UK and Ireland Joint Advisory Group (JAG) consensus statements for training and certification in diagnostic endoscopic ultrasound (EUS).

BACKGROUND AND AIMS: International endoscopy societies vary in their approach for credentialing individuals in endoscopic ultrasound (EUS) to enable independent practice; however, there is no consensus in this or its implementation. In 2019, the Joint Advisory Group on GI Endoscopy (JAG) commissioned a working group to examine the evidence relating to this process for EUS. The aim of this was to develop evidence-based recommendations for EUS training and certification in the UK. METHODS: Under the oversight of the JAG quality assurance team, a modified Delphi process was conducted which included major stakeholders from the UK and Ireland. A formal literature review was made, initial questions for study were proposed and recommendations for training and certification in EUS were formulated after a rigorous assessment using the Grading of Recommendation Assessment, Development and Evaluation tool and subjected to electronic voting to identify accepted statements. These were peer reviewed by JAG and relevant stakeholder societies before consensus on the final EUS certification pathway was achieved. RESULTS: 39 initial questions were proposed of which 33 were deemed worthy of assessment and finally formed the key recommendations. The statements covered four key domains, such as: definition of competence (13 statements), acquisition of competence (10), assessment of competence (5) and postcertification mentorship (5). Key recommendations include: (1) minimum of 250 hands-on cases before an assessment for competency can be made, (2) attendance at the JAG basic EUS course, (3) completing a minimum of one formative direct observation of procedural skills (DOPS) every 10 cases to allow the learning curve in EUS training to be adequately studied, (4) competent performance in summative DOPS assessments and (5) a period of mentorship over a 12-month period is recommended as minimum to support and mentor new service providers. CONCLUSIONS: An evidence-based certification pathway has been commissioned by JAG to support and quality assure EUS training. This will form the basis to improve quality of training and safety standards in EUS in the UK and Ireland.

Suturing a 20-mm lumen-apposing metal stent allows for safe same-session EUS-directed transgastric intervention in patients with Roux-en-Y gastric bypass anatomy: a multicenter study (with video).

BACKGROUND AND AIMS: EUS-directed transgastric intervention (EDGI) is an established technique for the management of pancreaticobiliary pathology in Roux-en-Y gastric bypass (RYGB) patients. There is an inherent risk of intraprocedural stent dislodgement, leading to perforation. The procedure is therefore often performed in 2 stages, 2 to 4 weeks apart, to allow for fistula maturation to mitigate the risk of lumen-apposing metal stent (LAMS) dislodgment. However, some clinical indications such as cholangitis require more urgent intervention, rendering this approach impractical. The aim of this study was to evaluate the safety and efficacy of same-session (SS)-EDGI with fixation of a 20-mm LAMS using endoscopic suturing. METHODS: This was a 2-center, retrospective study of consecutive RYGB patients who underwent SS-EDGI using a sutured 20-mm LAMS between February 2018 and May 2020. Patient demographics, procedural details, and clinical outcomes were recorded. RESULTS: Thirty-seven patients (mean age, 58.1 years; 86.5% women) underwent SS-EDGI with a median follow-up of 31.8 months. The procedural intervention was ERCP in 33 patients (89.2%) and ERCP with EUS in 4 patients (10.8%). Technical success was 100%. Access was achieved through the gastrogastric fistula in 26 patients (70.3%) and the jejunogastric fistula in 11 (29.7%). The LAMS was anchored with 2 endoscopic sutures in 33 patients (89.2%) and 1 suture in 4 (10.8%). Adverse events occurred in 4 patients (10.8%; 3 postprocedural bleeding, 1 cholangitis). There were no episodes of stent dislodgement or delayed stent migration. A persistent fistula was diagnosed in 7 patients (18.9%) who underwent objective testing (n = 28, 75.7%), of which 6 were successfully closed endoscopically. CONCLUSIONS: Single-stage EDGI using a sutured 20-mm LAMS was associated with a high rate of technical success, low rates of adverse events, and no episodes of stent migration. Persistent fistulas, although common, were amenable to endoscopic management.

Factors predictive of persistent fistulas in EUS-directed transgastric ERCP: a multicenter matched case-control study.

BACKGROUND AND AIMS: EUS-directed transgastric ERCP (EDGE) is an established method for managing pancreaticobiliary pathology in Roux-en-Y gastric bypass patients, with high rates of technical success and low rates of serious adverse events (AEs). However, widespread adoption of the technique has been limited because of concerns about the development of persistent gastrogastric or jejunogastric fistulas. Gastrogastric and jejunogastric fistulas have been reported in up to 20% of cases in some series, but predictive risk factors and long-term management and outcomes are lacking. Therefore, our aims were to assess factors associated with the development of persistent fistulas and the technical success of endoscopic fistula closure. METHODS: This is a case-control study involving 9 centers (8 USA, 1 Europe) from February 2015 to September 2021. Cases of persistent fistulas were defined as endoscopic or imaging evidence of fistula more than 8 weeks after lumen-apposing metal stent (LAMS) removal. Control subjects were defined as endoscopic or imaging confirmation of no fistula more than 8 weeks after LAMS removal. AEs were defined and graded according to the American Society for Gastrointestinal Endoscopy lexicon. RESULTS: Twenty-five patients identified to have evidence of a persistent fistula on follow-up surveillance (cases) were matched with 50 patients with no evidence of a persistent fistula on follow-up surveillance (control subjects) based on age and sex. Mean LAMS dwell time was 74.7 ± 106.2 days. After LAMS removal, argon plasma coagulation (APC) ablation of the fistula was performed in 46 patients (61.3%). Primary closure of the fistula was performed in 26.7% of patients (20: endoscopic suturing in 17, endoscopic tacking in 2, and over-the-scope clips + endoscopic suturing in 1). When comparing cases with control subjects, there was no difference in baseline demographics, fistula site, LAMS size, or primary closure frequency between the 2 groups (P > .05). However, in the persistent fistula group, the mean LAMS dwell time was significantly longer (127 vs 48 days, P = .02) and more patients had ≥5% total body weight gain (33.3% vs 10.3%, P = .03). LAMS dwell time was a significant predictor of persistent fistula (odds ratio, 4.5 after >40 days in situ, P = .01). The odds of developing a persistent fistula increased by 9.5% for every 7 days the LAMS was left in situ. In patients with a persistent fistula, endoscopic closure was attempted in 19 (76%) with successful resolution in 14 (73.7%). CONCLUSIONS: Longer LAMS dwell time was found to be associated with a higher risk of persistent fistulas in EDGE patients. APC or primary closure of the fistula on LAMS removal was not found to be protective against developing a persistent fistula, which, if present, can be effectively managed through endoscopic closure in most cases.

Assessment of the learning curve for EUS-guided gastroenterostomy for a single operator.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used as an alternative to surgery and enteral stent placement to manage gastric outlet obstruction (GOO). However, no data are available on the learning curve (LC) for EUS-GE. Defining the LC is necessary to create adequate subspecialty training programs and quality assurance. METHODS: This study is a retrospective analysis of a prospectively maintained dataset of patients who underwent EUS-GE at 1 tertiary referral center. Primary outcome was the LC for EUS-GE defined by the number of cases needed to achieve proficiency and mastery using cumulative sum (CUSUM) analysis. Moving average graphs and sequential time-block analysis were also performed to assess procedural time. Secondary outcomes included efficacy and safety of EUS-GE. RESULTS: Eighty-seven consecutive patients underwent EUS-GE, mostly for malignant GOO. For consistency, 14 patients were excluded from analysis (noncautery-assisted EUS-GE, 11; surgical anatomy, 3). The same endoscopist performed all procedures using the same freehand technique. Technical success was achieved in 68 of 73 patients (93%). Immediate adverse events occurred in 4 patients (5.5%), whereas late adverse events occurred only in 1 patient (1%), all managed conservatively or endoscopically. All immediate adverse events occurred during the first 39 cases. Clinical success (defined as resuming at least an oral liquid diet within a week) was achieved in 97% of patients. The mean procedural time was 36 minutes (standard deviation, 24). Evaluation of the CUSUM curve revealed that 25 cases were needed to achieve proficiency and 40 cases to achieve mastery. These results were confirmed with the average moving curve and sequential time-block analysis. CONCLUSIONS: We report, for the first time, data on the LC for EUS-GE. About 25 procedures can be considered as the threshold to achieve proficiency and about 40 cases are needed to reach mastery of the technique.

Agreement among Magnetic Resonance Imaging/Magnetic Resonance Cholangiopancreatography (MRI-MRCP) and Endoscopic Ultrasound (EUS) in the evaluation of morphological features of Branch Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN).

BACKGROUND/OBJECTIVES: To evaluate the agreement between the imaging modalities MRI-MRCP and EUS in cystic lesions of the pancreas which were thought to be a BD-IPMN. METHODS: Multicenter retrospective study included all patients between 2010 and 2015 with a suspected BD-IPMN who underwent an EUS and MRI-MRCP within 6 months or less of each other. Location, number, size, worrisome features and high-risk stigmata were evaluated. Interobserver agreement was evaluated by Kappa score. RESULTS: 173 patients were included (97 UHSC, 76 UCLH-RFH), mean age 65 (range 25-87 years), 66 males. When comparing both modalities there was good agreement for the location of the cyst. The median lesion size was larger by MRI-MRCP than EUS although it was not significant. With regards to worrisome features, there was moderate agreement for main PD of 5-9 mm and abrupt change (k = 0.45 and 0.52). Fair agreement was seen for the cyst wall thickening (k = 0.25). No agreement was seen between the presence of non-enhanced mural nodules or lymphadenopathy (k < 0). With regards to high-risk stigmata, poor agreement was obtained for the detection of an enhanced solid component (k = 0.12). No agreement was observed for main PD > 10 mm (k < 0). CONCLUSIONS: In this multicentre study of patients with a BD-IPMN under active surveillance, most disagreement between these modalities was seen in the proximal pancreas. There was generally only minimal concordance between the imaging findings of EUS and MRI-MRCP for the detection of high-risk stigmata and worrisome features.

Paediatric pancreaticobiliary endoscopy: a 21-year experience from a tertiary hepatobiliary centre and systematic literature review.

BACKGROUND: In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating many hepatopancreaticobiliary (HPB) conditions. HPB disease is being diagnosed with increasing frequency in children but information about role of ERCP and EUS and their outcomes in this population remain limited. Therefore the aims of this study were to describe the paediatric ERCP and EUS experience from a large tertiary referral HPB centre, and to systematically compare outcomes with those of other published series. METHODS: All patients <18 years undergoing an ERCP or EUS between January 1992-December 2014 were included. Indications for the procedure, rates of technical success, procedural adverse events and reinterventions were recorded in all cases. RESULTS: Ninety children underwent 111 procedures (87 ERCPs and 24 EUS). 53% (48) were female with a median age of 14 years (range: 3 months - 17 years). Procedures were performed under general anaesthesia (n = 48) or conscious sedation (n = 63). Common indications for ERCP included chronic or recurrent pancreatitis and biliary obstruction. Patients frequently had multiple comorbidities, with a median ASA grade of 2 (range 1-4). Therapeutic procedures performed included biliary or pancreatic sphincterotomy, common bile duct or pancreatic duct stone removal, biliary or pancreatic stent insertion, EUS-guided fine needle aspiration and endoscopic transmural drainage of pancreatic fluid collections. No adverse events were reported following ERCP but there was one complication requiring surgery following EUS guided cystenterostomy. CONCLUSION: ERCP and EUS in children and adolescents have high technical success rates and low rates of adverse events when performed in high volume HPB centres.

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology.

BACKGROUND: Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2-7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples. METHODS: Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture. Collected samples were frozen at -80 °C. The supernatant was washed and lysed cells incubated with HRP-labelled anti-MCM5 mouse monoclonal antibody. Test positivity was determined by optical density absorbance. Patients underwent biliary brush cytology or additional investigations as per clinical routine. RESULTS: Ninety-seven patients were included in the study; 50 had malignant strictures. Median age was 65 years (range 21-94) and 51 were male. Compared with final diagnosis the MCM5 assay had a sensitivity for malignancy of 65.4% compared with 25.0% for cytology. In the 72 patients with paired MCM5 assay and biliary brush cytology, MCM5 demonstrated an improved sensitivity (55.6% vs 25.0%; P=0.0002) for the detection of malignancy. CONCLUSIONS: Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology.

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature.

BACKGROUND: The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management. METHODS: A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015. RESULTS: MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%. CONCLUSIONS: Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.

Endoscopic versus percutaneous drainage of symptomatic pancreatic fluid collections: a 14-year experience from a tertiary hepatobiliary centre.

INTRODUCTION: Endoscopic transmural drainage (ED) or percutaneous drainage (PD) has mostly replaced surgery for the initial management of patients with symptomatic pancreatic fluid collections (PFCs). This study aimed to compare outcomes for patients undergoing ED or PD of symptomatic PFCs. METHODS: Between January 2000 and December 2013, all patients who required PD or ED of a PFC were included. Rates of treatment success, length of hospital stay, adverse events, re-interventions and length of follow-up were recorded retrospectively in all cases. RESULTS: In total, 164 patients were included in the study; 109 patients underwent ED; and 55 had PD alone. During the 14-year study period, the incidence of ED increased and PD fell. In the 109 patients who were managed by ED, treatment success was considerably higher than in those managed by PD (70 vs. 31 %). Rates of procedural adverse events were higher in the ED cohort compared to the PD group (10 vs. 1 %), but patients managed by ED required fewer interventions (median of 1.8 vs. 3.3) had lower rates of residual collections (21 vs. 67 %) and need for surgical intervention (4 vs. 11 %). In the ED group, treatment success was similar for walled-off pancreatic necrosis (WOPN) and pseudocysts (67 vs. 72 %, P = 0.77). There were no procedure-related deaths. CONCLUSION: Compared with PD, ED of symptomatic PFCs was associated with higher rates of treatment success, lower rates of re-intervention, including surgery and shorter lengths of hospital stay. Outcomes in WOPN were comparable to those in patients with pseudocysts.

Improving the identification and monitoring of cirrhosis.

Morbidity and mortality associated with cirrhosis are on the increase. In a recent UK cohort study the incidence of cirrhosis increased by 50.6% between 1998 and 2009. Although all causes of liver disease increased during this period, this trend was primarily attributed to rising levels of alcohol misuse and obesity. Cirrhosis generally results from chronic liver damage over many years. It is characterised by fibrosis and nodularity of the parenchyma, which interferes with the synthetic, metabolic and excretory functions of the liver. Common causes include: alcohol misuse, hepatitis B (± delta) and hepatitis C and non-alcoholic fatty liver disease. Abdominal ultrasonography is a good first-line investigation in patients with suspected liver disease. The most commonly used serum biomarker is the enhanced liver fibrosis panel. Transient elastography is a specialist radiological test, which quantifies liver compliance. Compared with a standard biopsy, it will assess a much larger proportion of the liver and therefore sampling errors should be reduced. The measurements are painless and quick and serial measurements for monitoring treatment response e.g. in chronic viral hepatitis, are feasible and acceptable to patients. Patients with confirmed cirrhosis should be assessed for potential complications (ascites, encephalopathy, oesophageal varices or hepatocellular carcinoma). Reviewing cirrhotic patients regularly in primary care provides a valuable opportunity to ensure hepatocellular carcinoma and variceal surveillance is being undertaken and to give advice on losing weight or reducing alcohol intake.

Endoscopic drainage of walled-off pancreatic necrosis using a novel self-expanding metal stent.

BACKGROUND AND STUDY AIMS: This report describes the use of a novel, fully covered, self-expanding metal stent (FCSEMS) for endoscopic ultrasound (EUS)-guided drainage of walled-off pancreatic necrosis (WON). PATIENTS AND METHODS: Patients with WON, as defined by the revised Atlanta Criteria, were included in this open-lable, two-center, observational study. The WON was punctured using a cystotome, and the FCSEMS was inserted under fluoroscopic guidance. Necrosectomy procedures were performed as necessary. RESULTS: A total of 19 patients were included. The median maximum collection size was 15 cm with a median of 50 % necrosis. A total of 14/19 patients underwent necrosectomy, requiring a median of 4 procedures. Resolution or reduction in the size of collection by at least 80 % was achieved in all patients. Percutaneous or surgical drainage was required in three patients. Five stents migrated or dislodged. One patient had abdominal pain post-procedure. Five patients died during follow-up (three from multi-organ failure, and two unrelated to pancreatitis). CONCLUSIONS: Use of this stent is feasible and safe for drainage of WON. However, stent displacement rates were high, and improvements to the stent design are required before it can be advocated for routine use in WON.

Diagnosis and treatment of gallstone disease.

Gallstones form when there is an imbalance in the composition of bile resulting in precipitation of one or more of its components. Between 37 and 86% of gallstones are cholesterol-rich stones, 2-27% are pigment stones and 4-16% are mixed. Cholesterol-rich gallstones are more common in Europe and North America. This has been attributed to obesity and diets containing a high proportion of refined carbohydrates and fat. Low-calorie diets and rapid weight loss are also associated with cholesterol-rich gallstones. Gallstone disease increases with age. Women have a higher prevalence of gallstones than men, which is attributed to exposure to oestrogen and progesterone. Of those with gallstones, around 1 to 4% will develop symptoms annually. Most patients (> 80%) will remain asymptomatic throughout their lifetime and the likelihood of developing symptoms diminishes with time. Liver function tests and an abdominal ultrasound should be offered to patients with symptoms suggestive of gallstone disease (e.g. abdominal pain, jaundice, fever). They should also be considered in patients with less typical but chronic abdominal or gastrointestinal symptoms. In patients with acute pancreatitis and evidence of ongoing bile duct obstruction and/or cholangitis, endoscopic retrograde cholangio-pancreatography and biliary sphincterotomy is recommended within 24-72 hours of the onset of symptoms. Patients with acute cholecystitis should be referred for laparoscopic cholecystectomy.

Detecting patients with cirrhosis in primary care.

Cirrhosis is a condition that arises as a result of chronic liver damage, typically over many years. It is characterised by fibrosis and nodularity of the liver parenchyma. Cirrhosis interferes with the normal functions of the liver, reducing its ability to produce proteins, which can lead to coagulopathy, low serum albumin and raised bilirubin. The incidence of cirrhosis is rising in the UK, this can primarily be attributed to increasing levels of alcohol consumption and obesity. Mortality from cirrhosis is also rising. Common causes of chronic liver disease include alcohol, non-alcoholic fatty liver disease and chronic viral hepatitis. Nearly half of patients with cirrhosis are asymptomatic. As a result the condition may only be discovered incidentally as a result of abnormalities in liver function tests or imaging of the abdomen performed for other reasons. Alternatively patients may present with signs and symptoms of the complications of cirrhosis e.g. jaundice, ascites, variceal bleeding, hepatic encephalopathy or hepatocellular carcinoma. Detecting patients with cirrhosis in primary care usually relies on identifying common risk factors. Currently, there are no standard criteria for the investigation of patients with suspected cirrhosis. If a patient is suspected of having cirrhosis, most GPs will arrange for blood tests and an ultrasound of the liver to be performed. The gold standard test for the diagnosis of cirrhosis remains a liver biopsy. Staging of liver fibrosis is an important predictor of prognosis and is necessary to guide management.

Improving detection and treatment of liver cancer.

Liver cancer is the sixth most common cancer worldwide. The majority (75-90%) of all primary liver tumours are hepatocellular carcinomas (HCC), arising from the liver parenchyma. Other primary liver cancers include cholangiocarcinomas (CC), which make up 10-25% of liver cancers. These tumours arise from cells lining the biliary tree. Chronic viral hepatitis, and in particular hepatitis B virus (HBV), remains the most important risk factor for the development of HCC. In the UK the incidence of CC is 1-2 cases per 100,000 population, but rates are increasing and in the mid-1990s CC overtook HCC as the most common cause of liver cancer-related death. Over the past decade survival in liver cancer has been steadily improving as a result of developments in surgery, transplantation and the introduction of a number of novel local, ablative and molecular targeted therapies. Symptoms associated with HCC include fatigue, weight loss, abdominal pain, pruritus and jaundice, which may also be caused by the underlying liver disease. However, HCCs are often relatively asymptomatic until late on, and 90% of cases are associated with one or more risk factors. Patients with risk factors should undergo surveillance by abdominal ultrasound every six months. Classical symptoms of CC include jaundice, dark urine, clay-coloured stools and pruritus and occur as a result of progressive bile duct obstruction by the tumour.

Appendixoscopy to evaluate a suspected mucinous appendiceal lesion.

Video 1Colonoscopy with "appendixoscopy" using a single-operator digital cholangioscope to exclude a mucinous lesion of the appendix.

Early diagnosis improves survival in colorectal cancer.

Colorectal cancer is the second most common cause of death from cancer in the UK. Common alarm symptoms include rectal bleeding, change in bowel habit and iron deficiency anaemia. Abdominal mass, weight loss, nausea and vomiting, anorexia and abdominal swelling are less common presenting symptoms. Patients meeting the NICE criteria for urgent referral should be referred via the two week wait pathway to the local colorectal department for prompt assessment to exclude colorectal cancer. Colorectal cancer has a male predominance and is strongly associated with age; 80% of new cases occur in patients aged over 60. Obesity and limited exercise are strong risk factors. Diets low in fruit and vegetables and fibre and high in red meat have also been associated with an increased risk. Patients with one first-degree relative under 45 or two first-degree relatives of any age have an approximate lifetime risk of developing colorectal cancer of 16-25% in men and 10-15% in women. Having one first-degree relative who developed the disease after the age of 65 barely increases lifetime risk. Patients with ulcerative colitis and Crohn's colitis also have an increased lifetime risk of colorectal cancer. In the NHS Bowel Cancer Screening Programme, patients are screened with a faecal occult blood test which they complete at home and return by post. Patients with positive tests are then offered further investigation, typically colonoscopy. The sensitivity of colonoscopy for detecting abnormalities is > 90% and hence it is the gold standard test for evaluating the large bowel. Once a diagnosis of colorectal cancer has been confirmed, the extent of disease is evaluated by a CT scan of the chest, abdomen and pelvis.

Cholangioscopy-guided double-guidewire technique for complex malignant hilar obstruction.

Video 1Cholangioscopy-guided double-guidewire technique for the management of complex malignant hilar obstruction.