Kevin E. Woods

In vivo endomicroscopy improves detection of Barrett's esophagus–related neoplasia: a multicenter international randomized controlled trial (with video)

BACKGROUND Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barretts esophagus (BE). OBJECTIVE To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. DESIGN Multicenter, randomized, controlled trial. SETTING Academic medical centers. PATIENTS Adult patients with BE undergoing routine surveillance or referred for early neoplasia. INTERVENTION Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. MAIN OUTCOME MEASUREMENTS Diagnostic yield, performance characteristics, clinical impact. RESULTS A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. LIMITATIONS Tertiary-care referral centers and expert endoscopists limit generalizability. CONCLUSION Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01124214.).

Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma

Objectives: Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. Methods: In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. Results: Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. Conclusions: A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.

Endoscopic retrograde cholangiopancreatography associated pancreatitis: A 15-year review

The aim of this article is to review the literature regarding post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We searched for and evaluated all articles describing the diagnosis, epidemiology, pathophysiology, morbidity, mortality and prevention of post-ERCP pancreatitis (PEP) in adult patients using the PubMed database. Search terms included endoscopic retrograde cholangiopancreatography, pancreatitis, ampulla of vater, endoscopic sphincterotomy, balloon dilatation, cholangiography, adverse events, standards and utilization. We limited our review of articles to those published between January 1, 1994 and August 15, 2009 regarding human adults and written in the English language. Publications from the reference sections were reviewed and included if they were salient and fell into the time period of interest. Between the dates queried, seventeen large (> 500 patients) prospective and four large retrospective trials were conducted. PEP occurred in 1%-15% in the prospective trials and in 1%-4% in the retrospective trials. PEP was also reduced with pancreatic duct stent placement and outcomes were improved with endoscopic sphincterotomy compared to balloon sphincter dilation in the setting of choledocholithiasis. Approximately 34 pharmacologic agents have been evaluated for the prevention of PEP over the last fifteen years in 63 trials. Although 22 of 63 trials published during our period of review suggested a reduction in PEP, no pharmacologic therapy has been widely accepted in clinical use in decreasing the development of PEP. In conclusion, PEP is a well-recognized complication of ERCP. Medical treatment for prevention has been disappointing. Proper patient selection and pancreatic duct stenting have been shown to reduce the complication rate in randomized clinical trials.

Increased Incidence of Benign Pancreatic Pathology following Pancreaticoduodenectomy for Presumed Malignancy over 10 Years despite Increased Use of Endoscopic Ultrasound.

Despite using imaging studies, tissue sampling, and serologic tests about 5–10% of surgeries done for presumed pancreatic malignancies will have benign findings on final pathology. Endoscopic ultrasound (EUS) is used with increasing frequency to study pancreatic masses. The aim of this study is to examine the effect of EUS on prevalence of benign diseases undergoing Whipple over the last decade. Patients who underwent Whipple procedure for presumed malignancy at Emory University Hospital from 1998 to 2011 were selected. Demographic data, history of smoking and drinking, history of diabetes and pancreatitis, imaging data, pathology reports, and tumor markers were extracted. 878 patients were found. 95 (10.82%) patients had benign disease. Prevalence of benign finding had increased over the recent years despite using more EUS. Logistic regression models showed that abdominal pain (OR: 5.829, 95% CI 2.681–12.674, P ≤ 0.001) and alcohol abuse (OR: 3.221, CI 95%: 1.362–7.261, P: 0.002) were predictors of benign diseases. Jaundice (OR: 0.221, 95% CI: 0.084–0.58, P: 0.002), mass (OR: 0.145, 95% CI: 0.043–0.485, P: 0.008), and ductal dilation (OR: 0.297, 95% CI 0.134–0.657, P: 0.003) were associated with malignancy. Use of imaging studies, ERCP, and EUS has not decreased the percentage of benign findings after surgery for presumed pancreatic malignancy.

Pancreatic Insufficiency Secondary to Tobacco Exposure: A Controlled Cross-Sectional Evaluation.

Objectives Tobacco exposure is an established risk factor for pancreatic cancer and chronic pancreatitis; however, its role in pancreatic insufficiency is not clear. Methods This controlled, cross-sectional study examined smokers and nonsmokers with no history of pancreatic disease. Histories and validated inventories of alcohol and tobacco use were obtained, and pancreatic insufficiency was assessed using the fecal elastase-1 assay. Results Of 7854 patients approached, 226 were interviewed and 200 enrolled. The rates of pancreatic insufficiency [18% (18/100)] and severe pancreatic insufficiency [10% (10/100)] were significantly higher in smokers than in controls [6% (6/100), P = 0.009 and 1% (1/100), P = 0.010, respectively]. On multivariate logistic regression, the risk of pancreatic insufficiency in smokers was significantly increased [odds ratio, 4.34 (1.37–13.75); P = 0.012], controlling for alcohol use and relevant covariates. Tobacco exposure was associated with the highest odds ratio for pancreatic insufficiency. Alcohol consumption was strongly associated with tobacco exposure (P < 0.001), but not with pancreatic insufficiency by multivariate analysis (P = 0.792). Conclusions This study suggests that tobacco exposure is independently associated with pancreatic exocrine insufficiency in patients without a prior diagnosis of pancreatic disease. Tobacco exposure seems to have greater detrimental effects on pancreatic function than alcohol in this population.

Mo1135 Trends in the Incidence of Esophageal Adenocarcinoma and Early Stage Esophageal Adenocarcinoma in the United States

G A A b st ra ct s difference with 139 (65%) females and 74 (35%) males having IEM-A versus 5 (33%) females and 10 (66%) males with IEM-P (p = 0.035). The mean age of IEM-P patients (61.7 years) was significantly higher (p < 0.05) than that of IEM-A (55.7 years). There was no significant difference in the race: 153 (72%) whites, 56 (26%) blacks in IEM-A versus 11 (73%) whites and 4 (27%) blacks in IEM-P. 147/228 patients had an ambulatory reflux study done. 88 (61%) were abnormal. Of those 84 were IEM-A (60%) and 4 IEM-P (80%) (p = 0.36). Finally, abnormal bolus transit for both liquid and viscous was present in 10/ 11 (91%) of IEM-P versus 128/182 (70% of 182) of IEM-A. Failure to find p < 0.05 for reflux and bolus transit likely due to type II statistical error. Conclusions: These results support the hypothesis that there are 2 distinct clinical subtypes of IEM. Furthermore, they suggest that IEM-P with an older male predominance and with a trend to more severe reflux and more abnormal bolus transit is a more severe manifestation than IEM-A. IEM subtypes: IEM-A and IEM-P

Automated risk prediction for esophageal optical endomicroscopic images

Biomedical in vivo imaging has been playing an essential role in diagnoses and treatment in modern medicine. However, compared with the fast development of medical imaging systems, the medical imaging informatics, especially automated prediction, has not been fully explored. In our paper, we compared different feature extraction and classification methods for prediction pipeline to analyze in vivo endomicroscopic images, obtained from patients who are at risks for the development of gastric disease, esophageal adenocarcionoma. Extensive experiment results show that the selected feature representation and prediction algorithms achieved high accuracy in both binary and multi-class prediction tasks.

Safety and efficacy of single-balloon enteroscopy in management of gastrointestinal bleeding in patients with a left ventricular assist device

Background and study aims Left ventricular assist devices (LVADs) are currently the standard of care in treatment of patients with end-stage heart failure waiting for heart transplant as well as destination therapy for non-transplant candidates. However, patients with LVADs are at increased risk of gastrointestinal bleeding due to the device’s unique effects on hemodynamics. A major source of gastrointestinal bleeding in these patients are gastrointestinal angioectasias located within the small bowel that can only be reached with deep enteroscopy. The goal of our study was to determine the safety and efficacy of single-balloon enteroscopy (SBE) in treating gastrointestinal bleeding in patients with LVADs. Patients and methods We present a retrospective case series performed on patients with LVADs who underwent SBE to treat episodes of gastrointestinal bleeding. All procedures were performed at Emory University Hospital by a single endoscopist. Patient demographics, diagnosis and treatment of gastrointestinal bleeding, episodes of re-bleeding, and procedure-related complications were examined. Results A total of 27 SBE procedures performed in 14 patients were reviewed. SBE was performed in an antegrade approach in 89 % (24/27) of cases. Deep intubation was achieved in all antegrade procedures, with the distal jejunum reached in 79 % (19/24) of cases. The diagnostic yield was 78 %. There were no reported complications associated with the procedures. Conclusions SBE is a safe and effective modality to manage gastrointestinal bleeding in patients with LVADs.

The effect of solid pancreatic mass lesions on pancreatic duct diameter at endoscopic ultrasound

Objectives: To evaluate the effect of solid pancreatic masses on the pancreatic duct (PD) at the endoscopic ultrasound (EUS) and the relationship of the location/size of a mass and PD dilation. Materials and Methods: Patients who underwent EUS for pancreatic indications from 2011 to 2013 at a single center were retrospectively identified. Those with biopsies that revealed adenocarcinoma or neuroendocrine tumors in the pancreas were identified and PD size was ascertained from EUS, computed tomography, or magnetic resonance imaging. Results: Of the 475 patients who had a pancreatic EUS, 239 had a dilated PD and 236 had a normal PD. Patients with a dilated PD had a significantly higher incidence of pancreatic malignancy than those with a normal PD diameter (106/239, 44.4% vs. 32/236, 13.6%, P< 0.001). Of the 138 patients with a pancreatic malignancy, 106 (76.8%) had a dilated PD at some location in the pancreas. Over 80% of patients with a mass within the head, neck, or body had a dilated PD. For a mass located at the uncinate process or the tail, PD dilation was 65% and 23%, respectively. Fifty-six (80.0%) of the masses in the head, 11 (78.6%) masses in the neck, and 16 (76.2%) masses in the body had a dilated PD upstream of the mass. In addition, a step-wise increase in the incidence of PD dilation was correlated with an increase in mass size. About 67.6% of patients with masses measuring in the 1st quartile had dilated a PD, while 77.8%, 91.0%, and 71.4% of those with masses measuring in the 2nd, 3rd, and 4th quartiles, respectively, had a dilated PD. Conclusion: PD dilation is a warning sign for pancreatic malignancies, however, small masses or masses at the uncinate process or the tail of the pancreas may not affect the size of the PD.

Sa2059 Ductal Dilatation As a Sign of Pancreatic Adenocarcinoma: An Analysis of 308 Pathologically-Confirmed Cases

G A A b st ra ct s for sonic hedgehog (PTCH and SMOO), GPCRs (AGTRI) and TNFaR I and II. Pancreatic mesenchymal cells were also found, using Luminex magnetic bead-based immunodetection, to be a significant source of proinflammatory cytokines IL-6 and IL-8, secreting high IL-6 levels at all times subsequent to early passages. TNF-a expression was detected only during early passage when cells exhibited an acinar-like phenotype. Interestingly, ethanol (50 mM) provided in serum free medium induced a hormetic effect, modestly stimulating cell viability associated with significant (~2-fold) elevations in HAS1, HAS2 and UGDH mRNA levels. Insulin alone (0.5-10 nM) dose-dependently suppressed HAS2 expression, but at 1 nM, modestly induced HAS1 in the presence or absence of ethanol. Ethanol-induced HAS2 gene induction was abolished in the presence of 1 nM insulin. These effects suggested some shifting between relative levels of HAS genes in response to changes in metabolic conditions. In addition, we tested the effect of conditioned medium from PDAC cell lines on HAS gene expression. The human cancer cell lines BXPC3 and MiaPaCa-2 were found to secrete high levels of IL-8, but only very low levels of IL-6 and TNF-a. Interestingly, BXPC3 and MiaPaCa2 conditioned media stimulated HAS1 and, more potently, HAS2 expression in pancreatic mesenchymal cells. We conclude that, in the tumor microenvironment, autocrine and paracrine signaling contribute to a hyaluronan synthetic phenotype that may promote tumor progression.