[Show abstract][Hide abstract] ABSTRACT: Next generation sequencing (NGS) is a state of the art technology for microRNA (miRNA) analysis. The quantitative interpretation of the primary output of NGS i.e. the read counts for a miRNA sequence that can vary by several orders of magnitude (1 to 107) remains incompletely understood.
NGS (SOLiD 3 technology) was performed on biopsies from 6 Barrett's esophagus (BE) and 5 Gastroesophageal Reflux Disease (GERD) patients. Read sequences were aligned to miRBase 18.0. Differential expression analysis was adjusted for false discovery rate of 5%. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for 36 miRNA in a validation cohort of 47 patients (27 BE and 20 GERD). Correlation coefficients, accuracy, precision and recall of NGS compared to qRT-PCR were calculated. Increase in NGS reads was associated with progressively lower Cq values, p < 0.05. Although absolute quantification between NGS reads and Cq values correlated modestly: -0.38, p = 0.01 for BE and -0.32, p = 0.05 for GERD, relative quantification (fold changes) of miRNA expression between BE &GERD by NGS correlated highly with qRT-PCR 0.86, p = 2.45E-11. Fold change correlations were unaffected when different thresholds of NGS read counts were compared (>1000 vs. <1000, >500 vs. <500 and >100 vs. <100). The accuracy, precision and recall of NGS to label a miRNA as differentially expressed were 0.71, 0.88 and 0.74 respectively.
Absolute NGS reads correlated modestly with qRT-PCR but fold changes correlated highly. NGS is robust at relative but not absolute quantification of miRNA levels and accurate for high-throughput identification of differentially expressed miRNA.
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether participation of a gastroenterology trainee had an impact on adenoma detection rate (ADR) during screening colonoscopies performed with standard-definition colonoscopes (SD-C) versus high-definition colonoscopes (HD-C).
ADR is an established quality indicator of colonoscopy and efforts to improve ADR have led to technological advancements including HD-C that have a greater angle of view and produce an image with higher pixel density compared with SD-C. Moreover, other factors like trainee participation have been shown to improve adenoma detection.
This is a retrospective review of screening colonoscopies performed during 2 different time periods by 4 experienced endoscopists with or without trainee participation. There are 2 arms of this study, based on whether screening colonoscopy was performed using SD-C or HD-C. Detailed review of endoscopy and histopathologic reports was conducted. Statistical analysis was performed and odds ratio and incidence rate ratios were calculated to adjust for numerous factors.
No significant differences were seen with trainee participation in the SD-C arm of the study. In the HD-C arm, the total number, and the proportion of subjects with: adenomas, diminutive adenomas, and right-sided adenomas were significantly higher with trainee participation.
Trainee participation significantly improved the overall adenoma detection, specifically diminutive adenoma and right-sided adenoma detection, but only when colonoscopies were performed with HD-C. The improved image quality and resolution provided by HD-C, coupled with enhanced visual scanning an additional pair of eyes provides, may account for the differential impact of trainee participation on ADR.
Journal of clinical gastroenterology 01/2014; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cigarette smoking has been associated with an increased risk of oesophageal adenocarcinoma (OAC). However, the impact of smoking and more importantly smoking cessation on Barrett's oesophagus (BO) is unclear.
United European gastroenterology journal. 12/2013; 1(6):430-7.
[Show abstract][Hide abstract] ABSTRACT: Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64 ± 12 vs. 60 ± 11 years, P = 0.001; whites 92% vs. 82%, P = 0.001; males 99.7% vs. 99.3%, P = NS; CLE length 3.4 ± 3.2 vears 1.4 ± 0.4 cm, P = 0.001 and hiatus hernia 64% vs. 56%, P = 0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P = 0.007) and 4.2-fold (95% CI 1.4-13, P = 0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P = 0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.
Diseases of the Esophagus 10/2013; · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Outcome data comparing endoscopic eradication therapy (EET) and esophagectomy are limited in patients with early esophageal cancer (EC).
To compare overall survival and EC-related mortality in patients with early EC treated with EET and esophagectomy.
Patients with early EC (stages T0 and T1) were identified from the Surveillance, Epidemiology, and End Results database (1998-2009). Demographics, tumor specific data, and survival were compared. Cox proportional hazards regression models were used to evaluate the association between treatment and EC-specific mortality.
EET and esophagectomy.
Mid- (2 years) and long- (5 years) term overall survival and EC-specific mortality, outcomes based on histology and stage, treatment patterns, and predictors of cancer-specific mortality.
A total of 430 (21%) and 1586 (79%) patients underwent EET and esophagectomy, respectively. There was no difference in the 2-year (EET: 10.5% vs esophagectomy: 12.7%, P = .27).and 5-year (EET: 36.7% vs esophagectomy: 42.8%, P = .16) EC-related mortality rates between the 2 groups. EET patients had higher mortality rates attributed to non-EC causes (5 years: 46.6% vs 20.6%, P < .001). Similar results were noted when comparisons were limited to patients with stage T0 and T1a disease and esophageal adenocarcinoma. There was no difference in EC-specific mortality in the EET compared with the surgery group (hazard ratio 1.4; 95% confidence interval, 0.9-2.03). Variables associated with mortality were older age, year of diagnosis, radiation therapy, higher stage, and esophageal squamous cell carcinoma.
Comorbidities and recurrence rates were not available.
This population-based study demonstrates comparable mid- and long-term EC-related mortality in patients with early EC undergoing EET and surgical resection.
[Show abstract][Hide abstract] ABSTRACT: Experts can accurately characterize the histology of diminutive polyps with narrow-band imaging (NBI). There are limited data on the performance of non-experts.
To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts (in academics and community practice) by using video clips.
Prospective, observational study.
Academic and community practice.
A total of 15 gastroenterologists participated-5 experts in NBI, 5 non-experts in academic practice, and 5 non-experts in community practice.
Participants reviewed a 20-minute, computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps.
Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before (pretest) and after (posttest) reviewing the teaching module.
Non-experts in academic practice showed a significant improvement in the sensitivity (54% vs 79%; P < .001), accuracy (64% vs 81%; P < .001), and proportion of high-confidence diagnoses (49% vs 69%; P < .001) in the posttest. Non-experts in community practice had significantly higher sensitivity (58% vs 75%; P = .004), specificity (76% vs 90%; P = .04), accuracy (64% vs 81%; P < .001), and proportion of high-confidence diagnoses (49% vs 72%; P < .001) in the posttest. Performance of experts in NBI was significantly better than both non-experts in academic and community practice.
Selection bias in selecting good quality videos. Performance not assessed during live colonoscopy.
Academic and community gastroenterologists without prior experience in NBI can achieve significant improvements in characterizing diminutive polyp histology after a brief computer-based training. The durability of these results and applicability in every day practice are uncertain.
[Show abstract][Hide abstract] ABSTRACT: Previously developed novel probe-based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high-grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low-grade dysplasia/high-grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4-82.3). The accuracy was higher when pathologists had 'high confidence' in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53-0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1-90.7) and the specificity was 70% (95% CI: 61.91-77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.
Diseases of the Esophagus 09/2013; · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Endoscopic management of Barrett's esophagus (BE) has evolved over the past decade; however, the practice patterns for managing BE among gastroenterologists remain unclear. OBJECTIVE: To assess practice patterns for management of BE among gastroenterologists working in various practice settings. DESIGN: A random questionnaire-based survey of practicing gastroenterologists in the United States. The questionnaire contained a total of 10 questions pertaining to practice setting, physician demographics, and strategies used for managing BE. SETTING: Survey of gastroenterologists working in various practice settings. INTERVENTION: Questionnaire. MAIN OUTCOME MEASUREMENTS: Practice patterns for endoscopic imaging and management of BE. RESULTS: The response rate was 45% (236/530). The majority (85%) were gastroenterologists in community practice, 72% were aged 41 to 60 years, 80% had >10 years of experience, and 81% had attended postgraduate courses and/or seminars on BE management. A total of 78% did not use the Prague C & M classification, and about a third used advanced endoscopic imaging routinely (37%) or in selected cases (31%). For nondysplastic BE, 86% practiced surveillance, 12% performed ablation, and 3% did no intervention. For BE with low-grade dysplasia, 56% practiced surveillance, 26% performed endoscopic ablation in all low-grade dysplasia cases, and 18% performed endoscopic ablation in only selected patients with low-grade dysplasia. The majority of respondents (58%) referred their patients with high-grade dysplasia to centers with BE expertise, 13% performed endoscopic ablation in all patients with high-grade dysplasia, 25% performed endoscopic ablation in selected cases only, and 3% referred these patients for surgery. The most frequently used endoscopic eradication therapy was radiofrequency ablation (39%) followed by EMR (17%). LIMITATIONS: The sample may be unrepresentative, participation in the study was voluntary, and responses may be skewed toward following the guidelines. CONCLUSION: Results from this survey show that the majority of practicing gastroenterologists in the United States practice surveillance endoscopy in patients with nondysplastic BE and provide endoscopic therapy for those with high-grade dysplasia. The Prague C & M classification and advanced imaging techniques are used by less than a third of gastroenterologists. Practice patterns did not appear to be affected by respondent age or duration of clinical practice.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND & AIMS: Recent population-based studies have demonstrated a low risk of esophageal adenocarcinoma (EAC) among patients with non-dysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with BE. METHODS: We performed a multicenter outcomes study of a large cohort of BE patients. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in Group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE in their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE in 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against cancer development. RESULTS: Of a total of 3515 BE patients, 1401 patients met the inclusion criteria (93.3% Caucasian, 87.5 % men, median age 60±17 y). The median follow-up was 5±3.9 y (7846 patient-years). The annual risks of EAC in groups 1-5 were 0.32%, 0.27%, 0.16%, 0.2%, and 0.11% respectively (P for trend=.03). After adjusting for age, sex, and BE length, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood for progression to EAC. CONCLUSION: Persistence of NDBE over several endoscopic examinations identifies patients who are at a low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND & AIMS: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with non-dysplastic BE (NDBE). We studied the risk of progression to HGD or EAC in patients with NDBE, based on segment length. METHODS: We analyzed data from large cohort of patients participating in the BE Study-a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia (LGD), HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 y of follow up (n=1175, 88% male) and excluded patients who developed HGD or EAC within 1 y of diagnosis of BE. The mean follow-up period was 5.5 y (6463 patient-y). Annual risk of HGD and EAC was plotted in 3 cm increments (≤3 cm, 4-6 cm, 7-9 cm, 10-12 cm, and ≥13 cm). We calculated the association between time to progression and length of BE. RESULTS: The mean length of BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared to non-progressors, patients who developed HGD or EAC had longer BE (6.1 vs 3.5 cm; P<.001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1 cm increase in BE length (P=.01). Patients with BE segment lengths ≤3 cm took longer to develop HGD or EAC than those with lengths >4 cm (6 y vs 4 y; P= non-significant) CONCLUSION: In patients with BE without dysplasia, length of BE is associated with progression to HGD or EAC. The results support for development of risk stratification scheme for these patients based on length of BE segment.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2013; · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett's esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. AIM: To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. METHODS: In this multicenter outcomes project, patients with Barrett's-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. RESULTS: One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions (p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions (p = 0.48). CONCLUSIONS: EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET.
Digestive Diseases and Sciences 04/2013; · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND & AIMS: Little is known about how teaching gastroenterology trainees polyp patterns using narrow band imaging (NBI) affects their ability to characterize the histology of diminutive colorectal polyps. We developed and tested a tool to teach trainees to characterize the histology of diminutive polyps using NBI. METHODS: Twelve gastroenterology trainees, with varying levels of colonoscopy experience, watched a teaching tool that described the NBI criteria to distinguish polyp histology. The trainees then watched 80 videos of NBI examination of diminutive polyps, recording their predictions of polyp histology and their degree of confidence. After each video, an expert provided feedback about actual polyp histology and the NBI criteria that supported each diagnosis. Twelve weeks later, without training or feedback during the interval, the trainees watched the same videos and predicted histologies of the polyps. Performance was evaluated by comparing predicted classification with actual histologic findings. Cumulative sum analysis was used to determine the learning curve for each trainee. RESULTS: Trainees made significant improvements in accuracy and the proportion of high-confidence predictions as they progressed through video blocks during the first session (P<.001). With active feedback, all trainees predicted polyp histologies with >90% accuracy, with a negative predictive value >90% for adenomatous histology. A median of 49 videos was required to achieve competency. For diagnoses made with high confidence, trainee performance exceeded 90% during the first and second sessions. Interobserver agreement was substantial (session 1: κ=0.71, session 2:κ=0.70). CONCLUSION: We developed a computer-based tool, combined with short videos and active feedback, to train gastroenterologists to identify poly histology using NBI. After training, gastroenterology trainees characterized the histology of diminutive polyps with ≥90% accuracy.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2013; · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Optical diagnosis of polyp histology can potentially result in enormous cost savings by way of the "resect and discard" strategy for diminutive polyps and the "do not resect" strategy for diminutive hyperplastic polyps in the distal colon. Narrow Band Imaging (NBI) highlights the surface mucosal and vascular pattern on polyps and has been shown to accurately characterize adenomatous and hyperplastic polyps by experts. However, the results have been a little discouraging amongst lesser experienced endoscopists. Studies have also shown that using the NBI diagnosis of diminutive polyp histology, experts can accurately define the future surveillance colonoscopy intervals. However nonexperts in academic or community setting have as yet failed to achieve the recommended thresholds. The subjectivity in assessment by endoscopists leads to the variable accuracy rates and can be circumvented by computer based automated tools. Although initial experience with a few computer based algorithms have shown accuracies comparable to experts, further refinement and validation will be required before these can be implemented in clinical practice. Incorporation of optical diagnosis of diminutive polyps into clinical practice is bound to face several hurdles. But the potential for enormous cost saving makes it an attractive strategy that can make colonoscopy more cost effective.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Sessile serrated adenomas/polyps (SSAs/Ps) are premalignant lesions susceptible to being easily overlooked by endoscopists. A detailed description of the endoscopic appearance of SSAs/Ps might help endoscopists to recognize these lesions to improve the effectiveness of colonoscopy. OBJECTIVE: To identify various endoscopic features of SSAs/Ps using high-resolution white-light endoscopy (HR-WLE) and narrow-band imaging (NBI). DESIGN: Retrospective image evaluation study. SETTING: Single tertiary referral center. PATIENTS: Forty-5 patients with serrated polyposis syndrome undergoing surveillance colonoscopies. INTERVENTION: HR-WLE and NBI images of 150 polyps (50 SSAs/Ps, 50 hyperplastic polyps [HPs], and 50 adenomas) were systematically assessed by 5 experts using various endoscopic descriptors. MAIN OUTCOME MEASUREMENTS: The prevalence of specific endoscopic features observed in SSAs/Ps versus HPs. RESULTS: Multivariate analysis demonstrated that indistinct borders (OR, 3.11; 95% CI, 1.57-6.15) and a cloud-like surface (OR, 2.65; 95% CI, 1.21-5.78) were associated with SSA/P histology on HR-WLE. On NBI, a cloud-like surface (OR, 4.91; 95% CI, 2.42-9.97), indistinct borders (OR, 2.38; 95% CI, 1.14-4.96), irregular shape (OR, 3.17; 95% CI, 1.59-6.29), and dark spots inside the crypts (OR, 2.05; 95% CI, 1.02-4.11) were found to be endoscopic predictors of SSA/P histology. The sensitivity, specificity, and accuracy of NBI for differentiating serrated polyps containing either none or all 4 endoscopic SSA/P features were, respectively, 89%, 96%, and 93%. LIMITATIONS: Retrospective, image evaluation analysis. CONCLUSIONS: The current study demonstrates that SSAs/Ps possess several specific endoscopic features compared with HPs. Recognition of these characteristics might assist endoscopists in the differentiation of these lesions and could possibly facilitate endoscopic detection of these rather subtle lesions.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: New endoscopic imaging techniques, such as autofluorescence imaging (AFI) and narrow-band imaging (NBI), have been developed to improve the detection of neoplastic lesions in Barrett's esophagus (BE). OBJECTIVE: To evaluate the clinical utility of AFI and magnification NBI to detect high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) and the interobserver agreement. DESIGN: Prospective tandem study of eligible patients. SETTING: Single, academic tertiary care center. PATIENTS: Forty-two patients with a history of confirmed BE were prospectively enrolled. INTERVENTIONS: The BE segment was examined under high-definition white-light endoscopy, and the presence of visible lesions was recorded. Subsequently, AFI and magnification NBI were performed in tandem on areas of the BE segment away from visible lesions; images obtained by these 2 systems were graded according to the color of reflected light and surface patterns, respectively. Biopsy specimens were obtained at the end of the procedure. MAIN OUTCOME MEASUREMENTS: The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the AFI and NBI patterns for the detection of HGD/EAC and interobserver agreement. RESULTS: Of the 42 patients enrolled, 14 (33%) had HGD/EAC. On patient-based analysis, AFI alone had a sensitivity, specificity, and NPV of 50%, 61%, and 71%, respectively, and the overall accuracy for the detection of HGD/EAC patients was 57%. By using magnification NBI in tandem fashion, the sensitivity and NPV improved to 71% and 76%, respectively, with a decrease in specificity to 46% and in overall accuracy to 55%. The 2 techniques had moderate interobserver agreement for both the patterns and prediction of histology. LIMITATIONS: Uncontrolled study performed at an academic center by expert endoscopists in a high-risk population. CONCLUSIONS: By using a multimodality endoscope, both AFI and magnification NBI had limited clinical accuracy and moderate overall interobserver agreement. AFI does not appear to be useful as a broad-based technique for the detection of neoplasia in patients with BE.
[Show abstract][Hide abstract] ABSTRACT: Objective:Weight gain is an important risk factor for gastroesophageal reflux disease (GERD); however, whether weight loss can lead to resolution of GERD symptoms is not clear. Our aim was to measure the impact of weight loss on GERD symptoms. Design and Methods:In a prospective cohort study at a tertiary referral center, overweight/obese subjects (BMI 25-39.9 kg/m2) were enrolled in a structured weight loss program. Weight loss strategies included dietary modifications, increased physical activity and behavioral changes. At baseline and at 6 months, BMI and waist circumference were measured and all participants completed a validated reflux disease questionnaire. Results: A total of 332 adult subjects, mean age 46 years and 66% women were prospectively enrolled. At baseline, the mean body weight, BMI, and waist circumference were 101 (±18) kg, 35 (±5) kg/m2 and 103 (±13) cm. At 6 months, majority of the subjects (97%) lost weight (average weight loss: 13 ± 7.7 kg) and as compared with baseline, there was a significant decrease in the overall prevalence of GERD (15 vs. 37%; P < 0.01) and the mean GERD symptom score (1.8 vs. 5.5; P < 0.01). Overall, 81% of the subjects had reduction in GERD symptom scores; 65% had complete resolution and 15% had partial resolution of reflux symptoms. There was a significant correlation between % body weight loss and reduction in GERD symptom scores (r = 0.17, P < 0.05). Conclusions: In conclusion, the overall prevalence of GERD symptoms is high (37%) in overweight and obese subjects. A structured weight loss program can lead to complete resolution of GERD symptoms in the majority of these subjects.
[Show abstract][Hide abstract] ABSTRACT: Background and study aims: It is uncertain if needle gauge impacts the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic mass lesions. Our aim was to use meta-analysis to more robustly define the diagnostic accuracy of EUS-FNA for pancreatic masses using 22 G and 25 G needles. Patients and methods: Studies were identified by searching nine medical databases for reports published between 1994 and 2011, using a reproducible search strategy comprised of relevant terms. Only studies comparing the overall diagnostic accuracy of 22 G vs. 25 G EUS needles that used surgical histology or at least 6 months clinical follow up for a gold standard were included. Two reviewers independently scored the identified studies for methodology and abstracted pertinent data. When required, the original investigators were contacted to provide additional data. Pooling was conducted by both fixed-effects and random-effects models. Diagnostic characteristics (sensitivity, specificity, positive and negative likelihood ratios) with 95 % confidence intervals (CIs) were calculated.Results: Eight studies involving 1292 subjects met the defined inclusion criteria. Of the 1292 patients, 799 were in the 22 G group and 565 were in the 25 G group (both needles were used in 72 patients). The pooled sensitivity and specificity of the 22 G needle were 0.85 (95 %CI 0.82 - 0.88) and 1 (95 %CI 0.98 - 1) respectively. The pooled sensitivity and specificity of the 25 G needle were 0.93 (95 %CI 0.91 - 0.96) and 0.97 (95 %CI 0.93 - 0.99) respectively. The bivariate generalized linear random-effect model indicated that the 25 G needle is associated with a higher sensitivity (P = 0.0003) but comparable specificity (P = 0.97) to the 22 G needle.Conclusions: This meta-analysis suggests 25 G needle systems are more sensitive than 22 G needles for diagnosing pancreatic malignancy.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Barrett's esophagus (BE) is transition from squamous to columnar mucosa as a result of gastroesophageal reflux disease (GERD). The role of microRNA during this transition has not been systematically studied. DESIGN: For initial screening, total RNA from 5 GERD and 6 BE patients was size fractionated. RNA <70 nucleotides was subjected to SOLiD 3 library preparation and next generation sequencing (NGS). Bioinformatics analysis was performed using R package "DEseq". A p value<0.05 adjusted for a false discovery rate of 5% was considered significant. NGS-identified miRNA were validated using qRT-PCR in an independent group of 40 GERD and 27 BE patients. MicroRNA expression of human BE tissues was also compared with three BE cell lines. RESULTS: NGS detected 19.6 million raw reads per sample. 53.1% of filtered reads mapped to miRBase version 18. NGS analysis followed by qRT-PCR validation found 10 differentially expressed miRNA; several are novel (-708-5p, -944, -224-5p and -3065-5p). Up- or down- regulation predicted by NGS was matched by qRT-PCR in every case. Human BE tissues and BE cell lines showed a high degree of concordance (70-80%) in miRNA expression. Prediction analysis identified targets that mapped to developmental signaling pathways such as TGFβ and Notch and inflammatory pathways such as toll-like receptor signaling and TGFβ. Cluster analysis found similarly regulated (up or down) miRNA to share common targets suggesting coordination between miRNA. CONCLUSION: Using highly sensitive next-generation sequencing, we have performed a comprehensive genome wide analysis of microRNA in BE and GERD patients. Differentially expressed miRNA between BE and GERD have been further validated. Expression of miRNA between BE human tissues and BE cell lines are highly correlated. These miRNA should be studied in biological models to further understand BE development.
PLoS ONE 01/2013; 8(1):e54240. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endoscopic resection of large colon polyps should be preferred over a surgical approach as it is less invasive. However, endoscopic mucosal resection of large colon polyps can be technically challenging for the endoscopist. The technique of large polypectomy has been evolving with advances in endoscopy equipment, imaging, and the use of techniques such as raising the polyp by submucosal injection and performing polypectomy in the retroflexed position. In this article, some important aspects of the technique for endoscopic resection of a large flat colon polyp are demonstrated. This article is part of an expert video encyclopedia.
Video Journal and Encyclopedia of GI Endoscopy. 01/2013; 1(2):340–342.