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BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment. ispartof: GASTROINTESTINAL ENDOSCOPY vol:94 issue:6 pages:1059-1068 ispartof: location:United States status: published

Background Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. Methods This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. Results 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. Conclusions The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Backgrounds Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. Methods We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). Results Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P Conclusions The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.

Background Most studies on endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) for palliation of malignant gastric outlet obstruction (GOO) utilized a 15-mm lumen-apposing metal stent (LAMS). More recently, a 20-mm LAMS has become available. This study aimed to compare rates of technical and clinical success and adverse events (AEs) in patients undergoing EUS-GE using a 20-mm vs. 15-mm LAMS. Methods Patients who underwent EUS-GE with 15-mm or 20-mm LAMS for malignant GOO during the period from January 2018 to October 2020 were included. The primary outcome was clinical success, defined as an increase in the gastric outlet obstruction score (GOOS) by at least 1 point during follow-up. Secondary outcomes were technical success, maximum tolerated diet, re-intervention rate, and rate/severity of AEs. Results 267 patients (mean age 67 years, 43 % women) with malignant GOO from 19 centers underwent EUS-GE. Clinical success rates were similar for the 15-mm and 20-mm stents (89.2 % [95 %CI 84.2 %–94.2 %] vs. 84.1 % [77.4%–90.6 %], respectively). However, a significantly higher proportion of patients in the 20-mm group tolerated a soft solid/complete diet at the end of follow-up (91.2 % [84.4 %–95.7 %] vs. 81.2 % [73.9 %–87.2 %], P = 0.04). Overall, AEs occurred in 33 patients (12.4 % [8.4 %–16.3 %]), with similar rates for 15-mm and 20-mm stents (12.8 % [7.5 %–18.2 %] vs. 11.8 % [6 %–17.6 %]), including incidence of severe/fatal AEs (2 % [0.4 %–5.8 %] vs. 3.4 % [0.9 %–8.4 %]). Conclusions The 20-mm and 15-mm LAMS show similar safety and efficacy for patients undergoing EUS-GE for malignant GOO. The 20-mm LAMS allows a more advanced diet and is, thus preferred for EUS-GE.

Background and Aims Stent misdeployment (SM) has hindered the dissemination of EUS-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction (GOO) management. We aimed to provide a classification system for SM during EUS-GE and study clinical outcomes and management accordingly. Methods This is a retrospective study involving 16 tertiary care centers (8 in the United States, 8 in Europe) from March 2015 to December 2020. Patients who developed SM during EUS-GE for GOO were included. We propose classifying SM into 4 types. The primary outcome was rate and severity of SM (per American Society for Gastrointestinal Endoscopy lexicon), whereas secondary outcomes were clinical outcomes and management of dislodgement according to the SM classification type, in addition to salvage management of GOO after SM. Results From 467 EUS-GEs performed for GOO during the study period, SM occurred in 46 patients (9.85%). Most SMs (73.2%) occurred during the first 13 EUS-GE cases by the performing operators. SM was graded as mild (n = 28, 60.9%), moderate (n = 11, 23.9%), severe (n = 6, 13.0%), or fatal (n = 1, 2.2%), with 5 patients (10.9%) requiring surgical intervention. Type I SM was the most common (n = 29, 63.1%), followed by type II (n = 14, 30.4%), type IV (n = 2, 4.3%), and type III (n = 1, 2.2%). Type I SM was more frequently rated as mild compared with type II SM (75.9% vs 42.9%, P = .04) despite an equivalent rate of surgical repair (10.3% vs 7.1%, P = .7). Overall, 4 patients (8.7%) required an intensive care unit stay (median, 2.5 days). The median length of stay was 4 days after SM. Conclusions Although SM is not infrequent during EUS-GE, most are type I, mild/moderate in severity, and can be managed endoscopically with a surgical intervention rate of approximately 11%.

IntroductionIn March 2020, severe acute respiratory syndrome SARS-CoV-2 was declared a pandemic. Specific shielding guidance produced by PHE aimed to protect clinically extremely vulnerable individuals. This included people with AIH on immunosuppressants. In the first wave, advice included not leaving home. The practicalities of this and impact of enforced shielding on mental health (MH) and well-being is not well documented, although suicide theories emphasise the negative effect of social isolation and loneliness. We conducted a patient survey to assess the impact of shielding in our AIH cohort.MethodsBetween 1Jul -10 Aug 2020,292 patients with AIH, fulfilling shielding criteria were invited to participate in a clinician designed survey on MSForms® online or by hand. Paper responses were entered online for analysis.Results36%(104)participated;79% female,74% age 25-69. Immunosuppression burden:50% single agent,47%dual, 3%on ≥3.Shielding compliance was ranked on a scale from 0-10:60% 9-10/10,29%7-8/10,11%0-6/10. Reasons for breaches included: exercise, shopping, to have a drive. Responses demonstrated assessment of risk by those breaching guidance. Ease with practical aspects of living were assessed on a scale from 0-10. One third found this ‘very easy’,1/3 ‘quite easy’,1/3 ‘not very easy’. For shopping, respondents used family members(49%),online(39%),shop in person(8%),other(4%).NHS volunteers were not used for shopping. Obtaining prescriptions was reported as easy in 79%: 76% used family/online pharmacy deliveries, other methods included: friend/neighbour, hospital delivery, NHS volunteer, collection in person. Of those with long-term partners 95% continued co-habiting but 4% lived separately in this period, remaining respondents previously lived alone. Respondents were asked to rank their MH and physical well-being. 27% reported MH as ‘high’, 27%‘moderate’,46%‘low’.Whilst 87% had access to outdoor space, only 46% had access to space large enough to exercise. Questions on the impact of shielding on other household members highlighted the perceived loss of independence and ‘guilt’ associated with the negative impact of shielding on others. Pertaining to work/employment, 38%(40/104) were employed in March 2020. Of those answering the question ‘How did you work during the shielding period’: 54% worked from home (WFH), prior to COVID-19 only 5% WFH. 2% continued to commute to work.ConclusionThis survey has provided a unique insight into shielding attitudes and behaviours in patients with AIH during the pandemic first wave demonstrating its negative impact on MH and well-being. As further evidence emerges regarding the risk of COVID-19 in adults taking immunosuppressants, more detailed risk stratification may be possible;this would be advantageous from a patient perspective.

Background and Aims Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDD) with an electrocautery enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with MDBO. Our aim was to assess the efficacy, safety, and outcomes in patients with malignant distal biliary obstruction (MDBO), who underwent EUS-CDD with EC-LAMS. Methods A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMS at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 to November 2020 was undertaken. Results One hundred twenty patients (55% male) with a median age of 73 years (IQR 17, range 43 – 94) were included. The median follow-up period in 117 patients was 70 days (IQR 169, range 3 – 869) and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% (92/97 patients). The adverse event (AE) rate was 17.5% (n=21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). Conclusion EUS-CDD with EC-LAMS at tertiary institutions within a regional HPB network for treatment of MDBO is effective in those where ERCP was not possible or unsuccessful. When technical failures or adverse events occur, the majority can be managed with conservative or endoscopic therapy

Immunoglobulin subclass 4 related disease (IgG4-RD) is an increasingly recognised autoimmune disease with the potential of affecting various organs. It has a predilection for certain anatomical hotspots and the pancreatobiliary tract is the the most common area involved. Due to the relative novelty of IgG4-RD, the understanding of the disease process continues to involve. Recent European guidelines on IgG4-RD have been published by a working group collaboration between the United European Gastroenterology and Swedish Society of Gastroenterology. In our commentary, we aim to extract the key practical points with an emphasis on diagnosis and management of IgG4-RD with specific focus on the pancreatobiliary tract.

Objective UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required.

Biliary drainage with ERCP is successful in only 80% to 90% of cases of extrahepatic cholangiocarcinoma and pancreatic cancer. We present the results of a multicenter prospective study assessing the safety, feasibility, and quality of life of patients after EUS-guided biliary drainage (EUS-BD) with lumen-apposing metal stents after failed ERCP.All consecutive adults with a dilated common bile duct (CBD) ≥14 mm secondary to inoperable malignant distal CBD stricture and failed ERCP biliary drainage were screened and recruited from 3 tertiary UK centers. Technical success of EUS-BD using lumen-apposing metal stents was the primary endpoint. Improvement in serum bilirubin level, 30-day mortality, procedure-related adverse events, and quality of life were secondary endpoints. Improvement in quality of life was measured using a validated questionnaire (EORTC QLQ-BIL21).Twenty patients were included in the analysis. EUS-BD was technically successful in all patients and the clinical success rate was 95% (19 of 20) at day 7 (50% reduction in bilirubin level) and 92.3% (12 of 13) at day 30 (bilirubin 50 μmol/L). There were significant improvements in overall quality of life score (49 vs 42, P = .03) at day 30. All-cause 30-day mortality was 20% and the moderate adverse event rate was 10% (1 cholangitis and 1 stent migration).EUS-BD has acceptable technical success and safety as a second-line palliative treatment for inoperable malignant distal CBD strictures. Randomized controlled studies comparing EUS-BD with percutaneous transhepatic biliary drainage are needed to determine their effectiveness in clinical practice. (ISCRTN registration number: ISRCTN13196704.).

Take home messages This article continues our ‘Controversies in’ series for the Frontline Gastroenterology Twitter debates. The focus of the debate was endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), in which training, service configuration and management of challenging cases were discussed. We aim to summarise the key points from the debate. ### Training and service delivery #### Is the current UK training system appropriately set up for training in ERCP? The discussion started with the current setup for ERCP training in the UK. ERCP, unlike oesophagogastroduodenoscopy (OGD) and colonoscopy, is optional for training in gastroenterology. Currently in the UK, gastroenterology training is combined with general internal medicine (GIM) and there are mandatory competencies in subspecialties like inflammatory bowel disease (IBD), hepatology and nutrition. Trainees often find it challenging to achieve competency in therapeutic OGD and level 2 colonoscopy, and it is anticipated that the situation may become even more difficult with the new internal medicine training system, which would leave less time for endoscopy training. Consequently, trainees with an interest in ERCP are unable to achieve competency in this domain of endoscopy during the completion of training (CCT) and are left with no other choice but to pursue further training in the form of a post-CCT fellowship. This, combined with service standards1 that require minimum numbers of procedures per annum, has led to a reduction in the number of consultants undertaking ERCP. With fewer people …

Background and study aims Bi-flanged metal stents (BFMS) have shown promise in the drainage of walled-off pancreatic necrosis (WON), but their placement requires multiple steps and the use of other devices. More recently, a novel device consisting of a combined lumen-apposing metal stent (LAMS) and electrocautery-enhanced delivery system has been introduced. The aim of this study was to compare the placement and outcomes of the two devices. Patients and methods This was a retrospective review of consecutive patients undergoing endoscopic ultrasound-guided placement of BFMS or LAMS for drainage of symptomatic WON. Data from procedures between October 2012 and December 2016 were taken from a prospectively maintained database. We compared technical and clinical success, procedure time, costs, and composite end point of significant events (adverse events, stent migration, additional percutaneous drainage) between BFMS and LAMS. Results 72 consecutive patients underwent placement of BFMS (40 patients, 44 stents) or LAMS (32 patients, 33 stents). Technical success was 91 % for BFMS and 97 % for LAMS. Clinical success was 65 % vs. 78 %, respectively. Median in-room procedure time was significantly shorter in the LAMS group (45 minutes [range 30 – 80]) than in the BFMS group (62.5 minutes [range 35 – 135]; P Conclusion LAMS was superior to BFMS in terms of procedure time, with comparable adverse events, success, and costs.

// Matthew T. Huggett 1, 2 , Slavica Tudzarova 2 , Ian Proctor 2 , Marco Loddo 2, 3 , Margaret G. Keane 1 , Kai Stoeber 2 , Gareth H. Williams 2, 3 , Stephen P. Pereira 1 1 UCL Institute for Liver and Digestive Health and UCL Cancer Institute, University College London, London, UK 2 The Research Department of Pathology, UCL Cancer Institute, University College London, London, UK 3 Oncologica Ltd, The Science Village, Chesterford Research Park, Cambridge, UK Correspondence to: Gareth Williams, e-mail: gareth.williams@oncologica.com Keywords: pancreatic cancer, cell cycle, DNA replication, Cdc7 Received: July 22, 2015 Accepted: January 23, 2016 Published: February 23, 2016 ABSTRACT Purpose: Cdc7 is a serine/threonine kinase which is responsible for the ‘firing’ of replication origins leading to initiation of DNA replication. Inhibition or depletion of Cdc7 in normal cells triggers a DNA origin activation checkpoint causing a reversible G1 arrest. Here we investigate Cdc7 as a novel therapeutic target in pancreatic cancer. Experimental design: Cdc7 target validation was performed by immunoexpression profiling in a cohort of 73 patients with pancreatic adenocarcinoma including 24 controls. Secondly Cdc7 kinase was targeted in Capan-1 and PANC-1 pancreatic cancer cell line models using either an siRNA against Cdc7 or alternatively a small molecule inhibitor (SMI) of Cdc7 (PHA-767491). Results: Cdc7 was significantly overexpressed in pancreatic adenocarcinoma compared to benign pancreatic tissue (median LI 34.3% vs. 1.3%; P

IgG subclass 4-related disease (IgG4-RD) is a rare but increasingly recognised fibroinflammatory condition known to affect multiple organs. IgG4-RD is characterised by unique histological features of lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis. In this review we describe the pancreaticobiliary manifestations of IgG4-RD, with particular emphasis on type 1 autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC). AIP and IgG4-SC can pose diagnostic challenges to the clinician as they may mimic pancreatic cancer and primary sclerosing cholangitis, respectively. We discuss current knowledge, clinical diagnostic criteria and recent advances and summarise the evidence base for current therapeutic approaches for AIP and IgG4-SC.

Background and study aims Pancreatic fluid collection (PFC) is a common complication of pancreatitis for which endoscopic ultrasound-guided drainage is first-line treatment. A new single-device, lumen-apposing, covered self-expanding metal stent (LAMS) has been licensed for PFC drainage. We therefore present our multicenter experience with the LAMS for PFC drainage in a multicenter prospective case series to assess success and complication rates. Patients and methods All adult patients from 11 tertiary centers who had LAMS placement for PFC from July 2015 to July 2016 were included. Data including indications, technical success, clinical success, collection resolution, stent removal, early and late adverse events (AEs), mortality and recurrence at 6 months were collected. Results 116 patients, median age 52.5 years (range 16 – 80) and 67 % male, were treated with a single LAMS in each case. The indication was walled off necrosis (WON) in 70 and pseudocyst in 46. Median size of the PFC was 11 cm (5 – 21 cm) and the estimated median necrotic volume in WON was 30 % (5 % – 90 %). Stent insertion was technically successful in 115 (99.1 %) and clinically successful in 109 (94 %). Early serious AEs (SAEs): n = 7 sepsis, n = 1 stent blockage with food, n = 1 stent migration requiring laparotomy, n = 1 stent dislodgement and n = 1 bleeding requiring emboliZation. Late AEs: n = 1 buried stent and n = 1 esophageal fistula. Non-procedure-related deaths: n = 3 (2.5 %). Conclusion This multicenter case series demonstrates that use of the new LAMS is feasible, effective and relatively safe in draining PFC with a technical success rate of 99 % and cumulative SAE rate of 11.2 %.

A 79-year-old man presented with signs of biliary obstruction (bilirubin 82 μmol/L, alanine aminotransferase 358 IU/L and alkaline phosphatase 250 IU/L) and normocytic anaemia (haemoglobin 120 g/L). He had a 4-month history of relapsed multiple myeloma and had been treated with five cycles of bortezomib (a proteasome inhibitor). Transabdominal ultrasound demonstrated an ill-defined mass in the pancreatic head associated with upstream biliary dilatation. CT demonstrated multiple uniformly enhancing soft tissue masses throughout the pancreas with enlargement of the pancreatic head, in particular, and associated biliary obstruction. There was a direct invasion into the main portal vein, suggesting a solid malignancy. There was no evidence of distal metastases, ascites or peritoneal carcinomatosis (figure 1). Immunoglobulin (Ig) G4 levels were normal but IgG2 …

This issue of Frontline Gastroenterology gives an overview of the rapidly developing field of pancreaticobiliary medicine in the UK. Currently, most hospitals in this country do not have gastroenterologists with a subspeciality interest in this area and there is not yet a defined curriculum in the field for training. These deficiencies now need to be addressed urgently to effectively manage the many patients who are increasingly being identified and diagnosed with pancreaticobiliary diseases. A career in pancreaticobiliary medicine is attractive to gastroenterologists, as it combines a range of skills to manage complex benign and malignant disease, including diagnostic and therapeutic endoscopic interventions and working in multidisciplinary teams. Over the last few years, evidence for endoscopic treatment in complex pancreaticobiliary conditions has been accumulating and, thanks to technological advances in equipment, endoscopy is complementing and competing with traditional surgical and radiological approaches. In several areas, such as treating patients with pancreatic cancer, the role of the physician can be expanded. Furthermore, the opportunities for service development and research are significant. The seven papers in this series review the broad range of conditions in pancreaticobiliary medicine in which clinicians require expertise.1–7 These discuss …

OBJECTIVES Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1–107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P < 0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio = 2.25, CI = 1.12–3.94, P = 0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio = 2.07, CI = 1.07–3.55, P = 0.02). CONCLUSIONS Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

Pancreatic fluid collections (PFCs) are a frequent complication of pancreatitis, or less commonly, pancreatic trauma or surgery. The revised Atlanta Classification categorizes PFCs as acute or chronic, with further subclassification of acute collections into acute peripancreatic collections and acute necrotic collections and of chronic fluid collections into pseudocysts and walled-off pancreatic necrosis. Acute PFCs are generally only subjected to an intervention when they are infected and not responding to antibiotics and are not managed endoscopically. Chronic PFCs, both pseudocysts and walled-off pancreatic necrosis, require intervention only when symptomatic or enlarging over time. Endoscopic ultrasound-guided drainage has become the mainstay of management for chronic PFCs that require intervention. Developments in medical devices over the past few years have significantly simplified and shortened the duration of the procedure itself, but the optimum choice of stent in different clinical scenarios remains to be defined, as does the place of endoscopic necrosectomy. To optimize outcomes, these patients should undergo a careful preprocedure workup and discussion in a multidisciplinary environment and procedures should be carried out in high-volume pancreatic units.

Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN9s related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.

BACKGROUND AND AIM We aimed to evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) for indeterminate biliary lesions and its usefulness in electrohydraulic lithotripsy (EHL) of biliary stones not amenable to conventional endoscopic therapy. PATIENTS AND METHODS All patients undergoing SpyGlass SOC in four UK tertiary centres between 2008 and 2010 were retrospectively enrolled. Patients were followed up until death or the last clinic visit until May 2011. The operating characteristics of SOC for detecting malignant lesions and the stone clearance rate after SOC-guided EHL were calculated. RESULTS A total of 165 patients underwent 179 SOC procedures. Sixty-six percent were referred for indeterminate biliary strictures, 13% for filling defects and 21% for SOC-guided EHL. Cannulation with the SOC system was successful in 95% but visualization was inadequate in 13%. Primary sclerosing cholangitis was a risk factor for failed cannulation and conscious sedation (vs. general anaesthesia) for inadequate visualization (P

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.

Pancreaticobiliary diseases, including acute and chronic pancreatitis and pancreatic cancer, are common, although there is currently no training curriculum for this subspecialty within medical gastroenterology. There is a need for medical gastroenterologists experienced in the management of these complex patients, which increasingly involves a multidisciplinary approach. For both acute and chronic pancreatitis, an aetiology should be sought and surveillance conducted for the development of complications, such as exocrine and endocrine failure, nutritional deficiencies and osteoporosis. Furthermore, some patients may require long-term support with smoking and alcohol cessation. Pancreatic cancer and cholangiocarcinoma have a poor prognosis that has not improved in recent years. Although physicians are involved in the initial diagnostic process, there are now evolving areas where they can contribute to the subsequent management. An increasing workload is the assessment and treatment of patients with cystic pancreatic lesions, detected incidentally on cross-sectional imaging. Additionally, the management of biliary disorders, such as complex strictures and Sphincter of Oddi dysfunction, is equally challenging and requires close working between hepaticopancreaticobiliary (HPB) physicians, radiologists, surgeons and hepatologists. A career in pancreaticobiliary medicine may appeal to doctors in training. There are rapidly developing diagnostic and therapeutic procedures for patients with pancreatic disease, emerging new clinical problems in the acute and long-term settings, together with a need for a personalised management approach. More physicians with such an interest will be required as the incidence of many pancreaticobiliary disorders is expected to rise as their aetiology is related to obesity and higher alcohol consumption. This paper discusses the potential development and components of a training programme in medical pancreatology, and the authors would welcome feedback on its suggestions. The Joint Royal Colleges of Physicians Training Board (JRCPTB) Gastroenterology and Hepatology curriculum 2010 defines the process of training and the required competencies for the award of a certificate …

The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R² = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

Aim. To assess the safety of photodynamic therapy (PDT) using talaporfin sodium on the pancreas and surrounding organs in normal hamsters.Methods. Fluorescence microscopy documented talaporfin levels in liver, duodenum, and pancreas up to 24 hours after photosensitisation. Lesion size in liver 3 days after PDT (50 J, 5 mg/kg, variable drug-light interval (DLI)) was documented to optimise the DLI. Using optimum DLI, pancreas and surrounding organs were treated with laser fibre touching the surface and animals were killed at 3 or 21 days.Results. Peak fluorescence was seen in duodenum and pancreas at 15 mins (second lower peak at 2 hours). Liver fluorescence was consistently high (peak 1 hour) until after 4 hours. Optimum DLI was seen at 15 minutes. The pancreas was relatively resistant to direct PDT injury (small lesions at high doses) but surrounding stomach, duodenum, and liver were more susceptible with evidence of adhesions and full thickness damage (localised peritonitis and duodenal perforation at highest doses).Conclusion. The safety profile is similar to PDT with longer acting photosensitisers. The pancreas appears safe to treat, but care is required to avoid high light doses to the intestinal tract, particularly the duodenum.

Dear editor, Bang et al 1 reported in Gut their recent experience with the Boston Scientific Hot AXIOS lumen-apposing metal stent (LAMS) in the treatment of walled-off necrosis (WON). They described a concerning 50% (6/12) rate of stent-related adverse events, in particular delayed bleeding (3/12) and buried stent syndrome (2/12). They postulated that rapid decompression of the WON facilitated by the wide-bore LAMS may lead to the LAMS impinging on the internal wall of the collection cavity resulting in damage to adjacent vasculature, causing haemorrhage, or inward migration of the outer flange of the stent causing buried stent …

The goal of this work was to determine the light dose required to induce necrosis in verteporfin-based photodynamic therapy, in the VERTPAC-1 trial. Patient CT scans were obtained of the abdomen, including the entire treatment zone of pancreas and surrounding tissues, before and after treatment, as well as fast scans during needle placement. These scans were used to estimate arterial and venous blood content, and provide structural information of the pancreas and nearby blood vessels. Using NIRFAST, a finite-element based package for modeling diffuse near-infrared light transport in tissue, simulations were run to create maps of light fluence within the pancreas. These maps provided visualizations of light dose overlaid on the original CT scans, and were used to estimate light dose at the boundary of the zone of necrosis, as observed in follow up treatment outcome CT scans. The aim of these simulation studies was to assist pre-treatment planning by informing the light treatment parameters. This paper presents a case study of the process used on a single patient.