Search

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]

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]

Vitamin D has been associated with reduced risk of many cancers, but evidence for esophageal cancer is mixed. To clarify the role of vitamin D, we performed a systematic review and meta-analysis to evaluate the association of vitamin D exposures and esophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's esophagus, and squamous dysplasia. Ovid MEDLINE, EMBASE, and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D [25(OH)D; n = 3], vitamin D intake (n = 4), UVB exposure (n = 1), and genetic factors (n = 7) were retrieved. Higher [25(OH)D] was associated with increased risk of cancer [adenocarcinoma or SCC, OR = 1.39; 95% confidence interval (CI), 1.04-1.74], with the majority of participants coming from China. No association was observed between vitamin D intake and risk of cancer overall (OR, 1.03; 0.65-1.42); however, a nonsignificantly increased risk for adenocarcinoma (OR, 1.45; 0.65-2.24) and nonsignificantly decreased risk for SCC (OR, 0.80; 0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers (OR, 0.45; 0.00-0.91), and a suggestive association was observed for rs2107301. In conclusion, no consistent associations were observed between vitamin D exposures and occurrence of esophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made. [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]