Endoscopic Submucosal Dissection for Early Gastric Cancer Exceeding Expanded Criteria-Long-Term Outcomes from the German ESD Registry.

Background and aims: Endoscopic submucosal dissection (ESD) has become a standard treatment for early gastric cancer (EGC), often fulfilling guideline criteria (GC) or expanded criteria (EC). When lesions exceed the EC, surgical resection is recommended. However, a subgroup of these patients are not treated surgically. The aim of this study was to investigate the long-term follow-up of patients after ESD for EGC outside the EC (out of indication; OI). Methods: Patients who were included in the prospective German ESD registry were analyzed when ESD was performed for EGC. Patients were stratified in three groups according to histopathological features (GC, EC and OI). The results were evaluated in terms of patient characteristics, procedure characteristics and follow-up data. Results: Over a 48-month period, 195 patients from 14 German centers were included. In total, 71 lesions (36.4%) met the guideline criteria, 70 lesions (35.9%) corresponded to the expanded criteria and 54 lesions (27.7%) turned out to be OI. The R0 resection rate was significantly higher for the GC and EC groups than for the OI group (94.4% vs. 84.3% vs. 55.6%, p < 0.001). Additional surgery was not performed in 72% (39/54) of patients in the OI group. During a mean follow-up of 37 months, overall survival showed no significant difference between the EC and OI groups when endoscopic follow-up was performed without additional surgery (p = 0.064). Conclusions: The results show that a good long-term survival can be achieved after ESD for patients with OI lesions without additional surgery. The treatment decision has to be made on an individual basis, taking the patient's comorbidities and the risk of surgical resection into account.

Cold Versus Hot Snare Endoscopic Resection of Large Nonpedunculated Colorectal Polyps: Randomized Controlled German CHRONICLE Trial.

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) is standard therapy for nonpedunculated colorectal polyps ≥20 mm. It has been suggested recently that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AEs), but evidence from a randomized trial is missing. METHODS: In this randomized controlled multicentric trial involving 19 centers, nonpedunculated colorectal polyps ≥20 mm were randomly assigned to cold or hot EMR. The primary outcome was major AE (eg, perforation or postendoscopic bleeding). Among secondary outcomes, major AE subcategories, postpolypectomy syndrome, and residual adenoma were most relevant. RESULTS: Between 2021 and 2023, there were 396 polyps in 363 patients (48.2% were female) enrolled for the intention-to-treat analysis. Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001; odds ratio [OR], 0.12; 95% CI, 0.03-0.54). Rates for perforation and postendoscopic bleeding were significantly lower in the cold group, with 0% vs 3.9% (P = .007) and 1.0% vs 4.4% (P = .040). Postpolypectomy syndrome occurred with similar frequency (3.1% vs 4.4%; P = .490). After cold resection, residual adenoma was found more frequently, with 23.7% vs 13.8% (P = .020; OR, 1.94; 95% CI, 1.12-3.38). In multivariable analysis, lesion diameter of ≥4 cm was an independent predictor both for major AEs (OR, 3.37) and residual adenoma (OR, 2.47) and high-grade dysplasia/cancer for residual adenoma (OR, 2.92). CONCLUSIONS: Cold resection of large, nonpedunculated colorectal polyps appears to be considerably safer than hot EMR; however, at the cost of a higher residual adenoma rate. Further studies have to confirm to what extent polyp size and histology can determine an individualized approach. German Clinical Trials Registry (Deutsches Register Klinischer Studien), Number DRKS00025170.

[Rapid growth and malignant transformation of a mucinous cystic neoplasm during pregnancy - a case report]. / Massive Größenprogredienz und maligne Transformation einer muzinös-zystischen Neoplasie des Pankreas in der Schwangerschaft ­ ein Fallbericht.

BACKGROUND: Mucinous-cystic neoplasms (MCN) account for 10% of all pancreatic cystic lesions. They are found almost exclusively in females. MCN have an ovarian-like stroma and often estrogen and progesterone receptors. During pregnancy, they can massively increase in size and transform into malignancy. CASE REPORT: We report on a 29-year-old woman in whom a 35mm cyst in the pancreatic tail had been diagnosed several years ago. After workup the lesions had been classified as a pseudocyst. During pregnancy, the cyst massively increased in size and finally was resected. Histology showed a mucinous-cystic neoplasia with focal malignant transformation. CONCLUSION: Cystic neoplasms of the pancreas require a differentiated management. While overtreatment should be avoided, malignant transformation always merits consideration - in particular if the cystic lesion is located in the pancreatic tail. Women with suspected MCN or cystic pancreatic lesions of uncertain etiology should be informed about the (rare) risk of a malignant transformation of an MCN and should be closely monitored during pregnancy.

The genetic regulation of the gastric transcriptome is associated with metabolic and obesity-related traits and diseases.

Tissue-specific gene expression and gene regulation lead to a better understanding of tissue-specific physiology and pathophysiology. We analyzed the transcriptome and genetic regulatory profiles of two distinct gastric sites, corpus and antrum, to identify tissue-specific gene expression and its regulation. Gastric corpus and antrum mucosa biopsies were collected during routine gastroscopies from up to 431 healthy individuals. We obtained genotype and transcriptome data and performed transcriptome profiling and expression quantitative trait locus (eQTL) studies. We further used data from genome-wide association studies (GWAS) of various diseases and traits to partition their heritability and to perform transcriptome-wide association studies (TWAS). The transcriptome data from corpus and antral mucosa highlights the heterogeneity of gene expression in the stomach. We identified enriched pathways revealing distinct and common physiological processes in gastric corpus and antrum. Furthermore, we found an enrichment of the single nucleotide polymorphism (SNP)-based heritability of metabolic, obesity-related, and cardiovascular traits and diseases by considering corpus- and antrum-specifically expressed genes. Particularly, we could prioritize gastric-specific candidate genes for multiple metabolic traits, like NQO1 which is involved in glucose metabolism, MUC1 which contributes to purine and protein metabolism or RAB27B being a regulator of weight and body composition. Our findings show that gastric corpus and antrum vary in their transcriptome and genetic regulatory profiles indicating physiological differences which are mostly related to digestion and epithelial protection. Moreover, our findings demonstrate that the genetic regulation of the gastric transcriptome is linked to biological mechanisms associated with metabolic, obesity-related, and cardiovascular traits and diseases. NEW & NOTEWORTHY We analyzed the transcriptomes and genetic regulatory profiles of gastric corpus and for the first time also of antrum mucosa in 431 healthy individuals. Through tissue-specific gene expression and eQTL analyses, we uncovered unique and common physiological processes across both primary gastric sites. Notably, our findings reveal that stomach-specific eQTLs are enriched in loci associated with metabolic traits and diseases, highlighting the pivotal role of gene expression regulation in gastric physiology and potential pathophysiology.

Endoscopic Treatment of T1 Colorectal Cancer.

Commonly accepted criteria for curative resection of T1 colorectal cancer include R0 resection with horizontal and vertical clear margins (R0), absence of lympho-vascular or vessel infiltration (L0, V0), a low to moderate histological grading (G1/2), low tumor cell budding, and limited (<1000 µm) infiltration into the submucosa. However, submucosal infiltration depth in the absence of other high-risk features has recently been questioned as a high-risk situation for lymph-node metastasis. Consequently, endoscopic resection techniques should focus on the acquisition of qualitatively and quantitively sufficient submucosal tissue. Here, we summarize the current literature on lymph-node metastasis risk after endoscopic resection of T1 colorectal cancer. Moreover, we discuss different endoscopic resection techniques with respect to the quality of the resected specimen.

Predictive Factors for the Outcome of Unsupervised Endoscopic Submucosal Dissection During the Initial Learning Curve with Prevalence-Based Indication.

BACKGROUND: For an adequate educational strategy of ESD in non-Asian settings with prevalence-based indication it is essential to define adequate lesions, suitable for the beginner without on-site expert-supervision. AIMS: We analyzed possible predictors for outcome parameters of effectiveness and safety during the initial learning curve. METHODS: The first 120 ESDs of four operators (n = 480), performed between 2007 and 2020 in four tertiary hospitals, were enrolled. Uni-/multivariable regression analysis was done with sex, age, pretreated lesion, lesion size, organ, and organ-based localization as possible independent predictors for en bloc resection (EBR), complication, and resection speed. RESULTS: Rates of EBR, complication, and resection speed were 84.5%, 14.2%, and 6.20 (± 4.45) cm2/h. Independent predictors for EBR were pretreated lesion (OR 0.27 [0.13-0.57], p < 0.001) and non-colonic ESD (OR 2.29 [1.26-4.17] (rectum)/5.72 [2.36-13.89] (stomach)/7.80 [2.60-23.42] (esophagus), p < 0.001), for complication pretreated lesion (OR 3.04 [1.46-6.34], p < 0.001) and lesion size (OR 1.02 [1.004-1.04], p = 0.012) and for resection speed pretreated lesion (RC - 3.10 [- 4.39 to - 1.81], p < 0.001), lesion size (RC 0.13 [0.11-0.16], p < 0.001) and male patient (RC - 1.11 [- 1.85 to - 0.37], p < 0.001). We found no significant difference in the incidence of technically unsuccessful resections in esophageal (1/84), gastric (3/113), rectal (7/181), and colonic (3/101) ESDs (p = 0.76). Technical failure was mainly caused by complication and fibrosis/pretreatment. CONCLUSION: During the initial learning curve of an unsupervised ESD program with prevalence-based indication, pretreated lesions and colonic ESDs should be avoided. In contrast, lesion size and organ-based localizations have less predictive value for the outcome.

Characteristics and endoscopic treatment of interventional and non-interventional iatrogenic colorectal perforations in centers with high endoscopic expertise: a retrospective multicenter study.

BACKGROUND: Iatrogenic colorectal perforation is a rare event with a relevant mortality and the need for surgical therapy in around ¾ of cases. METHODS: In this retrospective multicentric cohort study iatrogenic colorectal perforations from 2004 to 2021 were analyzed. Primary outcome parameters were incidence and clinical success of 1st line endoscopic treatment. Comparative analysis of interventional and non-interventional perforations was performed and predictors for clinical success of endoscopic therapy were identified. RESULTS: From 103,570 colonoscopies 213 (0.2%) iatrogenic perforations were identified. 68.4% were interventional (80 during polypectomy/EMR, 54 during ESD and 11 for other reasons) and 31.6% non-interventional perforations (39 by the tip, 19 by the shaft, 7 by inversion, two by biopsy and one by distension). Incidence of 1st line endoscopic therapy was 61.0% and clinical success 81.5%. Other non-surgical therapies were conducted in 8.9% with clinical success in 94.7% of cases. In interventional perforations both incidence and clinical success of 1st line endoscopic therapy were significantly higher compared to non-interventional perforations [71.7% vs. 38.2% (p < 0.01) resp. 86.5% vs. 61.5% (p < 0.01)]. Mortality was 2.3% and significantly lower in the group of interventional perforations (0.7% vs. 5.9%, p = 0.037). Multivariable analysis revealed perforation size < 5 mm as only independent predictor for clinical success of 1st line endoscopic treatment [OR 14.85 (1.57-140.69), p = 0.019]. CONCLUSIONS: Endoscopic therapy is treatment of choice in the majority of iatrogenic colorectal perforations. In case of interventional perforations it is highly effective but only a minority of non-interventional perforations are good candidates for endoscopic treatment.

Learning curve of endoscopic submucosal dissection (ESD) with prevalence-based indication in unsupervised Western settings: a retrospective multicenter analysis.

BACKGROUND AND AIMS: As there is still no consensus about the adequate training strategy for ESD in Western countries, we evaluated unsupervised prevalence-based learning curves including detailed organ-specific subgroup analysis. METHODS: The first 120 ESDs of four operators (n = 480) were divided into three groups (1: ESD 1-40, 2: ESD 41-80, 3: ESD 81-120). Outcome parameters were rates of technical success, en bloc and R0 resection, the resection speed, rates of conversion to EMR, curative resection, adverse events, surgery due to adverse events, and recurrence. In addition, we analyzed the achievement of quality benchmarks indicating levels of expertise. RESULTS: After exclusion of pretreated lesions, 438 procedures were enrolled in the final analysis. Technical success rates were > 96% with significant improvements regarding rate of en bloc resection (from 82.6 to 91.2%), resection speed (from 4.54 to 7.63 cm2/h), and rate of conversion to EMR (from 22.0 to 8.1%). No significant differences could be observed for rates of R0 resection (65.9 vs. 69.6%), curative resection (55.8 vs. 55.7%), adverse events (16.3 vs. 11.7%), surgery due to adverse events (1.5 vs. 1.3%), and recurrence (12.5 vs. 4.5%). Subgroup and benchmark analysis revealed an improvement in esophageal, gastric, and rectal ESD with achievement of competence levels for the esophagus and stomach within 80 and most of the benchmarks for proficiency level within 120 procedures. Some of the benchmarks could also be achieved in rectal ESD. CONCLUSIONS: This trial confirms safety and feasibility of unsupervised ESD along the initial learning curve with prevalence-based indication and exclusion of colonic cases.

German guideline diverticular disease/diverticulitis: Part II: Conservative, interventional and surgical management.

Diverticulosis and diverticular disease are ranked among the most common gastroenterological diseases and conditions. While for many years diverticulitis was found to be mainly an event occurring in the elder population, more recent work in epidemiology demonstrates increasing frequency in younger subjects. In addition, there is a noticeable trend towards more complicated disease. This may explain the significant increase in hospitalisations observed in recent years. It is not a surprise that the number of scientific studies addressing the clinical and socioeconomic consequences in the field is increasing. As a result, diagnosis and conservative as well as surgical management have changed in recent years. Diverticulosis, diverticular disease and diverticulitis are a complex entity and apparently an interdisciplinary challenge. To meet theses considerations the German Societies for Gastroenterology and Visceral Surgery decided to create joint guidelines addressing all aspects in a truely interdisciplinary fashion. The aim of the guideline is to summarise and to evaluate the current state of knowledge on diverticulosis and diverticular disease and to develop statements as well as recommendations to all physicians involved in the management of patients with diverticular disease.

Artificial Intelligence in the Management of Barrett's Esophagus and Early Esophageal Adenocarcinoma.

Esophageal adenocarcinoma is increasing in incidence and is the most common subtype of esophageal cancer in Western societies. The stepwise progression of Barrett´s metaplasia to high-grade dysplasia and invasive adenocarcinoma provides an opportunity for screening and surveillance. There are important unresolved issues, which include (i) refining the definition of the screening population in order to avoid unnecessary invasive diagnostics, (ii) a more precise prediction of the (very heterogeneous) individual progression risk from metaplasia to invasive cancer in order to better tailor surveillance recommendations, (iii) improvement of the quality of endoscopy in order to reduce the high miss rate for early neoplastic lesions, and (iv) support for the diagnosis of tumor infiltration depth in order to guide treatment decisions. Artificial intelligence (AI) systems might be useful as a support to better solve the above-mentioned issues.

Endoscopic submucosal resection: a technique using novel devices for incision and resection of neoplastic lesions.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established techniques for treatment of superficial gastrointestinal neoplasia. Limitations of EMR are low en bloc resection rates for larger lesions, resulting in frequent recurrences. Major disadvantages of ESD are technical difficulty and long procedure times. We evaluated technical feasibility and safety of newly designed devices for en bloc resection of lesions measuring 20-40 mm in a technique called endoscopic submucosal resection (ESR). METHODS: This case series included 93 lesions from different locations (11 stomach, 25 colon, 57 rectum) with a median size of 29 mm (range 10-70). ESR was performed using two novel instruments for circumferential mucosal incision and deep submucosal resection, respectively. RESULTS: Resection by ESR was feasible in all cases. En bloc and R0 rates were insufficient when ESR was attempted without prior circumferential mucosal incision, but were 70 % and 63 %, respectively, when mucosal incision was done before application of the submucosal resection device. We observed three complications (two delayed bleedings, one microperforation) but no cases of emergency surgery or 30-day mortality. CONCLUSIONS: Results demonstrated feasibility and excellent safety of ESR using two novel devices for en bloc resection of early gastrointestinal neoplasia. The technique offered relative technical ease and high efficacy.

Current Trends in Endoscopic Diagnosis and Treatment of Early Esophageal Cancer.

Diagnosis of esophageal adenocarcinoma mostly occurs in the context of reflux disease or surveillance of Barrett's metaplasia. Optimal detection rates are obtained with high definition and virtual or dye chromoendoscopy. Smaller lesions can be treated with endoscopic mucosal resection. Endoscopic submucosal dissection (ESD) is an option for larger lesions. Endoscopic resection is considered curative (i.e., without significant risk of lymph node metastasis) if histopathology confirms en bloc and R0 resection of a well-differentiated (G1/2) tumor without infiltration of lymphatic or blood vessels and the maximal submucosal infiltration depth is 500µm. Ablation of remaining Barrett's metaplasia is important, to reduce the risk of metachronous cancer. Esophageal squamous cell cancer is associated with different risk factors, and most of the detected lesions are diagnosed during upper gastrointestinal endoscopy for other indications. Virtual high definition and dye chromoendoscopy with Lugol's solution are used for screening and evaluation. ESD is the preferred resection technique. The criteria for curative resection are similar to Barrett's cancer, but the maximum infiltration depth must not exceed lamina propria mucosae. Although a submucosal infiltration depth of up to 200 µm carries a substantial risk of lymph node metastasis, ESD combined with adjuvant chemo-radiotherapy gives excellent results. The complication rates of endoscopic resection are low, and the functional outcomes are favorable compared to surgery.

Topical oro-dispersible budesonide tablets for stricture prevention after near circumferential ESD for esophageal squamous cell cancer - a case report.

BACKGROUND: Endoscopic resection is the treatment of choice for early esophageal cancers. However, resections comprising more than 70-80 % of the circumference are associated with a high risk of stricture formation. Currently, repetitive local injections and/or systemic steroids are given for prevention. CASE REPORT: We present here the case of a 78-year-old male patient who had a near circumferential endoscopic submucosal dissection for a pT1a mm, L0, V0, R0, G2 esophageal squamous cell cancer. At the end of endoscopic resection, 80 mg of triamcinolone was injected locally. The patient was then treated with oro-dispersible budesonide tablets (2 × 1 mg/day) and nystatin (4 × 100 000 I.E.) for 8 weeks. This treatment resulted in complete healing without any stricture formation and did not result in any complications. DISCUSSION: Treatment with orodispersible budesonide tablets could help prevent strictures after large endoscopic resections in the esophagus.

Long-term follow-up after colorectal endoscopic submucosal dissection in 182 cases.

Background and study aims We previously reported a case series of our first 182 colorectal endoscopic submucosal dissections (ESDs). In the initial series, 155 ESDs had been technically feasible, with 137 en bloc resections and 97 en bloc resections with free margins (R0). Here, we present long-term follow-up data, with particular emphasis on cases where either en bloc resection was not achieved or en bloc resection resulted in positive margins (R1). Patients and methods Between September 2012 and October 2015, we performed 182 consecutive ESD procedures in 178 patients (median size 41.0 ±â€Š17.4 mm; localization rectum vs. proximal rectum 63 vs. 119). Data on follow-up were obtained from our endoscopy database and from referring physicians. Results Of the initial cohort, 11 patients underwent surgery; follow-up data were available for 141 of the remaining 171 cases (82,5 %) with a median follow-up of 2.43 years (range 0.15-6.53). Recurrent adenoma was observed in 8 patients (n = 2 after margin positive en bloc ESD; n = 6 after fragmented resection). Recurrence rates were lower after en bloc resection, irrespective of involved margins (1.8 vs. 18,2 %; P < 0.01). All recurrences were low-grade adenomas and could be managed endoscopically. Conclusions The rate of recurrence is low after en bloc ESD, in particular if a one-piece resection can be achieved. Recurrence after fragmented resection is comparable to published data on piecemeal mucosal resection.

Endoscopic full-thickness resection using an over-the-scope device for treatment of recurrent / residual colorectal neoplasia: a single-center case series.

BACKGROUND: Endoscopic mucosal resection (EMR) in piecemeal technique is the treatment standard for larger flat or sessile colorectal lesions. The method is burdened by a high recurrence rate mostly presenting as difficult to resect lesions. In these situations, endoscopic full thickness resection (EFTR) with an over-the-scope device offers the option of complete resection despite scar formation. METHODS: We conducted a retrospective case review of 30 consecutive EFTR interventions on small (< 20 mm), difficult to resect recurrent / residual colorectal neoplastic lesions treated by EFTR. RESULTS: EFTR was technically feasible in 28/30 (93,3%) of the cases with an R0 resection in 24/30 (80%) and a median procedure time (marking to full thickness resection) of 34,5 min (11-120). After the first 15 procedures, the per-protocol rate increased from 13/15 to 15/15 and the R0 resection rate increased from 9/15 (69,2%) to 15/15 (100,0%; p < 0.01). One patient suffered from a delayed perforation the day after the procedure and needed emergency surgery (3,6%). Minor bleeding occurred in 3/28 patients (10,7%) and post-interventional fever in one patient (3,6%). The 30-day mortality rate was 0%. CONCLUSIONS: EFTR with an over-the-scope device is a useful method for endoscopic resection of difficult to treat recurrent or residual colorectal neoplasia after previous endoscopic therapy. High R0 resection rates were observed after a relatively short learning curve. The complication rate in this series seems acceptable given the complexity of the resected lesions.

Implementation of endoscopic submucosal dissection for early upper gastrointestinal tract cancer after primary experience in colorectal endoscopic submucosal dissection.

Background Current guidelines recommend endoscopic submucosal dissection (ESD) as a treatment option for early cancers of the upper gastrointestinal tract with absent or minimal risk of lymph node metastasis. However, due to the low prevalence of these entities, it is difficult to achieve a competence level for ESD of upper gastrointestinal tract cancers in the Western World. Here, we present single-center data on the implementation of upper gastrointestinal ESD after previous experience with 89 colorectal ESD cases. Methods Retrospective case series of 39 consecutive patients with early cancers of the esophagus (n = 13) or cardia and stomach (n = 26) treated with ESD over a 4-year period. Results ESD was technically feasible in all cases with en bloc, R0, and curative resection rates of 100 %, 76.9 %, and 71.8 %, respectively, and a mean procedure time of 100 minutes (30 - 360 minutes). After an initial 20 procedures, the R0 and curative resection rates increased from 65.0 % to 89.5 %, and from 60.0 % to 84.2 %, respectively. Complications were observed in four patients (10.3 %): three perforations, one case of delayed bleeding, and one esophageal stricture. No case required emergency surgery; the 30-day mortality rate was 0 %. Conclusion In this modest case series from Europe, we observed an effectiveness and complication rate for ESD for early esophageal and gastric cancer that are comparable to other series from Europe but also to more abundant data from Asia. The results indicate that even small numbers of upper gastrointestinal cancers can be managed adequately in centers with expertise in colorectal ESD.

Endoscopic resection techniques for colorectal neoplasia: Current developments.

Endoscopic polypectomy and endoscopic mucosal resection (EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller (< 5mm) polyps and is possibly also suitable for the removal of non-cancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection (ESD) offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer. The latest addition to endoscopic resection techniques is endoscopic full-thickness resection with specifically developed devices for flexible endoscopy. This method is very useful for the treatment of smaller difficult-to-resect lesions, e.g., recurrence with scar formation after previous endoscopic resections.