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.

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.

Endoscopic neo-anastomosis by Rendez-vous technique for the treatment of complete occlusion of bilioenteric anastomoses and distal bile ducts (case series).

BACKGROUND AND AIMS: The complete occlusion of bilioenteric anastomoses is a rare and challenging clinical condition. Repeated surgery is burdened with technical difficulties and significant morbidity. We report the first series of completely occluded bilioenteric anastomoses resp. distal bile duct successfully treated by simultaneous percutaneous and retrograde endoscopic interventions. PATIENTS AND METHODS: This case series includes 4 patients with obstructive jaundice and/or recurring cholangitis and pain due to complete fibrotic occlusion of a hepaticojejunostomy (3 patients) and the distal bile duct (1 patient). After performing PTCD and stepwise dilation of the biliocutaneous tract, we tried to approach the occluded anastomosis from 2 sides by simultaneous percutaneous cholangioscopy and peroral device-assisted enteroscopy/duodenoscopy. By cutting through the separating tissue layer with a needle knife under endoscopic and fluoroscopic control using diaphanoscopy, a new anastomosis should be established followed by dilation of the neoanastomosis with subsequent percutaneous transhepatic drainage for a minimum of 1 year to prevent re-occlusion. RESULTS: The Rendez-vous maneuver was successful in 3/4 cases. In one case, the retrograde access to the anastomosis failed, so the neoanastomosis was cut under cholangioscopic and fluoroscopic guidance only. The neoanastomosis could be established successfully in all 4 cases. Jaundice, cholangitis, and pain disappeared. Minor periinterventional adverse events were cholangitis (n = 1) and pneumonia (n = 1) due to aspiration, which could be managed conservatively. No serious adverse events were observed, and no re-occlusion of any neoanastomosis occurred during the follow-up before and after removal of the percutaneous drainage. CONCLUSION: Simultaneous percutaneous cholangioscopy and device-assisted enteroscopy/duodenoscopy with endoscopic creation of a neoanastomosis is a possible concept for the treatment of completely occluded bilioenteric anastomoses and distal bile ducts. This case series confirms the feasibility, safety, and long-term effectiveness of this treatment.

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.

Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline.

1 ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic resonance cholangiography (MRC) should be preferred over endoscopic retrograde cholangiopancreatography (ERCP).Moderate quality evidence, strong recommendation. 2 ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is equivocal or contraindicated in patients with persisting clinical suspicion of PSC. The risks of ERCP have to be weighed against the potential benefit with regard to surveillance and treatment recommendations.Low quality evidence, weak recommendation. 6 ESGE/EASL suggest that, in patients with an established diagnosis of PSC, MRC should be considered before therapeutic ERCP.Weak recommendation, low quality evidence. 7 ESGE/EASL suggest performing endoscopic treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies) of suspected significant strictures identified at MRC in PSC patients who present with symptoms likely to improve following endoscopic treatment.Strong recommendation, low quality evidence. 9 ESGE/EASL recommend weighing the anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a case-by-case basis.Strong recommendation, moderate quality evidence.Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation.Strong recommendation, low quality evidence. 16 ESGE/EASL suggest routine administration of prophylactic antibiotics before ERCP in patients with PSC.Strong recommendation, low quality evidence. 17 EASL/ESGE recommend that cholangiocarcinoma (CCA) should be suspected in any patient with worsening cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant stricture, particularly with an associated enhancing mass lesion.Strong recommendation, moderate quality evidence. 19 ESGE/EASL recommend ductal sampling (brush cytology, endobiliary biopsies) as part of the initial investigation for the diagnosis and staging of suspected CCA in patients with PSC.Strong recommendation, high quality evidence.

EUS Needle Identification Comparison and Evaluation study (with videos).

BACKGROUND AND AIMS: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. METHODS: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. RESULTS: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). CONCLUSIONS: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity.

Intraductal biliopancreatic imaging: European Society of Gastrointestinal Endoscopy (ESGE) technology review.

This technology review expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) on the available techniques for intraductal biliopancreatic imaging. The three cholangioscopy techniques are described: the "dual-operator" and " single-operator" mother-baby approaches using dedicated instruments, and the "direct" technique using currently available ultrathin gastroscopes. The mother-baby method is standardized and reproducible, while direct cholangioscopy is technically demanding and its safety requires further evaluation. As well as direct visualization of the bile ducts, cholangioscopy has the further advantage of allowing targeted biopsy. Image quality is still suboptimal for single-operator cholangioscopy, while the other techniques have achieved adequately detailed imaging. The costs of mother-baby cholangioscopy are high and its application in clinical practice should be restricted to selected cases (i.e. indeterminate biliary strictures/intraluminal lesions, difficult biliary stones) and to the setting of tertiary care centers. Peroral pancreatoscopy may find an indication in situations where other imaging modalities (mainly EUS) are inconclusive (i.e. delineation of main duct intraductal papillary mucinous neoplasia extension, sampling of indeterminate main pancreatic duct strictures). Intraductal ultrasonography (IDUS) has a poorer performance than EUS in the staging of pancreatic malignancies and can increase the risk of pancreatitis. A promising indication for IDUS could be the evaluation of indeterminate biliary strictures and ampullary tumors. Probe-based confocal laser endomicroscopy (pCLE) of the bile ducts is a difficult and expensive technique. Appropriate training needs to be established, since interpretation of images is challenging. pCLE can be an important diagnostic tool in the setting of indeterminate biliary strictures.

Impact of the quality of bowel cleansing on the efficacy of colonic cancer screening: a prospective, randomized, blinded study.

OBJECTIVES: Efficacy of two low volume bowel cleansing preparations, polyethylene glycol plus ascorbate (PEG + Asc) and sodium picosulfate/magnesium citrate (NaPic/MgCit), were compared for polyp and adenoma detection rate (PDR and ADR) and overall cleansing ability. Primary endpoint was PDR (the number of patients with ≥ 1 polypoid or flat lesion recorded by the colonoscopist). METHODS: Diagnostic, surveillance or screening colonoscopy patients were enrolled into this investigator-blinded, multi-center Phase IV study and randomized 1:1 to receive PEG + Asc (administered the evening before and the morning of colonoscopy, per label) or NaPic/MgCit (administered in the morning and afternoon the day before colonoscopy, per label). The blinded colonoscopist documented any lesion and assessed cleansing quality (Harefield Cleansing Scale). RESULTS: Of 394 patients who completed the study, 393 (PEG + Asc, N = 200; NaPic/MgCit, N = 193) had a colonoscopy. Overall PDR for PEG+Asc versus NaPic/MgCit was 51.5% versus 44.0%, p = 0.139. PDR and ADR on the right side of the bowel were significantly higher with PEG + Asc versus NaPic/MgCit (PDR: 56[28.0%] versus 32[16.6%], p = 0.007; ADR: 42[21.0%] versus 23[11.9%], p = 0.015), as was detection of flat lesions (43[21.5%] versus 25[13.0%], p = 0.025). Cleansing quality was better with PEG + Asc than NaPic/MgCit (98.5% versus 57.5% considered successful cleansing). Overall, there were 132 treatment-emergent adverse events (93 versus 39 for PEG+Asc and NaPic/MgCit, respectively). These were mainly mild abdominal symptoms, all of which were reported for higher proportions of patients in the PEG+Asc than NaPic/MgCit group. Twice as many patients in the NaPic/MgCit versus the PEG + Asc group reported tolerance of cleansing solution as 'very good'. CONCLUSIONS: Compared with NaPic/MgCit, PEG + Asc may be more efficacious for overall cleansing ability, and subsequent detection of right-sided and flat lesions. This is likely attributable to the different administration schedules of the two bowel cleansing preparations, which may positively impact the detection and prevention of colorectal cancer, thereby improving mortality rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT01689792.

Diagnostics and Early Diagnosis of Esophageal Cancer.

In the esophagus two different kinds of primary neoplasias may arise: squamocellular carcinomas (SCC) and esophageal adenocarcinomas (EAC). Although both types of carcinoma are rare diseases, especially the incidence of EAC rose in the last years. The management of esophageal cancer is challenging. There are no specific symptoms of early esophageal cancers. Due to this fact, most of the esophageal cancers are found incidentally, and only 12.5% of esophageal tumors are endoscopically resectable. Gastroscopy is the gold standard for the diagnosis of esophageal cancer. The sensitivity of detecting early-stage carcinoma may be improved by adjunct techniques such as chromoendoscopy, virtual chromoendoscopy, magnification endoscopy, and other advanced endoscopic imaging techniques. The diagnosis of esophageal cancer can be verified with targeted biopsies. Accurate staging information is crucial for establishing appropriate treatment choices for esophageal cancer, while the depth of the tumor determines the feasibility of therapy. In terms of staging, endosonography, abdominal ultrasound, and computed tomography scan of the thorax and abdomen should thus be performed before initiation of therapy.

Prospective study of acute complication rates and associated risk factors in endoscopic therapy for duodenal adenomas.

BACKGROUND: Endoscopic therapy for duodenal adenomas is becoming increasingly important. However, only a few studies have been published on the topic, mainly with retrospective data. METHODS: This prospective study was carried out to determine complication rates and associated risk factors during and after endoscopic therapy for duodenal adenomas. Between May 2011 and October 2012, 50 patients (with 61 duodenal adenomas) were included. Sixty-one duodenal adenomas were resected endoscopically. Complications (e.g., bleeding, pain, fever, pancreatitis, and perforation) were recorded. Associations between bleeding and other factors--sex, age, anticoagulation, location and size of adenomas, etiology, lesion morphology, resection type, and argon plasma coagulation (APC) for bleeding prophylaxis--were then investigated. RESULTS: Bleeding was the main complication. Major bleeding occurred in four cases (6.5%) and minor bleeding in 11 (18%). One occult perforation also occurred. There was a statistically significant association between bleeding and the size of the adenoma (P = 0.012). APC for bleeding prophylaxis showed a promising trend, with an odds ratio of 0.31, reducing the bleeding risk by two-thirds in this study. However, due to the small number of six patients that received bleeding prophylaxis with APC therapy, this result was not statistically significant (P = 0.31). CONCLUSIONS: Bleeding is the main complication in endoscopic therapy for duodenal adenomas. The bleeding risk increases significantly with adenoma size. Prophylactic APC seems to reduce the bleeding rate--however, because of the relatively small number of patients treated with APC, this partial result was not statistically relevant. Due to the relevant rate of complications, endoscopic resection of duodenal adenomas is only recommended in an in-patient setting.

Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MAIN RECOMMENDATIONS: 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % - 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). CONCLUSION: Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.