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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. [ABSTRACT FROM AUTHOR]

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). 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. 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. NanoNAM can serve as an adjunct to histopathologic evaluation of BE patients and aid in risk stratification. [ABSTRACT FROM AUTHOR]

Keywords: Achalasia; Myotomy; Peroral endoscopic myotomy (POEM); Timed barium esophagram; Eckardt score EN Achalasia Myotomy Peroral endoscopic myotomy (POEM) Timed barium esophagram Eckardt score 278 281 4 02/03/21 20210101 NES 210101 Madhusudan R. Sanaka and Pravallika Chadalavada are co-first authors. Both Eckardt score and TBE parameters had a trend towards pre-treatment baseline values. On the contrary, it could also be argued that the Eckardt score includes only limited differentiation of each symptom and might have limited utility in the post-treatment follow-up of achalasia patients. [Extracted from the article]

Gastric Per-oral Endoscopic pyloromyotomy (G-POEM) or per-oral pyloromyotomy (POP) is a novel procedure recently described for treatment of medically refractory gastroparesis; however, its efficacy and safety is not clear in patients with postsurgical gastroparesis (PsGP). We conducted a systematic review and meta-analysis to determine the efficacy and safety of G-POEM in PsGP. A total of 6 studies were included in the analysis. The pooled rate of success by gastroparesis cardinal symptom index (GCSI) and 4-h gastric emptying study (GES) were 89.6% (95% C.I. 72.7-96.5) and 81.5% (95% CI 47.8-95.5) respectively. There was a statistically significant improvement in GCSI score after 3 months of G-POEM as compared with pre G-POEM GCSI scores (2.7 (95% C.I. 0-5.5) vs 8.2 (95% C.I. 5.4-11) (p = 0.007). The mean pre G-POEM 4 h GES was 93.8% (95% C.I. 42.3-145.3) with improvement in post G-POEM GES to 44.5% (95% C.I. 0-95)(p = 0.2). The pooled rate of total adverse events was 9% (95% C.I. 2.7-25.9). Our study showed a good clinical success of G-POEM in PsGP patients along with significant improvement in 3-month GCSI scores. There was an improvement of GES after G-POEM, but it did not reach statistical significance. In conclusion, G-POEM is an effective and safe treatment option for PsGP. [ABSTRACT FROM AUTHOR]

Background & Aims European guidelines recommend different surveillance intervals of non-dysplastic Barrett's esophagus (NDBE) based on segment length, as opposed to guidelines in the United States, which do recommend surveillance intervals based on BE length. We studied rates of progression of NDBE to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with short-segment BE using the definition of BE in the latest guidelines (length ≥1 cm). Methods We collected demographic, clinical, endoscopy, and histopathology data from 1883 patients with endoscopic evidence of NDBE (mean age, 57.3 years; 83.5% male; 88.1% Caucasians) seen at 7 tertiary referral centers. Patients were followed for a median 6.4 years. Cases of dysplasia or EAC detected within 1 year of index endoscopy were considered prevalent and were excluded. Unadjusted rates of progression to HGD or EAC were compared between patients with short (≥1 and <3) and long (≥3) BE lengths using log-rank tests. A subgroup analysis was performed on patients with a documented Prague C&M classification. We used a multivariable proportional hazards model to evaluate the association between BE length and progression. Adjusted hazards ratios were calculated after adjusting for variables associated with progression. Results We found 822 patients to have a short-segment BE (SSBE) and 1061 to have long segment BE (LSBE). We found patients with SSBE to have a significantly lower annual rate of progression to EAC (0.07%) than of patients with LSBE (0.25%) (P =.001). For the combined endpoint of HGD or EAC, annual progression rates were significantly lower among patients with SSBE (0.29%) compared to compared to LSBE (0.91%) (P <.001). This effect persisted in multivariable analysis (hazard ratio, 0.32; 95% CI, 0.18–0.57; P <.001). Conclusion We analyzed progression of BE (length ≥1 cm) to HGD or EAC in a large cohort of patients seen at multiple centers and followed for a median 6.4 years. We found a lower annual rate of progression of SSBE to EAC (0.07%/year) than of LSBE (0.25%/year). We propose lengthening current surveillance intervals for patients with SSBE. [ABSTRACT FROM AUTHOR]

Background Few studies of reintervention after Heller myotomy for achalasia set patients' expectations, assist therapeutic decision making, and direct follow-up. Therefore, we investigated the frequency and type of symptoms and reinterventions after myotomy based on achalasia type. Methods From January 2006 to March 2013, 248 patients who had preoperative high-resolution manometry and a timed barium esophagram (TBE) underwent Heller myotomy, 62 (25%) for type I, 162 (65%) for type II, and 24 (10%) for type III achalasia. Postoperative surveillance, including TBE, was performed at 8 weeks, then annually. Median follow-up was 36 months. End points were all symptom types and modes of reintervention, endoscopic or surgical. Reintervention was based on both symptoms and objective TBE measurements. Results Eventually most patients (169 of 218; 69%) experienced at least one symptom after myotomy. Fifty patients underwent 85 reinterventions, 41 endoscopic only, 4 surgical only, and 5 both. Five-year freedom from reintervention was 62% for type I, 74% for type II, and 87% for type III, most occurring within 6 months, although later in type III. At 5 years, number of reinterventions per 100 patients was 72 for type I, 51 for type II, and 13 for type III. After each reintervention, there was approximately a 50% chance of another within 2 years. Conclusions Patients' expectations when undergoing Heller myotomy for achalasia must be that symptoms will only be palliated, and patients who have worse esophageal function—achalasia type I—may require one or more postoperative reinterventions. Thus, we recommend that patients with achalasia have lifelong annual surveillance after Heller myotomy that includes TBE. [ABSTRACT FROM AUTHOR]

Background & Aims Many patients with a < 1 cm segment of columnar metaplasia in the distal esophagus, also called an irregular Z line , are encountered. These patients, often referred to as patients with Barrett’s esophagus (BE), are enrolled in surveillance programs. However, little is known about their risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). We aimed to determine the incidence of HGD and EAC in patients with irregular Z line with intestinal metaplasia. Methods We performed a prospective, multicenter cohort study of patients who underwent endoscopic examination for BE at tertiary care referral centers in the United States and Europe. We analyzed data from 1791 patients (mean age, 56 ± 17 years) found to have non-dysplastic BE at the index endoscopy and after 1 year or more of follow-up. Patients were followed for a median of 5.9 years (interquartile range, 3.1–8.3 years). We calculated rates of progression to HGD or EAC between groups of patients with irregular Z line (n = 167) and those with BE of ≥ 1 cm (n = 1624). Results A higher proportion of patients in the irregular Z-line group were female (26.3%) than in the BE group (14.8% female BE) ( P <.001). A lower proportion of patients in the irregular Z-line group were smokers (33.5%) than in the BE group (52.6% smokers). None of the patients with irregular Z line developed HGD or EAC during a median follow-up period of 4.8 years (interquartile range, 3.2–8.3 years). All 71 incident cases of HGD or EAC developed in patients with BE of ≥1 cm in length. On multivariate analysis, patients with irregular Z line and patients with BE of ≥ 1 cm did not differ significantly in age, race, or duration of follow-up. Conclusions In a prospective, multicenter cohort study, we found that patients with irregular Z line do not develop HGD or esophageal cancer within 5 years after index endoscopy. [ABSTRACT FROM AUTHOR]

Increased lower esophageal sphincter integrated relaxation pressure (LES-IRP) is a cardinal feature of achalasia. However, some patients with characteristic features of achalasia have normal LES-IRP.1,2 The efficacy of peroral endoscopic myotomy (POEM) in achalasia patients with normal LES-IRP is not well known. Hence, we aimed to compare POEM outcomes in achalasia patients with normal (<15 mm Hg) and increased (≥15 mm Hg) LES-IRP. [ABSTRACT FROM AUTHOR]

Background Adenoma detection rates (ADRs) are established as quality targets in average-risk (AR) individuals undergoing colorectal cancer (CRC) screening colonoscopy. Little is known about the ADR in high-risk (HR) individuals undergoing index or surveillance colonoscopy. Objective To determine and compare ADR in HR versus AR individuals undergoing colonoscopy. Design and Setting Retrospective study, tertiary care center. Patients and Intervention We reviewed records of 7357 patients who underwent colonoscopy by 66 multispecialty endoscopists at our institution during the period 2008 to 2009. Both screening and surveillance colonoscopies in AR and HR patients for CRC were studied. HR patients were further divided into 3 subgroups: those with a (1) personal history of polyps (PHP), (2) family history of polyps (FHP), and (3) family history of CRC (FHCRC). Multivariable logistic regression analysis was performed to evaluate differences in ADR between the groups after adjusting for possible confounders. Main Outcome Measurements ADR in HR patients. Results The study included 4141 patients, of whom 2170 were AR and 1971 were HR. Patients in the HR group were older (64.5 ± 9.1 years vs 59.1 ± 7.9 years, P < .001). HR patients were more likely to have adenomas (30.7% vs 25.6%, P < .001). Adenomas were detected more often in the proximal colon than in the distal colon (29.3% vs 21.0%, P < .001 and 22.8% vs 15.8%, P < .001, respectively). Patients with a PHP had the highest ADR (33.1%, P < .001). However, after adjusting for confounders, HR status was not found to be associated with ADR (odds ratio [OR] 1.2; 95% confidence interval [CI], 0.93-1.6; P = .15 for females and 0.93; 95% CI, 0.70-1.2; P = .61 for males). HR females were found to have a 40% greater likelihood of having proximal adenomas than AR females (1.4; 95% CI, 1.01-2; P = .04). Limitations Retrospective design, single tertiary center. Conclusions Patients with a PHP have a significantly higher ADR compared with AR patients. Defining a minimum target ADR for individuals with a PHP undergoing surveillance colonoscopy is important. [ABSTRACT FROM AUTHOR]

Background & Aims: The adenoma detection rate (ADR) is an important measure of the quality of colonoscopy; it is associated with interval colorectal cancer and varies among sexes and locations. Recommended indicators of competence for colonoscopy include minimal ADRs >25% for average-risk men and >15% for women. These ADRs are rigorous, so polypectomy detection rate (PR) has been suggested as a surrogate. Colonoscopy is less effective in the proximal colon, where interval cancers are more likely to occur. We compared ADRs and PRs in different segments of colon and between sexes. Methods: We performed a cross-sectional review of findings from 2167 screening colonoscopies performed by 65 endoscopists on average-risk outpatients at the Cleveland Clinic, 2008–2009. We reviewed colonoscopy and pathology reports of randomly selected procedures (mean, 33 ± 16 procedures per endoscopist). We calculated PRs, ADRs, and correlation between PR and ADR for each colon segment and sex. Results: The mean overall PR was 42% ± 16.7%, and ADR was 25% ± 3.3%. The correlation between overall ADR and PR was strong (r = 0.80). PR of 40% in men and 30% in women correlated with the established minimum benchmark ADRs of 25% and 15% for men and women, respectively. PR was more strongly correlated with ADR in the proximal colon (r = 0.92) than the distal colon (r = 0.58). The correlation was stronger in men than in women, as well as in the entire colon (r = 0.88 vs 0.75), the proximal colon (r = 0.91 vs 0.87), and the distal colon (r = 0.75 vs 0.55). The advanced ADR was 4% and did not correlate with PR (r = 0.32). Conclusions: On the basis of a review of findings from screening colonoscopies, overall PR correlates with ADR for the entire colon, but PR and ADR correlate most strongly for the proximal colon, where many adenomas can be missed and interval cancers develop. The correlation between PR and ADR is weaker for women than men and for distal colon. If PR is used as a surrogate for ADR, colon location and patient sex should be considered. [Copyright &y& Elsevier]

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. 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. 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%; I 2 = 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%; I 2 = 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. 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. [ABSTRACT FROM AUTHOR]

Background & Aims: Barrett’s esophagus is traditionally considered a disease of older white men. The aims of this study were to compare the demographic features of Barrett’s esophagus in men and women and to determine the prevalence and incidence of high-grade dysplasia and cancer in these patients. Methods: All patients enrolled in the Cleveland Clinic Barrett’s Esophagus Registry from 1979–2002 were studied. Age, ethnicity, number of endoscopies, hiatal hernia size, length of Barrett’s segment, and prevalence and incidence of high-grade dysplasia and cancer were compared between men and women. Results: There were 839 patients in the registry (628 men and 211 women). Barrett’s segment length was greater in men than in women (mean, 5.06 ± 4.2 vs 4.05 ± 3.27 cm, respectively; P = .003). There were no significant differences for other parameters. There were 114 prevalence cases of high-grade dysplasia or cancer (96 men, 18 women). Women were less likely to have prevalent high-grade dysplasia or cancer than men (odds ratio, 0.52; 95% confidence interval, 0.31–0.88; P = .015). There were 13 incidence cases of high-grade dysplasia or cancer (11 men, 2 women) during a mean follow-up of 4.72 years, which was similar in both genders with an incidence rate of 1 in 179 patient-years of follow-up for women and 1 in 91 patient-years of follow-up in men. Conclusions: Twenty-five percent of patients in our registry are women. The length of Barrett’s esophagus is greater in men than in women, but other features are similar. The prevalence of high-grade dysplasia/cancer in women is approximately half that of men. Incidence rates for high-grade dysplasia/cancer are similar in men and women, although the number of cases is small. [Copyright &y& Elsevier]

Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer. Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression. Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE. RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials. [Display omitted] [ABSTRACT FROM AUTHOR]

Subsquamous intestinal metaplasia (SSIM) in the setting of Barrett's esophagus (BE) is a technically challenging diagnosis. While the risk for progression of BE involving the surface mucosa is well documented, the potential risk for development of advanced neoplasia associated with SSIM has been controversial. This study aimed to determine the effects of specimen adequacy, presence of dysplasia, and interobserver agreement for SSIM interpretation. Adult patients (n = 28) who underwent endoscopic therapy for BE with high-grade dysplasia or intramucosal carcinoma (HGD/IMC) between October 2005 and June 2013 were included. Initial evaluation (n = 140 slides) by an experienced gastrointestinal pathologist was followed by an interobserver study by 8 pathologists. Forty-seven (34%) slides had insufficient subsquamous tissue to assess for SSIM. SSIM was found in 19% of all slides and 29% of slides with sufficient subsquamous tissue. At least one slide had SSIM in 54% to 64% of patients. Subsquamous low grade dysplasia (LGD) was found in 4 (15%) slides with SSIM and subsquamous HGD/IMC was found in 5 (19%) slides with SSIM. At the patient level, 8 (53%) had no dysplasia, 4 (27%) had LGD and 3 (20%) had HGD/IMC. Overall agreement for SSIM by slide was 92% to 94% (κ = 0.73 to κ = 0.82, moderate to strong agreement), and by patient was 82% to 94% (κ = 0.65 to κ = 0.87, moderate to strong agreement). This study confirms the need for assessing specimen adequacy and assessing the prevalence of SSIM and is the first to assess interobserver agreement for SSIM and dysplasia within SSIM. • Biopsy adequacy essential for assessing subsquamous intestinal metaplasia • Assess per slide and per patient to understand biopsy adequacy • Strong to moderate interobserver agreement for subsquamous intestinal metaplasia • Dysplasia can be graded within subsquamous intestinal metaplasia. • Presence of subsquamous intestinal metaplasia can be indeterminate. [ABSTRACT FROM AUTHOR]

Objectives The value of routine timed barium esophagram (TBE) in longitudinal follow-up of achalasia after Heller myotomy is unknown. We prospectively prescribed a yearly follow-up TBE. Purposes were to characterize esophageal emptying over time after myotomy, identify preoperative TBE measures associated with follow-up TBE, and characterize follow-up TBE over time in relationship to reintervention. Methods From March 1995 to April 2013, 635 patients underwent Heller myotomy for achalasia; 559 had at least 1 follow-up TBE. Temporal trends of 1335 follow-up TBEs in all nonreintervention and reintervention patients were assessed. Multivariable longitudinal analysis identified preoperative TBE measures associated with follow-up TBE. Results On average, TBE height and width at 1 and 5 minutes decreased approximately 50% and 60%, respectively, at first postoperative follow-up, and remained stable or slightly decreased for up to 5 years. Wider TBE width at 5 minutes was associated with greater follow-up TBE height and width at 1 minute. Of 118 patients undergoing reintervention, 64 (57%) had only 1 reintervention, with follow-up TBE returning to that of nonreintervention patients. Patients whose follow-up TBE remained abnormal underwent a further reintervention, some normalizing on subsequent TBE, and some not. Conclusions Follow-up TBE is valuable postmyotomy, particularly if there is substantial esophageal dilatation preoperatively. Follow-up TBE reassures patients with stable or decreasing TBE measures, permitting decreased follow-up intensity. Reintervention should not be considered a myotomy failure, because a successful, single, nonsurgical reintervention often results in long-term successful palliation. More than 1 reintervention requires intensification of TBE follow-up, facilitating treatment planning. [ABSTRACT FROM AUTHOR]