading of HCC tissues. These mRNA levels were also high in three human HCC cell lines (HuH-7, HepG2 and HLF), irrespective of the growth state. We also demonstrate that sodium butyrate, an inducer of differentiation, downregulated the expression of AF and gp96 mRNAs, supporting in part our pathological observation. Immunohistochemical analysis revealed that gp96 and CDC34 proteins were preferentially accumulated in cytoplasm and nuclei of HCC cells, respectively. Overexpression of these genes could be an important manifestation of HCC phenotypes and should provide clues to understand the molecular basis of hepatocellular carcinogenesis.

Dynamic computed tomography (CT) was performed in nine patients with enlarged bronchial arteries documented by arteriography. Plain and contrast-material-enhanced CT scans of two more patients with prominent bronchial arteries were retrospectively reviewed. The study was conducted to determine visibility of the bronchial artery with CT and to depict the anatomic relationship of its mediastinal portion to surrounding structures. The mediastinal portion of the bronchial artery was successfully outlined as nodular or linear densities on all dynamic CT scans. The right bronchial artery was confirmed to arise from the medial wall of the thoracic aorta, whereas the left arises from the anterior wall. Because of its retroesophageal location, the enlarged right bronchial artery can compress the posterior wall of the esophagus. It is postulated that the left bronchial artery occasionally traverses the aorticopulmonary window, recognized as nodular or linear densities below the aortic arch on CT scans.

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AimSystemic inflammation and nutritional status are associated with clinical outcomes of cancer patients. We investigated the prognostic value of preoperative C‐reactive protein to albumin ratio (CAR) in patients with pancreatic ductal adenocarcinoma (PDA) after pancreatic resection.MethodsOne‐hundred and thirty‐six PDA patients who underwent pancreatic resection between January 2005 and June 2017 were retrospectively enrolled. Preoperative inflammation‐based scores including CAR, modified Glasgow prognostic score (mGPS), neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI) were evaluated as potential predictor of overall survival (OS) using Cox regression models. An optimal cutoff value for the continuous variable was estimated by receiver‐operating characteristic (ROC) analysis.ResultsPatients were categorized by CAR using a cutoff value of 0.09. High CAR was associated with advanced stage, increased mGPS and decreased LMR and PNI, but not with other factors such as tumor location, preoperative biliary drainage or preoperative chemotherapy. In univariate analysis, patients with high CAR had poor OS compared with those with low CAR (P = 0.01). Multivariate analysis indicated that high CAR was an independent predictor of poor OS (P = 0.03) in addition to advanced stage and residual tumors. The predictive ability of CAR evaluated by area under the ROC curve was consistently higher than that of other inflammation‐based factors.ConclusionPreoperative CAR was an independent and superior predictor of survival after pancreatic resection in patients with PDA.[Correction added on 17 January 2019, after first online publication: In Conclusion, “in” has been corrected to “independent” for clarity.]