• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1297-1303
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• 2012

Aims: Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-${\beta}$ pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver. Methods: Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting. Results: We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG). Conclusion: Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.17-30
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• 2022

Oncological scoring systems in surgery are used as evidence-based decision aids to best support management through assessing prognosis, effectiveness and recurrence. Currently, the use of scoring systems in the hepato-pancreato-biliary (HPB) field is limited as concerns over precision and applicability prevent their widespread clinical implementation. The aim of this review was to discuss clinically useful oncological scoring systems for surgical management of HPB patients. A narrative review was conducted to appraise oncological HPB scoring systems. Original research articles of established and novel scoring systems were searched using Google Scholar, PubMed, Cochrane, and Ovid Medline. Selected models were determined by authors. This review discusses nine scoring systems in cancers of the liver (CLIP, BCLC, ALBI Grade, RETREAT, Fong's score), pancreas (Genç's score, mGPS), and biliary tract (TMHSS, MEGNA). Eight models used exclusively objective measurements to compute their scores while one used a mixture of both subjective and objective inputs. Seven models evaluated their scoring performance in external populations, with reported discriminatory c-statistic ranging from 0.58 to 0.82. Selection of model variables was most frequently determined using a combination of univariate and multivariate analysis. Calibration, another determinant of model accuracy, was poorly reported amongst nine scoring systems. A diverse range of HPB surgical scoring systems may facilitate evidence-based decisions on patient management and treatment. Future scoring systems need to be developed using heterogenous patient cohorts with improved stratification, with future trends integrating machine learning and genetics to improve outcome prediction.