LIQUID NITROGEN SPRAY CRYOTHERAPY FOR ERADICATION OF DYSPLASTIC BARRETT'S ESOPHAGUS: RESULTS FROM A MULTICENTER PROSPECTIVE REGISTRY.

BACKGROUND AND AIMS: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry. METHODS: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma (IMC). Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated. RESULTS: Among 138 subjects, with LGD (24%), HGD (49%) and IMC (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after two years, and 67% and 92% after three years. In RFA-naive patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (adjusted hazard ratio [95% CI]:0.90 [0.83-0.96] per cm) and prior treatment with RFA (0.39 [0.22-0.69]) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n=6) at a mean follow-up of 2.5 years after CEIM. CONCLUSION: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort approximately 50% attained CEIM at 3 years.

Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study.

BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study. METHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-µm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. RESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. CONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.

Effect of Low-dose and Standard-dose Aspirin on PGE2 Biosynthesis Among Individuals with Colorectal Adenomas: A Randomized Clinical Trial.

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

Balloon catheter-based radiofrequency ablation monitoring in porcine esophagus using optical coherence tomography.

We present a microscopic image guidance platform for radiofrequency ablation (RFA) using a clinical balloon-catheter-based optical coherence tomography (OCT) system, currently used in the surveillance of Barrett's esophagus patients. Our integrated thermal therapy delivery and monitoring platform consists of a flexible, customized bipolar RFA electrode array designed for use with a clinical balloon OCT catheter and a processing algorithm to accurately map the thermal coagulation process. Non-uniform rotation distortion was corrected using a feature tracking-based technique, which enables robust, frame-to-frame analysis of the temporal fluctuation of the complex OCT signal. With proper noise calibration, precise delineation of the thermal therapy zone was demonstrated using cumulative complex differential variance in porcine esophagus ex vivo with the integrated OCT-RFA system, as validated by nitroblue tetrazolium chloride (NBTC) histology. The ability to directly and accurately visualize the thermal coagulation process at high resolution is critical to the precise delivery of thermal energy to a wide range of epithelial lesions.

Effect of video monitor size on polyp detection: a prospective, randomized, controlled trial.

BACKGROUND AND AIMS: The adenoma detection rate (ADR) is the most important quality metric for colonoscopy. Numerous factors are known to influence ADR. However, no data on the effect of monitor size on ADR exist. The aim of this study was to compare the ADR and polyp detection rate (PDR) achieved using 2 different-size video monitors (19-inch diagonal and 32-inch diagonal). METHODS: In a single-center, prospective, randomized clinical trial, endoscopists were randomized on a daily basis to perform routine ambulatory colonoscopies with either a 32-inch diagonal or a 19-inch diagonal video monitor. RESULTS: The study was conducted between October 2013 and April 2014 in an outpatient center of a tertiary referral hospital. Fifteen endoscopists performed 1795 outpatient colonoscopies (mean age, 55 years; 56% women; screening, 56%). There was no substantial difference in baseline patient characteristics between the 2 arms. The overall ADR (27.4% vs 27.9%; P = .80) and PDR (32.8% vs 34.4%; P = .50) were not significantly different between the 32-inch and 19-inch monitor group, respectively. The findings were not significantly altered when stratified by indication, cecal intubation, bowel preparation, operator experience, and time of endoscopy as well as in a multivariable model that included these variables as potential confounders (all P > .05). Overall, the ADR and PDR for each individual endoscopist did not appear to be influenced by monitor size. CONCLUSIONS: The results of this trial do not support the notion that larger video monitors improve ADR. Future efforts to increase ADR should focus on other aspects of colonoscopy. (Clinical trial registration number: NCT01952418.).

Optical coherence tomography-guided laser marking with tethered capsule endomicroscopy in unsedated patients.

Tethered capsule endomicroscopy (TCE) is an emerging screening technology that comprehensively obtains microstructural OCT images of the gastrointestinal (GI) tract in unsedated patients. To advance clinical adoption of this imaging technique, it will be important to validate TCE images with co-localized histology, the current diagnostic gold standard. One method for co-localizing OCT images with histology is image-targeted laser marking, which has previously been implemented using a driveshaft-based, balloon OCT catheter, deployed during endoscopy. In this paper, we present a TCE device that scans and targets the imaging beam using a low-cost stepper motor that is integrated inside the capsule. In combination with a 4-laser-diode, high power 1430/1450 nm marking laser system (800 mW on the sample and 1s pulse duration), this technology generated clearly visible marks, with a spatial targeting accuracy of better than 0.5 mm. A laser safety study was done on swine esophagus ex vivo, showing that these exposure parameters did not alter the submucosa, with a large, 4-5x safety margin. The technology was demonstrated in living human subjects and shown to be effective for co-localizing OCT TCE images to biopsies obtained during subsequent endoscopy.

Tethered capsule endomicroscopy for microscopic imaging of the esophagus, stomach, and duodenum without sedation in humans (with video).

BACKGROUND AND AIMS: Patients with many different digestive diseases undergo repeated EGDs throughout their lives. Tethered capsule endomicroscopy (TCE) is a less-invasive method for obtaining high-resolution images of the GI mucosa for diagnosis and treatment planning of GI tract diseases. In this article, we present our results from a single-center study aimed at testing the safety and feasibility of TCE for imaging the esophagus, stomach, and duodenum. METHODS: After being swallowed by a participant without sedation, the tethered capsule obtains cross-sectional, 10 µm-resolution, optical coherence tomography images as the device traverses the alimentary tract. After imaging, the device is withdrawn through the mouth, disinfected, and reused. Safety and feasibility of TCE were tested, focusing on imaging the esophagus of healthy volunteers and patients with Barrett's esophagus (BE) and the duodenum of healthy volunteers. Images were compared with endoscopy and histopathology findings when available. RESULTS: Thirty-eight patients were enrolled. No adverse effects were reported. The TCE device swallowing rate was 34 of 38 (89%). The appearance of a physiologic upper GI wall, including its microscopic pathology, was visualized with a tissue coverage of 85.4% ± 14.9% and 90.3% ± 6.8% in the esophagus of BE patients with and without endoscopic evidence of a hiatal hernia, respectively, as well as 84.8% ± 7.4% in the duodenum. A blinded comparison of TCE and endoscopic BE measurements showed a strong to very strong correlation (r = 0.7-0.83; P < .05) for circumferential extent and a strong correlation (r = 0.77-0.78; P < .01) for maximum extent (Prague classification). TCE interobserver correlation was very strong, at r = 0.92 and r = 0.84 (P < .01), for Prague classification circumferential (C) and maximal (M) length measurements, respectively. CONCLUSIONS: TCE is a safe and feasible procedure for obtaining high-resolution microscopic images of the upper GI tract without endoscopic assistance or sedation.

Analysis of factors associated with extended recovery time after colonoscopy.

BACKGROUND & AIMS: A common limiting factor in the throughput of gastrointestinal endoscopy units is the availability of space for patients to recover post-procedure. This study sought to identify predictors of abnormally long recovery time after colonoscopy performed with procedural sedation. In clinical research, this type of study would be performed using only one regression modeling approach. A goal of this study was to apply various "machine learning" techniques to see if better prediction could be achieved. METHODS: Procedural data for 31,442 colonoscopies performed on 29,905 adult patients at Massachusetts General Hospital from 2011 to 2015 were analyzed to identify potential predictors of long recovery times. These data included the identities of hospital personnel, and the initial statistical analysis focused on the impact of these personnel on recovery time via multivariate logistic regression. Secondary analyses included more information on patient vitals both to identify secondary predictors and to predict long recoveries using more complex techniques. RESULTS: In univariate analysis, the endoscopist, procedure room nurse, recovery room nurse, and surgical technician all showed a statistically significant relationship to long recovery times, with p-value below 0.0001 in all cases. In the multivariate logistic regression, the most significant predictor of a long recovery time was the identity of the recovery room nurse, with the endoscopist also showing a statistically significant relationship with a weaker effect. Complex techniques led to a negligible improvement over simple techniques in prediction of long recovery periods. CONCLUSION: The hospital personnel involved in performing a colonoscopy show a strong association with the likelihood of a patient spending an abnormally long time recovering from the procedure, with the most pronounced effect for the nurse in the recovery room. The application of more advanced approaches to improve prediction in this clinical data set only yielded modest improvements.

Clinical Translation of Tethered Confocal Microscopy Capsule for Unsedated Diagnosis of Eosinophilic Esophagitis.

Esophagogastroduodenoscopy (EGD) is a widely used procedure, posing significant financial burden on both healthcare systems and patients. Moreover, EGD is time consuming, sometimes difficult to tolerate, and suffers from an imperfect diagnostic yield as the limited number of collected biopsies does not represent the whole organ. In this paper, we report on technological and clinical feasibility of a swallowable tethered endomicroscopy capsule, which is administered without sedation, to image large regions of esophageal and gastric mucosa at the cellular level. To demonstrate imaging capabilities, we conducted a human pilot study (n = 17) on Eosinophilic Esophagitis (EoE) patients and healthy volunteers from which representative cases are presented and discussed. Results indicate that, compared to endoscopic biopsy, unsedated tethered capsule endomicroscopy obtains orders of magnitude more cellular information while successfully resolving characteristic tissue microscopic features such as stratified squamous epithelium, lamina propria papillae, intraepithelial eosinophils, and gastric cardia and body/fundic mucosa epithelia. Based on the major import of whole organ, cellular-level microscopy to obviate sampling error and the clear cost and convenience advantages of unsedated procedure, we believe that this tool has the potential to become a simpler and more effective device for diagnosing and monitoring the therapeutic response of EoE and other esophageal diseases.

Surgical vs Endoscopic Management of T1 Esophageal Adenocarcinoma: A Modeling Decision Analysis.

BACKGROUND & AIMS: Although treatment of T1a esophageal adenocarcinoma (EAC) is shifting from esophagectomy to endoscopic therapy, T1b EACs are considered too high risk to be treated endoscopically. We investigated the effectiveness and cost effectiveness of esophagectomy vs endoscopic therapy for T1a and T1b EACs, and the effects of age and comorbidities, using a decision analytic Markov model. METHODS: We developed a model to simulate a hypothetical cohort of men 75 years old with Charlson comorbidity index scores of 0 and either T1aN0M0 or T1bN0M0 EAC, as a base case. We used the model to compare the effects of esophagectomy vs serial endoscopic therapy. We performed sensitivity analyses based on age at diagnosis of 60-85 years, comorbidity indices of 0-2, and utilities. Post-procedure cancer-specific mortality was derived from the Surveillance, Epidemiology, and End Results Medicare database. RESULTS: In the T1a base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (6.97 vs 6.81), but fewer quality-adjusted life years (QALYs, 4.95 for esophagectomy vs 5.22 for endoscopic therapy). In the T1b base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (5.73 vs 5.01) and QALYs (4.07 vs 3.85 for endoscopic therapy), but was not cost effective (incremental cost-effectiveness ratio $156,981). Sensitivity analyses showed endoscopic therapy optimized QALYs for patients more than 80 years old with a comorbidity index of 1 or 2, or if the ratio of post-esophagectomy to post-endoscopic therapy utilities was below 0.875. CONCLUSION: In a Markov model, we showed that endoscopic therapy of T1a EAC yields more QALYs and is more cost effective than esophagectomy for patients of all ages and comorbidity indices tested. In contrast, selection of therapy for T1b EAC depends on age and comorbidities, due to surgical mortality and the competing risk of non-cancer death.

Optical coherence tomography in gastroenterology: a review and future outlook.

Optical coherence tomography (OCT) is an imaging technique optically analogous to ultrasound that can generate depth-resolved images with micrometer-scale resolution. Advances in fiber optics and miniaturized actuation technologies allow OCT imaging of the human body and further expand OCT utilization in applications including but not limited to cardiology and gastroenterology. This review article provides an overview of current OCT development and its clinical utility in the gastrointestinal tract, including disease detection/differentiation and endoscopic therapy guidance, as well as a discussion of its future applications.

ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial.

BACKGROUND: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. METHODS/DESIGN: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function. DISCUSSION: Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers. TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769 . Registered on 16 March 2015.

Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo.

BACKGROUND AND OBJECTIVE: Diagnosis of esophageal diseases is often hampered by sampling errors that are inherent in endoscopic biopsy, the standard of care. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal endomicroscopy technology that has the potential to visualize cellular features from large regions of the esophagus, greatly decreasing the likelihood of sampling error. In this paper, we report results from a pilot clinical study imaging the human esophagus in vivo with a prototype SECM endoscopic probe. MATERIALS AND METHODS: In this pilot clinical study, six patients undergoing esophagogastroduodenoscopy (EGD) for surveillance of Barrett's esophagus (BE) were imaged with the SECM endoscopic probe. The device had a diameter of 7 mm, a length of 2 m, and a rapid-exchange guide wire provision for esophageal placement. During EGD, the distal portion of the esophagus of each patient was sprayed with 2.5% acetic acid to enhance nuclear contrast. The SECM endoscopic probe was then introduced over the guide wire to the distal esophagus and large-area confocal images were obtained by helically scanning the optics within the SECM probe. RESULTS: Large area confocal images of the distal esophagus (image length = 4.3-10 cm; image width = 2.2 cm) were rapidly acquired at a rate of ∼9 mm2 /second, resulting in short procedural times (1.8-4 minutes). SECM enabled the visualization of clinically relevant architectural and cellular features of the proximal stomach and normal and diseased esophagus, including squamous cell nuclei, BE glands, and goblet cells. CONCLUSIONS: This study demonstrates that comprehensive spectrally encoded confocal endomicroscopy is feasible and can be used to visualize architectural and cellular microscopic features from large segments of the distal esophagus at the gastroesophageal junction. By providing microscopic images that are less subject to sampling error, this technology may find utility in guiding biopsy and planning and assessing endoscopic therapy. Lasers Surg. Med. 49:233-239, 2017. © 2016 Wiley Periodicals, Inc.

Automated segmentation and characterization of esophageal wall in vivo by tethered capsule optical coherence tomography endomicroscopy.

Optical coherence tomography (OCT) is an optical diagnostic modality that can acquire cross-sectional images of the microscopic structure of the esophagus, including Barrett's esophagus (BE) and associated dysplasia. We developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires high-resolution images of entire gastrointestinal (GI) tract luminal organs. This device has a potential to become a screening method that identifies patients with an abnormal esophagus that should be further referred for upper endoscopy. Currently, the characterization of the OCT-TCE esophageal wall data set is performed manually, which is time-consuming and inefficient. Additionally, since the capsule optics optimally focus light approximately 500 µm outside the capsule wall and the best quality images are obtained when the tissue is in full contact with the capsule, it is crucial to provide feedback for the operator about tissue contact during the imaging procedure. In this study, we developed a fully automated algorithm for the segmentation of in vivo OCT-TCE data sets and characterization of the esophageal wall. The algorithm provides a two-dimensional representation of both the contact map from the data collected in human clinical studies as well as a tissue map depicting areas of BE with or without dysplasia. Results suggest that these techniques can potentially improve the current TCE data acquisition procedure and provide an efficient characterization of the diseased esophageal wall.

Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study.

BACKGROUND: Biopsy surveillance protocols for the assessment of Barrett's esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. OBJECTIVE: The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. DESIGN: A pilot feasibility study. SETTING: Massachusetts General Hospital. PATIENTS: A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. INTERVENTION: Volumetric laser endomicroscopy. MAIN OUTCOME MEASUREMENTS: Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. RESULTS: There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. LIMITATIONS: This is a single-center feasibility study with a limited number of patients. CONCLUSION: Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01439633.).

Incidence and predictors of adenocarcinoma following endoscopic ablation of Barrett's esophagus.

BACKGROUND: The rate and risk factors of recurrent or metachronous adenocarcinoma following endoscopic ablation therapy in patients with Barrett's esophagus (BE) have not been specifically reported. AIM: The aim of this study was to determine the incidence and predictors of adenocarcinoma after ablation therapy for BE high-grade dysplasia (HGD) or intramucosal carcinoma (IMC). METHODS: This is a single center, retrospective review of prospectively collected data on consecutive cases of endoscopic ablation for BE. A total of 223 patients with BE (HGD or IMC) were treated by ablation between 1996 and 2011. Primary outcome measures were recurrence and new development of adenocarcinoma after ablation. Recurrence was defined as the presence of adenocarcinoma following the absence of adenocarcinoma in biopsy samples from two consecutive surveillance endoscopies. Logistic regression analysis was performed to assess predictors of adenocarcinoma after ablation. RESULTS: One hundred and eighty-three patients were included in the final analysis, and 40 patients were excluded: 22 for palliative ablation, eight lost to follow-up, five for residual carcinoma and five for postoperative state. Median follow-up was 39 months. Recurrence or new development of adenocarcinoma was found in 20 patients (11 %) and the median time to recurrence/development of adenocarcinoma was 11.5 months. Independent predictors of recurrent or metachronous adenocarcinoma were hiatal hernia size ≥ 4 cm (odds ratio 3.649, P = 0.0233) and histology (HGD/adenocarcinoma) after first ablation (odds ratio 4.141, P = 0.0065). CONCLUSIONS: Adenocarcinoma after endoscopic therapy for HGD or IMC in BE is associated with large hiatal hernia and histology status after initial ablation therapy.

Comprehensive confocal endomicroscopy of the esophagus in vivo.

BACKGROUND AND STUDY AIMS: Biopsy sampling error can be a problem for the diagnosis of certain gastrointestinal tract diseases. Spectrally-encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has the potential to overcome sampling error by imaging large regions of gastrointestinal tract tissues. The aim of this study was to test a recently developed SECM endoscopic probe for comprehensively imaging large segments of the esophagus at the microscopic level in vivo. METHODS: Topical acetic acid was endoscopically applied to the esophagus of a normal living swine. The 7 mm diameter SECM endoscopic probe was transorally introduced into the esophagus over a wire. Optics within the SECM probe were helically scanned over a 5 cm length of the esophagus. Confocal microscopy data was displayed and stored in real time. RESULTS: Very large confocal microscopy images (length = 5 cm; circumference = 2.2 cm) of swine esophagus from three imaging depths, spanning a total area of 33 cm(2), were obtained in about 2 minutes. SECM images enabled the visualization of cellular morphology of the swine esophagus, including stratified squamous cell nuclei, basal cells, and collagen within the lamina propria. CONCLUSIONS: The results from this study suggest that the SECM technology can rapidly provide large, contiguous confocal microscopy images of the esophagus in vivo. When applied to human subjects, the unique comprehensive, microscopic imaging capabilities of this technology may be utilized for improving the screening and surveillance of various esophageal diseases.

Photometric stereo endoscopy.

While color video endoscopy has enabled wide-field examination of the gastrointestinal tract, it often misses or incorrectly classifies lesions. Many of these missed lesions exhibit characteristic three-dimensional surface topographies. An endoscopic system that adds topographical measurements to conventional color imagery could therefore increase lesion detection and improve classification accuracy. We introduce photometric stereo endoscopy (PSE), a technique which allows high spatial frequency components of surface topography to be acquired simultaneously with conventional two-dimensional color imagery. We implement this technique in an endoscopic form factor and demonstrate that it can acquire the topography of small features with complex geometries and heterogeneous optical properties. PSE imaging of ex vivo human gastrointestinal tissue shows that surface topography measurements enable differentiation of abnormal shapes from surrounding normal tissue. Together, these results confirm that the topographical measurements can be obtained with relatively simple hardware in an endoscopic form factor, and suggest the potential of PSE to improve lesion detection and classification in gastrointestinal imaging.