Time-varying prognostic effects of primary tumor sidedness and grade after curative liver resection for colorectal liver metastases.

BACKGROUND: The veracity of the proportional hazards (PH) requirement is rarely scrutinized in most areas of cancer research, although fulfilment of this assumption underpins widely-used Cox survival models. We sought to critically appraise the existence of prognostic factors with time-dependent effects and to characterize their impact on survival among CLM patients. METHODS: Consecutive patients who underwent liver resection with curative intent for CLM at the Singapore General Hospital were identified from a prospectively-maintained database. We evaluated PH of 55 candidate variables, and parameters which departed significantly from proportionality were included in Cox models that incorporated an interaction term to account for time-dependent effects. As sensitivity analyses, we fitted Weibull mixture 'cure' models to handle long plateaus in the tails of survival curves, and also analyzed the restricted mean survival time. RESULTS: 318 consecutive patients who underwent curative liver resection for CLM between Jan 2000 and Nov 2016 were included in this analysis. Hazard ratios for tumor grade (poorly-versus well- and moderately-differentiated) were found to decrease from 3.135 (95% CI: 1.637-6.003) at 12 months to 2.048 (95% CI: 1.038-4.042) after 24 months, and ceased to be significant at 26 months. Compared to left-sided tumors, a right-sided tumor location was found to portend worse prognosis for the first 10 months after resection but subsequently confer a survival benefit due to a crossing of survival curves. Corroborating this observation, long-term cure fractions were estimated to be 25.5% (95% CI: 17.4%-33.6%) and 34.2% (95% CI: 17.4%-50.9%) among patients with left-sided and right-sided primary disease respectively. CONCLUSION: Primary tumor sidedness and grade appear to exert time-varying prognostic effects in CLM patients undergoing curative liver resection.

Obstructive jaundice due to intraductal tumour thrombus in recurrent hepatocellular carcinoma: what is the optimal therapeutic approach?

Icteric Hepatocellular Carcinoma (HCC) is known to cause intraluminal biliary obstruction by one of three mechanisms: hemobilia from the tumour, migration of tumor debris, or continuous growth along the biliary tree. It is however a very rare presentation of HCC and an important differential diagnosis in the approach to obstructive jaundice. We report a case of a recurrent intraductal hepatocellular carcinoma. The patient initially underwent surgical resection of segment five HCC nine months ago with clear margins. The patient now presents with obstructive jaundice and imaging showed a right intraductal tumour involving the confluence, left and common hepatic ducts. He underwent a right hepatectomy and bile duct tumour thrombectomy despite the apparent absence of a parenchymal tumour. Histological examination showed a 2 mm focus of parenchymal tumour with extension of the tumour into the bile duct. In this case report, we reviewed the literature and describe the different surgical approaches to intraductal hepatocellular carcinomas and discuss the pathological aspects of these bile duct tumour thrombus. We report the favourable outcome of surgical resection for intraductal hepatocellular carcinoma and emphasize that intraductal HCC is not a late stage of disease and adequate surgical resection can still provide a reasonable disease free survival.