Project description:This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (>0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis.
Project description:The optimal management for low-grade dysplasia (LGD) in Barrett's esophagus is unclear. In this article the importance of LGD is discussed, including the significant risk of progression to esophageal adenocarcinoma. Endoscopic surveillance is a management option but is plagued by sampling error and issues of suboptimal endoscopy. Furthermore endoscopic surveillance has not been demonstrated to be cost-effective or to reduce cancer mortality. The emergence of endoluminal therapy over the past decade has resulted in a paradigm shift in the management of LGD. Ablative therapy, including radiofrequency ablation, has demonstrated promising results in the management of LGD with regards to safety, cost-effectiveness, durability and reduction in cancer risk. It is, however, vital that a shared-decision making process occurs between the physician and the patient as to the preferred management of LGD. As such the management of LGD should be "individualised."
Project description:Background and aimsAngiogenesis is associated with neoplastic progression of Barrett's esophagus (BE). Volumetric optical coherence tomography angiography (OCTA) visualizes subsurface microvasculature without exogenous contrast agents. We investigated the association of OCTA microvascular features with low-grade dysplasia (LGD) and high-grade dysplasia (HGD).MethodsFifty-two patients undergoing BE surveillance or endoscopic eradication therapies for dysplasia were imaged using volumetric OCTA and corresponding histologic diagnoses wre obtained to yield 97 data sets (nondysplastic BE [NDBE], 74; LGD, 10; HGD, 13). After evaluating OCTA image quality, 54 datasets (NDBE, 35; LGD, 8; HGD, 11) from 32 patients were used to develop a training and reading protocol. The association of abnormal vessel branching and heterogeneous vessel size with LGD/HGD and a regular honeycomb vessel pattern with NDBE were investigated.ResultsBlinded OCTA reading of 41 OCTA datasets (NDBE, 27; LGD, 7; HGD, 7) was performed by readers with various levels of OCT/OCTA experience including 3 OCT trainees, 1 gastroenterologist, and 2 gastroenterology fellows. Among the 6 readers, OCTA features of abnormal vessel branching and heterogeneous vessel size had an overall 94% sensitivity (95% CI, 89-99) and 69% specificity (95% CI, 62-76) for differentiating LGD/HGD versus NDBE with a mean reading time of 45 seconds per data set and moderate (kappa = .58) interobserver agreement.ConclusionsVolumetric en face OCTA imaging enables rapid examination of depth resolved microvascular features with near-microscopic resolution. OCTA can visualize microvascular features associated with LGD/HGD with high accuracy, which motivates new technologic advances and future studies investigating the diagnostic performance of OCTA.
Project description:We present a novel Fourier-domain angle-resolved low-coherence interferometry (a /LCI) fiber probe designed for in vivo clinical application in gastrointestinal endoscopy. The a/LCI technique measures the depth-resolved angular scattering distribution to determine the size distribution and optical density of cell nuclei for assessing the health of epithelial tissues. Clinical application is enabled by an endoscopic fiber-optic probe that employs a 2.3-m-long coherent fiber bundle and is compatible with the standard 2.8-mm-diam biopsy channel of a gastroscope. The probe allows for real-time data acquisition by collecting the scattering from multiple angles in parallel, enabled by the Fourier domain approach. The performance of the probe is characterized through measurement of critical parameters. The depth-resolved sizing capability of the system is demonstrated using single- and double-layer microsphere phantoms with subwavelength sizing precision and accuracy achieved. Initial results from a clinical feasibility test are also presented to show in vivo application in the human esophagus.
Project description:Background & aimsBarrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress.MethodsWe performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n = 14) or EAC (n = 10). The control group (n = 73, called non-progressors) comprised patients with BE and at least 5 years of total endoscopic biopsy surveillance without progression to HGD or EAC. From each patient, we selected a single tissue sample obtained more than 1 year before progression (cases) or more than 2 years before the end of follow-up (controls). Pathogenic mutations, gene copy numbers, and ploidy were compared between samples from progressors and non-progressors.ResultsTP53 mutations were detected in 46% of samples from progressors and 5% of non-progressors. In this case-control sample set, TP53 mutations in BE tissues increased the adjusted risk of progression 13.8-fold (95% confidence interval, 3.2-61.0) (P < .001). We did not observe significant differences in ploidy or copy-number profile between groups. We identified 147 pathogenic mutations in 57 distinct genes-the average number of pathogenic mutations was higher in samples from progressors (n = 2.5) than non-progressors (n = 1.2) (P < .001). TP53 and other somatic mutations were recurrently detected in samples with limited copy-number changes (aneuploidy).ConclusionsIn genomic analyses of BE tissues from patients with or without later progression to HGD or EAC, we found significantly higher numbers of TP53 mutations in BE from patients with subsequent progression. These mutations were frequently detected before the onset of dysplasia or substantial changes in copy number.
Project description:BackgroundThe yield of early repeat endoscopy in patients with Barrett's esophagus (BE) is not well established.AimsTo determine how often early repeat endoscopy detected missed dysplasia or esophageal adenocarcinoma (EAC) in a population-based cohort of patients with BE. Secondary aims were to identify risk factors for missed dysplasia/EAC and compare detection of prevalent versus incident HGD/EAC.MethodsA population-based cohort of BE subjects in Olmsted County, MN, was studied. Patients with initial non-dysplastic BE or low-grade dysplasia (LGD) who underwent repeat endoscopy within 24 months were included. Those with a worse histologic diagnosis on repeat endoscopy were considered to have missed dysplasia/EAC. Baseline characteristics among patients with and without missed dysplasia/EAC were compared. The absolute numbers of asymptomatic prevalent or missed, and incident HGD/EAC in the entire cohort were ascertained.ResultsOf 488 BE cases, 210 were included for the primary aim of this study. Repeat endoscopy revealed four HGD/EAC (1.9 %) and 16 LGD (8.8 %) for a combined miss rate of 9.5 %. Long-segment BE (LSBE) and lack of PPI use were predictors of missed dysplasia/EAC (P = 0.008), but adherence to biopsy protocol was not. Increased prevalent HGD/EAC (n = 30) rather than incident HGD/EAC (n = 22) was identified during a median 4.8 years of follow-up in this cohort.ConclusionsDysplasia/EAC is commonly missed at initial BE diagnosis, particularly in patients with LSBE and no PPI use. Efforts should be made to enhance the sensitivity of detecting dysplasia/neoplasia around the time of initial BE diagnosis.
Project description:BackgroundThis study aimed to evaluate the use of ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography (OCT) with micromotor catheters for the in vivo assessment of Barrett's esophagus and dysplasia.Methods74 OCT datasets with correlated biopsy/endoscopic mucosal resection histology (49 nondysplastic Barrett's esophagus [NDBE], 25 neoplasia) were obtained from 14 patients with Barrett's esophagus and a history of dysplasia and 30 with NDBE. The associations between irregular mucosal patterns on en face OCT, absence of mucosal layering, surface signal > subsurface, and > 5 atypical glands on cross-sectional OCT vs. histology and treatment history were assessed by three blinded readers.ResultsAtypical glands under irregular mucosal patterns occurred in 75 % of neoplasia (96 % of treatment-naïve neoplasia) vs. 30 % of NDBE datasets (43 % of short- and 18 % of long-segment NDBE). Mucosal layering was absent in 35 % of neoplasia and 50 % of NDBE datasets, and surface signal > subsurface occurred in 29 % of neoplasia and 30 % of NDBE datasets.ConclusionsAtypical glands under irregular mucosal patterns are strongly associated with neoplasia, suggesting potential markers for dysplasia and a role in pathogenesis.
Project description:Background & aimsRadiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE.MethodsWe performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events.ResultsAfter 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years).ConclusionsIn subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.
Project description: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.