Risk of Colorectal Cancer and Cancer Related Mortality After Detection of Low-risk or High-risk Adenomas, Compared With No Adenoma, at Index Colonoscopy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The risk of metachronous colorectal cancer (CRC) among patients with no adenomas, low-risk adenomas (LRAs), or high-risk adenomas (HRAs), detected at index colonoscopy, is unclear. We performed a systematic review and meta-analysis to compare incidence rates of metachronous CRC and CRC-related mortality after a baseline colonoscopy for each group. METHODS: We searched the PubMed, Embase, Google Scholar, and Cochrane databases for studies that reported the incidence of CRC and adenoma characteristics after colonoscopy. The primary outcome was odds of metachronous CRC and CRC-related mortality per 10,000 person-years of follow-up after baseline colonoscopy for all the groups. RESULTS: Our final analysis included 12 studies with 510,019 patients (mean age, 59.2 ± 2.6 years; 55% male; mean duration of follow up, 8.5 ± 3.3 years). The incidence of CRC per 10,000 person-years was marginally higher for patients with LRAs compared to those with no adenomas (4.5 vs 3.4; odds ratio [OR], 1.26; 95% CI, 1.06-1.51; I2=0), but significantly higher for patients with HRAs compared to those with no adenoma ( 13.8 vs 3.4; odds ratio [OR], 2.92; 95% CI, 2.31-3.69; I2=0 ) and patients with HRAs compared to LRAs (13.81 vs 4.5; OR, 2.35; 95% CI, 1.72-3.20; I2=55%). However, the CRC-related mortality per 10,000 person-years did not differ significantly for patients with LRAs compared to no adenomas (OR, 1.15; 95% CI, 0.76-1.74; I2=0) but was significantly higher in persons with HRAs compared with LRAs (OR, 2.48; 95% CI, 1.30-4.75; I2=38%) and no adenomas (OR, 2.69; 95% CI, 1.87-3.87; I2=0). CONCLUSIONS: The results of this systematic review and meta-analysis demonstrate that the risk of metachronous CRC and mortality is significantly higher for patients with HRAs, but this risk is very low in patients with LRAs, comparable to patients with no adenomas. Follow-up of patients with LRAs detected at index colonoscopy should be the same as for persons with no adenomas.

Optical diagnosis of colorectal polyps using novel blue light imaging classification among trainee endoscopists.

BACKGROUND: Blue light imaging (BLI) has been shown to improve the characterization of colorectal polyps among the endoscopy experts. We aimed to determine if this technology could be taught to endoscopy trainees while maintaining high accuracy and interobserver agreement. METHODS: Twenty-one gastroenterology trainees (fellows) from two academic institutions participated in this prospective study. Each trainee completed a web-based learning comprising four modules: pre-test, didactic videos explaining the BLI Adenoma Serrated International Classification (BASIC), interactive examples, and post-test assessment. The pre- and post-test modules consisted of reviewing video images of colon polyps in high definition white light imaging and BLI and then applying the BASIC classification to determine if the polyps were likely to be adenomatous. Confidence in adenoma identification (rated '1' to '5'), accuracy in polyp (adenoma vs. non-adenoma) identification, and agreement in characterization per BASIC criteria were derived. RESULTS: Trainee accuracy in the adenoma diagnosis improved from 74.7% (pre-test) to 85.4% (post-test) (P < 0.01). There was a trend towards higher accuracy in polyp characterization with subsequent years of training (1st year fellows 77.4%, 2nd year 88.5%, and final year 94.0%) with consistent improvements after the e-learning across years of trainees. Overall, trainees were able to identify adenoma with a high sensitivity of 86.9%, specificity 83.9%, positive predictive value of 84.4%, and negative predictive value of 86.5%. However, their interobserver agreement in adenoma diagnosis was moderate (k = 0.52). CONCLUSION: The novel BLI classification can be easily taught to gastroenterology trainees using an online module and accuracy improves with years of training reaching >90% for colorectal polyp characterization.

Diagnostic accuracy of a novel third generation esophageal capsule as a non-invasive detection method for Barrett's esophagus: A pilot study.

BACKGROUND AND AIM: Previous two generations of esophageal capsule did not show adequate detection rates for Barrett's esophagus (BE). We assessed the diagnostic accuracy of a novel third generation capsule with an improved frame rate of 35 frames per second for the detection of BE in a pilot study. METHODS: This was a blinded prospective pilot study conducted at a tertiary medical center. Patients with known BE (at least C0M > 1) who presented for endoscopic surveillance (May to October 2017) were included. All patients underwent novel esophageal capsule (PillCam™ UGI; Medtronic) ingestion using the simplified ingestion protocol followed by standard high-definition upper endoscopy (esophagogastroduodenoscopy [EGD]). Capsule endoscopy findings were interpreted by examiners blinded to endoscopy results and compared with endoscopic findings (gold standard). Following completion of both tests, a subjective questionnaire was provided to all patients regarding their experience. RESULTS: Twenty patients (95%males, mean age 66.3 [±7.9] years) with BE undergoing surveillance EGD were eligible. The mean BE length was 3.5 (±2.7) cm. Novel esophageal capsule detected BE in 75% patients when images were compared with endoscopy. Novel capsule detected BE in 82% patients when the BE length was ≥2 cm. The mean esophageal transit time was 0.59 s. On a subjective questionnaire, all 20 patients reported novel capsule as being more convenient compared with EGD. CONCLUSIONS: In this pilot, single-center study, novel esophageal capsule was shown to be not ready for population screening of BE. Studies integrating artificial intelligence into improved quality novel esophageal capsule should be performed for BE screening.

Efficacy and Safety of Endoscopic Resection of Sessile Serrated Polyps 10 mm or Larger: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: The best method for endoscopic resection of sessile serrated polyps (SSP) 10 mm or larger is unclear; studies report variable outcomes in comparison to conventional adenomas. We performed a systematic review and meta-analysis to assess the efficacy and safety of resection of SSPs 10 mm or larger in size. METHODS: We searched the PubMed/MEDLINE, Google Scholar, Embase, and Cochrane databases for studies reporting data on endoscopic resection of SSPs 10 mm or larger, through May 31st, 2019. The primary outcome was rate of residual SSP, which was the rate of residual SSP found at the polypectomy site during the first follow-up colonoscopy. Secondary outcomes were: technical success (rate of complete macroscopic resection), R0 resection rate (complete histological resection with absence of any polyp tissue at the lateral and deep margins after en-bloc resection), and adverse events (immediate or delayed bleeding and perforation). We performed IQR,group analyses for outcomes based on polyp size and resection techniques. Pooled proportion rates (%) or odds ratio with 95% CIs with heterogeneity (I2) and P < .05. RESULTS: A total of 14 studies met the inclusion criteria: 911 patients (50.2% male; mean age, 62.8 ± 4.9 years) who underwent resection of 1137 SSPs (574 SSPs ≥ 20 mm) with a median polyp size of 19.4 mm (interquartile range, 15.9-29.6 mm). Follow-up information was available for 832 SSPs with a median follow-up duration of 12 months (interquartile range, 6-22.5 months). Piecemeal resection was performed in 58.5% SSPs. The pooled residual SSP rate was 4.3% (95% CI, 2%-6.5%). There was a higher residual SSP rate for polyps ≥ 20 mm compared to 10-19 mm (5.9% vs 1.2%; odds ratio, 3.02; 95% CI, 1-9.2; P = .049). Cold endoscopic mucosal resection (EMR) had significantly lower rates of delayed bleeding (0 vs 2.3%; P = .03) and residual polyp rate (0.9% vs 5%; P=.01) compared to hot EMR, based on univariate analysis. In multi-variate analysis there was no difference in residual polyp rate. There was no significant difference in other outcomes based on the size or method of resection. CONCLUSIONS: In a systematic review and meta-analysis, we found that SSPs ≥ 10 mm can be safely resected with low residual polyp rates. Polyp size ≥ 20 mm is a significant factor for residual polyp. Compared to hot EMR, cold EMR is associated with a lower rate of delayed bleeding. Randomized controlled trials comparing hot and cold resection are needed to standardize techniques and optimize outcomes.

Intralesional steroids and endoscopic dilation for anastomotic strictures after esophagectomy: systematic review and meta-analysis.

BACKGROUND: Post-esophagectomy anastomotic strictures are difficult to treat. The impact of adding local steroid injection to endoscopic dilation for the treatment of post-esophagectomy anastomotic strictures is unclear. We conducted a systematic review and meta-analysis to assess the efficacy of performing steroid injection in addition to dilation. METHODS: A search was conducted in MEDLINE, Cochrane Library, EMBASE, and Web of Science from inception to January 2019. Randomized controlled trials (RCTs) comparing the efficacy of endoscopic dilation plus either local steroid injection (steroid group) or saline injection (placebo group) were included in the analysis. RESULTS: Three RCTs were eligible for the final analysis: 72 patients (mean age 61.3 years, 74 % male) in the steroid group and 72 patients (mean age 59.6 years, 71 % male) in the placebo group. The mean number of dilations required to resolve the stricture was significantly lower in the steroid group compared with the placebo group, with a mean weighted difference of -1.62 (95 % confidence interval [CI] -2.73 to -0.50; P = 0.004). After 6 months of follow-up, there was a trend toward more patients in the steroid group remaining dysphagia free compared with the placebo group, with a pooled odds ratio of 2.36 (95 %CI 0.94 to 5.91; P = 0.07, I2  = 24 %). CONCLUSION: This meta-analysis showed that the addition of local steroid injection at the time of dilation for benign anastomotic strictures led to a significant decrease in the number of procedures required to resolve the stricture and may well reduce dysphagia symptoms during follow-up.

Surveillance of neo-squamous epithelium after ablation of Barrett's esophagus: is it better to use jumbo over standard biopsy forceps?

BACKGROUND AND AIMS: As obtaining adequate tissue on biopsy is critical for the detection of residual and recurrent intestinal metaplasia/dysplasia in Barrett's esophagus (BE) patients undergone Barrett's endoscopic eradication therapy (BET), we decided to compare the adequacy of biopsy specimens using jumbo versus standard biopsy forceps. METHODS: This is a two-center study of patients' post-radiofrequency ablation of dysplastic BE. After BET, jumbo (Boston Scientific©, Radial Jaw 4, opening diameter 2.8 mm) or standard (Boston Scientific©, Radial Jaw 4, opening diameter 2.2 mm) biopsy forceps were utilized to obtain surveillance biopsies from the neo-squamous epithelium. Presence of lamina propria and proportion of squamous epithelium with partial or full thickness lamina propria was recorded by two experienced gastrointestinal pathologists who were blinded. Squamous epithelial biopsies that contained at least two-thirds of lamina propria were considered 'adequate'. RESULTS: In a total of 211 biopsies from 55 BE patients, 145 biopsies (29 patients, 18 males, mean age 61 years, interquartile range [IQR] 33-83) were obtained using jumbo forceps and 66 biopsies (26 patients, all males, mean age 65 years, IQR 56-76) using standard forceps biopsies. Comparing jumbo versus standard forceps, the proportion of specimens with any subepithelial lamina propria was 51.7% versus 53%, P = 0.860 and the presence of adequate subepithelial lamina propria was 17.9% versus 9.1%, P = 0.096 respectively. CONCLUSIONS: Use of jumbo forceps does not appear to have added advantage over standard forceps to obtain adequate biopsy specimens from the neo-squamous mucosa post-ablation.

Improving serrated adenoma detection rate in the colon by electronic chromoendoscopy and distal attachment: systematic review and meta-analysis.

BACKGROUND AND AIMS: The evidence for modification of conventional colonoscopy using either "distal attachments" (DAs; endocap, endocuff, and endoring) or "electronic chromoendoscopy" (EC; narrow-band imaging [NBI], iScan, blue-light imaging, autofluorescence imaging, and linked-color imaging) to improve the detection of serrated adenomas during colonoscopy has shown conflicting results. METHODS: A comprehensive literature search was performed using Medline, Google Scholar, Embase, and Cochrane Library based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) comparing any DA or EC with high-definition white-light colonoscopy for detection of serrated adenomas (sessile serrated adenoma/polyp and traditional serrated adenoma) were included. The primary outcome was serrated adenoma detection rate (SADR) defined as the number of patients with at least 1 serrated adenoma of total patients in that group. The secondary outcome was the number of serrated adenomas per subject. Pooled rates were reported using risk ratio (RR) with 95% confidence interval. RESULTS: Seventeen studies with 13,631 patients (56% men; age range, 50-66 years) met the inclusion criteria. The use of DAs (RR, 1.21; P = .45) and EC (RR, 1.29; P = .09) during colonoscopy did not show a significant improvement in SADR. The SADR using EC was 6.9% (4 studies) and that with NBI alone was 3.7% (3 studies). CONCLUSIONS: The results indicate that, except for NBI, the use of DAs or EC during colonoscopy does not improve detection of serrated adenomas in the colon. More RCTs evaluating NBI are needed to explore the effect.

Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm: a systematic review and pooled-analysis.

BACKGROUND AND AIMS: Hot snare polypectomy and EMR are the standard of care in resecting colorectal polyps ≥10 mm. To avoid the risk of electrocautery-induced damage, there is recent evidence about using cold snare polypectomy and cold EMR for such lesions. The aim of this pooled analysis is to report outcomes of cold snare resection for polyps ≥10 mm. METHODS: PubMed/Medline, Embase, Google Scholar, and Cochrane databases were searched up to July 2018 to identify studies that performed cold snare resection for colorectal polyps ≥10 mm. Primary outcomes were adverse events (bleeding, perforation, and postpolypectomy abdominal pain), and secondary outcomes were the rates of complete resection, overall residual polyp rates, and rates for adenomas versus sessile serrated polyps (SSPs). Subgroup analysis was performed focusing on lesion size, location, and resection technique. RESULTS: Eight studies were included in the final analysis that included 522 colorectal polyps with a mean polyp size of 17.5 mm (range, 10-60). The overall adverse event rate was 1.1% (95% confidence interval, CI, 0.2%-2.0%; I2 = 0%). Intra- and postprocedural bleeding rates were .7% (95% CI, 0%-1.4%) and .5% (95% CI, .1%-1.2%), respectively, with abdominal pain rate being .6% (95% CI, .1%-1.3%). Polyps ≥20 mm had a higher intraprocedural bleeding rate of 1.3% (95% CI, .7%-3.3%) and abdominal pain rate of 1.2% (95% CI, .7%-3.0%) but no delayed bleedings. No perforations were reported. The complete resection rate was 99.3% (95% CI, 98.6%-100%). Overall pooled residual rates of polyps of any histology, adenomas, and SSPs were 4.1% (95% CI, .2%-8.4%), 11.1% (95% CI, 4.1%-18.1%), and 1.0% (95% CI, .4%-2.4%), respectively, during a follow-up period ranging from 154 to 258 days. CONCLUSIONS: The results of this systematic review and pooled analysis were excellent with cold snare resection of colorectal polyps >10 mm in terms of postpolypectomy bleeding, complete resection, and residual polyp rates. Randomized controlled trials comparing cold snare resection with hot snare resections of polyps ≥10 mm are required for further investigation.

Nonsteroidal Anti-inflammatory Drugs for Chemoprevention in Patients With Familial Adenomatous Polyposis: A Systematic Review and Meta-Analysis.

Background and Aims: Published literature shows mixed reports of the benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) on reducing colorectal polyps in patients with familial adenomatous polyposis (FAP). We conducted a systematic review and performed a meta-analysis to assess the impact of NSAIDs on colorectal polyp burden in patients with FAP. Methods: We searched PubMed, EMBASE, and Cochrane for randomized controlled trials (RCTs) comparing the effect of NSAIDs vs placebo on the percent change in polyp number and polyp size in patients with FAP. Mean differences between the 2 study arms were pooled using RevMan. The risk of bias (RoB) was assessed using the Cochrane Risk of Bias tool for RCTs, and certainty in the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: The search strategy identified 1021 studies, out of which we included 8 RCTs with a total of 279 patients. Treatment for 6.4 ± 2.2 months with NSAIDs reduced polyp numbers by -17.4% (95% confidence interval -26.41%, -8.29%) (low certainty [I2 89%] due to imprecision and issues with RoB) and polyp size by -15.9% (95% confidence interval -24.98%, -6.73%) (very low certainty (I2 84%) due to imprecision, inconsistency, and issues with RoB). The most common gastrointestinal adverse events reported were stomatitis, diarrhea, and abdominal pain. Side effects leading to drug discontinuation were gastroenteritis and drug allergy. Conclusion: Short-term use of NSAIDs reduced polyp number and polyp size but with low to very low certainty of evidence. Further large multicenter studies are needed to further explore NSAIDs as a chemopreventive measure in patients with FAP.

Comparing accuracy of high-risk features for detecting advanced neoplasia in pancreatic cystic lesions: a systematic review and meta-analysis.

BACKGROUND: The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF), whereas the American College of Gastroenterology recommends EUS for ≥1 HRF. This systematic review and meta-analysis compared the diagnostic accuracy of using ≥1 vs. ≥2 HRF for assessing the risk of advanced neoplasia (AN) and performing EUS in PCL. METHODS: An electronic database search was performed for eligible studies. AN was defined as pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm or mucinous cystadenoma with high-grade dysplasia, pancreatic intraepithelial neoplasia and pancreatic neuroendocrine tumors. HRF included cyst size ≥3 cm, solid component, and dilated pancreatic duct ≥5 mm. The primary outcome was the sensitivity and specificity of using ≥1 vs. ≥2 HRF as an indication for EUS to detect AN in PCL. RESULTS: Of 38 studies initially screened, 8 were included in the final analysis. Seven studies assessed the accuracy of ≥2 HRF and 4 studies assessed ≥1 HRF. The pooled sensitivity, specificity, positive and negative predictive values of EUS for detecting AN were 41.7% (95% confidence interval 19.5-67.8%), 90.8% (81.9-95.5%), 30.4% (19.4-44.2%) and 94.3% (89.6-97.0%) with ≥2HRFs, and 77.1% (66.1-85.3%), 72.7% (50.4-87.5%), 17.95% (10.3-29.4%), 98.1% (90.8-99.6%), respectively, with ≥1 HRF. CONCLUSION: Performing EUS for PCL with ≥1 HRF could offer greater sensitivity in detecting AN compared to ≥2 HRF, with a similar negative predictive value.

Role of endoscopic esophageal dilation in managing eosinophilic esophagitis: A systematic review and meta-analysis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus characterized by mucosal eosinophilic infiltration. Topical glucocorticoids are considered standard line of treatment, whereas endoscopic dilations are performed for patients presenting with treatment-resistant disease or manifestations of dysphagia and/or food impactions. Efficacy and safety of esophageal dilation in these patients are currently unclear. AIMS: Primary outcomes were to evaluate the efficacy, adverse events, and mortality rates of endoscopic esophageal dilation in patients with EoE. METHODS: STUDY SELECTION CRITERIA:: Studies that reported the use of esophageal dilation in EoE patients were included in this meta-analysis. DATA COLLECTION AND EXTRACTION: Articles were searched in Medline, Pubmed, and Ovid journals. Two authors independently searched and extracted data. The study design was written in accordance to PRISMA statement. Clinical improvement was defined as patient-reported symptom relief noted by the authors of individual studies. The symptoms were assessed on various nonstandardized, however, relevant questionnaires that were deemed appropriate by the senior authors of individual studies. STATISTICAL METHOD: Pooled proportions were calculated using fixed- and random-effects model. I statistic was used to assess heterogeneity among studies. RESULTS: Initial search identified 491 reference articles, in which 39 articles were selected and reviewed. Data were extracted from 14 studies (N = 1607) using esophageal dilation for EoE management, which met the inclusion criterion. Mean age of patients was 41years. Pooled patients included 75% males. The pooled proportion of patients that showed clinical improvement with esophageal dilations, after the median follow-up period of 12 months, was 84.95%. No procedure-related deaths were noted. The pooled proportion of patients with post procedural esophageal perforation, chest pain, hospitalization, deep mucosal tear (involving muscularis propria), small mucosal tear, and hemorrhage were 0.61%, 0.06%, 0.74%, 4.04%, 22.32%, and 0.38% respectively. I (inconsistency) was 0% (95% confidence interval [CI] = 0-49.8) and Egger: bias was 0.06 (95% CI = -0.30 to 0.42). CONCLUSIONS: In patients with conformed diagnosis of EoE, endoscopic esophageal dilation seems to be an effective and safe treatment option. Majority patients with chest pain and deep mucosal tears did not require hospitalization and symptoms were self-limiting.

Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma. METHODS: Included studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS: Ten studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups. CONCLUSION: In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.

Endoscopic versus Percutaneous Biliary Drainage in Palliation of Advanced Malignant Hilar Obstruction: A Meta-Analysis and Systematic Review.

Background. Palliation in advanced unresectable hilar malignancies can be achieved by endoscopic (EBD) or percutaneous transhepatic biliary drainage (PTBD). It is unclear if one approach is superior to the other in this group of patients. Aims. Compare clinical outcomes of EBD versus PTBD. Methods. (i) Study Selection Criterion. Studies using PTBD and EBD for palliation of advanced unresectable hilar malignancies. (ii) Data Collection and Extraction. Articles were searched in Medline, PubMed, and Ovid journals. (iii) Statistical Method. Fixed and random effects models were used to calculate the pooled proportions. Results. Initial search identified 786 reference articles, in which 62 articles were selected and reviewed. Data was extracted from nine studies (N = 546) that met the inclusion criterion. The pooled odds ratio for successful biliary drainage in PTBD versus EBD was 2.53 (95% CI = 1.57 to 4.08). Odds ratio for overall adverse effects in PTBD versus EBD groups was 0.81 (95% CI = 0.52 to 1.26). Odds ratio for 30-day mortality rate in PTBD group versus EBD group was 0.84 (95% CI = 0.37 to 1.91). Conclusions. In patients with advanced unresectable hilar malignancies, palliation with PTBD seems to be superior to EBD. PTBD is comparable to EBD in regard to overall adverse effects and 30-day mortality.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists.

AIM: To evaluate annual incidence of low grade dysplasia (LGD) progression to high grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC) when diagnosis was made by two or more expert pathologists. METHODS: Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS: Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies (n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate (AIR) of progression to HGD and or EAC was 10.35% (95%CI: 7.56-13.13) and progression to EAC was 5.18% (95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65% (95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42% (95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63% (95%CI: 13.98-43.27). CONCLUSION: When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.