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 (Steris, Mentor, Ohio, USA) (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. 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 low-grade dysplasia (24%), high-grade dysplasia (49%), and intramucosal adenocarcinoma (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 2 years and 67% and 92% after 3 years. In RFA-naïve patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (per centimeter: adjusted hazard ratio, 0.90; 95% confidence interval, 0.83-0.96) and prior treatment with RFA (adjusted hazard ratio, 0.39; 95% confidence interval, 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 the 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 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.).

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.

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.

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.

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.

The cost effectiveness of radiofrequency ablation for Barrett's esophagus.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) reduces the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD), but its effects in patients without dysplasia are debatable. We analyzed the effectiveness and cost effectiveness of RFA for the management of BE. METHODS: We constructed a decision analytic Markov model. We conducted separate analyses of hypothetical cohorts of patients with BE with dysplasia (HGD or low-grade [LGD]) and without dysplasia. In the analysis of the group with HGD, we compared results of initial RFA with endoscopic surveillance with surgery when cancer was detected. In analyzing the group with LGD or no dysplasia, we compared 3 strategies: endoscopic surveillance with surgery when cancer was detected (S1), endoscopic surveillance with RFA when HGD was detected (S2), and initial RFA followed by endoscopic surveillance (S3). RESULTS: Among patients with HGD, initial RFA was more effective and less costly than endoscopic surveillance. Among patients with LGD, when S3 was compared with S2, the incremental cost-effectiveness ratio was $18,231/quality-adjusted life-year, assuming an annual rate of progression rate from LGD to EAC of 0.5%/year. For patients without dysplasia, S2 was more effective and less costly than S1. In a comparison of S3 with S2, the incremental cost-effectiveness ratios were $205,500, $124,796, and $118,338/quality-adjusted life-year using annual rates of progression of no dysplasia to EAC of 0.12%, 0.33%, or 0.5% per year, respectively. CONCLUSIONS: By using updated data, initial RFA might not be cost effective for patients with BE without dysplasia, within the range of plausible rates of progression of BE to EAC, and be prohibitively expensive, from a policy perspective. RFA might be cost effective for confirmed and stable LGD. Initial RFA is more effective and less costly than endoscopic surveillance in HGD.

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Interobserver agreement for the detection of Barrett's esophagus with optical frequency domain imaging.

BACKGROUND: Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of ~7 µm. AIM: Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett's esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues. METHODS: OFDI images were obtained from nine subjects undergoing screening and surveillance for BE. Sixty-four OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The ten readers then interpreted images in a test set of 45 different images of squamous mucosa (n = 15), gastric cardia (n = 15), or BE (n = 15). Interobserver agreement differentiating the three tissue types and BE versus non-BE mucosa was determined using multi-rater Fleiss's κ value. The images were later randomized again and four readers repeated the test 3 weeks later to assess intraobserver reliability. RESULTS: All ten readers showed excellent agreement for the differentiation of BE versus non-BE mucosa (κ = 0.811 p < 0.0001) and for differentiating BE versus gastric cardia versus squamous mucosa (κ = 0.866, p < 0.0001). For the four readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (κ = 0.975, IQR: 0.94, 1.0). CONCLUSIONS: Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI.

Reflectance confocal microscopy for the diagnosis of eosinophilic esophagitis: a pilot study conducted on biopsy specimens.

BACKGROUND: Diagnosis of eosinophilic esophagitis (EoE) currently requires endoscopic biopsy and histopathologic analysis of the biopsy specimens to count intraepithelial eosinophils. Reflectance confocal microscopy (RCM) is an endomicroscopy technology that is capable of obtaining high-resolution, optically sectioned images of esophageal mucosa without the administration of exogenous contrast. OBJECTIVE: In this study, we investigated the capability of a high-speed form of RCM, termed spectrally encoded confocal microscopy (SECM), to count intraepithelial esophageal eosinophils and characterize other microscopic findings of EoE. DESIGN: A total of 43 biopsy samples from 35 pediatric patients and 8 biopsy samples from 8 adult patients undergoing EGD for EoE were imaged by SECM immediately after their removal and then processed for routine histopathology. Two SECM readers, trained on adult cases, prospectively counted intraepithelial eosinophils and detected the presence of abscess, degranulation, and basal cell hyperplasia on SECM images from the pediatric patients. A pathologist blinded to the SECM data analyzed the same from corresponding slides. SETTING: The Gastrointestinal Unit, Massachusetts General Hospital. RESULTS: Eosinophils by SECM demonstrated a higher reflectance than the surrounding cells and other inflammatory cells. There was good correlation between SECM and histology maximum eosinophil counts/high-power field (R = 0.76, P < .0001). Intra- and interobserver correlations for SECM counts were very good (R = 0.93 and R = 0.92, respectively; P < .0001). For the commonly used eosinophil count cutoff of 15 per high-power field, the sensitivity and specificity of SECM for EoE were 100%. The sensitivity and specificity for abscess, degranulation, and basal cell hyperplasia were 100% and 82%, 91% and 60%, and 94% and 80%, respectively. Intra- and interobserver agreements for these microscopic features of EoE were very good (κ = 0.9/0.9, 0.84/1.0, 0.91/0.81, respectively). LIMITATION: Ex vivo study. CONCLUSIONS: This study demonstrates that RCM can be used to accurately count intraepithelial eosinophils and identify other microscopic abnormalities associated with EoE on freshly excised biopsy samples. These findings suggest that RCM may be developed into a tool for assessing eosinophilic infiltration in the esophagus in vivo.

Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND & AIMS: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS: Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy.

BACKGROUND: Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution. OBJECTIVE: The goal of this study was to demonstrate large-area SECM in upper GI tissues and to determine whether the images contain microstructural information that is useful for pathologic diagnosis. DESIGN: A feasibility study. SETTING: Gastrointestinal Unit, Massachusetts General Hospital. PATIENTS: Fifty biopsy samples from 36 patients undergoing routine EGD were imaged by SECM, in their entirety, immediately after their removal. RESULTS: The microstructure seen in the SECM images was similar to that seen by histopathology. Gastric cardia mucosa was clearly differentiated from squamous mucosa. Gastric fundic/body type mucosa showed more tightly packed glands than gastric cardia mucosa. Fundic gland polyps showed cystically dilated glands lined with cuboidal epithelium. The presence of intraepithelial eosinophils was detected with the cells demonstrating a characteristic bilobed nucleus. Specialized intestinal metaplasia was identified by columnar epithelium and the presence of goblet cells. Barrett's esophagus (BE) with dysplasia was differentiated from specialized intestinal metaplasia by the loss of nuclear polarity and disorganized glandular architecture. LIMITATIONS: Ex vivo, descriptive study. CONCLUSIONS: Large-area SECM images of gastroesophageal biopsy samples enabled the visualization of both subcellular and architectural features of various upper GI mucosal types and were similar to the corresponding histopathologic slides. These results suggest that the development of an endoscopic SECM probe is merited.

Image-guided biopsy in the esophagus through comprehensive optical frequency domain imaging and laser marking: a study in living swine.

BACKGROUND: Random biopsy esophageal surveillance can be subject to sampling errors, resulting in diagnostic uncertainty. Optical frequency domain imaging (OFDI) is a high-speed, 3-dimensional endoscopic microscopy technique. When deployed through a balloon-centering catheter, OFDI can automatically image the entire distal esophagus (6.0 cm length) in approximately 2 minutes. OBJECTIVE: To test a new platform for guided biopsy that allows the operator to select target regions of interest on an OFDI dataset, and then use a laser to mark the esophagus at corresponding locations. The specific goals include determining the optimal laser parameters, testing the accuracy of the laser marking process, evaluating the endoscopic visibility of the laser marks, and assessing the amount of mucosal damage produced by the laser. DESIGN: Experimental study conducted in 5 swine in vivo. SETTING: Massachusetts General Hospital. MAIN OUTCOME MEASUREMENTS: Success rate, including endoscopic visibility of laser marks and accuracy of the laser marking process for selected target sites, and extent of the thermal damage caused by the laser marks. RESULTS: All of the laser-induced marks were visible by endoscopy. Target locations were correctly marked with a success rate of 97.07% (95% confidence interval, 89.8%-99.7%). Thermal damage was limited to the superficial layers of the mucosa and was observed to partially heal within 2 days. LIMITATIONS: An animal study with artificially placed targets to simulate pathology. CONCLUSIONS: The study demonstrates that laser marking of esophageal sites identified in comprehensive OFDI datasets is feasible and can be performed with sufficient accuracy, precision, and visibility to guide biopsy in vivo.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND: Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. OBJECTIVE: To assess the safety and efficacy of CRYO in BE with HGD. DESIGN: Multicenter, retrospective cohort study. SETTING: Nine academic and community centers; treatment period, 2007 to 2009. PATIENTS: Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. INTERVENTIONS: CRYO with follow-up biopsies. MAIN OUTCOME MEASUREMENTS: Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. RESULTS: Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). LIMITATIONS: Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. CONCLUSIONS: CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy.

BACKGROUND: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. OBJECTIVE: To assess the safety and efficacy of cryotherapy in esophageal carcinoma. DESIGN: Multicenter, retrospective cohort study. SETTING: Ten academic and community medical centers between 2006 and 2009. PATIENTS: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. INTERVENTIONS: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. MAIN OUTCOME MEASUREMENTS: Complete eradication of luminal cancer and adverse events. RESULTS: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. LIMITATIONS: Retrospective study design, short follow-up. CONCLUSIONS: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.

Secular trends in patients diagnosed with Barrett's esophagus.

BACKGROUND: It is not known whether there have been recent changes in demographic or clinical characteristics among patients newly diagnosed with Barrett's esophagus (BE), which could be a result of changes in disease epidemiology or of screening or surveillance effects, and could have clinical implications. AIMS: The aim of this study was to determine whether there has been a shift in age at diagnosis of BE over the past decade. Secondary aims were to determine whether there has been a shift in patient body mass index (BMI) or BE segment length. METHODS: An endoscopic database at a tertiary medical center was used to identify all esophagogastroduodenoscopies (EGDs) performed between 1997 and 2007. The cohort was restricted to patients newly diagnosed with BE. Pathology records were reviewed to confirm biopsy findings of intestinal metaplasia (IM). RESULTS: BE was diagnosed in 378 subjects between 1997 and 2007. Mean age at diagnosis of BE was 60.7 +/- 14.1 years, with mean BMI of 27.4 +/- 5.2 kg/m(2) and mean BE segment length of 4.7 +/- 3.7 cm. Between 1997 and 2007 there was no significant change in mean age at diagnosis, BMI, BE segment length or in proportion of men versus women newly diagnosed. CONCLUSIONS: Despite an increase in volume of EGDs performed in an open-access endoscopy unit between 1997 and 2007, there was no appreciable shift in age at diagnosis of BE. BMI and BE segment length among newly diagnosed patients also remained stable over this time period.

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.