Pramod Bonde

Rabeprazole impedes the development of reflux-induced esophageal cancer in a surgical rat model.

BackgroundThe role of proton pump inhibitors in Barrett’s metaplasia and esophageal adenocarcinoma has been an area of controversy.AimsWe evaluated the effectiveness of the proton pump inhibitor rabeprazole as a chemoprevention agent in a surgical rat reflux model of esophageal cancer.MethodsThe rat reflux model was created by performing a jejuno-esophagostomy on Sprague–Dawley rats. The surgery promoted the reflux of gastro-duodenal contents into the esophagus. Rabeprazole sodium (Eisai, Tokyo, Japan) was dissolved in 0.9% physiological saline to a desired concentration of 1.5% (W/V). Beginning 4xa0weeks post-surgery, all animals were administered either 0.2xa0ml per 100xa0g body weight injections of rabeprazole or equivalent injections of saline 3xa0days per week into the subcutaneous tissue of the back. Forty animals were killed 40xa0weeks after surgery and their esophagi were examined. Of these, 23 were included in the control group, while the remaining 17 were subjected to rabeprazole.ResultsWhile 74% (17/23) of the controls developed esophageal cancer, animals administered rabeprazole had an incidence of cancer of 29% (5/17) (pxa0<xa00.05, Fishers exact test). Barrett’s metaplasia was found on 100% (23/23) of the rats in the placebo group, but there was a protective effect in the rabeprazole group with 65% (11/17) of the rats displaying signs of Barrett’s metaplasia (pxa0<xa00.05, Fishers exact test). All of the rats developed proliferative hyperplasia.ConclusionsRabeprazole protected against the development of esophageal cancer in a clinically relevant surgical reflux model. Rabeprazole warrants further investigation for potential clinical use as a chemoprevention agent.

Vaccine Impedes the Development of Reflux-Induced Esophageal Cancer in a Surgical Rat Model: Efficacy of the Vaccine in a Pre-Barrett’s Esophagus Setting

Background & AimsWe developed a granulocyte-macrophage-colony-stimulating factor (GM-CSF) tumor vaccine for esophageal cancer. We evaluated the effectiveness of the vaccine as a prevention option in a surgical reflux rat model of esophageal cancer.MethodsA surgical model involving a jejuno-esophagostomy was used to create Barrett’s esophagus and esophageal cancer in rats. No carcinogen exposure was utilized. Cell lines derived from these tumors were stably passaged in vitro. GM-CSF-secreting tumor cells were generated using stable transfection. All rats underwent a total gastrectomy, followed by a jejuno-esophagostomy. The surgery promoted the reflux of duodenal contents into the esophagus. All animals were administered either a GM-CSF secreting whole cell vaccine or a phosphate-buffered saline (PBS) placebo injection 4, 6, 14, and 16xa0weeks post-surgery.ResultsWhile 15 of 16 animals in the non-vaccinated placebo group developed esophageal cancer, 94% (15 of 16), animals in the vaccine group had an incidence of cancer of 25% (4 of 16) (pu2009<u20090.05). Barrett’s esophagus was seen in 100% (16 of 16) of the controls and 83% (13 of 16) of the vaccinated animals.ConclusionsA GM-CSF-secreting whole cell tumor vaccine impeded esophageal tumor growth, but not the development of Barrett’s esophagus, in a clinically relevant surgical reflux model.

Long term results and functional outcomes following cardiac surgery in octogenarians

Objective. Cardiac surgery for patients >80 years has seen a dramatic increase in the last decade. The aim was to assess the long term survival and quality of life in this patient population. Method. Patients who underwent cardiac surgery between 1995 and 2007 were identified and case notes reviewed. Follow-up was undertaken by personal interview with the patient or the nearest kin to complete a pre-planned questionnaire. Results. Sixty six (M:F; 45:21) octogenarians had Coronary artery bypass grafting (CABG) only (55%), Aortic valve replacement (AVR) only (12%), Mitral valve replacement (MVR) only (3%), Valve and CABG (25%) and complex procedures (5%). Fifty-eight percent were elective procedures. Operative mortality was 8% (n = 5). Multivariate analysis identified complex procedures, prolonged bypass time and re-do/emergency surgery as predictors of death (p < 0.05). Median Intensive care unit (ICU) stay was 206 h (range 43–1176 h), with >70% leaving ICU in 72 h. Late mortality involved five patients (8%) who died at 10 yr; 7 yr; 3 yr; 1 yr; and 8 months; and 2 yr and 7 months, respectively. Survival by Kaplan–Meir was 8.8 yr (Standard Error (SE) = 0.66, Confidence interval (CI) 7.6–10.1), median survival was 10 yr and mean Barthels index 17.7 (min 0, max 20). Conclusions. Cardiac surgery can be accomplished in octogenarians with good long-term survival and quality of life. However, complex procedures, prolonged bypass and re-do/emergency surgery contribute significantly to mortality.

Vaccine Impedes the Development of Reflux-induced Esophageal Cancer in a Surgical Rat Model: Efficacy of the Vaccine in a Post-Barrett’s Esophagus Setting

Purpose We developed and evaluated a GM-CSF whole-cell tumor vaccine for esophageal cancer. Experimental design Cell lines derived from surgically induced rat reflux esophageal tumors were passaged inxa0vitro and transfected with GM-CSF. First, the GM-CSF whole cell vaccine was evaluated against subcutaneously transplanted esophageal tumor cells. In a subsequent study, the vaccine was tested to see if it could reduce the incidence of cancer in the surgical reflux model. Results While subcutaneously transplanted tumor cells produced lasting tumors in PBS non-vaccinated placebo rats, transplanted tumors regressed and were immunologically rejected in animals vaccinated prior to implantation. In the surgical reflux model, the vaccine reduced the incidence of cancer from 17/23 (74%) in the controls to 6/16 (38%) in the vaccinated animals (Pxa0=xa00.046). Conclusions The GM-CSF whole cell tumor vaccine effectively promoted a strong immune response against subcutaneously transplanted tumors and protected animals from developing esophageal cancer in the reflux model.