Digital pathology for reporting histopathology samples, including cancer screening samples - definitive evidence from a multisite study.

AIMS: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. METHODS: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings. Reports were compared for clinical management concordance (CMC), meaning identical diagnoses plus differences which do not affect patient management. Percentage CMCs were computed using logistic regression models with crossed random-effects terms for case and pathologist. The obtained percentage CMCs were referenced to 98.3% calculated from previous studies. RESULTS: For all cases LM versus DP comparisons showed the CMC rates were 99.95% [95% confidence interval (CI) = 99.90-99.97] and 98.96 (95% CI = 98.42-99.32) for cancer screening samples. In speciality groups CMC for LM versus DP showed: breast 99.40% (99.06-99.62) overall and 96.27% (94.63-97.43) for cancer screening samples; [gastrointestinal (GI) = 99.96% (99.89-99.99)] overall and 99.93% (99.68-99.98) for bowel cancer screening samples; skin 99.99% (99.92-100.0); renal 99.99% (99.57-100.0). Analysis of clinically significant differences revealed discrepancies in areas where interobserver variability is known to be high, in reads performed with both modalities and without apparent trends to either. CONCLUSIONS: Comparing LM and DP CMC, overall rates exceed the reference 98.3%, providing compelling evidence that pathologists provide equivalent results for both routine and cancer screening samples irrespective of the modality used.

Computer-aided diagnosis improves characterization of Barrett's neoplasia by general endoscopists (with video).

BACKGROUND AND AIMS: Characterization of visible abnormalities in patients with Barrett's esophagus (BE) can be challenging, especially for inexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CADx) systems may assist endoscopists. We aimed to develop, validate, and benchmark a CADx system for BE neoplasia. METHODS: The CADx system received pretraining with ImageNet and then consecutive domain-specific pretraining with GastroNet, which includes 5 million endoscopic images. It was subsequently trained and internally validated using 1758 narrow-band imaging (NBI) images of early BE neoplasia (352 patients) and 1838 NBI images of nondysplastic BE (173 patients) from 8 international centers. CADx was tested prospectively on corresponding image and video test sets with 30 cases (20 patients) of BE neoplasia and 60 cases (31 patients) of nondysplastic BE. The test set was benchmarked by 44 general endoscopists in 2 phases (phase 1, no CADx assistance; phase 2, with CADx assistance). Ten international BE experts provided additional benchmark performance. RESULTS: Stand-alone sensitivity and specificity of the CADx system were 100% and 98% for images and 93% and 96% for videos, respectively. CADx outperformed general endoscopists without CADx assistance in terms of sensitivity (P = .04). Sensitivity and specificity of general endoscopists increased from 84% to 96% and 90% to 98% with CAD assistance (P < .001). CADx assistance increased endoscopists' confidence in characterization (P < .001). CADx performance was similar to that of the BE experts. CONCLUSIONS: CADx assistance significantly increased characterization performance of BE neoplasia by general endoscopists to the level of expert endoscopists. The use of this CADx system may thereby improve daily Barrett surveillance.

Cytosponge procedures produce fewer respiratory aerosols and droplets than esophagogastroduodenoscopies.

Esophagogastroduodenoscopies (EGD) are aerosol-generating procedures that may spread respiratory pathogens. We aim to investigate the production of airborne aerosols and droplets during Cytosponge procedures, which are being evaluated in large-scale research studies and National Health Service (NHS)implementation pilots to reduce endoscopy backlogs. We measured 18 Cytosponge and 37 EGD procedures using a particle counter (diameters = 0.3-25 µm), taking measurements 10 cm from the mouth. Two particle count analyses were performed: whole procedure and event-based. Direct comparison with duration-standardized EGD procedures shows that Cytosponge procedures produce 2.16× reduction (P < 0.001) for aerosols and no significant change for droplets (P = 0.332). Event-based analysis shows that particle production is driven by throat spray (aerosols: 138.1× reference, droplets: 16.2×), which is optional, and removal of Cytosponge (aerosols: 14.6×, droplets: 62.6×). Cytosponge burping produces less aerosols than EGD (2.82×, P < 0.05). Cytosponge procedures produce significantly less aerosols and droplets than EGD procedures and thus reduce two potential transmission routes for respiratory viruses.

The effect of procedural time on dysplasia detection rate during endoscopic surveillance of Barrett's esophagus.

BACKGROUND : Endoscopic surveillance of Barrett's esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). METHODS : We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. RESULTS : Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0-19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00-1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04-1.40; P = 0.01). CONCLUSIONS : In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection.

Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

BACKGROUND: Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus. METHODS: We first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance. FINDINGS: The prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia. INTERPRETATION: Cytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways. FUNDING: Medical Research Council, Cancer Research UK, Innovate UK.

Image-Enhanced Endoscopy and Molecular Biomarkers Vs Seattle Protocol to Diagnose Dysplasia in Barrett's Esophagus.

BACKGROUND & AIMS: Dysplasia in Barrett's esophagus often is invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence imaging (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers vs HRWLE with Seattle protocol biopsies. METHODS: Barrett's esophagus patients with no dysplastic lesions were block-randomized to standard endoscopy (HRWLE with the Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6 to 12 weeks. The primary end point was the histologic diagnosis from all study biopsies (trial histology). A sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from the first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. The primary outcome was diagnostic accuracy for dysplasia by real-time pCLE vs HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P = .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P < .001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; P = .16), with an area under the receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. The addition of molecular biomarkers could improve diagnostic accuracy.

Radiofrequency ablation for Barrett's oesophagus related neoplasia with the 360 Express catheter: initial experience from the United Kingdom and Ireland-preliminary results.

BACKGROUND: Radio-frequency ablation (RFA) for Barrett's oesophagus (BE)-related neoplasia is currently used after endoscopic resection of visible neoplasia. The HALO 360 balloon has been used to ablate long segment BE. The Barrx™ 360 Express RFA self-sizing catheter ('RFA Express') may potentially allow quicker ablation times and improved treatment outcomes. The aim of this paper is to present real world data on the use of the 360 Express Device. METHODS: Centres in the UK and Ireland submitted cases where the RFA Express was used. The primary outcome was regression of BE at 3 months. Secondary outcomes were the rate of symptomatic stricture formation and resolution of intestinal metaplasia (CR-IM) and dysplasia (CR-D) at End of Treatment (EoT). RESULTS: 11 centres submitted 123 consecutive patients. 112 had a follow up endoscopy. The median age was 67 years (IQR 62-75). 3 dosimetries were used. The mean reduction in Circumferential (C) length was 78% ± 36 and mean reduction in Maximal length (M) was 55% ± 36. 17 patients (15%) developed strictures requiring dilation. There was a higher rate of stricture formation when the 12 J energy was used (p < 0.05). 47 patients had EoT biopsies, 40 (85%) had CR-D and 34(76%) had CR-IM. CONCLUSIONS: The RFA 360 Express catheter shows reduction in length of baseline BE at 3 months after index treatment, and eradication of intestinal metaplasia and dysplasia at 12 months similar to other studies with earlier devices. It appears that the symptomatic stricture rate is slightly higher than previous series with the HALO 360 catheter. This study was performed as part of the HALO registry and has been approved by the Research Ethics Committee - MREC Number 08/H0714/27 Local project reference 08/0104 Project ID 15,033 IRAS Number 54678 EudraCT 2009-015980-1. Registered on ISRCTN as below: ISRCTN93069556. https://doi.org/10.1186/ISRCTN93069556.

Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a leading cause of morbidity and is associated with a 2 % - 17 % mortality rate in the UK and USA. Bleeding peptic ulcers account for 50 % of UGIB cases. Endoscopic intervention in a timely manner can improve outcomes. Hemostatic spray is an endoscopic hemostatic powder for GI bleeding. This multicenter registry was created to collect data prospectively on the immediate endoscopic hemostasis of GI bleeding in patients with peptic ulcer disease when hemostatic spray is applied as endoscopic monotherapy, dual therapy, or rescue therapy. METHODS: Data were collected prospectively (January 2016 - March 2019) from 14 centers in the UK, France, Germany, and the USA. The application of hemostatic spray was decided upon at the endoscopist's discretion. RESULTS: 202 patients with UGIB secondary to peptic ulcers were recruited. Immediate hemostasis was achieved in 178/202 patients (88 %), 26/154 (17 %) experienced rebleeding, 21/175 (12 %) died within 7 days, and 38/175 (22 %) died within 30 days (all-cause mortality). Combination therapy of hemostatic spray with other endoscopic modalities had an associated lower 30-day mortality (16 %, P < 0.05) compared with monotherapy or rescue therapy. There were high immediate hemostasis rates across all peptic ulcer disease Forrest classifications. CONCLUSIONS: This is the largest case series of outcomes of peptic ulcer bleeding treated with hemostatic spray, with high immediate hemostasis rates for bleeding peptic ulcers.

Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes.

BACKGROUND AND AIM: Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy. METHODS: Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy. RESULTS: One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7-12). The median Rockall score was 8 (IQR, 7-9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P < 0.001) when comparing the number of units transfused 3 weeks before and after treatment. The mean reduction was one unit per patient. CONCLUSIONS: Hemospray achieved high rates of immediate hemostasis, with comparable rebleed rates following treatment of tumor-related upper gastrointestinal bleeds. Hemospray helped in improving transfusion requirements in these patients. This allows for patient stabilization and bridges towards definitive surgery or radiotherapy to treat the underlying tumor.

Risk factors for serious adverse events associated with multiband mucosectomy in Barrett's esophagus: an international multicenter analysis of 3827 endoscopic resection procedures.

BACKGROUND AND AIMS: Multiband mucosectomy (MBM) is a widely used technique for the treatment of Barrett's esophagus (BE). However, large multicenter studies enabling a generalizable estimation of the risk of serious adverse events, such as perforation and postprocedural bleeding, are lacking. The aim of this study was to estimate the rate of, and risk factors for, serious adverse events associated with MBM. METHODS: In this retrospective analysis, consecutive patients who underwent MBM for treatment of BE in 14 tertiary referral centers in Europe, the United States, Canada, and Australia were included. Primary outcomes were perforation and postprocedural bleeding rate. Potential risk factors were identified by logistic regression. RESULTS: Between 2001 and 2016, a total of 3827 MBM procedures were performed in 2447 patients (84% male, mean age 66 years, median BE length C2M4). Perforation occurred in 17 procedures (0.4%; 95% confidence interval [CI], 0.3-0.7), of which 15 could be treated endoscopically or conservatively. Female gender was an independent risk factor for perforation (odds ratio [OR], 2.77; 95% CI, 1.02-7.57; P = .05). Postprocedural bleeding occurred after 35 procedures (0.9%; 95% CI, 0.6-1.3). The number of resections (OR, 1.15; 95% CI, 1.06-1.25; P < .001) was significantly associated with postprocedural bleeding. CONCLUSION: The results of this study show that MBM for BE is safe with a low risk of serious adverse events. In addition, most of the adverse events could be managed endoscopically or conservatively. The number of resections was an independent risk factor for postprocedural bleeding.

The management and long-term outcomes of endoscopic and surgical treatment of early esophageal adenocarcinoma.

Endoscopic resection (ER) for early (pT1) esophageal adenocarcinoma can be justified if the rate of coexisting lymph node (LN) metastasis is less than the mortality rate from esophagectomy. This study examines endoscopic and surgical outcomes, histological assessment of submucosal (sm) disease, factors influencing LN metastasis, and the safety of treating pT1b disease endoscopically. Histopathological reexamination recorded thickness, width and depth of sm invasion, grade, presence of lymphovascular invasion (LVI), resection margin status and tumor stage. Multivariate analysis was employed to evaluate the factors influencing survival and LN metastasis. Rate of LN metastasis for pT1 low-risk (LR: sm invasion < 500 µm, G1-2, no LVI) or high-risk (HR: sm invasion >500 µm, G3-4 or LVI) disease were analyzed. Ninety three patients underwent ER and 96 underwent esophagectomy. We demonstrate conflicting histological methods of sm disease reporting, which may explain the difference in LN metastasis rate between reported surgical & endoscopic series. Multivariate analysis confirmed age, T stage, and presence of LN metastases were the independent factors predicting poor prognosis. Tumor thickness as well as grade, T stage, LVI were predictors of LN metastasis. Rates of LN metastasis are <2% in LR sm1 disease, and >15% in HR sm1 disease. Pathological reporting of sm invasion should be updated for uniform analysis of endoscopic and surgical specimens. Following rigorous histopathological examination and within a close endoscopic follow-up regimen, pT1a and pT1b LRsm1 disease may be treated with curative intent endoscopically, whereas pT1b HRsm1-sm3 disease should be offered surgery.

Surveillance of patients with Barrett's esophagus after complete eradication of intestinal metaplasia.

A 55-year-old Caucasian male with a long history of smoking and reflux disease underwent endoscopic evaluation for dyspepsia. During upper endoscopy, a 4 cm long Barrett's segment with an 8 mm nodular lesion was detected. The lesion was removed en-bloc by endoscopic mucosal resection and biopsies were taken from the adjacent columnar epithelium. The histology of the lesion revealed high-grade dysplasia with clear resection margins and no lymphovascular invasion. The remaining biopsies did not show any dysplastic changes. He subsequently underwent three sequential sessions of radiofrequency ablation (RFA) to eradicate the remaining Barrett's epithelium. When this type of case presents to the clinic for follow-up, what do you do next?

Timeline and location of recurrence following successful ablation in Barrett's oesophagus: an international multicentre study.

OBJECTIVE: Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett's oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. DESIGN: Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. RESULTS: 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4-4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI -7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). CONCLUSIONS: BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Acceptability, Accuracy, and Safety of Disposable Transnasal Capsule Endoscopy for Barrett's Esophagus Screening.

BACKGROUND & AIMS: Screening for Barrett's esophagus (BE) with conventional esophagogastroduodenoscopy (C-EGD) is expensive. We assessed the performance of a clinic-based, single use transnasal capsule endoscope (EG Scan II) for the detection of BE, compared to C-EGD as the reference standard. METHODS: We performed a prospective multicenter cohort study of patients with and without BE recruited from 3 referral centers (1 in the United States and 2 in the United Kingdom). Of 200 consenting participants, 178 (89%) completed both procedures (11% failed EG Scan due to the inability to intubate the nasopharynx). The mean age of participants was 57.9 years and 67% were male. The prevalence of BE was 53%. All subjects underwent the 2 procedures on the same day, performed by blinded endoscopists. Patients completed preference and validated tolerability (10-point visual analogue scale [VAS]) questionnaires within 14 days of the procedures. RESULTS: A higher proportion of patients preferred the EG Scan (54.2%) vs the C-EGD (16.7%) (P < .001) and the EG Scan had a higher VAS score (7.2) vs the C-EGD (6.4) (P = .0004). No serious adverse events occurred. The EG Scan identified any length BE with a sensitivity value of 0.90 (95% CI, 0.83-0.96) and a specificity value of 0.91 (95% CI, 0.82-0.96). The EG Scan identified long segment BE with a sensitivity value of 0.95 and short segment BE with a sensitivity values of 0.87. CONCLUSIONS: In a prospective study, we found the EG Scan to be safe and to detect BE with higher than 90% sensitivity and specificity. A higher proportion of patients preferred the EG Scan to C-EGD. This device might be used as a clinic-based tool to screen populations at risk for BE. ISRCTN registry identifier: 70595405; ClinicalTrials.gov no: NCT02066233.

A prospective multicenter study using a new multiband mucosectomy device for endoscopic resection of early neoplasia in Barrett's esophagus.

BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. METHODS: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. RESULTS: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.).

Narrow band imaging and serology in the assessment of premalignant gastric pathology.

BACKGROUND: Patient outcomes in gastric adenocarcinoma are poor due to late diagnosis. Detecting and treating at the premalignant stage has the potential to improve this. Helicobacter pylori is also a strong risk factor for this disease. AIMS: Primary aims were to assess the diagnostic accuracy of magnified narrow band imaging (NBI-Z) endoscopy and serology in detecting normal mucosa, H. pylori gastritis and gastric atrophy. Secondary aims were to compare the diagnostic accuracies of two classification systems using both NBI-Z and white light endoscopy with magnification (WLE-Z) and evaluate the inter-observer agreement. METHODS: Patients were prospectively recruited. Images of gastric mucosa were stored with histology and serum for IgG H. pylori and Pepsinogen (PG) I/II ELISAs. Blinded expert endoscopists agreed on mucosal pattern. Mucosal images and serological markers were compared with histology. Kappa statistics determined inter-observer variability for randomly allocated images among four experts and four non-experts. RESULTS: 116 patients were prospectively recruited. Diagnostic accuracy of NBI-Z for determining normal gastric mucosa was 0.87(95%CI 0.82-0.92), H. pylori gastritis 0.65(95%CI 0.55-0.75) and gastric atrophy 0.88(95%CI 0.81-0.94). NBI-Z was superior to serology at detecting gastric atrophy: NBI-Z gastric atrophy 0.88(95%CI 0.81-0.94) vs PGI/II ratio < 3 0.74(95%CI 0.62-0.85) p<.0001. Overall NBI-Z was superior to WLE-Z in detecting disease using two validated classifications. Inter-observer agreement was 0.63(95%CI 0.51-0.73). CONCLUSIONS: NBI-Z accurately detects changes in the GI mucosa which currently depend on histology. NBI-Z is useful in the detection of precancerous conditions, potentially improving patient outcomes with early intervention to prevent gastric cancer.

Systematic assessment with I-SCAN magnification endoscopy and acetic acid improves dysplasia detection in patients with Barrett's esophagus.

Background and study aims Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett's esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. Methods BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. Results The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a "pull-through" alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). Conclusions A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785).

The detection of oesophageal varices using a novel, disposable, probe-based transnasal endoscope: a prospective diagnostic pilot study.

BACKGROUND & AIMS: Screening for oesophageal varices (OV) using conventional oesophagogastroduodenoscopy (C-OGD) is invasive and requires costly monitoring, recovery, and decontamination facilities. We aimed to evaluate the technical feasibility, acceptability and accuracy of a novel, portable and disposable office-based transnasal endoscope (EG Scan™ ) compared to C-OGD as the reference standard. METHODS: This was a prospective cohort study. Consecutive adult patients with cirrhosis were invited to participate. All subjects underwent the two procedures on the same day performed by two endoscopists in a blinded design. Patients completed preference and validated tolerability (10-point visual analogue scale (VAS)) questionnaires on day 0 and day 14 post procedures. RESULTS: Forty-five of 50 patients (90%) completed both interventions. Mean age was 59 years and OV prevalence was 49%. Patients reported higher preference (percentage) and better experience (mean VAS) with EG Scan compared to C-OGD on day 0 (76.5% vs. 23.5%, P < 0.001; 7.8 vs. 6.8, P = 0.058, respectively) and day 14 (77.8% vs. 22.2%, P < 0.001; 7.0 vs. 5.5, P = 0.0013 respectively). Sensitivity and specificity of the EG Scan for the diagnosis of any size OV were 0.82 (95% confidence interval (CI) 0.60-0.95), and 0.78 (95% CI 0.56-0.93) respectively. Corresponding values for the diagnosis of clinically significant (medium/large) OV were 0.92 (95% CI 0.62-1.0), 0.97 (95% CI 0.84-1.0) respectively. No serious adverse events occurred. CONCLUSIONS: EG Scan accuracy was higher for the diagnosis of medium/large OV compared to any size OV. Patients' preference and overall experience of the EG Scan was favourable compared to C-OGD 14 days after procedures.

Performance characteristics of unsedated ultrathin video endoscopy in the assessment of the upper GI tract: systematic review and meta-analysis.

BACKGROUND AND AIMS: Reports on the performance of unsedated ultrathin endoscopy via the transnasal (uTNE) and transoral (uTOE) routes are conflicting. We aimed to estimate the technical success rate, patient preference, and acceptability of uTNE and uTOE alone and in comparison with conventional EGD (cEGD; with or without sedation). METHODS: A systematic review and meta-analysis was performed on all primary studies reporting the outcomes of interest. Electronic databases (Cochrane library, MEDLINE, EMBASE) were searched on February 1, 2014. RESULTS: Thirty-four studies met the inclusion criteria with 6659 patients in total. The pooled technical success rate was 94.0% for uTNE (95% confidence interval [CI], 91.6-95.8; 30 studies) and 97.8% for uTOE (95% CI, 95.6-98.9; 16 studies). The difference in proportion of success for uTNE compared with cEGD was -2.0% (95% CI, -4.0 to -1.0; 18 studies), but that difference was not significant when uTNE < 5.9 mm in diameter was used (-1.0%; 95% CI, -3.0 to .0; 9 studies). There was no significant difference in success rate between uTOE and cEGD (.0%; 95% CI, -1.0 to 2.0; 10 studies). The pooled difference in proportion of patients who preferred uTNE over cEGD was 63.0% (95% CI, 49.0-76.0; 10 studies), whereas preference for uTOE versus cEGD was not significantly different (38.0%; 95% CI, -4.0 to 80.0; 2 studies). Acceptability was high for both uTNE (85.2%; 95% CI, 79.1-89.9; 16 studies) and uTOE (88.7%; 95% CI, 82.4-92.9; 10 studies). CONCLUSIONS: Technical success rate for uTNE < 5.9 mm is equivalent to cEGD. uTNE has high patient acceptability, with better patient preference, and therefore could be a useful alternative to cEGD for screening purposes. uTOE had a similar technical success rate but an equivocal preference to cEGD.