Impact of genetic targets on cancer therapy: hepatocellular cancer.

Understanding cancer at the genetic level had gained significant attention over the last decade since the human genome was first sequenced in 2001. For hepatocellular carcinoma (HCC) a number of genome-wide profiling studies have been published. These studies have provided us with gene sets, based on which we can now classify tumors and have an idea about the likely clinical outcomes. In addition to that, genomic profiling for HCC has provided us a better understanding of the carcinogenesis process and identifies key steps at multiple levels (i.e. Genetics, molecular pathways) that can be potential targets for treatment and prevention. Although still an incurable disease, unresectable HCC has one proven systemic therapy, sorafenib, and many under active investigation. With advancement in technology and understanding of hepatocarcinogenesis, scientists hope to provide true personalized treatment for this disease in the near future. In this review article we discuss advances in understanding genetics and pathogenesis of HCC and the currently available and ongoing trials for targeted therapies. These emerging therapies may guide the development of more effective treatments or possibly a cure for HCC.

Additional organ resection combined with pancreaticoduodenectomy does not increase postoperative morbidity and mortality.

BACKGROUND: The mortality associated with pancreaticoduodenectomy (PD) has decreased substantially in recent times, but high morbidity continues to be a significant problem. With reductions in mortality, there is increasing willingness to combine organ resections with PD when indicated. There is, however, a paucity of information regarding the morbidity and mortality of multivisceral resection (MVR) that involves pancreaticoduodenectomy (MVR-PD). METHODS: Patients undergoing PD between January 2002 and November 2007 by a single surgeon were reviewed and perioperative outcomes determined. Those treated by PD alone were compared to those undergoing MVR-PD. RESULTS: There were 105 patients overall who underwent PD during the study period, with MVR-PD performed in 19 patients. Twelve (63%) patients required PD combined with right colectomy, two (11%) underwent PD combined with right nephrectomy, two (11%) required liver resection with PD, and the remaining three (16%) had various combinations of kidney, colon, adrenal and small bowel resection in addition to PD. In both groups, the main indication for surgery was pancreatic cancer; however, there were proportionally more patients in the MVR-PD group with gastrointestinal stromal tumors (two (11%) patients), sarcomas (two (11%) patients) and metastases to the periampullary region (three (16%) patients). The overall complication rate in this study was 60%. Delayed gastric emptying (39%) and pancreatic fistula (16%) were the most common complications. There was no significant difference in complications between the two groups. A non pylorus-preserving PD was more commonly performed in cases of MVR-PD (53% vs 28%; p = 0.007), operating times were longer (9.5 vs 8 h; p = 0.002), and surgical intensive care unit stay was greater (2 vs 1 days; p < 0.001). The overall median length of hospital stay (7 days) and readmission rate were similar between the groups. CONCLUSION: MVR-PD can be performed without significant added morbidity compared to PD alone. The main indication for MVR-PD is locally advanced pancreatic cancer requiring PD combined with right hemicolectomy.

A reduction in delayed gastric emptying by classic pancreaticoduodenectomy with an antecolic gastrojejunal anastomosis and a retrogastric omental patch.

BACKGROUND: Delayed gastric emptying (DGE) continues to be a major cause of morbidity following pancreaticoduodenectomy (PD). A change in the method of reconstruction following PD was instituted in an attempt to reduce the incidence DGE. METHODS: Patients undergoing PD from January 2002 to December 2008 were reviewed and outcomes determined. Pylorus-preserving pancreaticoduodenectomy (PPPD) with a retrocolic duodenojejunal anastomosis (n = 79) or a classic PD with a retrocolic gastrojejunostomy (n = 36) was performed prior to January 2008. Thereafter, a classic PD with an antecolic gastrojejunal anastomosis and placement of a retrogastric vascular omental patch was undertaken (n = 36). RESULTS: A statistically significant decrease in DGE was noted in the antecolic group compared to the entire retrocolic group (14% vs 40%; p = 0.004) and compared to patients treated by classic PD with a retrocolic anastomosis alone (14% vs 39%; p = 0.016). On multivariate analysis, the only modifiable factor associated with reduced DGE was the antecolic technique with an omental patch, odds ratio (OR) 0.3 (confidence interval (CI) 0.1-0.8) p = 0.022. Male gender was associated with an increased risk of DGE with OR 2.3 (CI 1.1-4.8) p = 0.026. CONCLUSION: A classic PD combined with an antecolic anastomosis and retrogastric vascular omental patch results in a significant reduction in DGE.

Surgical outcomes of patients with gastrointestinal stromal tumors in the era of targeted drug therapy.

BACKGROUND: The discovery of the c-KIT mutation and the advent of targeted drug therapy with imatinib mesylate have revolutionized the management of gastrointestinal stromal tumors (GISTs). The outcome of patients with surgically treated GISTs treated in the era of targeted drug therapy was assessed and factors associated with adverse outcomes determined. MATERIALS AND METHODS: Patients with GISTs requiring surgery at a tertiary care center from 2002 to 2007 were reviewed and prognostic factors determined. RESULTS: Forty patients were surgically treated for GISTs. The median age at presentation was 59 years. The stomach (55%) was the main site of primary disease. The median tumor size was 7 cm. Eleven (28%) patients had metastatic disease at presentation. Surgery was undertaken in all patients with curative intent. Multi-organ resection was required in 10 (25%) patients. Imatinib mesylate was administered postoperatively in 68% of cases. Median follow-up was 24 months. There was a 40% recurrence rate with 63% undergoing repeat surgical resection. The peritoneum and liver were the main sites of recurrent disease. The 5-year disease-specific survival and disease-free survival (DFS) were 65% and 35%, respectively. High mitotic rate (P = 0.017) and tumor size greater than 10 cm (P = 0.009) were the only prognostically significant adverse factors of DFS on multivariate analysis, independent of imatinib mesylate treatment. CONCLUSION: Aggressive surgical treatment and follow-up of GISTs, combined with targeted drug therapy, leads to long-term DFS survival. Tumor recurrence is independently associated with a high tumor mitotic rate and size greater than 10 cm, despite the use of adjuvant targeted drug therapy.