Colorectal cancer with synchronous unresectable liver metastases: resecting the primary tumor improves survival.

PURPOSE: The optimal treatment strategy of patients affected by colorectal cancer (CRC) with synchronous unresectable liver metastases (SULM) is at present undefined. It is not known if a palliative primary tumor resection followed by chemotherapy could have a survival benefit compared to upfront chemotherapy (CT). The aim of the study is to analyze the safety and effectiveness of both therapeutic strategies in a group of patients treated at one institution. METHODS: A prospectively collected database was queried for patients affected by colorectal cancer with synchronous unresectable liver metastases between January 2004 and December 2018, defining and comparing 2 groups: patients treated by chemotherapy alone (group 1) vs patients who underwent primary tumor resection with or without a first line chemotherapy (group 2). The primary end point was Overall Survival (OS), estimated by the Kaplan-Meier method. RESULTS: One hundred sixty-seven patients were included: 52 in group 1 and 115 in group 2, median follow-up 48 months (range 25-126). A difference of 14 months in overall survival was observed between group 2 compared to group 1 (28 vs 14 months respectively; p < 0.001). Furthermore, overall survival increased in patients who underwent liver metastases resection (p < 0.001) or percutaneous radiofrequency ablation after surgery (p < 0.001). CONCLUSION: With the limits of a retrospective analysis, the study shows that surgical resection of the primary tumor has a significant impact on survival compared to chemotherapy alone. Randomized controlled trials are needed to confirm these data.

A new Italian FHM2 family: clinical aspects and functional analysis of the disease-associated mutation.

OBJECTIVE: To describe a new FHM kindred, and to analyse the functional consequences of the disease-associated ATP1A2 p.G301R mutation in human cellular models grown at 37°C. PATIENTS AND METHODS: Seven patients were clinically evaluated and gave informed consent for molecular analysis. Extra-pyramidal rigidity of the limbs was present in four subjects and in three of them tongue apraxia was also observed. ATP1A2 and CACNA1A were analysed by direct sequencing. Functional consequences of the mutation were investigated by cell viability assays, Western blots, and immunocytochemistry. Three-dimensional models of the human Na(+)/K(+)-ATPase α2 subunit were generated by homology modelling using SWISS-MODEL. FINDINGS: Analysis of ATP1A2 showed a heterozygous mutation, c.901G>A predicting the replacement of arginine for glycine at residue 301 (p.G301R). Functional analysis suggested that the mutation completely abolished Na(+)/K(+)-ATPase function. CONCLUSIONS: The phenotypic spectrum of our FHM2 family includes some peculiar features. Functional data confirm that Na(+)/K(+)-ATPase haploinsufficiency caused by the ATP1A2 p.G301R mutation is responsible for FHM in the described family.