ABSTRACT
Variable survival outcomes are seen following treatment for aggressive non-Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B-cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress-related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline-based therapies. Their associations with progression-free survival (PFS) and overall survival (OS) were estimated by Cox proportional hazard regression; associations with hematologic toxicity were estimated by logistic regression. To validate the findings, the top three SNPs were tested in an independent cohort of 572 DLBCL patients. The top SNPs associated with PFS in the discovery cohort were the rare homozygotes for MPO rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14-3.06, P = 0.013), AKR1C3 rs10508293 (HR = 2.09, 95% CI = 1.28-3.41, P = 0.0032) and NCF4 rs1883112 (HR = 0.66, 95% CI = 0.43-1.02, P = 0.06). The association of the NCF4 SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44-1.01, P = 0.05) and the meta-analysis was significant (HR = 0.66, 95% CI = 0.49-0.89, P < 0.01). The association of the MPO SNP was attenuated in the validation dataset, while the meta-analysis remained significant (HR = 1.64, 95% CI = 1.12-2.41). These two SNPs showed similar trends with OS in the meta-analysis (for NCF4, HR = 0.72, 95% CI = 0.51-1.02, P = 0.07 and for MPO, HR = 2.06, 95% CI = 1.36-3.12, P < 0.01). In addition, patients with the rare homozygote of the NCF4 SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in NCF4 may contribute to treatment outcomes for patients with aggressive NHL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/genetics , Oxidative Stress/genetics , Adult , Aged , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Female , Humans , Lymphoma, B-Cell/metabolism , Male , Middle Aged , Multicenter Studies as Topic , Polymorphism, Single Nucleotide , Prognosis , Proportional Hazards Models , Randomized Controlled Trials as Topic , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Fellowships in advanced laparoscopy with emphasis in laparoscopic gastric bypass (LGBP) are available for obtaining experience in performing LGBP. The following is the first report in the literature prospectively documenting a single surgeon's experience with LGBP outcomes following completion of an advanced laparoscopic surgical fellowship. METHODS: Outcomes measured prospectively included length of stay, length of operation, complications, reduction in obesity-related co-morbidities, and percentage excess weight loss. Outcomes were analyzed by quartile to see if there was difference over time. Complications were also compared to outcomes in the literature. RESULTS: 175 patients (147 female, 28 male) underwent LGBP. The mean BMI was 49.2. Mean operative time was 123 minutes, and mean length of stay was 2.2 days. The percentage excess weight loss at 1 year was 73% (n = 79). One patient developed an internal hernia (0.6%) and 1 patient developed an anastomotic leak (0.6%). Post operative transfusion rate was 4.6%. There were no deep venous thromboses or pulmonary emboli detected. There were no conversions to open, and there was no mortality. Upon quartile analysis, there was no difference in complication rates. Complication rates were comparable to published outcomes in the literature. CONCLUSION: Fellowships in advanced laparoscopy with emphasis on LGBP provide the optimal training environment for acquisition of skills necessary to safely and effectively perform LGBP. With fellowship training, complication rates were comparable to published outcomes in the literature without a period of higher complications (the learning curve).
