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Background Endoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity of two intraductal brush cytology devices. Methods A randomized controlled trial in which consecutive patients with suspected malignant, extrahepatic biliary strictures were randomized (1:1) to a dense or conventional brush cytology device. Primary endpoint was sensitivity. Interim analysis was conducted after 50% of the patients completed follow-up. Results were interpreted by a data safety monitoring board. Results Between June 2016 and June 2021, 64 patients were randomized to the dense (27 patients, 42%) or conventional brush (37 patients, 58%). Malignancy was diagnosed in 60 patients (94%) and benign disease in 4 patients (6%). Diagnoses were confirmed by histopathology in 34 patients (53%), cytopathology in 24 patients (38%), and clinical or radiological follow up in 6 patients (9%). Sensitivity of the dense brush was 50%, compared to 44% for the conventional brush (p = 0·785). Discussion The results of this randomized controlled trial showed that the sensitivity of a dense brush is not superior to a conventional brush for diagnosing malignant extrahepatic pancreatobiliary strictures. This trial was prematurely ended for reasons of futility. Trial registration Netherlands Trial Register number; NTR5458.

Background: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American Gastroenterological Association (AGA), 2017 International Association of Pancreatology (IAP), and the 2018 European Study Group on Cystic tumours of the Pancreas (European) guidelines differ in their recommendations on indications for surgery. However, it remains unclear which guideline is most accurate in predicting advanced neoplasia in IPMN. Methods: Patients who underwent surgery were extracted from a prospective database (January 2006–January 2021). In patients with IPMN, final pathology was compared with the indication for surgery according to the guidelines. ROC-curves were calculated to determine the diagnostic accuracy for each guideline. Results: Overall, 247 patients underwent surgery for cystic lesions. In 145 patients with IPMN, 52 had advanced neoplasia, of which the AGA guideline would have advised surgery in 14 (27%), the IAP and European guideline in 49 (94%) and 50 (96%). In 93 patients without advanced neoplasia, the AGA, IAP, and European guidelines would incorrectly have advised surgery in 8 (8.6%), 77 (83%) and 71 (76%). Conclusion: The European and IAP guidelines are clearly superior in detecting advanced neoplasia in IPMN as compared to the AGA, albeit at the cost of a higher rate of unnecessary surgery. To harmonize care and to avoid confusion caused by conflicting statements, a global evidence-based guideline for PCN in collaboration with the various guidelines groups is required once the current guidelines require an update.

Background: The patients with unresectable perihilar cholangiocarcinoma require biliary drainage to relieve symptoms and allow for palliative systemic chemotherapy. The aim of this study was to establish the success, complication, and mortality rates of the initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma at presentation. Methods: In this retrospective multicenter study, patients with unresectable perihilar cholangiocarcinoma who underwent initial endoscopic or percutaneous transhepatic biliary drainage between 2002 and 2014 were included. The success of drainage was defined as a successful biliary stent or drain placement, no unscheduled reintervention within 14 days, and serum bilirubin levels 50% decrease in serum bilirubin after 14 days. Severe complications, and 90-day mortality were recorded. Results: Included were 186 patients: 161 (87%) underwent initial endoscopic biliary drainage and 25 (13%) underwent initial percutaneous transhepatic biliary drainage. The success of initial drainage was observed in 73 patients (45%) after endoscopic biliary drainage and 6 (24%) after percutaneous transhepatic biliary drainage. The reasons for an unsuccessful initial drainage were: the failure to place a drain or stent in 39 patients (21%), an unplanned reintervention within 14 days in 52 patients (28%), and the bilirubin level >50 μmol/L (or not halved) after 14 days of initial drainage in 16 patients (9%). Severe drainage-related complications occurred in 19 patients (12%) after endoscopic biliary drainage and in 3 (12%) after percutaneous transhepatic biliary drainage. Overall, 66 patients (36%) died within 90 days after initial biliary drainage. Conclusion: Initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma had a success rate of 45% and a 90-day mortality rate of 36%. Future studies for patients with perihilar cholangiocarcinoma should focus on improving biliary drainage.

PURPOSE Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A. METHODS Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound. RESULTS Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia. CONCLUSION This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.

Purpose To characterize the prevalence of missed pancreatic masses and pancreatic ductal adenocarcinoma (PDAC)-related findings on CT and MRI between pre-diagnostic patients and healthy individuals. Materials and methods Patients diagnosed with PDAC (2010–2016) were retrospectively reviewed for abdominal CT- or MRI-examinations 1 month—3 years prior to their diagnosis, and subsequently matched to controls in a 1:4 ratio. Two blinded radiologists scored each imaging exam on the presence of a pancreatic mass and secondary features of PDAC. Additionally, original radiology reports were graded based on the revised RADPEER criteria. Results The cohort of 595 PDAC patients contained 60 patients with a pre-diagnostic CT and 27 with an MRI. A pancreatic mass was suspected in hindsight on CT in 51.7% and 50% of cases and in 1.3% and 0.9% of controls by reviewer 1 (p p p p p Conclusion Radiological features as pancreatic duct dilation and interruption, and focal atrophy are common first signs of PDAC and are often missed or unrecognized. Further investigation with dedicated pancreas imaging is warranted in patients with PDAC-related radiological findings. Graphical abstract

Background: Neoadjuvant treatment for pancreatic ductal adenocarcinoma (PDAC) has increased, necessitating histopathologic confirmation of cancer. This study evaluates the performance of endoscopic tissue acquisition (TA) procedures for borderline resectable and resectable PDAC. Methods: Pathology reports of patients included in two nationwide randomized controlled trials (PREOPANC and PREOPANC-2) were reviewed. The primary outcome was sensitivity for malignancy (SFM), considering both “suspicious for” and “malignant” as positive. Secondary outcomes were rate of adequate sampling (RAS) and diagnoses other than PDAC. Results: Overall, 892 endoscopic procedures were performed in 617 patients, including endoscopic ultrasonography (EUS)-guided TA in 550 (89.1%), endoscopic retrograde cholangiopancreatography (ERCP)-guided brush cytology in 188 (30.5%), and periampullary biopsies in 61 patients (9.9%). The SFM was 85.2% for EUS, 88.2% for repeat EUS, 52.7% for ERCP, and 37.7% for periampullary biopsies. The RAS ranged 94–100%. Diagnoses other than PDAC were other periampullary cancers in 24 (5.4%), premalignant disease in five (1.1%), and pancreatitis in three patients (0.7%). Conclusions: EUS-guided TA of patients with borderline resectable and resectable PDAC included in RCTs had an SFM above 85% for both first and repeat procedures, meeting international standards. Two percent had false positive result for malignancy and 5% had other (non-PDAC) periampullary cancers.

ObjectiveLumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited.DesignPatients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs.ResultsA total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention—5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference −€6348, bias-corrected and accelerated 95% CI −€26 386 to €10 121).ConclusionOur comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.

Background The management of pancreatic body and tail lesions is underexposed. It remains unclear whether endoscopic ultrasonography (EUS) increases the accuracy of the preoperative workup. This study assessed the diagnostic value and safety of EUS in addition to cross-sectional imaging in a surgical cohort of patients with pancreatic body or tail lesions. Methods A multicenter retrospective cohort study was performed of patients who underwent distal pancreatectomy from 2010 to 2017. The composite primary outcome was the additional value of EUS, defined as: (a) EUS confirmed an uncertain diagnosis on cross-sectional imaging, (b) EUS was correct in case of discrepancy with cross-sectional imaging, or (c) EUS provided tissue diagnosis for neoadjuvant treatment. Furthermore, serious adverse events and needle tract seeding were assessed. Results In total, 181 patients were included, of whom 123 (68%) underwent EUS besides cross-sectional imaging. Postoperative pathology was heterogeneous: 91 was malignant, 49 premalignant, 41 benign. Most lesions were solid (n = 117). EUS had additional value in 59/123 (48%) patients; 27/50 (54%) of cystic and 32/73 (44%) of solid lesions. No serious adverse event or needle tract seeding following EUS occurred. Conclusion EUS had additional value besides cross-sectional imaging in half of the patients and showed low associated risks.

IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence. Introduction: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. Methods: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. Results: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. Conclusion: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Main Recommendations1 ESGE recommends the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) over percutaneous transhepatic biliary drainage (PTBD) after failed endoscopic retrograde cholangiopancreatography (ERCP) in malignant distal biliary obstruction when local expertise is available.Strong recommendation, moderate quality evidence.2 ESGE suggests EUS-BD with hepaticogastrostomy only for malignant inoperable hilar biliary obstruction with a dilated left hepatic duct when inadequately drained by ERCP and/or PTBD in high volume expert centers.Weak recommendation, moderate quality evidence.3 ESGE recommends that EUS-guided pancreatic duct (PD) drainage should only be considered in symptomatic patients with an obstructed PD when retrograde endoscopic intervention fails or is not possible.Strong recommendation, low quality evidence.4 ESGE recommends rendezvous EUS techniques over transmural PD drainage in patients with favorable anatomy owing to its lower rate of adverse events.Strong recommendation, low quality evidence.5 ESGE recommends that, in patients at high surgical risk, EUS-guided gallbladder drainage (GBD) should be favored over percutaneous gallbladder drainage where both techniques are available, owing to the lower rates of adverse events and need for re-interventions in EUS-GBD.Strong recommendation, high quality of evidence.6 ESGE recommends EUS-guided gastroenterostomy (EUS-GE), in an expert setting, for malignant gastric outlet obstruction, as an alternative to enteral stenting or surgery.Strong recommendation, low quality evidence.7 ESGE recommends that EUS-GE may be considered in the management of afferent loop syndrome, especially in the setting of malignancy or in poor surgical candidates.Strong recommendation, low quality evidence.8 ESGE suggests that endoscopic ultrasound-directed transgastric ERCP (EDGE) can be offered, in expert centers, to patients with a Roux-en-Y gastric bypass following multidisciplinary decision-making, with the aim of overcoming the invasiveness of laparoscopy-assisted ERCP and the limitations of enteroscopy-assisted ERCP.Weak recommendation, low quality evidence.

Recommendations 1 ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2 ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3 ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4 ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5 ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6 ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7 ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn’s disease.Weak recommendation, low quality of evidence. 8 ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9 ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10 ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence.

The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.

Item does not contain fulltext OBJECTIVES: We developed an epidemiological algorithm to classify types of diabetes mellitus (DM) in chronic pancreatitis (CP), and applied it to a nationwide prospective longitudinal cohort of CP patients. METHODS: Patients with definite CP (M-ANNHEIM criteria) were classified as having DM types 1, 2, or 3c, or no DM using an algorithm based on epidemiological characteristics: DM onset in relation to age, CP onset, exocrine insufficiency. Variables associated with development of DM were identified. RESULTS: Of 1130 included patients with CP between 2011 and 2018, 368 patients (33%) had DM at inclusion. Among patients with DM, 11 were classified as having type 1 (3%), 159 as type 2 (43%), and 191 as type 3c (52%). Patients with DM type 3c had longer duration of CP, more severe pain and lower physical quality of life. During longitudinal follow-up of median 47 months, 120 (20%) patients developed DM, of which 99 patients were classified as type 3c. This was independently associated with pancreatic endoscopy and surgery. CONCLUSIONS: The described algorithm based on epidemiological characteristics can help to classify types of DM in patients with CP. Diabetes mellitus type 3c is associated with longer duration of CP and more severe CP sequelae.

PURPOSE To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively ( P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively ( P = .15). CONCLUSION In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high‐risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high‐risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5‐yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery‐related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: −57% for “Progressive‐only” vs −41% for “Indolent Included”). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high‐risk individuals., What's new? About 10 percent of pancreatic cancers occur in individuals with inherited risk factors. While screening such high‐risk individuals can facilitate the detection of precursor lesions and early‐stage cancer, the extent to which benefits outweigh harms, including overdiagnosis, remains unknown. Here, using a microsimulation model, the authors explored uncertainties concerning the early detection of pancreatic cancer and analyzed the impact of these uncertainties on the effect of screening. In all simulated scenarios, screening was associated with reduced pancreatic cancer mortality. The effectiveness of screening was most strongly impacted by characteristics of natural disease course and level of pancreatic cancer risk

Main recommendations Malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliation of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass.Strong recommendation, high quality evidence. 2 ESGE recommends brachytherapy as a valid alternative, alone or in addition to stenting, in esophageal cancer patients with malignant dysphagia and expected longer life expectancy.Strong recommendation, high quality evidence. 3 ESGE recommends esophageal SEMS placement for sealing malignant tracheoesophageal or bronchoesophageal fistulas. Strong recommendation, low quality evidence. 4 ESGE does not recommend SEMS placement as a bridge to surgery or before preoperative chemoradiotherapy because it is associated with a high incidence of adverse events. Other options such as feeding tube placement are preferable. Strong recommendation, low quality evidence. Benign disease 5 ESGE recommends against the use of SEMSs as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and their cost. Strong recommendation, low quality evidence. 6 ESGE suggests consideration of temporary placement of self-expandable stents for refractory benign esophageal strictures. Weak recommendation, moderate quality evidence. 7 ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures because of their very low risk of embedment and ease of removability. Weak recommendation, low quality evidence. 8 ESGE recommends the stent-in-stent technique to remove partially covered SEMSs that are embedded in the esophageal wall. Strong recommendation, low quality evidence. 9 ESGE recommends that temporary stent placement can be considered for the treatment of leaks, fistulas, and perforations. No specific type of stent can be recommended, and the duration of stenting should be individualized. Strong recommendation, low quality of evidence. 10 ESGE recommends considering placement of a fully covered large-diameter SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive bleeding. Strong recommendation, moderate quality evidence.

Background and aims: Fully covered metal stents (FCSEMSs) are increasingly used for treatment of biliary anastomotic strictures (ASs) after liver transplantation (LT), requiring fewer endoscopic interventions than does treatment with multiple plastic stents (MPSs). Previous studies, however, have reported adverse events such as stent migration and pancreatitis. The intraductal FCSEMS (ID-FCSEMS) potentially avoids these disadvantages. This study aimed to assess the efficacy and safety of ID-FCSEMSs compared with MPSs for AS. Methods: The cohorts of LT patients treated for AS with endoscopic stenting between 2010 and 2019 from 2 Dutch liver transplantation centers were retrospectively analyzed. Patients treated with ID-FCSEMSs or MPSs were included. Results: 80 patients (44 with ID-FCSEMSs vs 36 with MPSs) were included, with a median follow-up time of 52 versus 64 months (P = .183). Stricture resolution was 93% in the ID-FCSEMS versus 97% in the MPS group (P = 1.000) after a median of 19 and 26 weeks, respectively (P = .031). The median number of ERCPs was 2 in the ID-FCSEMS group versus 4 in the MPS group (P < .001). Stricture recurrence occurred in 33% of ID-FCSEMS versus 29% of MPS patients (P = .653) after a median of 24 and 55 weeks (P = .403). Stent migration occurred in 16% of ID-FCSEMS versus 39% of MPS patients (P = .020). Post-ERCP fever was observed in 34% of ID-FCSEMS patients compared with 14% of MPS patients (P = .038). No significant differences were found in pancreatitis rate between the groups, being 6.8% for ID-FCSEMSs and 5.6% for MPSs (P = .816). Conclusion: ID-FCSEMSs for the treatment of AS after LT provides similar stricture resolution and recurrence rates as MPSs, though with a significant reduction of procedures needed.

Background & Aims: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years.Methods: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life.Results: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65–1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08–0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09–0.99). Pancreatic insufficiency and quality of life did not differ between groups.Conclusions: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

Background and study aims Endoscopic ultrasonography (EUS) is a tool widely used to diagnose bile duct lithiasis. In approximately one out of five patients with positive findings at EUS, sludge is detected in the bile duct instead of stones. The objective of this study was to establish the agreement among endosonographers regarding: 1. presence of common bile duct (CBD) stones, microlithiasis and sludge; and 2. the need for subsequent treatment. Patients and methods 30 EUS videos of patients with an intermediate probability of CBD stones were evaluated by 41 endosonographers. Experience in EUS and endoscopic retrograde cholangiopancreatography, and the endosonographers’ type of practices were recorded. Fleiss’ kappa statistics were used to quantify the agreement. Associations between levels of experience and both EUS ratings and treatment decisions were investigated using mixed effects models. Results A total of 1230 ratings and treatment decisions were evaluated. The overall agreement on EUS findings was fair (Fleiss’ κ 0.32). The agreement on presence of stones was moderate (κ 0.46). For microlithiasis it was fair (κ 0.25) and for sludge it was slight (κ 0.16). In cases with CBD stones there was an almost perfect agreement for the decision to subsequently perform an ERC + ES. In case of presumed microlithiasis or sludge an ERC was opted for in 78 % and 51 % of cases, respectively. Differences in experience and types of practice appear unrelated to the agreement on both EUS findings and the decision for subsequent treatment. Conclusions There is only slight agreement among endosonographers regarding the presence of bile duct sludge. Regarding the need for subsequent treatment of bile duct sludge there is no consensus.

Background Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course. Diagnosis of a disrupted pancreatic duct is not standardized in clinical practice or international guidelines. We performed a systematic review of the literature on imaging modalities for diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Methods A systematic search was performed in PubMed, Embase and Cochrane library databases to identify all studies evaluating diagnostic modalities for the diagnosis of a disrupted pancreatic duct in acute pancreatitis. All data regarding diagnostic accuracy were extracted. Results We included 8 studies, evaluating five different diagnostic modalities in 142 patients with severe acute pancreatitis. Study quality was assessed, with proportionally divided high and low risk of bias and low applicability concerns in 75% of the studies. A sensitivity of 100% was reported for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography. The sensitivity of magnetic resonance cholangiopancreatography with or without secretin was 83%. A sensitivity of 92% was demonstrated for a combined cohort of secretin-magnetic resonance cholangiopancreatography and magnetic resonance cholangiopancreatography. A sensitivity of 100% and specificity of 50% was found for amylase measurements in drain fluid compared with ERCP. Conclusions This review suggests that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Amylase measurement in drain fluid should be standardized. Given the invasive nature of other modalities, secretin-magnetic resonance cholangiopancreatography or magnetic resonance cholangiopancreatography would be recommended as first diagnostic modality. Further prospective studies, however, are needed. Electronic supplementary material The online version of this article (10.1007/s10620-020-06413-0) contains supplementary material, which is available to authorized users.

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (pConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP.The COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial.This is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice.ISRCTN, ISRCTN13042622. Registered on 5 September 2020.

Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice to remove sludge/stones from the common bile duct (CBD). In a small but clinically important proportion of patients with suspected choledocholithiasis ERCP is negative. This is undesirable because of ERCP associated morbidity. We aimed to map the diagnostic pathway leading up to ERCP and evaluate ERCP outcome.We established a prospective multicenter cohort of patients with suspected CBD stones. We assessed the determinants that were associated with CBD sludge or stone detection upon ERCP.We established a cohort of 707 patients with suspected CBD sludge or stones (62% female, median age 59 years). ERCP was negative for CBD sludge or stones in 155 patients (22%). Patients with positive ERCPs frequently had pre-procedural endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) imaging (44% vs. 35%; P = 0.045). The likelihood of ERCP sludge and stones detection was higher when the time interval between EUS or MRCP and ERCP was less than 2 days (odds ratio 2.35; 95% CI 1.25-4.44; P = 0.008; number needed to harm 7.7).Even in the current era of society guidelines and use of advanced imaging CBD sludge or stones are absent in one out of five ERCPs performed for suspected CBD stones. The proportion of unnecessary ERCPs is lower in case of pre-procedural EUS or MRCP. A shorter time interval between EUS or MRCP increases the yield of ERCP for suspected CBD stones and should, therefore, preferably be performed within 2 days before ERCP.

Main recommendationsESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and chromoendoscopy (virtual or dye-based).ESGE does not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection.ESGE recommends endoscopic submucosal dissection (ESD) as the treatment of choice for most superficial esophageal squamous cell and superficial gastric lesions.For Barrett’s esophagus (BE)-associated lesions, ESGE suggests the use of ESD for lesions suspicious of submucosal invasion (Paris type 0-Is, 0-IIc), for malignant lesions > 20 mm, and for lesions in scarred/fibrotic areas.ESGE does not recommend routine use of ESD for duodenal or small-bowel lesions.ESGE suggests that ESD should be considered for en bloc resection of colorectal (but particularly rectal) lesions with suspicion of limited submucosal invasion (demarcated depressed area with irregular surface pattern or a large protruding or bulky component, particularly if the lesions are larger than 20 mm) or for lesions that otherwise cannot be completely removed by snare-based techniques.ESGE recommends that an en bloc R0 resection of a superficial GI lesion with histology no more advanced than intramucosal cancer (no more than m2 in esophageal squamous cell carcinoma), well to moderately differentiated, with no lymphovascular invasion or ulceration, should be considered a very low risk (curative) resection, and no further staging procedure or treatment is generally recommended.ESGE recommends that the following should be considered to be a low risk (curative) resection and no further treatment is generally recommended: an en bloc R0 resection of a superficial GI lesion with superficial submucosal invasion (sm1), that is well to moderately differentiated, with no lymphovascular invasion, of size ≤ 20 mm for an esophageal squamous cell carcinoma or ≤ 30 mm for a stomach lesion or of any size for a BE-related or colorectal lesion, and with no lymphovascular invasion, and no budding grade 2 or 3 for colorectal lesions.ESGE recommends that, after an endoscopically complete resection, if there is a positive horizontal margin or if resection is piecemeal, but there is no submucosal invasion and no other high risk criteria are met, this should be considered a local-risk resection and endoscopic surveillance or re-treatment is recommended rather than surgery or other additional treatment.ESGE recommends that when there is a diagnosis of lymphovascular invasion, or deeper infiltration than sm1, or positive vertical margins, or undifferentiated tumor, or, for colorectal lesions, budding grade 2 or 3, this should be considered a high risk (noncurative) resection, and complete staging and strong consideration for additional treatments should be considered on an individual basis in a multidisciplinary discussion.ESGE recommends scheduled endoscopic surveillance with high definition white-light and chromoendoscopy (virtual or dye-based) with biopsies of only the suspicious areas after a curative ESD.

Acute resection for left-sided obstructive colon carcinoma is thought to be associated with higher mortality risk than a bridge to surgery approach using decompressing stoma or self-expandable metal stent, but prediction models are lacking.Determine the influence of treatment strategy on mortality within 90-days from first intervention using a prediction model in patients presenting with left-sided obstructive colon carcinoma.A national multicenter cohort study, using data of a prospective national audit.The study was performed in 75 Dutch hospital.Patients were included if they underwent a resection with curative intent for left-sided obstructive colon carcinoma between 2009 and 2016.First intervention was either acute resection, bridge to surgery with self-expandable metallic stent, or bridge to surgery with decompressing stoma.The main outcome measure was 90-day mortality after first intervention. Risk factors were identified using multivariable logistic analysis. Subsequently a risk model was developed.In total 2395 patients were included, with first intervention consisting of acute resection in 1848 (77%) patients, stoma as bridge to surgery in 332 (14%) patients, and stent as bridge to surgery in 215 (9%) patients. Overall, 152 patients (6.3%) died within 90-days from first intervention. A decompressing stoma was independently associated with a lower 90-day mortality risk (HR: 0.27, CI: 0.094-0.62). Other independent predictors for mortality were age, ASA classification, tumor location, and index levels of serum creatinine and C-reactive protein. The constructed risk model had an area under the curve of 0.84 (CI: 0.81-0.87).Only patients that underwent surgical resection were included.Treatment strategy had a significant impact on 90-day mortality. A decompressing stoma considerably lowers the risk of mortality, especially in older and frail patients. A risk model was developed, which needs further external validation. See Video Abstract at http://links.lww.com/DCR/B975.

In patients ≥ 70 years of age with left-sided obstructive colon cancer, emergency resection should be avoided in the curative setting, and a bridge to surgery technique with Self-Expandable Metal Stent (SEMS) or a decompressing stoma should be applied. In patients70 years of age, all three options (emergency resection, SEMS or a decompressing stoma) can be considered as curative intent treatment. If the construction of a decompressing stoma and SEMS placement are both suitable bridging options, the low chance of having a stoma at any time in case of SEMS, and avoiding the risk of SEMS-related complications (i.e. perforation) in case of a stoma might be an important factor within a shared decision making process. SEMS is the preferred treatment in the palliative setting, with decompressing stoma as a valid alternative. Contraindications for SEMS are unavailability of required expertise, technical unsuitability, and when patients are under anti-angiogenic therapy (e.g. bevacizumab).

Advanced endoscopic imaging is an emerging field in endoscopy practice, especially in optical diagnosis. Current technologies like virtual chromoendoscopy and small-field technologies allow visualization of subtle changes in mucosal and vascular patterns that are predictive of histology. The limiting factor in broadly utilizing these techniques is training and the need for reliable detection of these subtleties. This review provides the current evidence and limitations of training in advanced endoscopic imaging, and future directions of learning. A literature search was performed on PubMed and Medline through March 2020 with relevant keywords as advanced endoscopic imaging, training, and learning. References of relevant articles were screened for additional literature. Several didactic and web-based education programs are developed for training in virtual chromoendoscopy, autofluorescence imaging, confocal laser endomicroscopy, and volumetric laser endomicroscopy. Studies and post-hoc analysis on learning curves showed relatively steep learning curves after training, and web-based education seems to be as valuable as in-person didactic training for most techniques. However, consistent performance on expert level after training has not yet been demonstrated. Most advanced endoscopic imaging techniques are learned within a reasonable timeframe. Future efforts to enhance training and implementation of these techniques should focus on developing standardized and broadly incorporated training programs. The future role of artificial intelligence-assistance in advanced endoscopy and training has to be elucidated.

690 Background: Recent pancreatic cancer surveillance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) in patients with a CDKN2A/p16 pathogenic variant (PV) diagnosed during surveillance are better as compared to PDAC patients diagnosed outside surveillance. Methods: In a propensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage and survival between patients diagnosed in surveillance with non-surveillance PDAC patients. Survival analysis were repeated after adjustment for lead-time bias. Results: Between January 2000 and December 2020, 43 762 patients with PDAC were identified from the NCR. Thirty-one patients with PDAC in surveillance were matched in a 1:5 ratio with 155 non-surveillance patients based on age at diagnosis, sex, and year of diagnosis. In total, 71% of patients in surveillance, as compared to 16% of non-surveillance patients underwent a surgical resection (OR 14.03; 95% CI, 5.92 – 35.85). In surveillance, 39% of patients was diagnosed with stage I cancer, as compared to 6% of non-surveillance PDAC patients (OR 0.10; 95% CI, 0.04 – 0.21). Patients in surveillance had a better prognosis, reflected by a 3-year survival of 32.4% and a median overall survival (OS) of 26.8 months vs. 1.4% 3-year survival and 5.3 months median OS in non-surveillance patients (HR 0.22; 95% 0.14 – 0.36). After adjustment for lead time, PDAC diagnosis in surveillance remained strongly associated with improved survival. Conclusions: Surveillance for PDAC in carriers of a CDKN2A/p16 PV results in earlier detection, increased resectability and improved survival as compared to non-surveillance PDAC patients.[Table: see text]

Novel artificial intelligence techniques are emerging in all fields of healthcare, including gastroenterology. The aim of this review is to give an overview of artificial intelligence applications in the management of pancreatic diseases. We performed a systematic literature search in PubMed and Medline up to May 2020 to identify relevant articles. Our results showed that the development of machine-learning based applications is rapidly evolving in the management of pancreatic diseases, guiding precision medicine in clinical, endoscopic and radiologic settings. Before implementation into clinical practice, further research should focus on the external validation of novel techniques, clarifying the accuracy and robustness of these models.

Main recommendations1. ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. Strong recommendation, high quality evidence. ESGE/ESGAR do not recommend barium enema in this setting. Strong recommendation, high quality evidence.2. ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors. Strong recommendation, low quality evidence. ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete. Weak recommendation, low quality evidence.3. When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms. Strong recommendation, high quality evidence. Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation. Very low quality evidence. ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms. Strong recommendation, high quality evidence. In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms. Weak recommendation, low quality evidence.4. Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors. Strong recommendation, high quality evidence. ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer. Weak recommendation, low quality evidence.5. ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs. Strong recommendation, moderate quality evidence. ESGE/ESGAR also suggest the use of CCE in this setting based on availability. Weak recommendation, moderate quality evidence.6. ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in this setting. Very low quality evidence.7. ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in post-polypectomy surveillance. Very low quality evidence.8. ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation. Strong recommendation, low quality evidence. 9. ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp >= 6 mm detected at CTC or CCE. Follow-up CTC may be clinically considered for 6-9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia. Strong recommendation, moderate quality evidence.Source and scopeThis is an update of the 2014-15 Guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of imaging alternatives to standard colonoscopy. A targeted literature search was performed to evaluate the evidence supporting the use of computed tomographic colonography (CTC) or colon capsule endoscopy (CCE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.