Jason W. Denbo

Is hepatectomy justified for patients with RAS mutant colorectal liver metastases? An analysis of 524 patients undergoing curative liver resection

BACKGROUND RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with RAS mutant colorectal liver metastases. METHODS Of 1,163 patients who underwent liver resection for colorectal liver metastases during 2005–2014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis. RESULTS A total of 524 patients met the inclusion criteria; 212 (40%) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14%). At median follow‐up of 38 months, median overall survival was 72.6 months for wild‐type RAS and 50.9 months for mutated RAS (P < .001). Median overall survival for patients with codon 12 and 13 mutations was 51.9 and 50.9 months, respectively (P = .839), significantly worse than for patients with wild‐type RAS (P = .005, and P = .038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node‐positive primary tumor, tumor >3 cm, and >7 cycles of preoperative chemotherapy. Major and 2‐stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4‐year survivors in the highest‐risk group. CONCLUSION Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.

Impact of pancreatectomy on long‐term patient‐reported symptoms and quality of life in recurrence‐free survivors of pancreatic and periampullary neoplasms

Long term patient‐reported symptoms and quality of life (QOL) are important outcome metrics following cancer operations, but have been poorly described in patients who have previously undergone pancreatectomy.

Selective Perioperative Administration of Pasireotide is More Cost-Effective Than Routine Administration for Pancreatic Fistula Prophylaxis

BackgroundIn a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective.Study DesignConsecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors. The costs of treating hypothetical patients in each risk group were then computed based upon actual institutional hospital costs and previously published relative risk values associated with pasireotide.ResultsAmong 315 patients who underwent pancreatectomy, grade B/C POPF occurred in 64 (20%). RPA allocated patients who underwent PD into four groups with a risk for grade B/C POPF of 0, 10, 29, or 60% (P < 0.001) on the basis of diagnosis, pancreatic duct diameter, and body mass index. Patients who underwent DP were allocated to three groups with a grade B/C POPF risk of 14, 26, or 44% (P = 0.05) on the basis of pancreatic duct diameter alone. Although the routine administration of pasireotide to all 315 patients would have theoretically saved

Definition and Management of Borderline Resectable Pancreatic Cancer

30,892 over standard care, restriction of pasireotide to only patients at high risk for POPF would have led to a cost savings of

Current survival and treatment trends for surgically resected intrahepatic cholangiocarcinoma in the United States

831,916.ConclusionPreoperative clinical characteristics can be used to characterize patients’ risk for POPF following pancreatectomy. Selective administration of pasireotide only to patients at high risk for grade B/C POPF may maximize the cost-efficacy of prophylactic pasireotide.

Current issues of borderline resectable pancreatic ductal adenocarcinoma

Patients with localized pancreatic ductal adenocarcinoma seek potentially curative treatment, but this group represents a spectrum of disease. Patients with borderline resectable primary tumors are a unique subset whose successful therapy requires a care team with expertise in medical care, imaging, surgery, medical oncology, and radiation oncology. This team must identify patients with borderline tumors then carefully prescribe and execute a combined treatment strategy with the highest possibility of cure. This article addresses the issues of clinical evaluation, imaging techniques, and criteria, as well as multidisciplinary treatment of patients with borderline resectable pancreatic ductal adenocarcinoma.

Preoperative Chemoradiation for Pancreatic Adenocarcinoma Does Not Increase 90-Day Postoperative Morbidity or Mortality

Background Intrahepatic cholangiocarcinoma (ICC) is a rare and aggressive disease with an increasing incidence in the United States, and there is no level 1 evidence to help guide treatment decisions. We sought to determine national trends in surgical and medical management of patients with resected ICC, and more specifically, the role of lymphadenectomy (LAD) and utilization of chemotherapy. Methods An augmented version of the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) cancer database registry was used to identify all surgically resected ICC patients from 2000 to 2014. We evaluated the incidence and adequacy of LAD, and receipt of chemotherapy over time. Next, multivariable logistic regressions were performed to determine the predictors of LAD and receipt of chemotherapy. Overall survival (OS) was evaluated using Kaplan-Meier and Cox proportional hazard models. Results We identified 1,263 patients who underwent resection for ICC. Lymph nodes (LNs) were removed in 49% of patients, however, only 10% of patients received adequate LAD by the American Joint Committee on Cancer (AJCC) criteria (≥6 nodes). LN metastases were found in 29% of patients who underwent nodal evaluation. Chemotherapy was administered to 40% of patients, was utilized more frequently over time (P<0.05), and was associated with improved survival in node positive patients (P<0.05). Patients who did not have LNs evaluated were significantly less likely to receive chemotherapy than those who did. Lastly, OS for the entire cohort improved over time (P<0.05). Conclusions After analyzing the treatment and outcomes of resectable ICC, we concluded: (I) LN evaluation at the time of surgical resection remains inadequate; (II) utilization of chemotherapy has increased over time; (III) the lack of LAD likely results in under-staging and underutilization of chemotherapy; and (IV) despite less than ideal surgical and medical therapy median OS continues to improve.

RAS Mutation Is Associated with Decreased Survival in Patients Undergoing Repeat Hepatectomy for Colorectal Liver Metastases

Patients with localized pancreatic ductal adenocarcinoma seek potentially curative treatment, but experience with this patient group has taught clinicians that this group is a spectrum. Patients with borderline resectable primary tumors are a unique subset whose successful therapy requires a care team with expertise in medical care, imaging, surgery, medical, and radiation oncology. This team must identify patients with borderline tumors and then carefully prescribe and execute a combined treatment strategy with the highest possibility of cure. For this reason, this chapter will address the issues of clinical evaluation, imaging techniques and criteria, as well as multidisciplinary treatment and surgery as they relate to the patient with borderline resectable pancreatic ductal adenocarcinoma.