Migrated lumen-apposing stent trapped within a pancreatic fluid collection: Forward-view EUS for the rescue!

Video 1Migrated lumen-apposing stent trapped within a pancreatic fluid collection: forward-view EUS for the rescue!

Defining "true acid reflux" after peroral endoscopic myotomy for achalasia: a prospective cohort study.

BACKGROUND AND AIMS: The symptoms of reflux in achalasia patients undergoing peroral endoscopic myotomy (POEM) are believed to result from gastroesophageal reflux, and the current treatment primarily focuses on acid suppression. Nevertheless, other factors such as nonreflux acidification caused by fermentation or stasis might play a role. This study aimed to identify patients with "true acid reflux" who actually require acid suppression and fundoplication. METHODS: In this prospective large cohort study, the primary objective was to assess the incidence and risk factors for true acid reflux in achalasia patients undergoing POEM. Acid reflux with normal and delayed clearance defined true acid reflux, whereas other patterns were labeled as nonreflux acidification patterns on manual analysis of pH tracings. These findings were corroborated with a symptom questionnaire, esophagogastroscopy, esophageal manometry, and timed barium esophagogram at 3 months after the POEM procedure. RESULTS: Fifty-four achalasia patients aged 18 to 80 years (mean age, 41.1 ± 12.8 years; 59.3% men; 90.7% with type II achalasia) underwent POEM, which resulted in a significant mean Eckardt score improvement (6.7 to 1.6, P < .05). True acid reflux was noted in 29.6% of patients as compared with 64.8% on automated analysis. Acid fermentation was the predominant acidification pattern seen in 42.7% of patients. On multivariable logistic regression analysis, increasing age (odds ratio, 1.12; 95% confidence interval, 1.02-1.27; P = .04) and preprocedural integrated relaxation pressure (IRP; odds ratio, 1.13; 95% confidence interval, 1.04-1.30; P = .02) were significantly associated with true acid reflux in patients after undergoing POEM. CONCLUSIONS: A manual review of pH tracings helps to identify true acid reflux in patients with achalasia after undergoing POEM. Preprocedural IRP can be a predictive factor in determining patients at risk for this outcome. (Clinical trial registration number: NCT04951739.).

To push or to pull? A clinical audit on the efficacy and safety of the pull and push percutaneous endoscopic gastrostomy techniques in oncological patients.

BACKGROUND: The peroral "pull" technique and the direct "push" procedure are the two main methods for percutaneous endoscopic gastrostomy (PEG) placement. Although pull-PEG is generally recommended as the first-line modality, many oncological patients require a push-PEG approach to prevent tumor seeding or overcome tumor-related obstruction. OBJECTIVE: We aimed to compare the efficacy and safety of both PEG procedures in cancer patients. METHODS: We retrospectively analyzed all consecutive PEG procedures within a tertiary oncological center. Patients were followed up with the hospital databases and National Cancer Registry to assess the technical success rate for PEG placement, the rate of minor and major adverse events (AEs), and 30-day mortality rates. We compared those outcomes between the two PEG techniques. Finally, risk factors for PEG-related adverse events were analyzed using a multivariable Cox proportional-hazard regression model adjusted for patients' sex, age, performance status (ECOG), Body Mass Index (BMI), diabetes, chemoradiotherapy (CRT) status (pre-/current-/post-treatment), and type of PEG. RESULTS: We included 1055 PEG procedures (58.7% push-PEG/41.4% pull-PEG) performed in 994 patients between 2014 and 2021 (mean age 62.0 [±10.7] yrs.; 70.2% males; indication: head-and-neck cancer 75.9%/other cancer 24.1%). The overall technical success for PEG placement was 96.5%. Although the "push" technique had a higher rate of all AEs (21.4% vs. 7.1%, Hazard Ratio [HR]  = 2.9; 95% CI = 1.9-4.3, p < 0.001), most of these constituted minor AEs (71.9%), such as tube dislodgement. The methods had no significant difference regarding major AEs and 30-day mortality rates. Previous CRT was associated with an increased risk of major AEs (hazard ratio = 2.7, 95% CI = 1.0-7.2, p = 0.042). CONCLUSION: The risk of major AEs was comparable between the push- and pull-PEG techniques in cancer patients. Due to frequent tube dislodgement in push-PEG, the pull technique may be more suitable for long-term feeding. Previous CRT increases the risk of major AEs, favoring early ("prophylactic") PEG placement when such treatment is expected.

A Randomized, Controlled Trial Comparing the Total Enteroscopy Rate and Diagnostic Efficacy of Novel Motorized Spiral Enteroscopy and Single-Balloon Enteroscopy in Patients With Small-Bowel Disorders: The Motor Trial (NCT 05548140).

INTRODUCTION: Device-assisted enteroscopy has revolutionized the management of small-bowel disorders (SBD). No study to date has compared both novel motorized spiral enteroscopy (NMSE) and single-balloon enteroscopy (SBE) as a randomized controlled trial. Hence, this study was planned to include patients having SBD with the primary aim to compare the total enteroscopy rate (TER). METHODS: This study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India, from September 20, 2022, to December 15, 2022. All consecutive patients, older than 18 years with suspected SBD, and planned for total enteroscopy were screened for inclusion. The primary outcome was to compare the TER, and secondary outcomes were to compare the technical success, time taken to reach the depth of maximal insertion, withdrawal time, total procedure time, diagnostic yield, therapeutic success, and adverse events (AE). RESULTS: Seventy-two patients of the 110 patients screened were randomized in either NMSE (n = 35) or SBE (n = 37) group. The most common indication for the procedures was obscure gastrointestinal bleed (48%), others being unexplained abdominal pain with indeterminate radiologic findings (32%) and chronic diarrhea (20%). In NMSE group, the TER was 71.4%, whereas in the SBE group, it was 10.8% ( P < 0.0001). The total procedure time (minutes) was much lesser with NMSE (58.17 ± 21.5 minutes) vs SBE (114.2 ± 33.5 minutes) ( P < 0.0001). The diagnostic yield of NMSE (80%) was comparatively higher than SBE (62.1%) ( P = 0.096). Minor AE (grade I) were observed in both the groups: NMSE 8.5% (3/35) and SBE 5.4% (2/37). DISCUSSION: This randomized controlled trial shows that with NMSE higher TER can be achieved in shorter duration with minimal AE, compared with SBE.

Narrow-band imaging vs Lugol chromoendoscopy in screening for esophageal squamous cell neoplasia: a randomized trial.

INTRODUCTION: To date, there is no established optimal method for endoscopic detection of esophageal squamous cell neoplasia in high­risk individuals. OBJECTIVES: We aimed to compare the performance of narrow­band imaging (NBI) and Lugol chromoendoscopy in screening for esophageal neoplasia among patients with a history of treatment for head and neck squamous cell cancer (HNSCC). PATIENTS AND METHODS: We randomly assigned 300 patients who had completed curative treatment for HNSCC at least 1 year prior to the inclusion to undergo either NBI or Lugol endoscopy (2:1 ratio). Following white­light examination of the esophagus, the assigned imaging study was performed, and biopsies were taken from any suspicious lesions identified using NBI or Lugol chromoendoscopy. The primary end point was positive predictive value (PPV) of the biopsied lesion for a diagnosis of esophageal neoplasia (high­grade intraepithelial neoplasia [HG­IEN] or invasive esophageal squamous cell carcinoma [ESCC]). The secondary end points included the number of biopsied lesions, duration of esophagus examination, and endoscopy tolerance. RESULTS: In 294 patients included in the final analysis (NBI, n = 204; Lugol chromoendoscopy, n = 90), we diagnosed 3 ESCCs (1.02%) and 2 HG­IENs (0.68%). The PPV of NBI and Lugol chromoendoscopy in per­lesion analysis was 7.69% (95% CI, 0.94%-25.1%) and 8.11% (95% CI, 1.7%-21.9%), respectively (P >0.99). NBI outperformed Lugol chromoendoscopy in terms of the rate of patients requiring biopsy (12.75% vs 41.11%; P = 0.003), duration of esophagus examination (3.5 min vs 5.15 min; P <0.001), and endoscopy tolerance assessed on the visual analog scale (25 mm vs 36.5 mm; P = 0.002). CONCLUSIONS: With a PPV comparable to that of Lugol chromoendoscopy, but a lower number of biopsies required, shorter examination time, and better patient tolerance, NBI could be considered the primary screening method for ESCC in patients with HNSCC.

Single-Cell RNA Sequencing Unifies Developmental Programs of Esophageal and Gastric Intestinal Metaplasia.

Intestinal metaplasia in the esophagus (Barrett's esophagus IM, or BE-IM) and stomach (GIM) are considered precursors for esophageal and gastric adenocarcinoma, respectively. We hypothesize that BE-IM and GIM follow parallel developmental trajectories in response to differing inflammatory insults. Here, we construct a single-cell RNA-sequencing atlas, supported by protein expression studies, of the entire gastrointestinal tract spanning physiologically normal and pathologic states including gastric metaplasia in the esophagus (E-GM), BE-IM, atrophic gastritis, and GIM. We demonstrate that BE-IM and GIM share molecular features, and individual cells simultaneously possess transcriptional properties of gastric and intestinal epithelia, suggesting phenotypic mosaicism. Transcriptionally E-GM resembles atrophic gastritis; genetically, it is clonal and has a lower mutational burden than BE-IM. Finally, we show that GIM and BE-IM acquire a protumorigenic, activated fibroblast microenvironment. These findings suggest that BE-IM and GIM can be considered molecularly similar entities in adjacent organs, opening the path for shared detection and treatment strategies. SIGNIFICANCE: Our data capture the gradual molecular and phenotypic transition from a gastric to intestinal phenotype (IM) in the esophagus and stomach. Because BE-IM and GIM can predispose to cancer, this new understanding of a common developmental trajectory could pave the way for a more unified approach to detection and treatment. See related commentary by Stachler, p. 1291. This article is highlighted in the In This Issue feature, p. 1275.

A Global Perspective on Gastric Cancer Screening: Which Concepts Are Feasible, and When?

BACKGROUND: Gastric cancer (GC) remains the fifth most common cancer and the third most common cause of cancer-related death globally. In 2022, GC fell into the scope of the updated EU recommendations for targeted cancer screening. Given the growing awareness of the GC burden, we aimed to review the existing screening strategies for GC in high-risk regions and discuss potentially applicable modalities in countries with low-to-intermediate incidence. METHODS: The references for this Review article were identified through searches of PubMed with the search terms "gastric cancer", "stomach cancer", "Helicobacter pylori", and "screening" over the period from 1995 until August 2022. RESULTS: As Helicobacter pylori (H. pylori)-induced gastritis is the primary step in the development of GC, the focus on GC prevention may be directed toward testing for and treating this infection. Such a strategy may be appealing in countries with low- and intermediate- GC incidence. Other biomarker-based approaches to identify at-risk individuals in such regions are being evaluated. Within high-incidence areas, both primary endoscopic screening and population-based H. pylori "test-and-treat" strategies represent cost-effective models. CONCLUSIONS: Given the significant variations in GC incidence and healthcare resources around the globe, screening strategies for GC should be adjusted to the actual conditions in each region. While several proven tools exist for accurate GC diagnosis, a universal modality for the screening of GC populations remains elusive.

The effect of procedural time on dysplasia detection rate during endoscopic surveillance of Barrett's esophagus.

BACKGROUND : Endoscopic surveillance of Barrett's esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). METHODS : We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. RESULTS : Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0-19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00-1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04-1.40; P = 0.01). CONCLUSIONS : In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection.

Comparison of Quality Measures for Detection of Neoplasia at Screening Colonoscopy.

BACKGROUND & AIMS: The proportion of colonoscopies with at least one adenoma (adenoma detection rate [ADR]) is inversely associated with colorectal cancer (CRC) risk and death. The aim of this study was to examine whether such associations exist for colonoscopy quality measures other than ADR. METHODS: We used data from the Polish Colorectal Cancer Screening Program collected in 2000-2011. For all endoscopists who performed ≥100 colonoscopies we calculated detection rates of adenomas (ADR), polyps (PDR), and advanced adenomas (≥10 mm/villous component/high-grade dysplasia [AADR]); and number of adenomas per colonoscopy (APC) and per colonoscopy with ≥1 adenoma (APPC). We followed patients until CRC diagnosed before recommended surveillance, death, or December 31, 2019. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional-hazard models. We used Harrell's C statistic to compare the predictive power of the quality measures. RESULTS: Data on 173,287 patients (median age, 56 years; 37.8% male) and 262 endoscopists were used. During a median follow-up of 10 years and 1,490,683 person-years, we identified 395 CRCs. All quality measures were significantly associated with CRC risk and death. The relative reductions in CRC risk were as follows: for ADR ≥24.9% (reference <12.1%; HR, 0.41; 95% CI, 0.25-0.66), PDR ≥42.7% (reference <19.9%; HR, 0.35; 95% CI, 0.24-0.51), AADR ≥9.1% (reference <4.1%; HR, 0.69; 95% CI, 0.49-0.96), APC ≥0.37 (reference <0.15; HR, 0.35; 95% CI, 0.21-0.58), and APPC ≥1.54 (reference <1.19; HR, 0.54; 95% CI, 0.35-0.83). AADR was the only quality measure with significantly lower predictive power than ADR (Harrell's C, 59.7 vs 63.4; P = .001). Similar relative reductions were observed for CRC death. CONCLUSIONS: This large observational study confirmed the inverse association between ADR and CRC risk and death. The PDR and APC quality measures appear to be comparable with ADR.

The utility of P53 immunohistochemistry in the diagnosis of Barrett's oesophagus with indefinite for dysplasia.

AIMS: Barrett's oesophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens. METHODS AND RESULTS: Archive endoscopic biopsies with a BE-IND diagnosis from two academic centres were analysed. First, haematoxylin and eosin-stained slides (H&E) were reviewed by four expert gastrointestinal (GI) pathologists allocated into two groups (A and B). After a washout period of at least 8 weeks, H&E slides were reassessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. We included 216 BE-IND specimens from 185 patients, 44.0 and 32.9% of which were confirmed after H&E slide revision by groups A and B, respectively. More than half the cases were reclassified to a non-dysplastic BE (NDBE), while 5.6% of cases in group A and 7.4% in group B were reclassified to definite dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03 and -0.02, respectively. Use of p53-IHC led to a >40% reduction in BE-IND diagnoses (P < 0.001) and increased IOA for all BE grades [κ = 0.46 (NDBE), 0.26 (BE-IND), 0.49 (LGD), 0.35 (HGD/IMC)]. An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio = 44.3, 95% confidence interval = 18.8-113.0). CONCLUSION: P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.

Confocal laser endomicroscopy in gastro-intestinal endoscopy: technical aspects and clinical applications.

Confocal laser endomicroscopy (CLE) is an advanced endoscopic imaging technology that provides a magnified, cellular level view of gastrointestinal epithelia. In conjunction with topical or intravenous fluorescent dyes, CLE allows for an "optical biopsy" for real-time diagnosis. Two different CLE system have been used in clinical endoscopy, probe-based CLE (pCLE) and endoscope-based CLE (eCLE). Using pCLE, the device can be delivered: (I) into the luminal gastrointestinal tract through the working channel of standard endoscopes; (II) into extraluminal cystic and solid parenchymal lesions through an endoscopic ultrasound (EUS) needle; or (III) into the biliary system through an endoscopic retrograde cholangiopancreatography (ERCP) accessory channel. With eCLE, the probe is directly integrated into the tip of a conventional endoscope, however, these endoscopes are no longer commercially available. CLE has moderate to high diagnostic accuracy for neoplastic and inflammatory conditions through the gastrointestinal tract including: oesophageal, gastric and colonic neoplasia, pancreatic cysts and solid lesions, malignant pancreatobiliary strictures and inflammatory bowel disease. Some studies have demonstrated the diagnostic benefit of CLE imaging when combined with either conventional white light endoscopy or advanced imaging technologies. Therefore, optical biopsies using CLE can resolve diagnostic dilemmas in some cases where conventional imaging fails to achieve conclusive results. CLE could also reduce the requirement for extensive tissue sampling during surveillance procedures. In the future, CLE in combination with molecular probes, could allow for the molecular characterization of diseases and assess response to targeted therapy. However, the narrow field of view, high capital costs and specialized operator training requirements remain the main limitations. Future multi-center, randomized trials with a focus on conventional diagnostic applications, cost-effectiveness and standardized training will be required for definitive evidence. The objective of this review is to evaluate the technical aspects and current applications of CLE in patients with gastrointestinal and pancreatobiliary diseases and discuss future directions for this technique.

Image-Enhanced Endoscopy and Molecular Biomarkers Vs Seattle Protocol to Diagnose Dysplasia in Barrett's Esophagus.

BACKGROUND & AIMS: Dysplasia in Barrett's esophagus often is invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence imaging (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers vs HRWLE with Seattle protocol biopsies. METHODS: Barrett's esophagus patients with no dysplastic lesions were block-randomized to standard endoscopy (HRWLE with the Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6 to 12 weeks. The primary end point was the histologic diagnosis from all study biopsies (trial histology). A sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from the first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. The primary outcome was diagnostic accuracy for dysplasia by real-time pCLE vs HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P = .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P < .001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; P = .16), with an area under the receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. The addition of molecular biomarkers could improve diagnostic accuracy.

Complete polyp resection with cold snare versus hot snare polypectomy for polyps of 4-9 mm: a randomized controlled trial.

BACKGROUND: Endoscopic screening with polypectomy reduces the incidence of colorectal cancer (CRC). Incomplete polyp removal may attenuate the effect of screening. This randomized trial compared cold snare polypectomy (CSP) with hot snare polypectomy (HSP) in terms of complete polyp resection. METHODS: We included patients ≥ 40 years of age at eight hospitals in four countries who had at least one non-pedunculated polyp of 4-9 mm detected at colonoscopy. Patients were randomized 1:1 to CSP or HSP. Biopsies from the resection margins were obtained systematically after polypectomy in both groups. We hypothesized that CSP would be non-inferior to HSP, with a non-inferiority margin of 5 %. Logistic regression models were fitted to identify the factors explaining incomplete resection. RESULTS: 425 patients, with 601 polyps, randomized to either CSP or HSP were included in the analysis. Of 318 polyps removed by CSP and 283 polyps removed by HSP, 34 (10.7 %) and 21 (7.4 %) were incompletely resected, respectively, with an adjusted risk difference of 3.2 % (95 %CI -1.4 % to 7.8 %). There was no difference between the groups in terms of post-polypectomy bleeding, perforation, or abdominal pain. Independent risk factors for incomplete removal were serrated histology (odds ratio [OR] 3.96; 95 %CI 1.63 to 9.66) and hyperplastic histology (OR 2.52; 95 %CI 1.30 to 4.86) in adjusted analyses. CONCLUSION: In this randomized trial, non-inferiority for CSP could not be demonstrated. Polyps with serrated histology are more prone to incomplete resection compared with adenomas. CSP can be used safely for small polyps in routine colonoscopy practice.

The Colon Endoscopic Bubble Scale (CEBuS): a two-phase evaluation study.

BACKGROUND: To date, no scale has been validated to assess bubbles associated with bowel preparation. This study aimed to develop and assess the reliability of a novel scale - the Colon Endoscopic Bubble Scale (CEBuS). METHODS: This was a multicenter, prospective, observational study with two online evaluation phases of 45 randomly distributed still colonoscopy images (15 per scale grade). Observers assessed images twice, 2 weeks apart, using CEBuS (CEBuS-0 - no or minimal bubbles, covering < 5 % of the surface; CEBuS-1 - bubbles covering 5 %-50 %; CEBuS-2 - bubbles covering > 50 %) and reporting the clinical action (do nothing; wash with water; wash with simethicone). RESULTS: CEBuS provided high levels of agreement both in evaluation Phase 1 (4 experts) and Phase 2 (6 experts and 13 non-experts), with almost perfect intraobserver reliability: kappa 0.82 (95 % confidence interval 0.75-0.88) and 0.86 (0.85-0.88); interobserver agreement - intraclass correlation coefficient (ICC) 0.83 (0.73-0.89) and 0.90 (0.86-0.94). Previous endoscopic experience had no influence on agreement among experts vs. non-experts: kappa 0.86 (0.80-0.91) vs. 0.87 (0.84-0.89) and ICC 0.91 (0.87-0.94) vs. 0.90 (0.86-0.94), respectively. Interobserver agreement on clinical action was ICC 0.63 (0.43-0.78) in Phase 1 and 0.77 (0.68-0.84) in Phase 2. Absolute agreement on clinical action per scale grade was 85 % (82-88) for CEBuS-0, 21 % (16-26) for CEBuS-1, and 74 % (70-78) for CEBuS-2. CONCLUSION: CEBuS proved to be a reliable instrument to standardize the evaluation of colonic bubbles during colonoscopy. Assessment in daily practice is warranted.

Prevalence and risk factors of upper gastrointestinal cancers missed during endoscopy: a nationwide registry-based study.

BACKGROUND: A significant proportion of upper gastrointestinal cancers (UGICs) remain undetected during esophagogastroduodenoscopy (EGD). We investigated the characteristics and risk factors of UGICs missed during endoscopy. METHODS: In this nationwide registry-based study, we analyzed two large Polish datasets (National Health Fund and National Cancer Registry) to identify individuals who underwent EGD and were subsequently diagnosed with UGIC. Cancers diagnosed < 6 months after EGD were defined as "prevalent" and those within ≥ 6- < 36 months as "missed." We compared the characteristics of missed and prevalent cancers, and analyzed the risk factors for missed UGICs in a multivariable regression model. RESULTS: We included 4 105 399 patients (mean age 56.0 years [SD 17.4]; 57.5 % female) who underwent 5 877 674 EGDs in 2012-2018. Within this cohort, 33 241 UGICs were diagnosed, of which 1993 (6.0 %) were missed. Within esophageal neoplasms, adenocarcinomas were more frequently missed than squamous cell cancers (6.1 % vs. 4.2 %), with a relative risk of 1.4 (95 % confidence interval [CI] 1.1-1.8, P = 0.01). Most gastric cancers were adenocarcinomas, of which 5.7 % were classified as missed. Overall, a higher proportion of missed UGICs than prevalent cancers presented at an advanced stage (42.2 % vs. 36.2 %, P < 0.001). Risk factors for missed UGICs included initial EGD performed within primary (vs. secondary) care (odds ratio [OR] 1.3, 95 %CI 1.2-1.5), female sex (OR 1.3, 95 %CI 1.2-1.4), and higher comorbidity (Charlson comorbidity index ≥ 5 vs. 0; OR 6.0, 95 %CI 4.7-7.5). CONCLUSIONS: Among UGICs, esophageal adenocarcinomas were missed most frequently. Missed cancers occur more frequently within the primary care sector and are found more often in women and individuals with multiple comorbidities.

First-in-human pilot study of snapshot multispectral endoscopy for early detection of Barrett's-related neoplasia.

SIGNIFICANCE: The early detection of dysplasia in patients with Barrett's esophagus could improve outcomes by enabling curative intervention; however, dysplasia is often inconspicuous using conventional white-light endoscopy. AIM: We sought to determine whether multispectral imaging (MSI) could be applied in endoscopy to improve detection of dysplasia in the upper gastrointestinal (GI) tract. APPROACH: We used a commercial fiberscope to relay imaging data from within the upper GI tract to a snapshot MSI camera capable of collecting data from nine spectral bands. The system was deployed in a pilot clinical study of 20 patients (ClinicalTrials.gov NCT03388047) to capture 727 in vivo image cubes matched with gold-standard diagnosis from histopathology. We compared the performance of seven learning-based methods for data classification, including linear discriminant analysis, k-nearest neighbor classification, and a neural network. RESULTS: Validation of our approach using a Macbeth color chart achieved an image-based classification accuracy of 96.5%. Although our patient cohort showed significant intra- and interpatient variance, we were able to resolve disease-specific contributions to the recorded MSI data. In classification, a combined principal component analysis and k-nearest-neighbor approach performed best, achieving accuracies of 95.8%, 90.7%, and 76.1%, respectively, for squamous, non-dysplastic Barrett's esophagus and neoplasia based on majority decisions per-image. CONCLUSIONS: MSI shows promise for disease classification in Barrett's esophagus and merits further investigation as a tool in high-definition "chip-on-tip" endoscopes.

Spectral Endoscopy Enhances Contrast for Neoplasia in Surveillance of Barrett's Esophagus.

Early detection of esophageal neoplasia enables curative endoscopic therapy, but the current diagnostic standard of care has low sensitivity because early neoplasia is often inconspicuous with conventional white-light endoscopy. Here, we hypothesized that spectral endoscopy could enhance contrast for neoplasia in surveillance of patients with Barrett's esophagus. A custom spectral endoscope was deployed in a pilot clinical study of 20 patients to capture 715 in vivo tissue spectra matched with gold standard diagnosis from histopathology. Spectral endoscopy was sensitive to changes in neovascularization during the progression of disease; both non-dysplastic and neoplastic Barrett's esophagus showed higher blood volume relative to healthy squamous tissue (P = 0.001 and 0.02, respectively), and vessel radius appeared larger in neoplasia relative to non-dysplastic Barrett's esophagus (P = 0.06). We further developed a deep learning algorithm capable of classifying spectra of neoplasia versus non-dysplastic Barrett's esophagus with high accuracy (84.8% accuracy, 83.7% sensitivity, 85.5% specificity, 78.3% positive predictive value, and 89.4% negative predictive value). Exploiting the newly acquired library of labeled spectra to model custom color filter sets identified a potential 12-fold enhancement in contrast between neoplasia and non-dysplastic Barrett's esophagus using application-specific color filters compared with standard-of-care white-light imaging (perceptible color difference = 32.4 and 2.7, respectively). This work demonstrates the potential of endoscopic spectral imaging to extract vascular properties in Barrett's esophagus, to classify disease stages using deep learning, and to enable high-contrast endoscopy. SIGNIFICANCE: The results of this pilot first-in-human clinical trial demonstrate the potential of spectral endoscopy to reveal disease-associated vascular changes and to provide high-contrast delineation of neoplasia in the esophagus. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3415/F1.large.jpg.

The risk of neoplasia in patients with Barrett's esophagus indefinite for dysplasia: a multicenter cohort study.

BACKGROUND AND AIMS: Current understanding of the risk of neoplastic progression in patients with Barrett's esophagus with indefinite dysplasia (BE-IND) stems from small retrospective and pathology registry studies. In this multicenter cohort study, we aimed to determine the incidence and prevalence of neoplasia in BE-IND. METHODS: Patients with confirmed BE-IND from 2 academic centers were included if they had no previous evidence of dysplasia and underwent endoscopic follow-up (FU) of ≥1 year. The rate of progression to neoplasia was calculated and categorized as prevalent (progression within 1 year of FU) and incident (progression after 1 year of FU). Multivariable regression adjusted for relevant clinical features was performed to identify risk factors for progression. RESULTS: Four hundred sixty-five patients diagnosed with BE-IND were identified between 1997 and 2017, of which 223 (48.0%) were excluded. Of the remaining 242 patients, 184 (76.0%) had no evidence of dysplasia during FU. In 23 patients (9.5%), prevalent neoplasia occurred (20 low-grade dysplasia [LGD], 2 high-grade dysplasia [HGD], 1 intramucosal cancer [IMC]), whereas 35 patients (14.5%) developed incident neoplasia (27 LGD, 5 HGD, 3 IMC), after a median 1.5 years (interquartile range, 0.6-3.2 years). The incidence rates of any neoplasia and HGD/IMC were 3.2 and 0.6 cases/100 patient-years, respectively. BE length correlated with an increased risk of prevalent (odds ratio, 1.18 per 1 cm; 95% confidence interval, 1.02-1.38; P = .033) and incident neoplasia (odds ratio, 1.02; 95% confidence interval, 1.00-1.03; P = .016). CONCLUSION: Patients with BE-IND should be closely monitored, because nearly a quarter harbor or will shortly develop dysplasia. BE length is a clinical predictor of neoplastic progression; however, more-accurate molecular biomarkers for risk stratification are warranted.

Peroral Endoscopic Myotomy in the Management of Zenker's Diverticulum: A Retrospective Multicenter Study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging technique in the treatment of Zenker's diverticulum (ZD). This study aimed to analyze the feasibility of Zenker's POEM (Z-POEM) in a multicenter setting and assess its performance using a validated Kothari-Haber Scoring System newly developed for symptom measurement in ZD. MATERIALS AND METHODS: This was a multicenter retrospective study involving three Polish tertiary referral endoscopic units. The data of consecutive patients with symptomatic ZD treated with Z-POEM in Poland between May 2019 and August 2020 were retrieved and analyzed. Primary outcome measures were technical success and clinical success rate (<3 points in Kothari-Haber Score at 2-3 months follow-up). Secondary outcome measures included procedures' duration, length of hospital stay, and adverse events. RESULTS: 22 patients with symptomatic ZD were included. The mean age was 67.6 (±10.7) years, and 14 (63.6%) were male. All but two patients were treatment naïve. The average size of the ZD was 30 mm (IQR, 24-40 mm). Technical success was achieved in all patients (100%), whereas clinical success was 90.9%. The average Kothari-Haber Score was 6.35 before treatment and has dropped to 0.65 after the treatment (p < 0.0001). The mean procedure time was 48.8 (±19.3) minutes, and the median length of hospital stay was 2 days (IQR, 2-3). Three patients (13.6%) had post-procedural emphysema, of which two were mild and self-resolving (9.1%), and one was moderate (4.5%) and complicated with laryngeal edema and prolonged intubation. CONCLUSIONS: This feasibility study suggests that Z-POEM is a highly effective and safe treatment for ZD, particularly among treatment-naïve patients. Comparative studies with other treatment modalities over longer follow-up are warranted.