Vertical tumor-positive resection margins and the risk of residual neoplasia after endoscopic resection of Barrett's neoplasia: a nationwide cohort with pathology reassessment.

BACKGROUND: This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v). METHODS: This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins. RESULTS: 101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12-50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities. CONCLUSIONS: After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8-12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v.

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

Predicting procedure duration of colorectal endoscopic submucosal dissection at Western endoscopy centers.

Background and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to evaluate existing and new prediction models for ESD duration. Patients and methods Records of all consecutive patients who underwent single, non-hybrid colorectal ESDs before 2020 at three Dutch centers were reviewed. The performance of an Eastern prediction model [GIE 2021;94(1):133-144] was assessed in the Dutch cohort. A prediction model for procedure duration was built using multivariable linear regression. The model's performance was validated using internal validation by bootstrap resampling, internal-external cross-validation and external validation in an independent Swedish ESD cohort. Results A total of 435 colorectal ESDs were analyzed (92% en bloc resections, mean duration 139 minutes, mean tumor size 39 mm). The performance of current unstandardized time scheduling practice was suboptimal (explained variance: R 2 =27%). We successfully validated the Eastern prediction model for colorectal ESD duration <60 minutes (c-statistic 0.70, 95% CI 0.62-0.77), but this model was limited due to dichotomization of the outcome and a relatively low frequency (14%) of ESDs completed <60 minutes in the Dutch centers. The model was more useful with a dichotomization cut-off of 120 minutes (c-statistic: 0.75; 88% and 17% of "easy" and "very difficult" ESDs completed <120 minutes, respectively). To predict ESD duration as continuous outcome, we developed and validated the six-variable cESD-TIME formula ( https://cesdtimeformula.shinyapps.io/calculator/ ; optimism-corrected R 2 =61%; R 2 =66% after recalibration of the slope). Conclusions We provided two useful tools for predicting colorectal ESD duration at Western centers. Further improvements and validations are encouraged with potential local adaptation to optimize time planning.

Correction: Predicting procedure duration of colorectal endoscopic submucosal dissection at Western endoscopy centers.

[This corrects the article DOI: 10.1055/a-2122-0419.].

Increased risk of esophageal squamous cell carcinoma in patients with squamous dysplasia: a nationwide cohort study in the Netherlands.

Squamous dysplasia is the histological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. We aimed to assess the ESCC risk in patients with esophageal squamous dysplasia in a Western country. This nationwide cohort study included all patients with esophageal squamous dysplasia, diagnosed between 1991 and 2020 in the Dutch nationwide pathology databank (Palga). Squamous dysplasia was divided in mild-to-moderate dysplasia (mild, low-grade, and moderate dysplasia) and higher-grade dysplasia (high-grade dysplasia, severe dysplasia, carcinoma in situ). ESCC were identified in Palga and the Netherlands Cancer Registry. The primary endpoint was diagnosis of prevalent (≤6 months) and incident (>6 months after squamous dysplasia) ESCC. In total, 873 patients (55% male, aged 68 years SD ± 13.2) were diagnosed with esophageal squamous dysplasia, comprising mild-to-moderate dysplasia (n = 456), higher-grade dysplasia (n = 393), and dysplasia not otherwise specified (n = 24). ESCC was diagnosed in 77 (17%) patients with mild-to-moderate dysplasia (49 prevalent, 28 incident ESCC) and in 162 (41%) patients with higher-grade dysplasia (128 prevalent, 34 incident ESCC). After excluding prevalent ESCC, the annual risk of ESCC was 4.0% (95% CI: 2.7-5.7%) in patients with mild-to-moderate dysplasia and 8.5% (95% CI: 5.9-11.7%) in patients with higher-grade dysplasia. All patients with squamous dysplasia, including those with mild-to-moderate dysplasia, have a substantial risk of developing ESCC. Consequently, endoscopic surveillance of the esophageal mucosa or endoscopic resection of dysplasia should be considered for patients with mild-to-moderate dysplasia in Western countries. KEY MESSAGES What is already known on this topic? Squamous dysplasia is the histological precursor of ESCC and is divided in distinct grades, based on the proportion of the squamous epithelium with histopathological abnormalities. In Western countries, the optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. What this study adds The ESCC risk of patients with squamous dysplasia was increased for all patients with squamous dysplasia in a Western country; 2.1% for patients with mild dysplasia, 5.1% for low-grade dysplasia, and 5.2% for moderate dysplasia. Increasing grades of squamous dysplasia were associated with an increased ESCC risk. How this study might affect research, practice, or policy We recommend that endoscopic follow-up or treatment should be considered in all patients with esophageal squamous dysplasia in Western countries: 1) for patients with mild, low-grade, and moderate dysplasia, endoscopic surveillance with careful inspection with narrow band imaging or dye-based chromoendoscopy of the esophageal mucosa is indicated; and 2) for patients with high-grade dysplasia, severe dysplasia and carcinoma in situ adequate endoscopic staging and in case of suspected neoplasia endoscopic treatment should be performed.

Endoscopic screening of the upper gastrointestinal tract for second primary tumors in patients with head and neck cancer in a Western country.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival. METHODS: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma. RESULTS: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. CONCLUSION: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities.

Prevalence of lung tumors in patients with esophageal squamous cell carcinoma and vice versa: a systematic review and meta-analysis.

PURPOSE: Recent reports suggest an increased prevalence of lung second primary tumors (LSPTs) in esophageal squamous cell carcinoma (ESCC) patients and vice versa. However, the exact prevalence of SPTs remains unclear and screening for these SPTs is currently not routinely performed in western countries. We aimed to report on the prevalence of LSPTs in patients with ESCC and esophageal second primary tumors (ESPTs) in patients with lung cancer (LC). METHODS: Databases were searched until 25 March 2021 for studies reporting the prevalence of LSPTs in ESCC or vice versa. Pooled prevalences with 95% confidence intervals (CI) of SPTs were calculated with inverse variance, random-effects models and Clopper-Pearson. RESULTS: Nineteen studies in ESCC patients and 20 studies in LC patients were included. The pooled prevalence of LSPTs in patients with ESCC was 1.8% (95% CI 1.4-2.3%). For ESPTs in LC patients, the pooled prevalence was 0.2% (95% CI 0.1-0.4%). The prevalence of LSPTs in ESCC patients was significantly higher in patients treated curatively compared to studies also including palliative patients (median 2.5% versus 1.3%). This difference was consistent for the ESPT prevalence in LC patients (treated curatively median 1.3% versus 0.1% for all treatments). Over 50% of the detected SPTs were squamous cell carcinomas and were diagnosed metachronously. CONCLUSION: Patients with ESCC and LC have an increased risk of developing SPTs in the lungs and esophagus. However, the relatively low SPT prevalence rates do not justify screening in these patients. Further research should focus on risk stratification to identify subgroups of patients at highest risk of SPT development.

Low risk of local recurrence after a successful en bloc endoscopic submucosal dissection for noninvasive colorectal lesions with positive horizontal resection margins (R-ESD study).

BACKGROUND : During endoscopic submucosal dissection (ESD), the normal mucosa is cut under constant optical control. We studied whether a positive horizontal resection margin after a complete en bloc ESD predicts local recurrence. METHODS: In this European multicenter cohort study, patients with a complete en bloc colorectal ESD were selected from prospective registries. Cases were defined by a horizontal resection margin that was positive or indeterminate for dysplasia (HM1), whereas controls had a free resection margin (HM0). Low risk lesions with submucosal invasion (T1) and margins free of carcinoma were analyzed separately. The main outcome was local recurrence. RESULTS: From 928 consecutive ESDs (2011-2020), 354 patients (40 % female; mean age 67 years, median follow-up 23.6 months), with 308 noninvasive lesions and 46 T1 lesions, were included. The recurrence rate for noninvasive lesions was 1/212 (0.5 %; 95 %CI 0.02 %-2.6 %) for HM0 vs. 2/96 (2.1 %; 95 %CI 0.57 %-7.3 %) for HM1. The recurrence rate for T1 lesions was 1/38 (2.6 %; 95 %CI 0.14 %-13.5 %) for HM0 vs. 2/8 (25 %; 95 %CI 7.2 %-59.1 %) for HM1. CONCLUSION: A positive horizontal resection margin after an en bloc ESD for noninvasive lesions is associated with a marginal nonsignificant increase in the local recurrence rate, equal to an ESD with clear horizontal margins. This could not be confirmed for T1 lesions.

Screening for head and neck tumors in patients with esophageal squamous cell carcinoma and vice versa: a nationwide survey among medical specialists.

Background and study aims Retrospectively, minimally 5% of patients with esophageal squamous cell carcinoma (ESCC) and 11 % with head and neck squamous cell carcinoma (HNSCC) in Western countries developed a second primary tumor (SPT). SPT screening in ESCC and HNSCC patients is not implemented routinely in daily practice in many Western countries. This study aimed to assess medical specialist knowledge and opinions regarding screening for head and neck SPTs (HNSPTs) in ESCC patients and vice versa in the Netherlands. Methods A nationwide survey among gastroenterologists and head and neck (HN) surgeons was conducted between December 2020 and March 2021. The survey consisted of 27 questions and focused on knowledge of medical specialists of the prevalence and opinions toward implementing screening for HNSPTs in ESCC patients and vice versa. Results One hundred twenty-eight gastroenterologists (20.5 %) and 31 HN surgeons (50.0 %) completed the survey. The expected median prevalence of HNSPTs in ESCC was 7.0 % (interquartile range [IQR]: 5.0-15.0) among gastroenterologists and 5.0 % (IQR:3.0-8.0) among HN surgeons. For ESPTs in HNSCC, the expected median prevalence was 9.5 % (IQR: 5.0-12.0) among gastroenterologists and 4.0 % (IQR: 2.0-5.0) among HN surgeons. Screening for HNSPTs and ESPTs was considered promising by 35.2 % and 39.6 %, respectively, which increased to 54.7 % of the specialists after providing incidence data on SPTs. Of the HN surgeons, 41.3 % felt they were as capable as gastroenterologists of performing esophageal screening. Conclusions This Dutch nationwide survey revealed a lack of knowledge and different perspectives among specialists about screening to detect SPTs in ESCC and HNSCC patients. Adequate education seems essential to increase awareness among specialists and improve SPT detection, independent of the need for implementation of screening for SPTs in ESCC and HNSCC patients.

Extending treatment criteria for Barrett's neoplasia: results of a nationwide cohort of 138 endoscopic submucosal dissection procedures.

BACKGROUND: The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett's esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed in the Netherlands. METHODS: Retrospective assessment of outcomes, using treatment and follow-up data from a joint database. RESULTS: 130/138 patients had complete ESDs, with 126/130 (97 %) en bloc resections. Median (interquartile range (IQR)) procedure time was 121 minutes (90-180). Pathology findings were high grade dysplasia (HGD) (5 %) or esophageal adenocarcinoma (EAC) T1a (43 %) or T1b (52 %; 19 % sm1, 33 % ≥ sm2). Among resections of HGD or T1a EAC lesions, 87 % (95 %CI 75 %-92 %) were both en bloc and R0; the corresponding value for T1b EAC lesions was 49 % (36 %-60 %). Among R1 resections, 10/34 (29 %) showed residual cancer, all detected at first endoscopic follow-up. The remaining 24 patients (71 %) showed no residual neoplasia. Six of these patients underwent surgery with no residual tumor; the remaining 18 underwent endoscopic follow-up during median 31 months with 1 local recurrence (annual recurrence rate 2 %). Among R0 resections, annual local recurrence rate during median 27 months was 0.5 %. CONCLUSION: In expert hands, ESD allows safe removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter showed R1 resection margins in 50 %, yet only one third had persisting neoplasia at follow-up. To better stratify R1 patients with an indication for additional surgery, repeat endoscopy after healing of the ESD might be a helpful possible prognostic factor for residual cancer.

Artificial Intelligence in Upper Gastrointestinal Endoscopy.

BACKGROUND: Over the past decade, several artificial intelligence (AI) systems are developed to assist in endoscopic assessment of (pre-)cancerous lesions of the gastrointestinal (GI) tract. In this review, we aimed to provide an overview of the possible indications of AI technology in upper GI endoscopy and hypothesize about potential challenges for its use in clinical practice. SUMMARY: Application of AI in upper GI endoscopy has been investigated for several indications: (1) detection, characterization, and delineation of esophageal and gastric cancer (GC) and their premalignant conditions; (2) prediction of tumor invasion; and (3) detection of Helicobacter pylori. AI systems show promising results with an accuracy of up to 99% for the detection of superficial and advanced upper GI cancers. AI outperformed trainee and experienced endoscopists for the detection of esophageal lesions and atrophic gastritis. For GC, AI outperformed mid-level and trainee endoscopists but not expert endoscopists. KEY MESSAGES: Application of artificial intelligence (AI) in upper gastrointestinal endoscopy may improve early diagnosis of esophageal and gastric cancer and may enable endoscopists to better identify patients eligible for endoscopic resection. The benefit of AI on the quality of upper endoscopy still needs to be demonstrated, while prospective trials are needed to confirm accuracy and feasibility during real-time daily endoscopy.

The Yield and Safety of Screening Colonoscopy in Patients Evaluated for Liver Transplantation.

Colorectal cancer (CRC) screening with colonoscopy is commonly used in patients who are candidates for liver transplantation. We initiated this study to define the risk-benefit ratio of performing screening colonoscopy in this population. A retrospective observational study of all consecutive patients undergoing colonoscopy during pre-liver transplantation screening between 2004 and 2017 was conducted. Endoscopic and pathological findings and clinical events potentially related to the colonoscopy in the 30 days after the procedure were registered and compared with a 30-day inpatient control time frame. A total of 858 colonoscopies were performed in 808 patients (65% male; median age, 55 years [interquartile range (IQR), 47-62]; median model for end-stage liver disease (MELD) score, 15 [IQR, 11-18]). CRC was found in 2 patients (0.2%), and advanced adenomas were found in 44 patients (5.4%). The only independent risk factor for an advanced neoplasm was age (odds ratio, 1.072 per year; 95% confidence interval, 1.031-1.115; P < 0.001). During the 30-day postprocedure period, 178 clinical events occurred in 128 patients compared with 101 clinical events in 72 patients in the control time frames (P < 0.001). After colonoscopy, there was a significantly increased risk for renal failure (P = 0.001) and gastrointestinal (GI) bleeding (P = 0.023). Presence of ascites and MELD score were identified as independent risk factors for acute renal failure and GI bleeding. During the study observation period, 53.5% of the screened population actually underwent liver transplantation. Conclusion: CRC screening in pre-liver transplantation patients is associated with a relatively low prevalence of CRC and an increased risk of postcolonoscopy complications such as acute renal failure and GI bleeding, especially in patients with advanced liver disease. Because the risk-benefit ratio of standard performance of a screening colonoscopy in this population appears questionable, alternative screening strategies should be considered.