Endoscopic Submucosal Dissection for Early Esophageal Adenocarcinoma: Low Rates of Metastases in Mucosal Cancers with Poor Differentiation.

BACKGROUND AND AIMS: Endoscopic resection (ER) is accepted as standard treatment for intramucosal esophageal adenocarcinoma (EAC) with well or moderate differentiation. Poor differentiation (PD) is judged as a risk factor for lymph node metastasis (LNM) and surgery is recommended. However, the evidence for this recommendation is weak. Study aim was to analyze the clinical course of patients after ER of EAC with PD. PATIENTS AND METHODS: Patients undergoing endoscopic submucosal dissection for EAC were included from 16 German centers. Inclusion criteria were PD in the resection specimen, R0 resection and endoscopic follow-up. Primary outcome was the metastasis rate during follow-up. Analysis was performed retrospectively in a prospectively collected database. RESULTS: 25 patients with PD as single risk factor (group A) and 15 patients with PD and additional risk factors (submucosal invasion and/or lymphovascular invasion) were included. The metastasis rate was was 1/25 (4.0%; 95%CI 0.4-17.2) in group A and 3/15 (20.0%; 95%CI 6.0-44.4%) in group B, respectively (p=0.293). The rate of EAC-associated deaths was 1/25 (4%; 95%CI 0.4-17.2%) versus 3/15 (20%; 95%CI 6.0-44.4%) in group B (p=0.293) while the overall death rate was 7/25 (28.0%; 95%CI 13.5-47.3%) versus 3/15 (20%; 95%CI 6.0-44.4%) (p=0.715). Median follow-up was 30 months (IQR 15-53). CONCLUSIONS: During long-term follow-up the risk of metastasis is low after ER of mucosal EAC with PD as single risk factor. A conservative approach seems justified in this small patient group. However, the treatment strategy has to be determined on an individualized basis until further prospective data are available.

Detection of duodenal villous atrophy on endoscopic images using a deep learning algorithm.

BACKGROUND AND AIMS: Celiac disease with its endoscopic manifestation of villous atrophy (VA) is underdiagnosed worldwide. The application of artificial intelligence (AI) for the macroscopic detection of VA at routine EGD may improve diagnostic performance. METHODS: A dataset of 858 endoscopic images of 182 patients with VA and 846 images from 323 patients with normal duodenal mucosa was collected and used to train a ResNet18 deep learning model to detect VA. An external dataset was used to test the algorithm, in addition to 6 fellows and 4 board-certified gastroenterologists. Fellows could consult the AI algorithm's result during the test. From their consultation distribution, a stratification of test images into "easy" and "difficult" was performed and used for classified performance measurement. RESULTS: External validation of the AI algorithm yielded values of 90%, 76%, and 84% for sensitivity, specificity, and accuracy, respectively. Fellows scored corresponding values of 63%, 72%, and 67% and experts scored 72%, 69%, and 71%, respectively. AI consultation significantly improved all trainee performance statistics. Although fellows and experts showed significantly lower performance for difficult images, the performance of the AI algorithm was stable. CONCLUSIONS: In this study, an AI algorithm outperformed endoscopy fellows and experts in the detection of VA on endoscopic still images. AI decision support significantly improved the performance of nonexpert endoscopists. The stable performance on difficult images suggests a further positive add-on effect in challenging cases.

Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: long-term follow-up in a Western center.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been established as a treatment modality for superficial esophageal squamous cell carcinoma (ESCC). Long-term follow-up data are lacking in Western countries. The aim of this study was to analyze long-term survival in a Western center. METHODS: Patients undergoing ESD for ESCC were included. The analysis was performed retrospectively using a prospectively collected database. RESULTS: R0 resection rate was 96.7% (59/61 lesions in 58 patients). Twenty-seven patients (46.6%) fulfilled the curative resection criteria (M1/M2) (group A), 11 patients (19.0%) had M3 lesions without lymphovascular invasion (LVI) (group B), and 20 patients (34.5%) had lesions with submucosal invasion or LVI (group C). Additional treatment was recommended after non-curative resection. It was not performed in 20/31 patients (64.5%), mainly because of comorbidities (75%). Twenty-nine out of 58 (50.0%) patients died during a mean follow-up of 3.7 years. Death was related to ESCC in 17.2% (5/29) of patients. The disease-specific survival rate after curative resection was 100%. Overall survival rates after 5 years were 61.5%, 63.6% and 28.1% for groups A, B, and C, respectively. The overall survival was significantly worse after non-curative resection (p=0.038). CONCLUSION: Non-curative resection is frequent after ESD for ESCC in Western patients. The long-term prognosis is limited and mainly determined by comorbidity. Early diagnosis and pre-interventional assessments need to be improved.

Efficacy and Safety of Vedolizumab in Patients with Inflammatory Bowel Disease in Association with Vedolizumab Drug Levels.

BACKGROUND: Vedolizumab (VDZ) is a well-established and important therapeutic option in the treatment of patients with inflammatory bowel disease (IBD). However, the significance of therapeutic drug monitoring (TDM) with VDZ remains a contradictory field in daily clinical practice. Our study aims to clarify the predictive impact of VDZ drug levels in long-term clinical outcomes in a real-world cohort. METHODS: Patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from a tertiary IBD referral center at the University Hospital Augsburg, Germany, were enrolled in this single-center retrospective data analysis. Clinical and endoscopic data were collected at month 6, month 12, and at the last time of follow-up, and outcomes were correlated with VDZ levels at week 6. RESULTS: This study included 95 patients, 68.4% (n = 65) with UC, 24.2% (n = 23) with CD, and 7.4% (n = 7) with indeterminate colitis (CI). Patients with a mean VDZ treatment time of 17.83 months ± 14.56 showed clinical response in 29.5% (n = 28) and clinical remission in 45.3% (n = 43) at the end of the study. Endoscopic response occurred in 20.0% (n = 19) and endoscopic remission in 29.5% (n = 28) at the end of the study. The sustained beneficial effect of VDZ was also reflected in a significant change in biomarker levels. VDZ trough level at week 6 was determined in 48.4% (n = 46) with a mean of 41.79 µg/mL ± 24.58. A significant association between VDZ level at week 6 and both short and long-term outcomes could not be demonstrated. However, numerically higher VDZ levels were seen in patients with endoscopic and clinical improvement at month 6 and at the time of last follow-up. CONCLUSIONS: This study demonstrated efficacy and safety for VDZ in a real-world cohort. Although, for some parameters, a clear trend for higher VDZ levels at week 6 was seen, the efficacy of VDZ was not significantly correlated to VDZ level at week 6, which questions the predictive value of VDZ levels in the real world.

Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm.

In this study, we aimed to develop an artificial intelligence clinical decision support solution to mitigate operator-dependent limitations during complex endoscopic procedures such as endoscopic submucosal dissection and peroral endoscopic myotomy, for example, bleeding and perforation. A DeepLabv3-based model was trained to delineate vessels, tissue structures and instruments on endoscopic still images from such procedures. The mean cross-validated Intersection over Union and Dice Score were 63% and 76%, respectively. Applied to standardised video clips from third-space endoscopic procedures, the algorithm showed a mean vessel detection rate of 85% with a false-positive rate of 0.75/min. These performance statistics suggest a potential clinical benefit for procedure safety, time and also training.

An artificial intelligence algorithm is highly accurate for detecting endoscopic features of eosinophilic esophagitis.

The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level.

Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer.

OBJECTIVE: Endoscopic submucosal dissection (ESD) in a curative intent for submucosa-invasive early (T1) colorectal cancers (T1-CRCs) often leads to subsequent surgical resection in case of histologic parameters indicating higher risk of nodal involvement. In some cases, however, the expected benefit may be offset by the surgical risks, suggesting a more conservative approach. DESIGN: Retrospective analysis of consecutive patients with T1-CRC who underwent ESD at 13 centres ending inclusion in 2019 (n=3373). Cases with high risk of nodal involvement (non-curative ESD: G3, submucosal invasion>1000 µm, lymphovascular involvement, budding or incomplete resection/R1) were analysed if follow-up data (endoscopy/imaging) were available, regardless of the postendoscopic management (follow-up vs surgery) selected by the multidisciplinary teams in these institutions. Comorbidities were classified according to Charlson Comorbidity Index (CCI). Outcomes were disease recurrence, death and disease-related death rates in the two groups. Rate of residual disease (RD) at both the previous resection site and regional lymph nodes was assessed in the surgical cases as well as from follow-up in the follow-up group. RESULTS: Of 604 patients treated by colorectal ESD for submucosally invasive cancer, 207 non-curative resections (34.3%) were included (138 male; mean age 67.6±10.9 years); in 65.2% of cases, no complete resection was achieved (R1). Of the 207 cases, 60.9% (n=126; median CCI: 3; IQR: 2-4) underwent surgical treatment with RD in 19.8% (25/126), while 39.1% (n=81, median CCI: 5; IQR: 4-6) were followed up by endoscopy in all cases. Patients in the follow-up group had a higher overall mortality (HR=3.95) due to non-CRC causes (n=9, mean survival after ESD 23.7±13.7 months). During this follow-up time, tumour recurrence and disease-specific survival rates were not different between the groups (median follow-up 30 months; range: 6-105). CONCLUSION: Following ESD for a lesion at high risk of RD, follow-up only may be a reasonable choice in patients at high risk for surgery. Also, endoscopic resection quality should be improved. TRIAL REGISTRATION NUMBER: NCT03987828.

Antibody Response to SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease: Results of a Single-Center Cohort Study in a Tertiary Hospital in Germany.

BACKGROUND: COVID-19 is a viral disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), first described in 2019, with a significant impact on everyday life since then. In December 2020, the first vaccine against COVID-19 from BioNTech/Pfizer was approved for the first time. However, little is known about the immune response to vaccination in patients with inflammatory bowel disease (IBD) and immunomodulators or biologics. The aim of our study was to investigate antibody response to SARS-CoV-2 vaccination in patients with IBD receiving immunomodulators or biologics compared to healthy controls. METHODS: This was a single-center study with a retrospective observational design. Seventy-two patients with ulcerative colitis or Crohn's disease were included. Matching data from 72 healthy employees of our hospital were used as the control group. Data were matched by propensity score to patients with IBD. Blood samples were taken from both groups for antibody response, and both groups received an accompanying questionnaire. RESULTS: Sixty-five (90.3%) patients of the IBD group reported taking immunomodulatory therapy. The mean antibody level for all IBD patients was 1,257.1 U/mL (standard deviation [SD] 1,109.626) in males and 1,500.1 U/mL (SD 1142.760) in female IBD patients after full vaccination. Compared to the healthy group, reduced antibody response could be detected (IBD group 1,383.76 U/mL SD 1,125.617; control group 1,885.65 U/mL SD 727.572, p < 0.05). In this group, blood samples were taken with an average of 61.9 days after the first vaccination. There was no vaccination failure in the IBD group after 2 vaccinations. After the first vaccination, side effects, including muscle pain, pain at the injection site, and fatigue, were reported more often in IBD patients than in the control group (total symptoms IBD group 58.3%, control group 34.5%, p < 0.007). The opposite occurred after the second vaccination when side effects were higher in the control group (total symptoms IBD group 55.4%, control group 76%, p = 0.077). There was a trend to a reduced immune response in elderly patients. Disease duration and concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on the immune response. However, longer time to last medication given and time passed to vaccination in patients with IBD seems to have a positive impact on antibody levels. CONCLUSION: Overall, we could show a high antibody response to vaccination with COVID-19 in all patients with IBD after 2 vaccinations. Vaccination was well tolerated, and no other adverse events were detected. Concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on seroconversion. Further evaluation of antibody titers over time is mandatory to detect early the need for re-vaccination in these patients.

Endoscopic Submucosal Dissection in Europe: Results of 1000 Neoplastic Lesions From the German Endoscopic Submucosal Dissection Registry.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) enables the curative resection of early malignant lesions and is associated with reduced recurrence risk. Due to the lack of comprehensive ESD data in the West, the German ESD registry was set up to evaluate relevant outcomes of ESD. METHODS: The German ESD registry is a prospective uncontrolled multicenter study. During a 35-month period, 20 centers included 1000 ESDs of neoplastic lesions. The results were evaluated in terms of en bloc, R0, curative resection rates, and recurrence rate after a 3-month and 12-month follow-up. Additionally, participating centers were grouped into low-volume (≤20 ESDs/y), middle-volume (20-50/y), and high-volume centers (>50/y). A multivariate analysis investigating risk factors for noncurative resection was performed. RESULTS: Overall, en bloc, R0, and curative resection rates of 92.4% (95% confidence interval [CI], 0.90-0.94), 78.8% (95% CI, 0.76-0.81), and 72.3% (95% CI, 0.69-0.75) were achieved, respectively. The overall complication rate was 8.3% (95% CI, 0.067-0.102), whereas the recurrence rate after 12 months was 2.1%. High-volume centers had significantly higher en bloc, R0, curative resection rates, and recurrence rates and lower complication rates than middle- or low-volume centers. The lesion size, hybrid ESD, age, stage T1b carcinoma, and treatment outside high-volume centers were identified as risk factors for noncurative ESD. CONCLUSION: In Germany, ESD achieves excellent en bloc resection rates but only modest curative resection rates. ESD requires a high level of expertise, and results vary significantly depending on the center's yearly case volume.

[Black esophagus and black duodenum - rare cause of an upper gastrointestinal bleeding]. / Black esophagus und black duodenum ­ seltene Ursache einer oberen gastrointestinalen Blutung.

We present the case of a 73-year-old female patient with acute esophageal necrosis, or black esophagus, and consecutive distal esophageal perforation. Additionally, the patient had the rare coincidence of duodenal necrosis or black duodenum. Black esophagus is usually diagnosed endoscopically and is characterized by a circular necrosis of the esophagus with abrupt normalization at the gastroesophageal junction. Black esophagus is a rare cause of symptoms of upper gastrointestinal bleeding with a mortality rate of up to 30 %. Complications include esophageal perforation and esophageal stricture formation. No causal therapy is available.

Endoscopic submucosal dissection for rectal neoplasia extending to the dentate line: European experience.

Background and study aims The ideal treatment strategy for rectal neoplasia extending to the dentate line (RNDL) is not well defined. Endoscopic mucosal resection (EMR) and submucosal dissection (ESD) compete with surgical techniques such as transanal endoscopic microsurgery (TEM). Non-Asian data and prospective data on ESD are lacking. The study aim was to evaluate the role of ESD in treatment of RNDL in a Western center. Patients and methods Eighty-six patients with rectal adenomas were included. ESD was performed in 86 rectal adenomas including 24 RNDLs (27.9 %) and 62 lesions distant from the dentate line (72.1 %). Results En bloc resection rate was comparable (91.7 % vs. 93.5 %, P  = 0.670) between ESD for RNDL and non-RNDL. R0 resection rate was significantly lower in ESD for RNDL compared to that for non-RNDL (70.8 % vs 88.7 %; P  = 0.039), but most non-R0 resection was unclear margin (Rx) and was not obvious positive margin (R1). Accordingly, the recurrence rate after ESD for RNDL (4.5 %) was not statistically different from that for non-RNDL (0 %, P  = 0.275) and was lower than that previously reported for EMR. Median procedure time was 127 vs. 110 minutes ( P  = 0.182). Risk of delayed bleeding (20.8 % vs. 0 %, P  = 0.001) and postinterventional pain (33.3 % vs. 14.5 %, P  = 0.07) increased in RNDL cases, but they were managed conservatively. Incidence of stricture (4.2 % vs. 1.6 %, P  = 0.483) and perforation (0 % vs. 1.6 %, P  = 1.000) were similar. Conclusions ESD is a feasible and safe resection technique for RNDLs. A randomized controlled trial comparing ESD to other methods (EMR or transanal surgery) is warranted.

Endoscopic treatment of early esophageal squamous neoplasia.

Esophageal squamous cell carcinoma (ESCC) remains the most common esophageal cancer in the world, though a rising incidence of esophageal adenocarcinoma could be seen during the last decade in the western world. There are several known risk factors for ESCC, such as smoking, alcohol consumption, radiation or others. As there is a risk of lymph node metastasis already in early stages, early endoscopic detection is crucial for curative endoscopic treatment options. Therefore, newest technical improvements such as enhancement techniques or virtual chromoendoscopy are helpful for the diagnosis of mucosal carcinoma. Lugol's iodine remains the gold standard to detect early esophageal cancer, however, it should be combined with these newer techniques. For the prediction of invasion depth, a new classification was developed by the Japan Esophageal society. By using magnifying endoscopy and Narrow Band Imaging, the microvascular morphology allows a prediction of invasion depth of early squamous cell carcinoma. Endoscopic resection is suitable for patients with early-stage ESCC (m1-m2), because of the low risk of lymph node metastasis. EMR should be performed if the lesion is smaller than 15 mm, because a R0 resection can be achieved. Larger lesions (>15 mm) should be resected via endoscopic submucosal dissection to reach an en bloc resection, a lower recurrence rate and a R0 situation.

Endoscopic submucosal dissection for early rectal neoplasia: experience from a European center.

Background and study aims Endoscopic resection is a curative treatment option for large nonpedunculated colorectal polyps (LNPCPs). Endoscopic submucosal dissection (ESD) allows en bloc resection but ESD experience is still limited outside Asia. The aim of our study was to evaluate the role of ESD in the treatment of early rectal neoplasia in a European center. Patients and methods 330 patients referred for endoscopic resection of rectal LNPCPs were included prospectively. Results ESD was performed for 302 LNPCPs (median diameter 40 mm). Submucosal invasive cancer (SMIC) was present in 17.2 % (n = 52). SMIC was associated with Paris type (54.5 % among type 0-Is lesions, 100 % of 0-Is-IIc type, 0 % of 0-IIa, 14.9 % of 0-IIa-Is, and 59.3 % of 0-IIa-IIc type; P < 0.001) and with surface pattern (71.4 % among nongranular plus mixed surface lesions, 17.9 % of lesions with granular surface and nodule ≥ 10 mm). For SMICs, resection rates were en bloc 81.4 %, R0 65.1 %, and curative 30.2 %. Curative resection rate improved from 13.6 % to 47.6 % over the study period (P = 0.036). The reason for 83.3 % (25/30) of noncurative resections was submucosal invasion exceeding 1000 µm. For benign lesions (n = 250, 82.8 %), the R0 resection increased from 55.2 % to 84.8 % over the study period (P < 0.001). Recurrence rate was 4.8 %, bleeding rate 5.2 %, and perforation rate 0.8 % (all complications managed conservatively). Median follow-up was 35 months. Conclusions The majority of rectal LNPCPs are benign lesions. ESD offers high R0 resection and low recurrence rates but EMR may be appropriate. In lesions with a risk for SMIC, ESD should be offered to achieve R0 resection. Despite high rates of R0 resection the curative resection rate of ESD for rectal SMIC is < 50 %. Pretherapeutic lesion selection needs improvement.