Shailesh Bajaj

Laparoscopic Nissen Fundoplication Decreases Gastroesophageal Junction Distensibility in Patients With Gastroesophageal Reflux Disease

Laparoscopic Nissen fundoplication (LNF) is the surgical treatment of choice for gastroesophageal reflux disease (GERD). Post-LNF complications, such as gas bloat syndrome, inability to belch and vomit, and dysphagia, remain too common and prevent LNF from being more highly recommended. It remains controversial as to whether preoperative assessment can predict the development of post-LNF complications. Some authors have shown a correlation between pre-LNF manometry characteristics and post-LNF dysphagia, and others have not. We hypothesize that many post-LNF complications are caused by a decrease in the distensibility of the GEJ and that standard manometry is at best an indirect measure of this. The aim of this study is to directly measure the effect of LNF on gastroesophageal junction (GEJ) distensibility (GEJD).The lower esophageal sphincter (LES) of 15 patients undergoing LNF was characterized using standard manometry. The GEJD before and after a standardized LNF was measured using a specialized catheter, containing an infinitely compliant bag, placed within the LES. GEJD was measured, as dV/dP over volumes 5 to 25 mL distended at a rate of 20 mL/min. Mean dP ± standard error of the mean for each volume was calculated, and distensibility curves were generated and compared. Measurements were also taken after abolishing LES tone by mid-esophageal balloon distension. Patient symptoms were recorded before and after surgery. Statistical analysis was performed by two-way repeated-measures analysis of variance, paired t test, and the Tukey test. Laparoscopic Nissen fundoplication led to a statistically significant increase in Dpressure over each volume tested and therefore a significant decrease in the distensibility of the GEJ. Abolition of LES tone had no statistical effect on GEJD after fundoplication. There were no complications, and none of the patients developed the symptom of dysphagia postoperatively. These are the first direct measurements to show that LNF significantly reduces the distensibility of the GEJ. We hypothesize that the magnitude of this reduction may be the vital variable in the development of post-LNF complications and specifically post-LNF dysphagia. The intraoperative measurement of LES distensibility may provide a means for avoiding this feared and other post-LNF complications in the future.

Performance and Optimal Technique for Pharyngeal Impedance Recording: A Simulated Pharyngeal Reflux Study

BACKGROUND AND AIMS:Detection rate, influence of recording site, and subject posture for impedance monitoring of pharyngeal reflux of gastric contents remain unknown. We evaluated the ability of the impedance sensor for detection of various volumes of intrapharyngeal infusate at two sites and in two subject positions.METHODS:Nineteen healthy subjects were studied using concurrent videoendoscopic, manometric, impedance, and pH recording.RESULTS:Detection rate of simulated pharyngeal reflux events ranged between 87% and 100% for 1–4 mL. Detection rate for 0.1–1 mL volumes in the upright position was significantly higher (78–85%) when the impedance sensor was located at the proximal margin of the upper esophageal sphincter (UES) compared to 2 cm proximally (38–68%) (P < 0.001). With the sensor at 2 cm above the UES, the average detection rate for all volumes in the upright position was significantly less (P < 0.001) compared to the supine position (48% vs 84%). There was substantial variability in the magnitude of impedance changes induced by different infusates.CONCLUSIONS:Impedance sensors can detect as small a volume as 0.1 mL and combined with a pH sensor can detect acidic and nonacidic liquid and mist reflux events. Sensor placement at the proximal margin of the UES yields the highest detection rate irrespective of subject posture compared to placement 2 cm proximally. Depending on the volume of refluxate and location of the impedance sensor, a substantial minority of simulated reflux events can be missed.

1022 Targeting Fatty Acid Synthase (FASN) As a Modality to Ameliorate Obesity Related Colorectal Cancer (CRC)

Background: Recent research demonstrates association between colonic polyps and insulin resistance(IR). However, it is unclear if this association correlates with polyp neoplastic potential(NP) and whether metabolic features such as non-alcoholic fatty liver disease(NAFLD) or components of the metabolic syndrome(MS) are also associated with colonic neoplasia. Aim: To evaluate the associations between various colonic polyps and metabolic alterations. Methods: Case-control study in consecutive subjects(40-70y), undergoing colonoscopy. Cases with colonic polyps and controls with no polyps were evaluated for metabolic and anthropometric parameters, including ultrasound for NAFLD and liver steatosis quantitation by Hepato-Renal-Index(HRI). We excluded subjects at high risk for colonic neoplasia and severe systemic/metabolic illness. T test, Chi-square test and logistic regression analysis were used. Results: Out of 538 participants (mean age 58.8±6.3, 53.5% men) 269 cases with colonic polyps were compared to 269 controls (Table 1). Dose response association was detected between polyp NP(hyperplastic, non advanced and advanced adenomas), HOMA IR score(P for trend=0.03) and HRI (P for trend=0.01). Polyp risk factors in multivariate analysis, adjusting for age and gender, were: MS(OR=1.92, 95%CI 1.34-2.75, P<0.001), low HDL (OR=1.67, 1.14-2.44, P<0.001), abdominal obesity(OR=1.60, 1.10-2.32, P=0.01), and NAFLD (OR=1.47, 1.04-2.08, P=0.02). In cases of advanced adenoma, number of polyps was positively correlated with fasting serum HOMA IR(r=0.258, P<0.01), waist circumference(r=0.206, P=0.03), HRI(r=0.202, P=0.04), and MS components(r=0.224, P= 0.02). Conclusions: Our initial results strongly suggest that IR, MS and NAFLD predict colonic polyps and their neoplastic potential. This data opens venue for prediction models to improve CRC prevention programs. Comparison of Cases with Colonic Polyps and Controls

MicroRNA Expression Alterations in Duodenal Mucosa of Patients With IPMNs: Potential Diagnostic/Prognostic Biomarker

Background: Diagnostic and prognostication of IPMNs represents a vexing and increasingly common clinical problem. Current diagnostic and prognostic approaches remain suboptimal. Our group has focused on field carcinogenesis detection for risk stratification (reviewed in Gastro 2011). We have noted that in the peri-ampullary duodenal biopsies, there are microarchitectural alterations as detectable by our novel optical technologies, low coherence enhanced backscattering spectroscopy and partial wave spectroscopy (Clin Cancer res 2007, Dis Biomarkers 2008, Cancer Res 2009). However, the biological basis of duodenal alterations has been LEBS (micro-architectural) alterations have been unexplored. MicroRNAs have been implicated in pancreatic carcinogenesis at both the initiation and progression phase. We wanted to compare the miRNA expression in duodenal mucosa in IPMN patients and control patients and correlate miRNA profile with the disease. Methods:We obtained endoscopic biopsies from patients with IPMNs undergoing endoscopic ultrasound for evaluation. Controls were age and gender matched. The RNA was recovered from formalin fixed paraffin embedded sections) using Ribopure kit (Ambion). The total RNA was then reverse transcribed using Taqman miRNA kit using Megaplex RT Primer set A (Applied Biosystems). The cDNA was then diluted and loaded into Taqman Low Density Array (TLDA) for miRNA (ABI). Real time RT-PCR was performed on ABI Prism 7900HT system. The data analysis was done using the SDS RQ manager and Data Assist software. Results: The comprehensive miRNA profiling of duodenal mucosal RNA from IPMN and control patients showed downregulation of 15 miRNAs and upregulation of miR-212, miR-130b and miR-100. Importantly, the miRNA reported to be upregulated in pancreatic cancer (miR-212 and MiR-100) were also seen to be upregulated in duodenal mucosa. Similarly, miR-24, which is the key regulator of p16, was also significantly modulated in the duodenal mucosa, thus underscoring the field effect for miRNA expression in pancreatic cancer. Conclusions: We report, herein, for the first time, that microRNA in the duodenal mucosa are dysregulated in patients harboring IPMNs when compared to matched controls. Importantly, these demonstrate important molecular alterations in extended field carcinogenesis of pancreas cancer. Future studies will be to develop prediction rules of duodenal microRNA with or without LEBS (microarchitectural biomarkers). The future goals are both for diagnostics and more significantly from a clinical perspective for prognosis/natural history.