Citations

INTRODUCTION: The adjunctive use of p53 immunohistochemistry has been proposed as a potential tool to improve risk stratification in Barrett's esophagus (BE) with conflicting results. We performed a systematic review and meta-analysis to evaluate the performance of p53 in predicting progression to advanced neoplasia (high-grade dysplasia [HGD] and esophageal adenocarcinoma [EAC]) among patients with BE. METHODS: We searched multiple databases for studies that evaluated the use of aberrant p53 in esophageal biopsies among patients with BE and reported progression rates to HGD/EAC. The outcomes were p53 test characteristics and incidence and risk ratio (RR) for progression to HGD/EAC in patients with and without aberrant p53 using random effects models. RESULTS: Among the 27 included studies, the proportion of patients with aberrant p53 expression at baseline was 20% (95% CI: 14%, 27%). The rate of progression with and without aberrant p53 was 8 per 100 person-years (95% CI: 6, 11) and 0.3 per 100 person-years (95% CI: 0.1, 0.6), respectively. Compared with patients without aberrant p53 expression, those with aberrant p53 had a higher risk for progression to HGD/EAC in cohort studies (RR = 10.2 [95% CI: 6.9, 15.0]) and case control studies (RR = 3.3 [95% CI: 2.5, 4.4]). The sensitivity for progression for non-dysplastic Barrett's esophagus and low-grade dysplasia/indefinite for dysplasia was 42% and 77% and specificity was 96% and 76%, respectively. DISCUSSION: While aberrant p53 expression has been associated with an increased risk of progression to advanced neoplasia in patients with BE undergoing surveillance, the diagnostic characteristics are suboptimal precluding uniform clinical adoption. Prospective studies with standardized grading protocols are needed to determine whether p53-guided surveillance strategies can meaningfully improve patient outcomes.

Summary Central obesity is a risk factor for esophageal adenocarcinoma (EAC) independent of acid reflux. However, about a quarter of patients with Barrett’s esophagus (BE) and EAC have a normal body mass index (BMI). One hypothesis is that chronic systemic inflammation is as critical to the cancer pathway than the BMI alone. Therefore, we hypothesized that lean patients with BE/EAC would have a high prevalence of metabolic diseases. We aimed to compare metabolic diseases among lean patients with BE/EAC and overweight/obese BE/EAC and lean control without BE/EAC. We performed a propensity score–matched case–control study including patients with BE/EAC and a control group without BE/EAC from the Rochester Epidemiology Project (REP). The groups were compared using chi-square χ 2 and Student t-test as appropriate. Adjusted logistic regression models were used to compare the association with metabolic diseases. We included a total of 2504 patients (631 EAC, 621 BE, and 1252 controls). A quarter of patients (24.6%) with BE/EAC were lean. When compared to controls without BE/EAC, lean patients with BE were more likely to have diabetes (32.2% vs. 11.2%, P < 0.001) and hyperlipidemia (76.2% vs. 53%, P < 0.001). When comparing lean EAC patients to controls without BE/EAC, lean patients had a higher association with smoking (73.3% vs. 58.6%, P: 0.002) and diabetes (18.7% vs. 11.2%, P: 0.03). When compared to overweight/obese BE patients, lean BE were less likely to have NASH (7.7% vs. 20.3%, P: 0.001), diabetes (32.3% vs. 42.1%, P: 0.03), hyperlipidemia (77.2% vs. 87%, P: 0.003), and metabolic syndrome (24% vs. 54%, P < 0.001). Similarly, when compared to overweight/obese patients with EAC, lean EAC patients were less likely to have NASH (0% vs. 15.5%, P < 0.001), diabetes (18.7% vs. 34.1%, P < 0.001), hyperlipidemia (37.3% vs. 51.8%, P: 0.002), hypertension (37.3% vs. 55.3%, P < 0.001), and metabolic syndrome (8% vs. 37.6%, P < 0.001). A quarter of patients with BE/EAC are lean. Although lean BE/EAC patients have a more favorable metabolic profile compared to overweight/obese BE/EAC patients, diabetes and smoking are more common among lean patients with EAC compared to lean controls. The higher association with smoking and diabetes among lean EAC challenges traditional risk factor paradigms, suggesting a significant role for insulin resistance and chronic inflammation in EAC pathogenesis, especially in patients without typical risk factors. BMI-determined obesity may need to be supplemented with inflammatory metabolic diseases to improve assessment of BE/EAC risk in lean patients.

INTRODUCTION: The risk of progression to esophageal adenocarcinoma in Barrett's esophagus (BE) increases with advancing degrees of dysplasia. There is a critical need to improve the diagnosis of BE dysplasia, given substantial interobserver variability and overcalls of dysplasia during manual community pathologist reads. We aimed to externally validate a previously cross-validated BE dysplasia diagnosis deep learning model (BEDDLM) that predicts dysplasia grade on whole slide images (WSIs). METHODS: We digitized nondysplastic BE (NDBE), low-grade (LGD), and high-grade dysplasia (HGD) histology slides from 3 external academic centers. A consensus read by 2 expert study pathologists was used as the criterion standard. Slide stain characteristics were normalized using cycle-generative adversarial networks. WSIs were assessed by BEDDLM using an ensemble approach, combining a “You Only Look Once” model followed by a ResNet101 classifier model. RESULTS: We included 489 WSIs. Consensus histopathology revealed 232 NDBE, 117 LGD, and 140 HGD WSIs. The mean age (SD) was 66.9 (11.4) years; 413 (84.7%) were men. Using the BEDDLM ensemble model, sensitivity and specificity for NDBE were 73.3% (95% confidence interval [CI]: 67.09%–78.85%) and 93.4% (95% CI: 89.62%–96.10%); for LGD, 84.6% (95% CI: 76.78%–90.62%) and 80.6% (95% CI: 76.26%–84.54%); and for HGD, 80.7% (95% CI: 73.19%–86.89%) and 94.8% (95% CI: 91.97%–96.91%), respectively. The F1 score was 0.81, 0 0.69, and 0.83 for NDBE, LGD, and HGD, respectively. DISCUSSION: Our externally validated deep learning model demonstrates substantial accuracy for the diagnosis of BE dysplasia grade on WSIs.

INTRODUCTION: Current guidelines recommend endoscopic surveillance of Barrett's esophagus (BE) but do not account for competing mortality unrelated to esophageal cancer (EC). We conducted a systematic review and meta-analysis to estimate EC and non-EC mortality risk in BE patients. METHODS: We searched multiple databases for studies reporting mortality in BE. We included population-based studies providing standardized mortality ratio (SMR). The primary outcome was SMR from all causes and EC and non-EC etiologies. SMR was calculated by dividing the observed mortality over the expected mortality. Logarithmic form of SMRs was pooled using random-effects model. RESULTS: Our search yielded 2,826 articles, of which 7 studies (n = 34,454) were included. All-cause mortality was elevated in BE patients compared with population controls (pooled SMR 1.24, 95% confident interval [CI] 1.01–1.53) driven in part by increased EC mortality risk (SMR 8.98, 95 CI 5.12–15.77). The mortality risk was still increased but attenuated after excluding EC mortality (SMR 1.21, 95% CI 1–1.46). There was no increased mortality risk of non-EC malignancies (SMR 1.22, 95% CI 0.82–1.82) or mortality due to noncancer etiologies (SMR 1.13, 95% CI 0.90–1.43). Death due to cardiovascular diseases was higher in BE (SMR 1.16, 95% CI 1.02–1.33). BE patients were 10 times more likely to die from noncancer etiologies than EC (risk ratio 10.71, 95% CI 5.98–19.16). Subgroup analysis of studies that excluded prevalent EC at baseline (3 studies) also showed increased all-cause (SMR 1.12, 95% CI 1.07–1.18) and EC mortality (SMR 4.7, 95% CI 3.58–6.17) among BE patients. DISCUSSION: BE patients exhibit a higher all-cause mortality, driven in part by risk of EC mortality. A personalized approach to surveillance, mitigating risk of EC while recognizing the broader mortality risks, is warranted.

Background/Objectives: Performing endoscopic retrograde cholangiopancreatography (ERCP) in surgically altered gastrointestinal anatomy remains challenging, frequently necessitating the use of forward-viewing endoscopes. Given the challenge in endoscope selection based on the type of altered anatomy, the aim of this study was to examine ERCP success rates by specific endoscopes for different anatomy types. Methods: This single-center retrospective study examined ERCPs performed in patients with surgically altered gastrointestinal anatomy during an 18-year period. Enteroscopy success, cannulation success, and intervention success rates were compared between the different anatomy and endoscope types. Results: This study included a total of 334 adult patients (665 total ERCPs) with altered anatomy. The pediatric colonoscope was most frequently utilized (32.2%), and the majority of procedures were performed for biliary indications. Enteroscopy success was 82.2% in Roux-en-Y gastric bypass (RYGB), 97% in Billroth II, 91.5% in Whipple, and 93.2% in Roux-en-Y hepaticojejunostomy (RYHJ). Cannulation success was 90.5% in RYGB, 90.5% in Billroth II, 83.6% in Whipple, and 90.6% in RYHJ. Intervention success was 88.2% in Billroth II, 65.1% in RYGB, 81.6% in Whipple, and 87.5% in RYHJ. In patients with RYGB and RYHJ, SBE was utilized most frequently, with rotational enteroscopy having the highest success rates. The overall adverse event rate was 5.1%, with the majority of these being mild in severity. Conclusions: This large retrospective study found ERCP with forward-viewing endoscopes to be safe and effective for a variety of surgically altered anatomy types. Despite recent advances seen with endoscopic ultrasound-guided drainage procedures, this study advocates for ERCP as the initial approach for pancreaticobiliary access in surgically altered anatomy.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37–1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73–3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63–1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65–1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49–1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic disrupted endoscopy practices, creating unprecedented decreases in cancer screening and surveillance services. We aimed to assess the impact of the pandemic on the proportion of patients diagnosed with Barrett's esophagus (BE) and BE-related dysplasia and adherence to established quality indicators. METHODS: Data from all esophagogastroduodenoscopies in the GI Quality Improvement Consortium, a national repository of matched endoscopy and pathology data, were analyzed from January 2018 to December 2022. Four cohorts were created based on procedure date and COVID-19 data: pre-pandemic (January 2018 to February 2020), pandemic-phase I (March 2020 to July 2020), pandemic-phase II (August 2020 to May 2021), and pandemic-phase III (June 2021 to December 2022). Observed and expected number of BE and BE-related dysplasia cases per month and adherence to the Seattle biopsy protocol and recommended surveillance intervals for nondysplastic BE (NDBE) were evaluated. RESULTS: Among 2,446,857 esophagogastroduodenoscopies performed during the study period, 104,124 (4.3%) had pathology-confirmed BE. The histologic distribution was 87.4% NDBE, 1.8% low-grade dysplasia, 2.4% indefinite for dysplasia, and 1.4% high-grade dysplasia. The number of monthly BE (−47.9% pandemic-phase I, −21.5% pandemic-phase II, and −19.0% pandemic-phase III) and BE-related dysplasia (high-grade dysplasia: 41.2%, −27.7%, and −19.0%; low-grade dysplasia: 49.1%, −35.3%, and −26.5%; any dysplasia: 46.7%, −32.3%, and −27.9%) diagnoses were significantly reduced during the pandemic phases compared with pre-pandemic data. Adherence rates to the Seattle protocol and recommended surveillance intervals for NDBE did not decline during the pandemic. DISCUSSION: There was a significant decline in the number of BE and BE-related dysplasia diagnoses during the COVID-19 pandemic, with an approximately 50% reduction in the number of cases of dysplasia diagnosed in the early pandemic. The absence of a compensatory increase in diagnoses in the pandemic-phase II and III periods may result in deleterious downstream effects on esophageal adenocarcinoma morbidity and mortality.

Background Methods: The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts “What general questions should patients ask when given a new diagnosis of Barrett’s esophagus” and “What questions do I not hear patients asking, but given my expertise, I believe they should be asking?” Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as “essential” or “important” were included in Barrett’s esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1). Results: Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds. Conclusions: With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.