The Concept of Stroma AReactive Invasion Front Areas (SARIFA) as a new prognostic biomarker for lipid-driven cancers holds true in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are areas at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression. METHODS: We reviewed the SARIFA status of 166 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised. RESULTS: In total, 53 cases (32%) were classified as SARIFA positive and 113 (68%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 11.0 months vs. 22.0 months, HR: 1.570 (1.082-2.278), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p < 0.0001) and higher concentrations of CD68+ macrophages (p = 0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm2 and 1812 ± 1008 µm2 for the SARIFA-negative and -positive cases, respectively (p < 0.001). CONCLUSIONS: SARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.

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.

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.

Influence of artificial intelligence on the diagnostic performance of endoscopists in the assessment of Barrett's esophagus: a tandem randomized and video trial.

BACKGROUND: This study evaluated the effect of an artificial intelligence (AI)-based clinical decision support system on the performance and diagnostic confidence of endoscopists in their assessment of Barrett's esophagus (BE). METHODS: 96 standardized endoscopy videos were assessed by 22 endoscopists with varying degrees of BE experience from 12 centers. Assessment was randomized into two video sets: group A (review first without AI and second with AI) and group B (review first with AI and second without AI). Endoscopists were required to evaluate each video for the presence of Barrett's esophagus-related neoplasia (BERN) and then decide on a spot for a targeted biopsy. After the second assessment, they were allowed to change their clinical decision and confidence level. RESULTS: AI had a stand-alone sensitivity, specificity, and accuracy of 92.2%, 68.9%, and 81.3%, respectively. Without AI, BE experts had an overall sensitivity, specificity, and accuracy of 83.3%, 58.1%, and 71.5%, respectively. With AI, BE nonexperts showed a significant improvement in sensitivity and specificity when videos were assessed a second time with AI (sensitivity 69.8% [95%CI 65.2%-74.2%] to 78.0% [95%CI 74.0%-82.0%]; specificity 67.3% [95%CI 62.5%-72.2%] to 72.7% [95%CI 68.2%-77.3%]). In addition, the diagnostic confidence of BE nonexperts improved significantly with AI. CONCLUSION: BE nonexperts benefitted significantly from additional AI. BE experts and nonexperts remained significantly below the stand-alone performance of AI, suggesting that there may be other factors influencing endoscopists' decisions to follow or discard AI advice.

Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024.

1: ESGE recommends cold snare polypectomy (CSP), to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of diminutive polyps (≤ 5 mm).Strong recommendation, high quality of evidence. 2: ESGE recommends against the use of cold biopsy forceps excision because of its high rate of incomplete resection.Strong recommendation, moderate quality of evidence. 3: ESGE recommends CSP, to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of small polyps (6-9 mm).Strong recommendation, high quality of evidence. 4: ESGE recommends hot snare polypectomy for the removal of nonpedunculated adenomatous polyps of 10-19 mm in size.Strong recommendation, high quality of evidence. 5: ESGE recommends conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥ 20 mm) nonpedunculated adenomatous polyps (LNPCPs).Strong recommendation, high quality of evidence. 6: ESGE suggests that underwater EMR can be considered an alternative to conventional hot EMR for the treatment of adenomatous LNPCPs.Weak recommendation, moderate quality of evidence. 7: Endoscopic submucosal dissection (ESD) may also be suggested as an alternative for removal of LNPCPs of ≥ 20 mm in selected cases and in high-volume centers.Weak recommendation, low quality evidence. 8: ESGE recommends that, after piecemeal EMR of LNPCPs by hot snare, the resection margins should be treated by thermal ablation using snare-tip soft coagulation to prevent adenoma recurrence.Strong recommendation, high quality of evidence. 9: ESGE recommends (piecemeal) cold snare polypectomy or cold EMR for SSLs of all sizes without suspected dysplasia.Strong recommendation, moderate quality of evidence. 10: ESGE recommends prophylactic endoscopic clip closure of the mucosal defect after EMR of LNPCPs in the right colon to reduce to reduce the risk of delayed bleeding.Strong recommendation, high quality of evidence. 11: ESGE recommends that en bloc resection techniques, such as en bloc EMR, ESD, endoscopic intermuscular dissection, endoscopic full-thickness resection, or surgery should be the techniques of choice in cases with suspected superficial invasive carcinoma, which otherwise cannot be removed en bloc by standard polypectomy or EMR.Strong recommendation, moderate quality of evidence.

Stroma AReactive Invasion Front Areas (SARIFA) proves prognostic relevance in gastric carcinoma and is based on a tumor-adipocyte interaction indicating an altered immune response.

BACKGROUND: Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. METHODS: To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). RESULTS: SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expression analyses showed an upregulation of FABP4 in SARIFA-positive tumors. In addition, the transcriptional regulations of white adipocyte differentiation, triglyceride metabolism, and catabolism were upregulated in pathway analyses. In the DSP analysis of SARIFA-positive tumors, FABP4 and the transcriptional regulation of white adipocyte differentiation were upregulated in macrophages. Additionally, a significantly lower expression of the cytokines IL6 and TNFα was observed at the invasion front. CONCLUSIONS: SARIFA proves to be a strong negative prognostic biomarker in advanced gastric cancer, implicating an interaction of tumor cells with tumor-promoting adipocytes with crucial changes in tumor cell metabolism. SARIFA is not driven by tumor genetics but is very likely driven by an altered immune response as a causative mechanism.

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.

Evaluation of a single-use gastroscope in patients presenting with suspected upper gastrointestinal hemorrhage: a pilot feasibility study (One-Scope I).

BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95 %). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.

Wide-area transepithelial sampling with computer-assisted analysis to detect high grade dysplasia and cancer in Barrett's esophagus: a multicenter randomized study.

BACKGROUND: Current surveillance for Barrett's esophagus (BE), consisting of four-quadrant random forceps biopsies (FBs), has an inherent risk of sampling error. Wide-area transepithelial sampling (WATS) may increase detection of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). In this multicenter randomized trial, we aimed to evaluate WATS as a substitute for FB. METHODS: Patients with known BE and a recent history of dysplasia, without visible lesions, at 17 hospitals were randomized to receive either WATS followed by FB or vice versa. All WATS samples were examined, with computer assistance, by at least two experienced pathologists at the CDx Diagnostics laboratory. Similarly, all FBs were examined by two expert pathologists. The primary end point was concordance/discordance for detection of HGD/EAC between the two techniques. RESULTS: 172 patients were included, of whom 21 had HGD/EAC detected by both modalities, 18 had HGD/EAC detected by WATS but missed by FB, and 12 were detected by FB but missed by WATS. The detection rate of HGD/EAC did not differ between WATS and FB (P = 0.36). Using WATS as an adjunct to FB significantly increased the detection of HGD/EAC vs. FB alone (absolute increase 10 % [95 %CI 6 % to 16 %]). Mean procedural times in minutes for FB alone, WATS alone, and the combination were 6.6 (95 %CI 5.9 to 7.1), 4.9 (95 %CI 4.1 to 5.4), and 11.2 (95 %CI 10.5 to 14.0), respectively. CONCLUSIONS: Although the combination of WATS and FB increases dysplasia detection in a population of BE patients enriched for dysplasia, we did not find a statistically significant difference between WATS and FB for the detection of HGD/EAC as single modality.

Stroma AReactive Invasion Front Areas (SARIFA) - a new prognostic biomarker in gastric cancer related to tumor-promoting adipocytes.

Compared to other malignancies, there is a lack of easy-to-evaluate biomarkers for gastric cancer, which is associated with an adverse clinical outcome in many cases. Here, we present Stroma AReactive Invasion Front Areas (SARIFA) as a new histological prognostic marker. We defined SARIFA as the direct contact between a cluster of tumor glands/cells comprising at least five tumor cells and inconspicuous surrounding adipose tissue at the invasion front. A total of 480 adenocarcinomas of the stomach and the gastroesophageal junction from two different collections were classified according to SARIFA. To understand the potential underlying mechanisms, a transcriptome analysis was conducted using digital spatial profiling (DSP). It was found that 20% of the tumors were SARIFA-positive. Kappa values between the three pathologists were good in both collections: 0.74 and 0.78. Patients who presented SARIFA-positive tumors had a significantly lower overall survival in Collections A (median: 20.0 versus 44.0 months; p = 0.014, n = 160) and B (median: 15.0 versus 41.0 months; p < 0.0001, n = 320). SARIFA positivity emerged as a negative independent prognostic factor for overall survival (HR 1.638, 95% CI 1.153-2.326, p = 0.006). Using DSP, the most upregulated genes in SARIFA-positive cases were those associated with triglyceride catabolism and endogenous sterols. COL15A1, FABP2, and FABP4 were differentially expressed in positive cases. At the protein level, the expression of proteins related to lipid metabolism was confirmed. SARIFA combines low inter-observer variability, minimal effort, and high prognostic relevance, and is therefore an extremely promising biomarker related to tumor-promoting adipocytes in gastric cancer. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

First report from the International Evaluation of Endoscopic classification Japan NBI Expert Team: International multicenter web trial.

OBJECTIVES: Narrow-band imaging (NBI) contributes to real-time optical diagnosis and classification of colorectal lesions. The Japan NBI Expert Team (JNET) was introduced in 2011. The aim of this study was to explore the diagnostic accuracy of JNET when applied by European and Japanese endoscopists not familiar with this classification. METHODS: This study was conducted by 36 European Society of Gastrointestinal Endoscopy (ESGE) and 49 Japan Gastroenterological Endoscopy Society (JGES) non-JNET endoscopists using still images of 150 lesions. For each lesion, nonmagnified white-light, nonmagnified NBI, and magnified NBI images were presented. In the magnified NBI, the evaluation area was designated by region of interest (ROI). The endoscopists scored histological prediction for each lesion. RESULTS: In ESGE members, the sensitivity, specificity, and accuracy were respectively 73.3%, 94.7%, and 93.0% for JNET Type 1; 53.0%, 64.9%, and 62.1% for Type 2A; 43.9%, 67.7%, and 55.1% for Type 2B; and 38.1%, 93.7%, and 85.1% for Type 3. When Type 2B and 3 were considered as one category of cancer, the sensitivity, specificity, and accuracy for differentiating high-grade dysplasia and cancer from the others were 59.9%, 72.5%, and 63.8%, respectively. These trends were the same for JGES endoscopists. CONCLUSION: The diagnostic accuracy of the JNET classification was similar between ESGE and JGES and considered to be sufficient for JNET Type 1. On the other hand, the accuracy for Types 2 and 3 is not sufficient; however, JNET 2B lesions should be resected en bloc due to the risk of cancers and JNET 3 can be treated by surgery due to its high specificity.

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.

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.

Underwater vs Conventional Endoscopic Mucosal Resection of Large Sessile or Flat Colorectal Polyps: A Prospective Randomized Controlled Trial.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. We investigated whether underwater endoscopic mucosal resection (UEMR) is superior to CEMR for large (20-40mm) sessile or flat colorectal polyps. METHODS: In this prospective randomized controlled study, patients with sessile or flat colorectal polyps between 20 and 40 mm in size were randomly assigned to UEMR or CEMR. The primary outcome was the recurrence rate after 6 months. Secondary outcomes included en bloc and R0 resection rates, number of resected pieces, procedure time, and adverse events. RESULTS: En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group (P = .045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = .025). UEMR was performed with significantly fewer pieces compared to CEMR (2 pieces: 45.5% UEMR vs 17.7% CEMR; P = .001). The overall recurrence rate did not differ between both groups (P = .253); however, subgroup analysis showed a significant difference in favor of UEMR for lesions of >30 mm to ≤40 mm in size (P = .031). The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P < .001). Adverse events did not differ between both groups (P = .611). CONCLUSIONS: UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to ≤40 mm in size. UEMR should be considered for the endoscopic resection of large colorectal polyps.

Quantitative analysis of submucosal excision depth in endoscopic resection for early Barrett's cancer.

BACKGROUND : Following endoscopic resection of early-stage Barrett's esophageal adenocarcinoma (BEA), further oncologic management then fundamentally relies upon the accurate assessment of histopathologic risk criteria, which requires there to be sufficient amounts of submucosal tissue in the resection specimens. METHODS : In 1685 digitized tissue sections from endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) performed for 76 early BEA cases from three experienced centers, the submucosal thickness was determined, using software developed in-house. Neoplastic lesions were manually annotated. RESULTS : No submucosa was seen in about a third of the entire resection area (mean 33.8 % [SD 17.2 %]), as well as underneath cancers (33.3 % [28.3 %]), with similar results for both resection methods and with respect to submucosal thickness. ESD results showed a greater variability between centers than EMR. In T1b cancers, a higher rate of submucosal defects tended to correlate with R1 resections. CONCLUSION : The absence of submucosa underneath about one third of the tissue of endoscopically resected BEAs should be improved. Results were more center-dependent for ESD than for EMR. Submucosal defects can potentially serve as a parameter for standardized reports.

Endoscopic prediction of submucosal invasion in Barrett's cancer with the use of artificial intelligence: a pilot study.

BACKGROUND: The accurate differentiation between T1a and T1b Barrett's-related cancer has both therapeutic and prognostic implications but is challenging even for experienced physicians. We trained an artificial intelligence (AI) system on the basis of deep artificial neural networks (deep learning) to differentiate between T1a and T1b Barrett's cancer on white-light images. METHODS: Endoscopic images from three tertiary care centers in Germany were collected retrospectively. A deep learning system was trained and tested using the principles of cross validation. A total of 230 white-light endoscopic images (108 T1a and 122 T1b) were evaluated using the AI system. For comparison, the images were also classified by experts specialized in endoscopic diagnosis and treatment of Barrett's cancer. RESULTS: The sensitivity, specificity, F1 score, and accuracy of the AI system in the differentiation between T1a and T1b cancer lesions was 0.77, 0.64, 0.74, and 0.71, respectively. There was no statistically significant difference between the performance of the AI system and that of experts, who showed sensitivity, specificity, F1, and accuracy of 0.63, 0.78, 0.67, and 0.70, respectively. CONCLUSION: This pilot study demonstrates the first multicenter application of an AI-based system in the prediction of submucosal invasion in endoscopic images of Barrett's cancer. AI scored equally to international experts in the field, but more work is necessary to improve the system and apply it to video sequences and real-life settings. Nevertheless, the correct prediction of submucosal invasion in Barrett's cancer remains challenging for both experts and AI.

Complication risk despite preventive endoscopic measures in patients undergoing endoscopic mucosal resection of large duodenal adenomas.

BACKGROUND : Endoscopic mucosal resection (EMR) is the standard treatment of ampullary and nonampullary duodenal adenomas. EMR of large (10-29 mm) and giant (≥ 30 mm) lesions carries a risk of complications such as delayed bleeding and perforation. Prospective data on duodenal EMR are scarce. This study aimed to evaluate the efficacy of endoscopic procedures (clipping and coagulation of visible vessels) to prevent complications after EMR of large and giant lesions. METHODS : 110 patients with 118 adenomas (29 ampullary and 89 nonampullary) were included prospectively. RESULTS : 15 lesions were small (12.7 %), 68 were large (57.6 %), and 35 were giant (29.7 %). Endoscopic prevention of delayed complications was performed in 81.4 % (n = 96) of all lesions and 94.3 % (n = 33) of giant lesions. Complete resection was achieved in 111 lesions (94.1 %). Complications were 22 delayed bleedings (18.6 %), 3 intraprocedural perforations (2.5 %), 2 delayed perforations (1.7 %), and 1 stricture (0.8 %). Major complications were associated with lesions size ≥ 30 mm (28.6 % vs. 9.6 %; P = 0.02) and ampullary adenomas (27.6 % vs. 11.2 %; P = 0.07). All minor bleeding and 75 % of major bleeding episodes were treated endoscopically; 25 % of major bleedings needed radiologic embolization. Two fatal courses were observed when delayed perforation occurred after EMR of giant lesions. Residual adenoma was detected in 20.4 % at first follow-up. CONCLUSIONS : EMR of giant duodenal neoplasia carries a substantial risk of major complications and recurrences. Resection technique and prevention of delayed complications need to be improved. Further measures should be evaluated in randomized studies.

[Screening gastroscopy in Germany - first results of the pilot phase of the Prä-GIT study]. / Vorsorgegastroskopie in Deutschland ­ erste Ergebnisse der Pilotphase der Prä-GIT-Studie.

The primary aim of the Prä-GIT study is to collect information on the prevalence and course of precancerous and early malignant lesions in the upper GIT (uGIT) as well as risk factors associated with these lesions in asymptomatic individuals. Study participants presenting for a screening colonoscopy will undergo an additional endoscopic examination of the uGIT in the same session. 5000 participants in 30 endoscopy clinics in Bayern will be included. The pilot study presented here was performed to test the main study protocol as well as the acceptance of an additional uGIT endoscopic examination. METHODS: Three endoscopy clinics in Bayern took part in the three-month pilot study between October and December 2018. Patients presenting for a screening colonoscopy in these clinics were offered an additional endoscopic examination of the uGIT which was performed according to a standard operating procedure (SOP). Furthermore, data on dietary habits and lifestyle, as well as biological samples, were collected. RESULTS: 52 participants were included in three clinics in Altötting, Augsburg and Regensburg. The average age was 63.4 years. The average time spent per uGIT endoscopy was 11 minutes. No complications occurred. One participant showed a polyp of the recessus piriformis. Refluxesophagitis was seen in 21 participants, four participants had Barrett's esophagus with histological evidence of low-grade dysplasia in one patient, and an esophageal polyp with low-grade dysplasia was seen in one participant. Helicobacter-pylori gastritis was documented in 12 participants. Corpus-dominant atrophy was described in one participant, while a duodenal adenoma with low-grade dysplasia was seen in two participants. 100 % and 89 % of study participants gave a blood or a stool sample, respectively. All participants answered the questionnaire on dietary and lifestyle habits. CONCLUSION: The Prä-GIT study was designed to generate a database for premalignant and early cancerous lesions of the uGIT in Germany in asymptomatic individuals presenting for a regular screening colonoscopy. The current pilot study has delivered important insights into the feasibility of the main study protocol. Additionally, the pilot study has shown a high rate of acceptance of an additional uGIT examination in this study population.

Favorable radiation field decrease in gastric marginal zone lymphoma : Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL).

PURPOSE: Long-term impact of stage-adapted field reduction in a large cohort of gastric marginal zone lymphoma (gMZL) patients treated conservatively with curative radiation therapy (RT). PATIENTS AND METHODS: Prospective analysis of paper records of 290 patients with stage IE-IIE gMZL, treated in 78 radiotherapeutic institutions in Germany from 1992-2013. Stage-adapted radiation fields decreased from extended field (EF) to involved field (IF) over the course of three consecutive prospective trials of the German Study Group on Gastrointestinal Lymphoma (DSGL). Treatment results were compared between the three cohorts. RESULTS: Overall collective with median age of 60 years, slight male predominance (m:f = 1.1:1) and ratio of disease stage I:stage II = 2.1:1. Median follow-up 6.4 years in total: 13.0 years in the first gastrointestinal study (GIT 1992), 8.2 years in the second (GIT 1996) and 4.7 years in the third study (DSGL 01/2003). Stage-adapted radiation field decrease together with further technological development led to reduced relative frequencies of acute/chronic adverse effects and until now was accompanied by lower disease recurrence. The third study design with smallest field size (IF in stage I, locoregional EF in stage II) achieved the best survival outcome at the 5­year follow-up (overall survival 92.7%, event-free survival 89.5% and lymphoma-specific survival 100.0%). Disease relapse observed in 10 patients. Cumulative incidence of disease-specific death was 1.7% of the followed patients. Primary disease stage associated with lymphoma-specific survival. CONCLUSION: Stage-adapted reduction towards IF in gMZL resulted in favorable adverse effects, local control and survival rates. These results support further decreases in modern RT of gMZL.