Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

Discrete improvement in racial disparity in survival among patients with stage IV colorectal cancer: a 21-year population-based analysis.

PURPOSE: Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent. PATIENTS AND METHODS: Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988-2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses. RESULTS: Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p < 0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991-1.000) per year (p = 0.03). CONCLUSION: A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008.

We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization.

AIM: Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction. METHODS: In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay. RESULTS: Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014). CONCLUSIONS: A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.

Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas.

PURPOSE: To determine the clinical outcomes and potential impact of adjuvant chemoradiation in patients undergoing surgical resection of ampullary carcinoma. PATIENTS AND METHODS: Between 1988 and 1997, 39 patients underwent pancreaticoduodenectomy for ampullary adenocarcinomas. Clinical and pathologic factors, adjuvant therapy records, and disease status were obtained from chart review. Thirteen (33%) patients received adjuvant chemoradiation. Radiation therapy was delivered to the surgical bed and regional nodes to a median dose of 4,860 cGy with concurrent bolus or continuous infusion of 5-fluorouracil. Outcomes measures included locoregional control, disease-free survival, and overall survival. Univariate analysis was used to assess the impact of various patient- and tumor-related factors and the use of adjuvant therapy. Twenty (51%) patients with tumor invasion into the pancreas (T3) or node-positive disease were classified in a "high-risk" subgroup. RESULTS: After a median follow-up of 45 months for survivors, overall 3-year survival was 55%. Survival was significantly worse for patients with positive nodes (23% vs. 73%, p < 0.001) and high-risk status (30% vs. 80%, p = 0.002). Disease-free survival was 54% at 3 years. There were 3 postoperative deaths, and these patients (all high risk) are excluded from further analysis on adjuvant therapy. In univariate analysis, the use of adjuvant chemoradiation had no clear impact on local-regional control or overall survival. However, by controlling for risk status in multivariate analysis, the use of adjuvant therapy reached statistical significance for overall survival (p = 0. 03). Among the high-risk patients, 7 (77%) of 9 patients receiving adjuvant therapy remained disease-free during follow-up compared with only 1 (14%) of 7 patients not receiving adjuvant therapy (p = 0.012). CONCLUSION: Despite the relatively favorable prognosis of ampullary carcinomas compared with other pancreaticobiliary tumors, patients with nodal metastases or T3 disease are at high risk for disease relapse. The use of adjuvant chemoradiation may improve long-term disease control in these patients.