Search

The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC.A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests.Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin.This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Eukaryotic Initiation Factor 4E (eIF4E) plays a crucial role in translation control. High eIF4E increase in tumor specimens independently predicted recurrence by multivariate analysis. This prospective trial of node-negative only breast cancer patients was initiated to test the hypothesis that high eIF4E increase predicts cancer recurrence and death, independent of nodal status.The trial was powered to detect a 2.4-fold increase in relative risk for cancer recurrence in 240 node-negative patients on the basis of high versus low eIF4E increase in tumor specimens (type I error = .05, statistical power = .08). eIF4E level was quantified by using Western blot test. Treatment and surveillance regimens were standardized. Primary endpoints were cancer recurrence and cancer-related death.Of the 242 patients accrued, 112 were in the low eIF4E group (7.5-fold), 82 were in the intermediate eIF4E group (7.5- to 15-fold), and 48 were in the high eIF4E group (15-fold). Patients in the high eIF4E group had a statistically significant higher rate of cancer recurrence and cancer-related death (P = .0001 and Por = .0001, log rank test). The relative risk for cancer recurrence was 2.2-fold higher in the high eIF4E group (P = .001, Cox model), and 3.7-fold higher for cancer-related death (P = .0009).In node-negative breast cancer, high eIF4E increase predicted a higher rate of cancer recurrence and death. High eIF4E patients had a2-fold increase in relative risk for cancer recurrence and nearly a 4-fold increase in relative risk for death. This supports our hypothesis that high eIF4E is an independent predictor for breast cancer outcome independent of nodal status.

The role of radical resection for gallbladder cancer is an ongoing area of debate. In this review, we present our experience managing gallbladder cancer at a tertiary center by using an aggressive surgical approach for T2 or greater disease, reserving simple cholecystectomy only for T1 lesions.Seventy-six patients with histologically confirmed gallbladder cancer were identified from our cancer registry. Estimated survival distributions were calculated by the Kaplan-Meier method, and comparisons were made by using the log-rank test. The Cox proportional hazards model was used to determine the effect on survival of T stage, nodal status, age, and margins.Sixty-four patients were assessable for this study. Simple cholecystectomy was the only procedure performed in 10 T2 and 15 T3 cases. Radical cholecystectomy was performed as the primary procedure in two T2, two T3, and six T4 cases. Radical re-resection was accomplished in seven T2 and two T3 cases. Excluding the T4 group, there was a significant survival advantage (P = .007) for the radical resection group (n = 13; median survival not yet reached) compared with the simple cholecystectomy group (n = 25; median survival, 17 months; 95% confidence interval, 7-27 months). Analysis of the 13 T2 and T3 patients who underwent radical resections revealed that the radical re-resection group (n = 9) had an overall survival similar to that of the primarily resected group (n = 4). All T2N(+) and T3N(-) patients are still alive and disease free after 5 years of follow-up, whereas none of the T3N(+) or T4 patients survived beyond 24 months. Increasing T stage and age (65 years) were independent predictors of a poor prognosis.Radical resection for T2 and T3 disease resulted in a significant survival advantage compared with simple cholecystectomy. Patients who undergo radical re-resection after an incidentally discovered gallbladder cancer experience the same survival benefit as primarily resected patients. Radical resection for T2N(-), T2N(+), and T3N0 cases can achieve long-term survival. Conversely, the prognosis for T3N(+) and T4 patients is poor, and improved outcome for this group will likely depend on the development of multi-institutional neoadjuvant clinical trials that can identify effective systemic regimens.

Although HER-2 negative tumors are thought to be less aggressive than their counterpart, there is a subset that behaves poorly. The molecular mechanism to account for this is unknown. The chemokine receptor CXCR4 is often upregulated in a wide array of cancers. Using a training dataset, we previously reported that high CXCR4 overexpression portends a poor outcome among patients with HER-2 negative breast tumors. This study aims to validate these findings, using our validation dataset.There were 115 patients with stages I-III, HER-2 negative breast cancers who were prospectively accrued and analyzed. CXCR4 levels from primary tumors were detected using Western blots, and results were quantified against 1 microg of HeLa cells. CXCR4 expression was defined as low (6.6 fold) or high (or =6.6 fold). Primary endpoint was cancer recurrence. Statistical analysis performed included Spearman correlation, Fisher exact test, Kaplan-Meier survival analysis, Cox proportional hazard ratio model, and log-rank test.There were 13 patients in the high (or =6.6 fold) and 102 patients in the low CXCR4 group (6.6 fold). Overall survival (OS) and disease-free survival (DFS) for the cohort was 84 and 71%, respectively. The 5-year OS for the high CXCR4 group was 52% and for the low CXCR4 group was 86% (P = 0.08). The 5-year DFS for the high CXCR4 and low CXCR4 group was 38 and 74%, respectively (P = 0.01).We validated that high CXCR4 overexpression in primary tumors of patients with HER-2 negative tumors portend a poor outcome. These findings should be confirmed with either a prospective clinical trial and/or an external validation study.

Adenocarcinoma of the pancreas continues to be a formidable disease. In the United States, patients who have had resected disease are generally offered adjuvant chemoradiation. The current National Comprehensive Cancer Network practice guidelines uniformly support this practice. We reviewed seven selected series to evaluate the efficacy of adjuvant therapy for patients who had resected adenocarcinoma of the pancreas. Current evidence-based analysis demonstrates that an adjuvant therapy regimen as a standard of care is lacking. We, therefore, believe that it should be used judiciously because its benefit is confined to only a fraction of patients treated by complete resection (R0); patients with residual microscopic disease (R1) derived negligible benefits. Given the financial constraints and the small effect that current therapies have on this fatal disease, clinicians should concentrate on developing novel therapies and new paradigms to address this age-old problem.

Neuroendocrine tumors of the pancreas are rare tumors. We identified predictive factors that are associated with long-term survival (or=5 years).Fifty patients with a diagnosis of neuroendocrine tumors of the pancreas were retrospectively evaluated. The following factors were evaluated for disease-specific mortality: age, sex, primary tumor location, functional status, type of primary tumor treatment, presence or absence of liver metastases, timing of liver metastases occurrence, and type of liver metastases treatment. Aggressive treatment of the liver metastases included surgery, chemoembolization, or intrahepatic arterial infusion chemotherapy.Twenty-three patients (47%) had tumor located in the head of the pancreas, and 29 patients (58%) had nonfunctioning tumor. Thirty-nine patients (78%) had liver metastases. The median follow-up for the entire group was 35 months (range,.76-206 months). The median survival for the entire group was 40 months, and the overall 1-, 2-, and 5-year survival rates were 84%, 69%, and 36%, respectively. Factors that had a significant favorable effect on survival included curative resection of the primary tumor, metachronous liver metastases, absence of liver metastases, and aggressive treatment of the liver metastases.Definitive surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of the liver metastases were predictors of long-term survival in patients with neuroendocrine tumors of the pancreas.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement