A deep learning system for detection of early Barrett's neoplasia: a model development and validation study.

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus. METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs). FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video). INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases. FUNDING: Olympus.

Adherence to guideline recommendations for Barrett's esophagus (BE) surveillance endoscopies: Effects of dedicated BE endoscopy lists.

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

Optimal timing of simethicone administration prior to upper endoscopy: A multicenter, single-blind, randomized controlled trial.

Background and study aims Simethicone is useful as premedication for upper endoscopy because of its antifoaming effects. We aimed to evaluate the effect of timing of simethicone administration on mucosal visibility. Patients and methods In this multicenter, randomized, endoscopist-blinded study, patients scheduled for upper endoscopy were randomized to receive 40 mg simethicone at the following time points prior to the procedure: 20 to 30 minutes (early group), 0 to 10 minutes (late group) or 20 mg simethicone at both time points (split-dose group). Images were taken from nine predefined locations in the esophagus, stomach, and duodenum before endoscopic flushing. Each image was scored on mucosal visibility by three independent endoscopists on a 4-point scale (lower scores indicating better visibility), with adequate mucosal visibility defined as a score ≤ 2. Primary outcome was the percentage of patients with adequate total mucosal visibility (TMV), reached if all median subscores for each location were ≤ 2. Results A total of 386 patients were included (early group: 132; late group: 128; split-dose group: 126). Percentages of adequate TMV were 55%, 42%, and 61% in the early, late, and split-dose group, respectively ( P < 0.01). Adequate TMV was significantly higher in the split-dose group compared to the late group ( P < 0.01), but not compared to the early group ( P = 0.29). Differences between groups were largest in the stomach, where percentages of adequate mucosal visibility were higher in the early (68% vs 53%, P = 0.03) and split-dose group (69% vs 53%, P = 0.02) compared to the late group. Conclusions Mucosal visibility can be optimized with early simethicone administration, either as a single administration or in a split-dose regimen.

Safety and Feasibility of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) with Three-Field Lymphadenectomy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Esophageal Cancer and Cervical Lymph Node Metastasis.

BACKGROUND: In the West, patients with cervical lymph node metastasis of resectable esophageal cancer at diagnosis are generally precluded from curative treatment. This study prospectively explored the safety and feasibility of neoadjuvant chemoradiotherapy followed by robot-assisted minimally invasive esophagectomy (RAMIE) with three-field lymphadenectomy for these patients. METHODS: Between 2015 and 2021, patients with resectable thoracic esophageal cancer and cervical lymph node metastasis were recruited nationwide in the Netherlands. Patients without interval metastasis following neoadjuvant chemoradiotherapy and good physical condition underwent RAMIE with bilateral three-field lymphadenectomy. Safety was predefined as ≤50% Clavien-Dindo grade ≥3b postoperative complications. RESULTS: Neoadjuvant chemoradiotherapy was administered to 29 patients (19 (66%) adenocarcinoma and 10 (34%) squamous cell carcinoma). After restaging, nine (31%) patients were excluded (interval metastasis, clinical deterioration, or withdrawn consent). RAMIE was performed in 20 patients (R0-rate 95%). A median of 42 [range 21-71] lymph nodes were resected of which 13 [range 2-35] were cervical. Only 1 (5%) patient had an unexpected contralateral cervical lymph node metastasis. Complications grade ≥3b occurred in 50%. Most frequent complications of any grade were recurrent laryngeal nerve palsy (45%) and pneumonia (40%). Overall survival at 1 year was 85% and quality of life at 6 months was comparable to esophageal cancer patients treated with curative intent. CONCLUSIONS: RAMIE with three-field lymphadenectomy following neoadjuvant chemoradiotherapy for patients with resectable esophageal cancer presenting with cervical lymph node metastasis is feasible in a Western population. Because contralateral cervical metastasis is rare, a unilateral neck dissection would suffice in the majority of cases. CLINICAL TRIAL: gov Identifier: NCT02426879. Dutch trial register Identifier: NTR 4552.

Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

The SpaTemp cohort: 168 nondysplastic Barrett's esophagus surveillance patients with and without progression to early neoplasia to evaluate the distribution of biomarkers over space and time.

The ReBus cohort is a matched nested case-control cohort of patients with nondysplastic (ND) Barrett's esophagus (BE) at baseline who progressed (progressors) or did not progress (nonprogressors) to high-grade dysplasia (HGD) or cancer. This cohort is constructed using the most stringent inclusion criteria to optimize explorative studies on biomarkers predicting malignant progression in NDBE. These explorative studies may benefit from expanding the number of cases and by incorporating samples that allow assessment of the biomarker over space (spatial variability) and over time (temporal variability). To (i) update the ReBus cohort by identifying new progressors and (ii) identify progressors and nonprogressors within the updated ReBus cohort containing spatial and temporal information. The ReBus cohort was updated by identifying Barrett's patients referred for endoscopic work-up of neoplasia at 4 tertiary referral centers. Progressors and nonprogressors with a multilevel (spatial) endoscopy and additional prior (temporal) endoscopies were identified to evaluate biomarkers over space and over time. The original ReBus cohort consisted of 165 progressors and 723 nonprogressors. We identified 65 new progressors meeting the same strict selection criteria, resulting in a total number of 230 progressors and 723 matched nonprogressors in the updated ReBus cohort. Within the updated cohort, 61 progressors and 107 nonprogressors (mean age 61 ± 10 years) with a spatial endoscopy (median level 3 [2-4]) were identified. 33/61 progressors and 50/107 nonprogressors had a median of 3 (2-4) additional temporal endoscopies. Our updated ReBus cohort consists of 230 progressors and 723 matched nonprogressors using the most strict selection criteria. In a subgroup of 168 Barrett's patients (the SpaTemp cohort), multiple levels have been sampled at baseline and during follow-up providing a unique platform to study spatial and temporal distribution of biomarkers in BE.

Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia: Endoscopic Findings and Long-Term Mortality.

INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett's esophagus neoplasia with histopathology correlation.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Single-Step Treatment with Limited Endoscopic Resection and Cryoballoon Ablation Is Feasible and Safe in an Esophageal Porcine Model.

BACKGROUND: Treatment of Barrett's neoplasia consists of two steps: endoscopic resection of visible lesions with subsequent ablation of remaining Barrett's epithelium. However, extensive resection might hamper subsequent ablation due to stenosis. Combining both modalities in one session therefore offers potential advantages. Single-step treatment with radiofrequency ablation and resection appeared to be unsafe. AIMS: To evaluate feasibility and safety of single-step treatment with cryoballoon ablation and endoscopic resection. METHODS: Two single-step treatment regimens (15 treatment areas per regimen) were evaluated: (1) CRYO-EMR: four side-by-side focal ablations of 10 seconds followed by resection in the treated area; (2) EMR-CRYO: resection followed by 10-s ablation targeted on the resection wound. Primary outcome for both regimens was safety (perforations, clinically relevant strictures) and for CRYO-EMR also feasibility of resection and histopathological evaluation. Secondly, all CRYO-EMR and esophageal resection specimens were histopathologically evaluated. RESULTS: Six female pigs were treated (five treatment areas per animal). During 28 days of follow-up, no perforations or clinically relevant stenosis occurred. All resections were technically successful. For all CRYO-EMR specimens, histopathological evaluation was feasible with ablation effects present throughout all layers, while the architecture requisite for histopathological analysis remained intact. After 28 days, histopathological evaluation of the esophagi was performed. For EMR-CRYO, post-treatment fibrosis was present throughout the submucosa. The muscularis propria was the deepest layer involved for CRYO-EMR. CONCLUSIONS: Single-step treatment with limited endoscopic resection and cryoballoon ablation is feasible and safe in a porcine model and justifies further evaluation in a clinical trial.

Results of a two-phased clinical study evaluating a new multiband mucosectomy device for early Barrett's neoplasia: a randomized pre-esophagectomy trial and a pilot therapeutic pilot study.

BACKGROUND: Multiband mucosectomy (MBM) is the preferred technique for piecemeal resection of early neoplastic lesions in Barrett's esophagus (BE). The currently most widely used device for MBM is the Duette device. Recently, the Captivator EMR device has come available which might have practical advantages over the Duette device. METHODS: Phase I was a randomized pre-esophagectomy trial with a non-inferiority design aiming to compare EMR specimens obtained with the Captivator and the Duette device. PRIMARY OUTCOME: max diameter of the EMR specimens, secondary outcomes: min diameter, max thickness of the EMR specimens and resected submucosal stroma. Phase II were clinical pilot cases aiming to evaluate the feasibility of EMR using the Captivator device. Primary outcome was the successful EMR rate and secondary outcomes included procedure time and adverse events. RESULTS: Phase I: 24 EMR specimens (12 pairs) were obtained from six patients. The median max diameter of EMR specimens obtained with the Captivator device was 16 mm [IQR 12-21] versus 18 mm [IQR 13-23] for the Duette device. Non-inferiority of the max diameter of the Captivator specimens could not be demonstrated (median difference 1 mm, 95% CI - 3.26 to + 5.26). However, when using paired analysis, no significant difference was found (p 0.573). In addition, no statistically significant differences were found in the min diameter, max thickness of EMR specimens, and max thickness of resected submucosal stroma. Phase II: 5 BE patients with early neoplastic lesions were included. Successful EMR was achieved in 100%. Median procedure time was 33 min (IQR 25-39). One patient developed transient dysphagia, without signs of stenosis on endoscopy. CONCLUSIONS: EMR of early Barrett's neoplasia using the Captivator device is comparable to Duette EMR when looking at size of resected specimens. In the first patients, EMR using the Captivator was feasible, resulting in successful resection without acute adverse events.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study.

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

Reflux and Belching after Laparoscopic 270 degree Posterior Versus 180 degree Anterior Partial Fundoplication.

BACKGROUND: Laparoscopic 270 degree posterior, or Toupet (LTF), and 180 degree anterior partial fundoplication (LAF) ensure equal reflux control and reduce the risk of gas-related symptoms compared to 360 degree (Nissen) fundoplication. It is unclear which type of partial fundoplication is superior in preventing gas-related side-effects. The aim of this study was to determine differences in effect of LTF and LAF on reflux characteristics and belching patterns. METHODS: Upper gastrointestinal endoscopy, esophageal manometry, and 24-h combined pH-impedance monitoring were performed before and 6 months after fundoplication (n = 10, LTF vs. n = 10, LAF). Observed changes after surgery (∆) were compared between the two procedures. RESULTS: Symptomatic reflux control as well as the reduction in the mean number of acid (∆ - 58.5 vs. - 66.5; P = 0.912), liquid (∆ - 17.0 vs. - 43.5; P = 0.247), and mixed liquid gas reflux episodes (∆ - 38.0 vs. - 40.0; P = 0.579) were comparable following LTF and LAF. There were no differences in the mean number of weakly acidic reflux episodes after LTF and LAF (1.0 (0.8-4) vs. 1.0 (0-3), P = 0.436). The reduction in proximal (P = 1.000), mid-esophageal (P = 0.063), and distal reflux episodes (P = 0.315) was comparable. Both procedures equally reduced the number of gastric belches (P = 0.278) and supragastric belches (P = 0.123), with no significant reduction in the number of air swallows after either procedure (P = 0.278). CONCLUSION: LTF and LAF provide similar reflux control, with a comparable effect on acidic, liquid, and gas reflux. Both procedures equally reduced the number of belches and supragastric belches. This study provides the physiological evidence for the published randomized trials reporting similar symptomatic outcome after both types of partial fundoplication.

Evaluation of a novel cryoballoon swipe ablation system in bench, porcine, and human esophagus models.

Current ablation devices for dysplastic Barrett's esophagus are effective but have significant limitations. This pilot study aims to evaluate the safety, feasibility, and dose response of a novel cryoballoon swipe ablation system (CbSAS) in three experimental in vitro and in vivo models. CbSAS is a through-the-scope compliant balloon that is simultaneously inflated and cooled by liquid nitrous oxide delivered from a disposable handheld unit. When the cryogen is applied through a special diffuser it covers a 90° section of the circumference of the esophagus for 3 cm length. Doses range from 0.9 to 0.5 mm/second. (1) Bench model: The fixture consisted of an 'esophagus-like' tube lined with agar at 37°C to create an inner diameter of 20 or 30 mm, within which thermocouples were embedded. (2) In vivo porcine esophagus: CbSAS ablations were performed in animals that were euthanized and histological assessments of depth and percentage of esophageal mucosa successfully ablated were done. (3) In vivo, pre-esophagectomy human esophagus. After CbSAS ablations, histological assessments were performed (at 0, 4, and 28 days) to assess the depth and percentage of ablated mucosa. As outcomes, we assessed the safety and tolerability (pain and serious, device-related adverse events); efficacy (depth and uniformity) of ablation; and device performance (ease of deployment and device malfunction). In the bench model, during CbSAS, thermocouples measured minimal temperatures of -40 to -48 °C at all doses. In the porcine model, maximal effect on the mucosa was reached with a dose of 0.8 mm/second that extended to superficial submucosa, while 0.5 mm/second extended through the submucosa. All animals tolerated the treatments and, regardless of ablation dose, continued oral intake and gained weight. In the human model, six patients (5 male, 1 female, mean age 68) tolerated the procedure without adverse events. CbSAS was simple to operate, and balloon contact with tissue was easily and uniformly maintained. The maximal effect on the mucosa is achieved with a 0.8 mm/second dose. We concluded that the CbSAS device enables uniform 3 cm long, quarter-circumferential mucosal ablation in a one-step process by using a novel, through-the-scope balloon. The CbSAS delivers predictable ablation with mucosal and limited submucosal necrosis in bench, animal, and human esophagus. Because of its ease of use, this new device merits further clinical study in the treatment of patients with dysplastic Barrett's esophagus.

Pilot-study on the feasibility of sentinel node navigation surgery in combination with thoracolaparoscopic lymphadenectomy without esophagectomy in early esophageal adenocarcinoma patients.

High-risk submucosal esophageal adenocarcinoma's might be treated curatively by means of radical endoscopic resection, followed by thoracolaparoscopic lymphadenectomy without concomitant esophagectomy. A preclinical study has shown the feasibility and safety of this approach; however, no studies are performed in a clinical setting. In addition, sentinel node navigation surgery could be valuable in tailoring the extent of the lymphadenectomy. This study aimed to evaluate the feasibility and safety of thoracolaparoscopic lymphadenectomy without esophagectomy (phase I) and sentinel node navigation surgery (phase II) in patients with early esophageal adenocarcinoma. Patients with T1N0M0 early esophageal adenocarcinoma scheduled for esophagectomy without neoadjuvant therapy were included. Phase I: Two-field, esophagus preserving, thoracolaparoscopic lymphadenectomy was performed, followed by esophagectomy in the same session. Primary outcome parameters were the number of lymph nodes resected, and number of retained lymph nodes in the esophagectomy specimen. Phase II: A radioactive tracer was injected endoscopically the day before surgery. Static imaging was performed 15 and 120 minutes after injection. The day of surgery, sentinel node navigation surgery followed by esophagectomy was performed. Primary outcome parameters were the percentage of patients with a detectable sentinel node, and the concordance between static imaging and probe-based detection of sentinel node. Phase I: Five patients were included, and a median of 30 (IQR: 25-46) lymph nodes was resected. A median of 6 (IQR: 2-9) retained lymph nodes was found in the esophagectomy specimen. No acute adverse events occurred, but near the end of lymphadenectomy esophageal discoloration was observed, possibly indicating ischemia. Phase II: In all five included patients sentinel nodes could be visualized and resected, at a median of 3 (IQR: 2-5) locations. There was a high concordance between imaging and probe-based detection of sentinel nodes. In conclusion, sentinel node navigation surgery followed by lymphadenectomy without concomitant esophagectomy seems feasible in patients with high-risk submucosal early esophageal adenocarcinoma. More evidence is however needed before applying this technique in clinical practice.

Circumferential cryoablation in a strictured esophagus: a feasibility and dose-finding study in a porcine model after inducing stenosis by endoscopic mucosal resection.

In the treatment of early esophageal Barrett's neoplasia, radiofrequency ablation may be hindered by stenosis due to prior endoscopic resection (ER). The flexible balloon-based circumferential CryoBalloon Ablation System (CBAS) may overcome this problem by the conformability of the compliant balloon which might enable circumferential cryoablation in a stenosis. The aim of the current study was to evaluate the feasibility of the CBAS as well as the dose-response effect of cryoablation in a strictured esophagus model. In six pigs, a stenosis was induced by ER (3 cm in length, 75% of circumference) in the proximal, mid, and distal esophagus. After 28 days, cryoablation with the CBAS was performed, with the length of ablation time (6, 8, or 10 seconds) randomly assigned per stricture location within the esophagus. Four days post-ablation, the esophagi were harvested for histopathological assessment of the percentage of the total circumference affected by cryoablation and the maximum depth of necrosis. At 28 days, all 18 ER areas had transformed into strictures with ±50% of its original diameter remaining. In 9 of 18 strictures, more than one attempt for cryoablation was necessary due to displacement of the balloon. Histopathological evaluation showed a wide range in circumferential uniformity (0-100%) and maximum necrosis depth (epithelium to external proper muscle layer) of cryoablation, both independent of ablation times. Deepest ablation effects were seen at the center of the resection-induced scar. This first generation CryoBalloon Focal Ablation System was not feasible for ablation within severe stenoses, since it results in inconsistent circumferential uniformity of cryoablation with subsequent differences in depth of ablation. Further research with a next generation CBAS in a more realistic stricture model is warranted.

Volumetric laser endomicroscopy in Barrett's esophagus: a feasibility study on histological correlation.

Volumetric laser endomicroscopy (VLE) is a novel balloon-based optical coherence tomography (OCT) imaging technique that may improve detection of early neoplasia in Barrett's esophagus (BE). Most OCT studies lack a direct correlation between histology and OCT images. The aim is to investigate the optimal approach for achieving one-to-one correlation of ex-vivo VLE images of endoscopic resection (ER) specimens with histology. BE patients with and without early neoplasia underwent ER after delineating areas with electrocoagulation markers (ECM). After ER, specimens underwent additional ex-vivo marking with several different markers (ink, pin, Gold Probe) followed by ex-vivo VLE scanning. ER specimens were carefully sectioned into tissue blocks guided by the markers. Histology and VLE slides were considered a match if ≥ 2 markers were visible on both modalities and mucosal patterns aside from these markers matched on both histology and VLE. From 16 ER specimens 120 tissue blocks were sectioned of which 23 contained multiple markers. Fourteen histology-VLE matches were identified. ECMs and ink markers proved to be the most effective combination for matching. The last 6/16 ER specimens yielded 9/14 matches, demonstrating a learning curve due to methodological improvements in marker placement and tissue block sectioning. One-to-one correlation of VLE and histology is complex but feasible. The groundwork laid in this study will provide high-quality histology-VLE correlations that will allow further research on VLE features of early neoplasia in BE.

In vitro assessment of the performance of a new multiband mucosectomy device for endoscopic resection of early upper gastrointestinal neoplasia.

BACKGROUND AND STUDY AIMS: Multiband mucosectomy (MBM) is widely used for the endoscopic resection of early neoplasia in the upper gastrointestinal tract. A new MBM-device may have advantages over the current MBM-device with improved visualization, easier passage of accessories, and higher suction power due to different trip wire and cap. METHODS: Rubber bands were released one by one for both MBM-devices while endoscopic images were collected. First, free endoscopic view was assessed by computer-assisted measurements (quantitative) and by ranking the images by a panel of 11 endoscopists (qualitative). Second, using a visual analog scale, three 'blinded' endoscopists assessed introduction and advancement of three types of endoscopic devices through the working channel of a diagnostic endoscope with the MBM-devices assembled. Third, suction power was evaluated by a manometer attached to the cap of the assembled MBM-devices in four endoscopes. Negative pressures were measured after 5 and 10 s of suction and repeated five times. The passage and suction experiments were performed with dry trip wires and repeated after soaking with bloody, mucous fluids. RESULTS: With all bands present, endoscopic views were 90 and 40% in the new and current MBM-device, respectively. With the release of more bands, differences slowly disappeared. The panel scored a better endoscopic view in the new MBM-device (p = 0.03). Passage of all accessories was considered significantly easier in the new MBM-device. With the associated snare in the working channel, suction power was significantly better with the new MBM-device. CONCLUSION: Compared to the currently available MBM-device, the new MBM-device provides improved endoscopic visibility, smoother passage of accessories, and higher suction power.

Simultaneous use of endoscopic resection and radiofrequency ablation is not safe in an esophageal porcine model.

Radiofrequency ablation (RFA) is safe and effective for eradication of Barrett's esophagus after endoscopic resection (ER) of neoplasia. Widespread ER, however, is likely to induce stenosis, hampering subsequent circumferential RFA. A 'single step' procedure with ER and circumferential RFA in the same session may avoid this problem. Two variants are possible: circumferential RFA of Barrett's esophagus including the lesion followed by ER of the ablated lesion ('RFA→ER'), or ER of the lesion directly followed by circumferential RFA of remaining Barrett's esophagus including the resection wound ('ER→RFA'). First aim was to evaluate perforation risk of 'ER→RFA' using increasing RFA energies. Second aim was to compare stenosis rate after 'ER→RFA' versus 'RFA→ER'. In Experiment 1, 24 areas in six pigs underwent widespread ER directly followed by circumferential RFA with increasing energies (2 x 10, 2 x 12-6 x 12 J/cm(2)) in the esophagus. In Experiment 2, eight pigs each had four treatment areas randomized: 'ER→RFA', RFA alone, ER alone, and 'RFA→ER'. No acute perforations occurred when ablating ER wounds. Two delayed perforations occurred: one in experiment 1, another in experiment n2 at the 'ER→RFA' area. The remaining seven pigs in experiment 2 showed stenosis in all 'ER→RFA' and 'RFA→ER' areas versus 5/7 RFA alone areas, and 0/7 ER alone areas. In conclusion, the 'single step' variant 'ER→RFA' is not safe in this porcine model and seems therefore not ethical to evaluate in humans at this stage. Given the high rate of stenosis after 'RFA→ER' and RFA alone, one might question the validity of the porcine model for this type of experiments.