Liver resection for metastatic GIST tumor improves survival in the era of tyrosine kinase inhibitors: a systematic review and meta-analysis.

INTRODUCTION: Survival for gastrointestinal stromal tumor (GIST) has been increasing over the years after the introduction of tyrosine kinase inhibitors. However, the role of metastasectomy for GIST is still controversial. Patients are currently treated with imatinib or sunitinib in case of imatinib failures as optimal medical therapy for metastatic GIST. METHODS: The Pubmed, EMBASE, and Cochrane Library were systematically searched. Overall survival following liver resection ± tyrosine kinase inhibitor treatment for metastatic GIST was compared to treatment with tyrosine kinase inhibitors alone. RESULTS: Eleven studies including both randomized control trials and retrospective cohort studies were included in the final analysis with a total of 988 patients. Seven studies encompassed data on 556 patients with isolated liver metastases (219 surgery ± drug groups and 337 drug-only groups) were included. Overall survival was significantly improved in patients undergoing liver resection ± drug therapy in comparison to drug therapy alone. [HR (95%CI) = 2.10 (1.58, 2.79); p<0.00001]. Subgroup analysis showed that patients also had improved progression free survival based on 4 studies. [HR (95%CI) = 1.92 (1.43, 2.56); p<0.00001]. In case of concurrent liver and peritoneal metastases, patients showed improved overall survival with aggressive surgical approaches based on 10 studies. [HR (95%CI) = 1.90 (1.56, 2.31); p<0.00001]. CONCLUSION: This meta-analysis found that liver resection for patients with metastatic GIST regardless of peritoneal metastases improved progression free and overall survival in conjunction with tyrosine kinase inhibitors as compared with medical therapy alone. Furthermore, liver resections did not have any immediate detrimental impact on survival in the group of patients selected.

Concurrent major hepatic resection with primary colorectal cancer increases risk of organ space infections.

INTRODUCTION: Patients with colorectal cancer frequently present with liver metastases requiring either concurrent colon and liver resection or staged resection for curative therapy. The goal of this study is to determine if synchronous resection increases risk of perioperative adverse outcomes such as surgical site infections (SSIs). METHODS AND PROCEDURES: We conducted a cross-sectional retrospective analysis of the targeted hepatectomy NSQIP database from 2015 to 2019. The primary outcome was surgical site infections stratified into superficial, deep, organ space, and wound dehiscence. We performed univariate followed by a multivariate logistic regression to determine if there were higher odds of SSIs in patients undergoing hepatic resection concurrently with primary colorectal resection. Additionally, we performed stratified analyses by size of hepatic resections (partial, total left, total right, and trisegmentectomy). RESULTS: Of the 7,445 patients included in the study, 431(5.8%) underwent synchronous resection and 7,014 metachronous resection. On average, synchronous resections prolonged surgery by 62 min. There was no difference in superficial and deep SSIs between the groups; however, there was a significant difference in organ space SSIs. Patients undergoing synchronous resection had 1.51 times the odds of developing an organ space SSI (OR 1.51, 95%CI 1.10, 2.17, p = 0.04) compared to patients with metachronous resection on multivariate analysis. Patients undergoing a total right hepatectomy concurrently with a colorectal resection had 2.30 times the odds of developing an organ space SSI (OR 2.30, 95%CI 1.20, 6.86, p = 0.010). CONCLUSIONS: Prior studies demonstrated that synchronous resections are safe in properly selected patients with no difference in long-term outcomes. Few studies have explored immediate perioperative outcomes between the two approaches. After controlling for confounders, we demonstrate that synchronous resection with major hepatic surgery increases the risk of organ space SSIs. Future studies should elucidate the precise source of organ space SSIs in order to decrease the risk of this adverse outcome.

Role of rat sarcoma virus mutations in cancer and potential target for cancer therapy.

The prevalence of oncogenic rat sarcoma virus (RAS) mutations has made RAS a popular target for cancer therapies. Significant discoveries have been reported regarding cancer molecular biology following the study of RAS mutations. These discoveries are integral in shaping the era of targeted cancer therapy, with direct targeting of RAS or downstream RAS effectors, such as Grb2 and MAPK a possibility. Novel agents such as farnesyltransferase directly bind and sequester RAS. While these new agents and approaches have shown promise in preclinical and clinical studies, the complexity of RAS signaling and the potential for robust adaptive feedback continue to present substantial challenges. Therefore, the development of targeted therapies will require a detailed understanding of the properties and dependencies of specific cancers to a RAS mutation. This review provides an overview of RAS mutations and their relationship with cancer and discusses their potential as therapeutic targets.