Neoplastic progression risk in females with Barrett's esophagus: a systematic review and meta-analysis of individual patient data.

BACKGROUND AND AIMS: Females with Barrett's esophagus (BE) have a lower risk of neoplastic progression than males, but sufficiently powered risk analyses are lacking. This systematic review and meta-analysis of individual patient data (IPD) aims to provide more robust evidence on neoplastic progression risk in females. METHODS: Systematic literature search of three electronic databases (Medline, Embase, Google Scholar) from inception until August 2023. Eligible studies (1) reported original data on progression from non-dysplastic BE (NDBE), indefinite for dysplasia (IND) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), and (2) included female and male patients. IPD were quality controlled by two independent reviewers. Primary outcome was the association between sex and neoplastic progression risk, adjusted for risk factors using multivariable Cox regression analysis. Secondary outcomes were sex differences in time to progression and annual progression rate. RESULTS: IPD were obtained from 11/66 eligible studies, including 2.196 (31%) females. Neoplastic progression risk was lower in females (HR 1.44 for males vs females, 95%CI 1.13-1.82) after adjusting for age, smoking, medication use, hiatal hernia, BE length, and baseline pathology. Annual progression rate was 0.88% in females vs 1.29% in males. Time to progression was similar in both sexes; 3.7 years (IQR 2.1-7.7) in females, and 4.2 years (IQR 2.0-8.1) in males. CONCLUSION: Although females had a lower neoplastic progression risk, sex differences were smaller than previously reported and time to progression was similar for both sexes. Future research should focus on other factors than sex to identify low- and high-risk BE patients.

Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

INTRODUCTION: Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature. METHODS: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1. RESULTS: A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18). DISCUSSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

A Tissue Systems Pathology Test Outperforms the Standard-of-Care Variables in Predicting Progression in Patients With Barrett's Esophagus.

INTRODUCTION: Objective risk stratification is needed for patients with Barrett's esophagus (BE) to enable risk-aligned management to improve health outcomes. This study evaluated the predictive performance of a tissue systems pathology [TSP-9] test (TissueCypher) vs current clinicopathologic variables in a multicenter cohort of patients with BE. METHODS: Data from 699 patients with BE from 5 published studies on the TSP-9 test were evaluated. Five hundred nine patients did not progress during surveillance, 40 were diagnosed with high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) within 12 months, and 150 progressed to HGD/EAC after 12 months. Age, sex, segment length, hiatal hernia, original and expert pathology review diagnoses, and TSP-9 risk classes were collected. The predictive performance of clinicopathologic variables and the TSP-9 test was compared, and the TSP-9 test was evaluated in clinically relevant patient subsets. RESULTS: The sensitivity of the TSP-9 test in detecting progressors was 62.3% compared with 28.3% for expert-confirmed low-grade dysplasia (LGD), while the original diagnosis abstracted from medical records did not provide any significant risk stratification. The TSP-9 test identified 57% of progressors with nondysplastic Barrett's esophagus (NDBE) ( P < 0.0001). Patients with NDBE who scored TSP-9 high risk progressed at a similar rate (3.2%/yr) to patients with expert-confirmed LGD (3.7%/yr). The TSP-9 test provided significant risk stratification in clinically low-risk patients (NDBE, female, short-segment BE) and clinically high-risk patients (IND/LGD, male, long-segment BE) ( P < 0.0001 for comparison of high-risk classes vs low-risk classes). DISCUSSION: The TSP-9 test predicts risk of progression to HGD/EAC independently of current clinicopathologic variables in patients with BE. The test provides objective risk stratification results that may guide management decisions to improve health outcomes for patients with BE.

Neoplastic Progression of Barrett's Esophagus Among Organ Transplant Recipients: a Retrospective Cohort Study.

BACKGROUND: Several small studies reported high risk of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) patients who undergo solid organ transplantation (SOT) and implied that this may be due to immunosuppressant use. However, the major shortcoming of these studies was the lack of a control population. Therefore, we aimed to determine the rates of neoplastic progression in BE patients who underwent SOT and compare to that in controls and identify the predictors of progression. METHODS: This was a retrospective cohort study of BE patients seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. Demographics, endoscopic and histological findings, history of SOT and fundoplication, immunosuppressant use, and follow-up were abstracted. RESULTS: The study population consisted of 3466 patients with BE, of which 115 had SOT (lung 35, liver 34, kidney 32, heart 14, and pancreas 2) and 704 patients on chronic immunosuppressants but no history of SOT. During a median follow-up of 5.1 years, there was no difference in the annual risk of progression between the three groups (SOT=0.61%, no SOT but on immunosuppressants= 0.82%, and no SOT/no immunosuppressants= 0.94%, p=0.72). On multivariate analysis, immunosuppressant use (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.04-1.82, p=0.025) but not SOT (OR 0.39, 95%CI 0.15-1.01, p=0.053) was associated with neoplastic progression in BE patients. CONCLUSION: Immunosuppression is a risk factor for progression of BE to HGD/EAC. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered.

NON-ENDOSCOPIC ESOPHAGEAL SAMPLING DEVICE AND BIOMARKER PANEL FOR DETECTION OF BARRETT'S ESOPHAGUS (BE) AND ESOPHAGEAL ADENOCARCINOMA (EAC).

BACKGROUND: We previously reported an encapsulated balloon (EsoCheck TM , EC), which selectively samples the distal esophagus, that coupled with a two methylated DNA biomarker panel (EsoGuard TM , EG), detected Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), with a sensitivity and specificity of 90.3% and 91.7%, respectively. This previous study utilized frozen EC samples. AIM: To assess a next generation EC sampling device and EG assay that utilizes a room temperature sample preservative to enable office-based testing. METHODS: Cases with nondysplastic (ND) and dysplastic (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD) BE, EAC, junctional adenocarcinoma (JAC) and controls with no intestinal metaplasia (IM) were included. Nurses or physician assistants at six institutions, who were trained in EC administration, delivered the encapsulated balloon per orally and inflated it in the stomach. The inflated balloon was pulled back to sample 5 cm of the distal esophagus, then deflated and retracted into the EC capsule to prevent sample contamination from proximal esophagus. Nextgen EG sequencing assays performed on bisulfite-treated DNA extracted from EC samples determined levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1) in a CLIA-certified laboratory, blinded to patients' phenotypes. RESULTS: A total of 243 evaluable patients - 88 cases (median age 68 years, 78% men, 92% white) and 155 controls (median age 57 years, 41% men, 88% white) - underwent adequate EC sampling. Mean time for EC sampling was just over 3 minutes. The cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) of the non-dysplastic and dysplastic BE cases were short-segment BE (SSBE; < 3 cm). Overall sensitivity for detecting all cases was 85% (95% CI= 0.78-0.93) and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84% (n=37). The EC/EG test detected 100% of cancers. CONCLUSION: The next-generation EC/EG technology has been both successfully updated to incorporate a room temperature sample collection preservative and successfully implemented in a CLIA certified laboratory. When performed by trained personnel, EC/EG detects non-dysplastic BE, dysplastic BE, and cancer with high sensitivity and specificity, replicating the operating characteristics of the initial pilot study of this technology. Future applications utilizing EC/EG to screen broader populations at risk for developing cancer are proposed. SIGNIFICANCE: This multi-center study demonstrates the successful performance of a commercially available clinically implementable non-endoscopic screening test for BE in the U.S., as recommended in the most recent ACG Guideline and AGA Clinical Update. It transitions and validates a prior academic laboratory-based study of frozen research samples over to a CLIA laboratory, one that also integrates a clinically practical room temperature method for sample acquisition and storage, enabling office-based screening.

Evaluation and management of gastroesophageal reflux disease: A brief look at the updated guidelines.

Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disorder seen in primary care offices and is usually managed with proton pump inhibitors (PPIs). The authors present an overview of the updated guidelines from the American College of Gastroenterology, which address the evaluation and management of GERD, including the consequences of long-term PPI therapy and emerging therapies.

Anti-reflux mucosectomy for refractory gastroesophageal reflux disease: a systematic review and meta-analysis.

Background and study aims Anti-reflux mucosectomy (ARMS) is an emerging endoscopic treatment for refractory gastroesophageal reflux disease (GERD). We conducted a systematic review and meta-analysis to evaluate the safety and efficacy ARMS in refractory GERD. Methods A comprehensive search of multiple databases (through March 2020) was performed to identify studies that reported outcomes of ARMS for refractory GERD. Outcomes assessed included technical success, clinical response, and adverse events (AEs). Clinical response was defined as discontinuation (complete) or reduction (partial) of proton pump inhibitors post-ARMS at follow up. Results A total of 307 patients (mean age 46.9 [8.1] years, 41.5 % females) were included from 10 studies. The technical success and clinical response rates were 97.7 % (95 % confidence interval [CI], 94.6-99.0) and 80.1 % (95 % CI, 61.6-91.0), respectively. The pooled rate of complete and partial clinical response was 65.3 % (95 % CI, 51.4-77.0) and 21.5 % (95 % CI, 14.2-31.2), respectively. The rate of AEs was 17.2 % (95 % CI, 13.1-22.2) with most common AE being dysphagia/esophageal stricture followed by bleeding with rates of 11.4 % and 5.0 %, respectively. GERD health-related quality of life (GERD-HRQL) (mean difference [MD] = 14.9, P  < 0.001), GERD questionnaire (GERD-Q) (MD = 4.85, P  < 0.001) and mean acid exposure time (MD = 2.39, P  = 0.01) decreased significantly post-ARMS as compared to pre-procedure. There was no difference in terms of clinical response and AEs between ARMS and ARMS with banding on subgroup analysis. Conclusions ARMS is a safe and effective procedure for treatment of refractory GERD with high rates of clinical response, acceptable safety profile and significant improvement in GERD-related quality of life. Prospective studies are needed to validate our findings.

Management of nondysplastic Barrett's esophagus: When to survey? When to ablate?

Barrett's esophagus (BE), a precursor for esophageal adenocarcinoma (EAC), is defined as salmon-colored mucosa extending more than 1 cm proximal to the gastroesophageal junction with histological evidence of intestinal metaplasia. The actual risk of EAC in nondysplastic Barrett's esophagus (NDBE) is low with an annual incidence of 0.3%. The mainstay in the management of NDBE is control of gastroesophageal reflux disease (GERD) along with enrollment in surveillance programs. The current recommendation for surveillance is four-quadrant biopsies every 2 cm (or 1 cm in known or suspected dysplasia) followed by biopsy of mucosal irregularity (nodules, ulcers, or other visible lesions) performed at 3- to 5-year intervals. Challenges to surveillance include missed cancers, suboptimal adherence to surveillance guidelines, and lack of strong evidence for efficacy. There is minimal role for endoscopic eradication therapy in NDBE. The role for enhanced imaging techniques, artificial intelligence, and risk prediction models using clinical data and molecular markers is evolving.

Pneumatic dilation for esophageal achalasia: patient selection and perspectives.

Achalasia is an esophageal motility disorder characterized by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter. Treatment is palliative, aimed at decreasing the lower esophageal sphincter pressure. Pneumatic dilation (PD) is a safe and effective treatment for achalasia. Several other invasive and minimally invasive treatment modalities, such as Laparoscopic Heller Myotomy (LHM) and Peroral Endoscopic Myotomy (POEM), also have a comparable safety and efficacy profile to PD. The current review focuses on the indications, contraindications, techniques, and outcomes of PD in various patient populations and its comparison to LHM and POEM. This review also provides relevant information to help endoscopists identify those patients who will benefit the most from PD.

Prediction of neoplastic progression in Barrett's esophagus using nanoscale nuclear architecture mapping: a pilot study.

BACKGROUND AND AIMS: Nanoscale nuclear architecture mapping (nanoNAM), an optical coherence tomography-derived approach, is capable of detecting with nanoscale sensitivity structural alterations in the chromatin of epithelial cell nuclei at risk for malignant transformation. Because these alterations predate the development of dysplasia, we aimed to use nanoNAM to identify patients with Barrett's esophagus (BE) who might progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: This is a nested case-control study of 46 BE patients, of which 21 progressed to HGD/EAC over 3.7 ± 2.37 years (cases/progressors) and 25 patients who did not progress over 6.3 ± 3.1 years (control subjects/nonprogressors). The archived formalin-fixed paraffin-embedded tissue blocks collected as part of standard clinical care at the index endoscopy were used. nanoNAM imaging was performed on a 5-µm formalin-fixed paraffin-embedded section, and each nucleus was mapped to a 3-dimensional (3D) depth-resolved optical path difference (drOPD) nuclear representation, quantifying nanoscale-sensitive alterations in the 3D nuclear architecture of the cell. Using 3D-drOPD representation of each nucleus, we computed 12 patient-level nanoNAM features summarizing the alterations in intrinsic nuclear architecture. A risk prediction model was built incorporating nanoNAM features and clinical features. RESULTS: A statistically significant differential shift was observed in the drOPD cumulative distributions between progressors and nonprogressors. Of the 12 nanoNAM features, 6 (mean-maximum, mean-mean, mean-median, entropy-median, entropy-entropy, entropy-skewness) showed a statistically significant difference between cases and control subjects. NanoNAM features based prediction model identified progression in independent validation sets, with an area under the receiver operating characteristic curve of 80.8% ± .35% (mean ± standard error), with an increase to 82.54% ± .46% when combined with length of the BE segment. CONCLUSIONS: NanoNAM can serve as an adjunct to histopathologic evaluation of BE patients and aid in risk stratification.

Wide-area transepithelial sampling for dysplasia detection in Barrett's esophagus: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Seattle protocol forceps biopsy sampling (FB) is currently recommended for surveillance in Barrett's esophagus (BE) but limited by sampling error and lack of compliance. Wide-area transepithelial sampling with 3-dimensional analysis (WATS3D; CDx Diagnostics, Suffern, NY, USA) is reported to increase BE dysplasia detection. We assessed the incremental yield and clinical significance of WATS3D for dysplasia detection over FB in a systematic review and meta-analysis. METHODS: We queried major scientific databases for studies using WATS3D and FB from 2000 to 2020. The primary outcome was the incremental yield of WATS3D-detected dysplasia (defined as a composite of indefinite for dysplasia, low- and high-grade dysplasia [HGD] and esophageal adenocarcinoma [EAC]) over FB. Secondary outcomes were incremental yields of HGD/EAC and rate of reconfirmation of WATS3D dysplasia on subsequent FB. RESULTS: Meta-analysis of 7 eligible studies demonstrated that FB diagnosed dysplasia in 15.9% of cases, whereas the incremental yield with WATS3D was 7.2% (95% confidence interval, 3.9%-11.5%; I2= 92.1%). Meta-analysis of 6 studies demonstrated that FB diagnosed HGD/EAC in 2.3% of patients, whereas the incremental yield with WATS3D was 2.1% (95% confidence interval, .4%-5.3%; I2= 92.7%). Notably, WATS3D was negative in 62.5% of cases where FB identified dysplasia. Two studies reported reconfirmation of WATS3D dysplasia with FB histology in only 20 patients. CONCLUSIONS: WATS3D increases dysplasia detection; however, the clinical significance of this increased dysplasia detection remains uncertain. Data from endoscopic follow-up to ascertain FB histology in patients with dysplasia based solely on WATS3D are needed to determine the optimal clinical application and significance of WATS3D-only dysplasia.

Minimally Invasive "3-Stitch" Modification of the Dor Fundoplication: Simple and Effective.

BACKGROUND: A 180-degree anterior (Dor) fundoplication is usually paired with an esophagogastric myotomy in the surgical treatment of achalasia. The traditional technique, however, is not easily reversible and the execution is variable. This study examined a simplified ''3-stitch'' Dor fundoplication that addressed these challenges and presented the results. METHODS: A prospectively collected, longitudinal surgical achalasia database was queried for patients undergoing a Heller myotomy with '3-stitch 180-degree fundoplication from 2008 to 2019. Preoperative and postoperative Eckardt score, postoperative DeMeester score (24- or 48-hour pH studies), and endoscopic evidence of esophagitis were collected and analyzed to determine the effectiveness and safety of the fundoplication. Length of stay and complications were also considered. RESULTS: The pH testing was performed in 296 patients, with 17% (50 of 296) demonstrating abnormal esophageal acid exposure. Of this group, only 8% (16 of 201) manifested clinical esophagitis on upper endoscopy. A total of 14% (7 of 50) of patients with abnormal esophageal acid exposure were symptomatic. Total postoperative Eckhardt scores for this cohort were 3 or lower in 92% of patients, with a dysphagia-specific score of 0 in 92%. The technical details of a modified 180-degree anterior fundoplication are described. CONCLUSIONS: The 3-stitch Dor fundoplication is an effective addition to a minimally invasive Heller myotomy, with good palliation of symptoms and an acceptable rate of acid reflux. The simplified construction anticipates the potential progression of esophageal dysmotility in patients with achalasia, and the modified technique is reproducible and readily teachable.

Peroral endoscopic myotomy provides effective palliation in type III achalasia.

BACKGROUND: Type III achalasia outcomes have historically been met with limited success after conventional laparoscopic Heller myotomy (LHM) and pneumatic dilation. Peroral endoscopic myotomy (POEM) has emerged as a promising alterative for a multitude of reasons. Our objective was to investigate POEM outcomes in palliating type III achalasia. METHODS: A retrospective analysis of a prospectively maintained database was conducted in a tertiary care institution between April 2014 and July 2019. The primary outcome was postoperative Eckardt score. We also explored the effect of lower esophageal sphincter (LES) integrated resting pressure (IRP) on manometry, barium column height and width, and complications. Standard statistical methods were applied using R. RESULTS: A total of 518 patients in the achalasia database were identified, with 308 patients undergoing LHM and 210 undergoing POEM during the study period. POEM was used for type III achalasia in 36 patients (median age, 60 years; 61.7% male), with a median operative time of 85 minutes (interquartile range [IQR], 71-115 minutes) and follow-up of 1 year (IQR, 0.16-2.25 years). Within the POEM group, 11 patients (33%) had previous interventions, including Botox injections to the LES (n = 7), pneumatic dilation (n = 1), and LHM (n = 3). A significant decrease in median Eckardt score was observed (7 preoperatively [IQR, 6-8.75] vs 0 postoperatively [IQR, 0-1]; P < .01). Similar improvements after POEM were noted in median LES IRPs (25.5 mmHg vs 4.5 mmgHg; P < .01), 1-minute barium column height (10 cm vs 0 cm; P < .01), and 1-minute barium column width (2 cm vs 0 cm; P < .01). Patients reported a return to activities of daily living in a median of 7 days (IQR, 3-7 days). Three patients experienced complications, including mucosal perforation resolving with conservative management (n = 1), readmission for bleeding duodenal ulcer responding to proton pump inhibitors (n = 1), and readmission for dysphagia and rehydration (n = 1). Postoperative esophageal pH studies were conducted in 21 patients (62%), demonstrating a Demeester score of >14.72 in 13 patients (62%). CONCLUSIONS: POEM provides effective and durable palliation for type III achalasia, as demonstrated by symptom relief, esophageal manometry, and radiographic measurement. Considering its low morbidity profile, POEM should be considered as first-line therapy in this challenging disease subtype.

Age of diagnosis in familial Barrett's associated neoplasia.

The identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to non-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed high-grade dysplasia (HGD) or EAC. The Familial Barrett's Esophagus Consortium database was used to identify individuals with HGD and EAC. These individuals were subsequently split into three kindred groups: non-familial-a single affected family member, duplex-two affected family members, and multiplex-three or more affected family members. Age of cancer diagnosis and other risk factors were compared between individuals in these groups. The study included 441 non-familial, 46 duplex, and 13 multiplex individuals. There was a statistically significant difference for age of diagnosis for individuals in the multiplex families compared to the non-familial and duplex families (56.0 versus 64.3, 63.5; p = 0.049). There was no significant difference between demographic factors and other cancer risk factors between family types. The results of this study support a genetic basis for familial Barrett's associated neoplasia and evaluation of the genetic susceptibility to this disease should continue to focus on families with multiple (three or more) affected members.

Clinical Risk Prediction Model for Neoadjuvant Therapy in Resectable Esophageal Adenocarcinoma.

GOALS AND BACKGROUND: Clinical staging with endoscopic ultrasound (EUS) and positron emission tomography (PET) is used to identify esophageal adenocarcinoma (EAC) patients with locally advanced disease and therefore, benefit from neoadjuvant therapy. However, EUS is operator dependent and subject to interobserver variability. Therefore, we aimed to identify clinical predictors of locally advanced EAC and build a predictive model that can be used as an adjunct to current staging methods. STUDY: This was a cross-sectional study of patients with EAC who underwent preoperative staging with EUS and PET scan followed by definitive therapy at our institution from January 2011 to December 2017. Demographic data, symptoms, endoscopic findings, EUS, and PET scan findings were obtained. RESULTS: Four hundred and twenty-six patients met the study criteria, of which 86 (20.2%) patients had limited stage EAC and 340 (79.8%) had locally advanced disease. The mean age was 65.4±10.3 years of which 356 (83.6%) were men and 393 (92.3%) were White. On multivariable analysis, age (above 75 or below 65 y), dysphagia [odds ratio (OR): 2.84], weight loss (OR: 2.06), protruding tumor (OR: 2.99), and tumor size >2 cm (OR: 3.3) were predictive of locally advanced disease, while gastrointestinal bleeding (OR: 0.36) and presence of visible Barrett's esophagus (OR: 0.4) were more likely to be associated with limited stage. A nomogram for predicting the risk of locally advanced EAC was constructed and internally validated. CONCLUSIONS: We constructed a nomogram to facilitate an individualized prediction of the risk of locally advanced EAC. This model can aid in decision making for neoadjuvant therapy in EAC.

The Incidence of Endoscopic Retrograde Cholangiopancreatography-Related Complications in Patients With Liver Transplant: A Meta-Analysis and Systematic Review.

BACKGROUND: Existing literature on post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with liver transplant remains scarce and largely inconsistent. We therefore aimed to systematically review and analyze the literature on complication rates associated with ERCP in patients with liver transplant. METHODS: We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through March 2020 to identify all the studies that evaluated post-ERCP complications in patients with liver transplant. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird, and a pooled odds ratio (OR) and event rates were calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques. RESULTS: Fourteen studies with a total of 1,787 patients were analyzed. In total, 3,192 ERCPs were performed on these patients. The pooled all-complication rate was 5.2% (95% confidence interval (CI): 0.035 - 0.075). Procedural complications analyzed included post-ERCP pancreatitis 3.4% (95% CI: 0.025 - 0.047), bleeding 1.1% (95% CI: 0.006 - 0.020), infections 0.2% (95% CI: 0.025 - 0.047), and cholangitis 0.8% (95% CI: 0.004 - 0.020). No cases of periprocedural death were reported. The pooled OR for post-ERCP pancreatitis in patients with liver transplant compared to patients without liver transplant was 1.289 (95% CI: 0.455 - 3.653, P = 0.633, I2 = 72.88%). CONCLUSION: Post-ERCP complication rates in liver transplant patients are comparable to the general population and hence, peri-procedural evaluation and management may follow the current standards of care in this patient population.

Clinical Predictors of Locally Advanced Pathology in Esophageal Adenocarcinoma.

Background In patients with resectable esophageal adenocarcinoma (EAC), the decision for neoadjuvant treatment depends on clinical staging with endoscopic ultrasound (EUS) and positron-emission tomography (PET) scan. Patients with locally advanced EAC pathology misclassified as early EAC by clinical staging are missing the opportunity to receive neoadjuvant therapy. We aim to identify predictors of locally advanced pathology in EAC to determine more accurately those who benefit from neoadjuvant therapy.  Methods Retrospective study of patients who underwent upfront endoscopic or surgical resection for EAC without neoadjuvant therapy from January 2011 to December 2017 was performed. Clinical characteristics, EUS, PET scan and histologic findings were analyzed. Multivariable analysis of predictors of locally advanced stage was performed and a risk prediction score was developed. Results A total of 97 patients were included; 68 patients were staged as early EAC (pT1 or pT2 and pN0) and 29 patients were staged as locally advanced EAC (pT1 or pT2 with pN1 and pT3 or pT4 irrespective of N status). In a predictive model of EAC, patients presenting with dysphagia, tumor size >2 cm, exophytic mass appearance on endoscopy and absence of hiatal hernia were more likely to be have locally advanced pathology with a probability of 70% (C-statistic 0.766). Conclusions A risk prediction model based on the presence of dysphagia, tumor size >2 cm, exophytic mass appearance and absence of hiatal hernia can be used to identify locally advanced pathology in EAC patients.