The role of intraoperative pancreatoscopy in the surgical management of intraductal papillary mucinous neoplasms of the pancreas: a systematic scoping review.

BACKGROUND: The type and the extent of surgery is still debatable for intraductal papillary mucinous neoplasm (IPMN). Intraoperative pancreatoscopy (IOP) allows the visualization of the main pancreatic duct (MPD) in its entire length and could help determine the extent of MPD involvement and the type and extent of pancreatic resection. However, current guidelines do not advise its routine use as there is a lack of evidence supporting its safety and feasibility. The present study aims to perform a scoping review of published evidence on the safety and feasibility of IOP in IPMN surgical management. METHODS: We systematically searched PubMed, Cochrane, Medline and EMbase to identify studies reporting the use of IOP in IPMN surgical management. The research was completed in June 2023. Data extracted included patient selection criteria, demographics, safety of the procedure, intraoperative findings, impact on surgical strategy, histology results and postoperative outcomes. RESULTS: Four retrospective and one prospective study were included in this scoping review. A total of 142 patients had IOP. The selection criteria for inclusion were heterogenous, with one out of five studies including branch duct (BD), main duct (MD) and mixed type IPMN. Indications for IOP and surgical resection were only reported in two studies. A median of seven outcomes (range 5-8) was described, including the type of surgical resection, additional lesions and change of surgical plan, and complications after IOP. IOP showed additional lesions in 48 patients (34%) and a change of surgical plan in 48(34%). No IOP-related complications were reported. CONCLUSIONS: This scoping review suggests IOP is safe and identifies additional lesions impacting the surgical strategy for IPMN. However, the included studies were small and heterogeneous regarding IPMN definition and indications for surgery and IOP. There is a need for a large multi-centre prospective study to determine the role of IOP and its impact on surgical strategy for IPMN.

Bacterial contamination of endoscopist and assistant face visors during gastrointestinal endoscopy: a pilot study.

Background and aim: During the COVID-19 pandemic, health workers' facial exposure to pathogens has been brought into focus. In this study, we aimed to determine the occurrence and degree of facial contamination to both endoscopists and their assistants during endoscopic procedures to help inform future safety measures. Methods: Non-sterile visors worn by endoscopist, assistant and room control visors from 50 procedures were swabbed post procedure for culture. Procedure type, therapy, duration and evidence of visible visor contamination were recorded. After 48-hour incubation, all bacterial colonies were identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. Organisms were classified into skin/environmental, oronasal and enteric. Results: A total of 104 visors were available for assessment (93 staff; 11 control). In worn visors, skin/environmental flora were isolated from 70, oronasal flora from 8, and enteric flora from 3 with an average colony count of >9.5. Notably, bacteria of enteric origin (Escherichia coli and Enterobacter cloacae) were isolated from three worn visors. In room control, skin/environmental flora were isolated from seven and oronasal flora from one with average colony count of five. No room control visors grew enteric flora. Overall, 9.1% room control and 10.8% worn visors were contaminated with organisms that could possibly have originated from patients. However, enteric flora were only obtained from worn visors. No visors were visibly contaminated. Conclusion: This pilot study demonstrates risk of contamination to faces of endoscopists and assistants. Larger studies are required to determine degree of risk and to give guidance on facial protection during gastrointestinal endoscopy.

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.

UK ERCP sedation practices, patient comfort and endoscopist characteristics: National Endoscopy Database (NED) analysis on behalf of the JAG and BSG.

Objectives: This analysis assessed current endoscopic retrograde cholangiopancreatography (ERCP) practice within the UK, including use of sedation and patient comfort. Methods: ERCPs conducted over 1 year (1 July 2021-30 June 2022) and uploaded to the National Endoscopy Database (NED) were analysed. The endoscopist workforce was classified by gender and specialty, use of sedation was analysed. Logistic regression was used to assess associations between patient age, gender and procedure indications on moderate to severe discomfort risk. Results: 27 812 ERCPs were performed by 491 endoscopists in 175 sites and uploaded to NED, an estimated 50% of total UK activity. 13% were training procedures, 94% of the endoscopists were male, with 72% being gastroenterologists. Most ERCPs were performed under conscious sedation (89%). The discomfort rate among patients aged 60-90 undergoing ERCP under conscious sedation was 4.2% (95% CI 3.9% to 4.5%), with only 5.5% (95% CI 5.2% to 5.9%) receiving greater than 5 mg midazolam or 100 µg fentanyl.Younger patients (<30 years) had a higher discomfort risk during conscious sedation ERCPs than those aged 70-79 (OR 3.0, 95% CI 2.2 to 4.3, p<0.05), while male patients had a lower discomfort risk compared with females (OR 0.9, 95% CI 0.8 to 1.0, p=0.05).Enhanced sedation (propofol or general anaesthetic) was associated with lower frequency of discomfort (0.3%, 95% CI 0.1 to 0.6) compared with conscious sedation (5.1%, 95% CI 4.9% to 5.4%, p<0.05). Conclusions: Conscious sedation is well tolerated for most patients and prescribing practices have improved. However, triage of more patients, particularly young females, to enhanced sedation lists should be considered to reduce discomfort rates in future.

Endoscopic Ultrasound-Guided Gallbladder Drainage for Malignant Biliary Obstruction: A Systematic Review.

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is a rescue technique for patients with malignant biliary obstruction who fail conventional treatment with ERCP or EUS-guided biliary drainage. The technique has been successfully employed in the management of acute cholecystitis in patients not fit for surgery. However, the evidence for its use in malignant obstruction is less robust. This review article aims to evaluate the data available at present to better understand the safety and efficacy of EUS-guided gallbladder drainage. METHODS: A detailed literature review was conducted and several databases were searched for any studies relating to EUS-GBD in malignant biliary obstruction. Pooled rates with 95% confidence intervals were calculated for clinical success and adverse events. RESULTS: Our search identified 298 studies related to EUS-GBD. The final analysis included 7 studies with 136 patients. The pooled rate of clinical success (95% CI) was 85% (78-90%, I2: 0%). The pooled rate of adverse events (95% CI) was 13% (7-19%, I2: 0%). Adverse events included: peritonitis, bleeding, bile leakage, stent migration, and stent occlusion. No deaths directly related to the procedure were reported; however, in some of the studies, deaths occurred due to disease progression. CONCLUSION: This review supports the use of EUS-guided gallbladder drainage as a rescue option for patients who have failed conventional measures.

Pancreaticobiliary versus head and neck presentation of immunoglobulin G4-related disease: different sides of the same coin?

BACKGROUND AND STUDY AIM: Immunoglobulin G4-related disease (IgG4-RD) is a rare immune mediated fibroinflammatory condition. Pancreaticobiliary (PB) and head and neck (HN) are two of the most commonly involved anatomical sites. It has been postulated that PB IgG4-RD and HN IgG4-RD have distinct clinical phenotypes. Whether the optimum treatment regimen or response to therapy differs between them is unknown. We aimed to assess differences between PB and HN IgG4-RD in a cohort of IgG4 disease managed by an IgG4-RD multispecialty team. METHODS: We performed a retrospective study of a prospectively maintained multidisciplinary IgG4-RD database to identify patients diagnosed with PB and HN IgG4-RD (based on initial presentation) between 2005 and 2019. The electronic patient records were reviewed. Use of immunosuppressive agents and clinical course was analysed. RESULTS: 60 patients with PB IgG4-RD and 14 with HN IgG4-RD were included in the study. PB IgG4-RD was associated with older age at diagnosis 64 versus 51 years (p<0.001), higher serum IgG4 level as a multiple of upper limit of normal median (IQR) 2 (1-3.75) vs 1 (1-2), (p=0.04) and greater proportion with more than one organ involved 68% vs 33% (p=0.03). HN IgG4-RD was more likely to receive second-line therapy 71% versus 36% (p=0.03). Persistent elevation of serum IgG4 after therapy was more common in PB IgG4-RD 84% versus 43% (p=0.03). CONCLUSION: These findings support the contention that PB IgG4-RD and HN IgG4-RD have different clinical profiles and represent distinct subtypes of IgG4-RD.

Rate of pancreatic cancer following a negative endoscopic ultrasound and associated factors.

BACKGROUND : Data are limited regarding pancreatic cancer diagnosed following a pancreaticobiliary endoscopic ultrasound (EUS) that does not diagnose pancreatic cancer. We have studied the frequency of, and factors associated with, post-EUS pancreatic cancer (PEPC) and 1-year mortality. METHODS : Between 2010 and 2017, patients with pancreatic cancer and a preceding pancreaticobiliary EUS were identified in a national cohort using Hospital Episode Statistics. Patients with a pancreaticobiliary EUS 6-18 months before a later pancreatic cancer diagnosis were the PEPC cases; controls were those with pancreatic cancer diagnosed within 6 months of pancreaticobiliary EUS. Multivariable logistic regression models examined the factors associated with PEPC and a Cox regression model examined factors associated with 1-year cumulative mortality. RESULTS : 9363 pancreatic cancer patients were studied; 93.5 % identified as controls (men 53.2 %; median age 68 [interquartile range (IQR) 61-75]); 6.5 % as PEPC cases (men 58.2 %; median age 69 [IQR 61-77]). PEPC was associated with older age (≥ 75 years compared with < 65 years, odds ratio [OR] 1.42, 95 %CI 1.15-1.76), increasing co-morbidity (Charlson co-morbidity score > 5, OR 1.90, 95 %CI 1.49-2.43), chronic pancreatitis (OR 3.13, 95 %CI 2.50-3.92), and diabetes mellitus (OR 1.58, 95 %CI 1.31-1.90). Metal biliary stents (OR 0.57, 95 %CI 0.38-0.86) and EUS-FNA (OR 0.49, 95 %CI 0.41-0.58) were inversely associated with PEPC. PEPC was associated with a higher cumulative mortality at 1 year (hazard ratio 1.12, 95 %CI 1.02-1.24), with only 14 % of PEPC patients (95 %CI 12 %-17 %) having a surgical resection, compared with 21 % (95 %CI 20 %-22 %) of controls. CONCLUSIONS : PEPC occurred in 6.5 % of patients and was associated with chronic pancreatitis, older age, more co-morbidities, and specifically diabetes mellitus. PEPC was associated with a worse prognosis and lower surgical resection rates.

Impact of prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy.

OBJECTIVE: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN: A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS: Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS: EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.

Erratum: UK Joint Advisory Group consensus statements for training and certification in endoscopic retrograde cholangiopancreatography.

[This corrects the article DOI: 10.1055/a-1629-7540.].

UK Joint Advisory Group consensus statements for training and certification in endoscopic retrograde cholangiopancreatography.

Background and study aims Despite the high-risk nature of endoscopic retrograde cholangiopancreatography (ERCP), a robust and standardized credentialing process to ensure competency before independent practice is lacking worldwide. On behalf of the Joint Advisory Group (JAG), we aimed to develop evidence-based recommendations to form the framework of ERCP training and certification in the UK. Methods Under the oversight of the JAG, a modified Delphi process was conducted with stakeholder representation from the British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on ERCP training and certification were formulated after formal literature review and appraised using the GRADE tool. These were subjected to electronic voting to achieve consensus. Accepted statements were peer-reviewed by JAG and relevant Specialist Advisory Committees before incorporation into the ERCP certification pathway. Results In total, 27 recommendation statements were generated for the following domains: definition of competence (9 statements), acquisition of competence (8 statements), assessment of competence (6 statements) and post-certification support (4 statements). The consensus process led to the following criteria for ERCP certification: 1) performing ≥ 300 hands-on procedures; 2) attending a JAG-accredited ERCP skills course; 3) in modified Schutz 1-2 procedures: achieving native papilla cannulation rate ≥80%, complete bile duct clearance ≥ 70 %, successful stenting of distal biliary strictures ≥ 75 %, physically unassisted in ≥ 80 % of cases; 4) 30-day post-ERCP pancreatitis rates ≤5 %; and 5) satisfactory performance in formative and summative direct observation of procedural skills (DOPS) assessments. Conclusions JAG certification in ERCP has been developed following evidence-based consensus to quality assure training and to ultimately improve future standards of ERCP practice.

Analgesia in the Initial Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown. OBJECTIVE: The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP. METHODS: A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2. RESULTS: Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting. CONCLUSIONS: There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h.

Controversies in ERCP: Technical aspects.

The aim of the series of papers on controversies of biliopancreatic drainage procedures is to discuss pros and cons of the varying clinical practices and techniques in ERCP and EUS for drainage of biliary and pancreatic ducts. While the first part focuses on indications, clinical and imaging prerequisites prior to ERCP, sedation options, post-ERCP pancreatitis prophylaxis, and other related technical topics, the second part discusses specific procedural ERCP techniques including precut techniques and their timing as well as management algorithms. In addition, reviews on controversies in EUS-guided bile duct and pancreatic drainage procedures are under preparation.

Controversies in ERCP: Indications and preparation.

The aim of the series of papers on controversies of biliopancreatic drainage procedures is to discuss the pros and cons of the varying clinical practices and techniques in ERCP and EUS for drainage of biliary and pancreatic ducts. The first part focuses on indications, clinical and imaging prerequisites before ERCP, sedation options, post-ERCP pancreatitis (PEP) prophylaxis, and other related technical topics. In the second part, specific procedural ERCP-techniques including precut techniques and its timing as well as management algorithms are discussed. In addition, controversies in EUS-guided bile duct and pancreatic drainage procedures are under preparation.

EUS-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing metal stents in patients with malignant distal biliary obstruction: multicenter collaboration from the United Kingdom and Ireland.

BACKGROUND AND AIMS: EUS-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 malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. METHODS: A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. RESULTS: One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 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% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). CONCLUSIONS: EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy.

Pancreaticobiliary endoscopic ultrasound in England 2007 to 2016: Changing practice and outcomes.

Background and study aims Population-level data on the outcomes of pancreaticobiliary endoscopic ultrasound (PB-EUS) are limited. We examined national PB-EUS and fine-needle aspiration (FNA) activity, its relation to pancreatic cancer therapy, associated mortality and adverse events. Patients and methods Adults undergoing PB-EUS in England from 2007-2016 were identified in Hospital Episode Statistics. A pancreatic cancer cohort diagnosed within 6 months of PB-EUS were studied separately. Multivariable logistic regression models examined associations with 30-day mortality and therapies for pancreatic cancer. Results 79,269 PB-EUS in 68,908 subjects were identified. Annual numbers increased from 2,874 (28 % FNA) to 12,752 (35 % FNA) from 2007 to 2016. 8,840 subjects (13 %) were diagnosed with pancreatic cancer. Sedation related adverse events were coded in 0.5 % and emergency admission with acute pancreatitis in 0.2 % within 48 hours of PB-EUS. 1.5 % of subjects died within 30 days of PB-EUS. Factors associated with 30-day mortality included increasing age (odds ratio 1.03 [95 % CI 1.03-1.04]); male sex (1.38 [1.24-1.56]); increasing comorbidity (1.49 [1.27-1.74]); EUS-FNA (2.26 [1.98-2.57]); pancreatic cancer (1.39 [1.19-1.62]); increasing deprivation (least deprived quintile 0.76 [0.62-0.93]) and lower provider PB-EUS volume (2.83 [2.15-3.73]). Factors associated with surgical resection in the pancreatic cancer cohort included lower provider PB-EUS volume (0.44 [0.26-0.74]) and the least deprived subjects (1.33 [1.12-1.57]). 33 % of pancreatic cancer subjects who underwent EUS, did not subsequently receive active cancer treatment. Conclusions Lower provider PB-EUS volume was associated with higher 30-day mortality and reduced rates of both pancreatic cancer surgery and chemotherapy. These results suggest potential issues with case selection in lower-volume EUS providers.

Morphological and p40 immunohistochemical analysis of squamous differentiation in endoscopic ultrasound guided fine needle biopsies of pancreatic ductal adenocarcinoma.

The basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and upregulation in TP63ΔN (p40) network. Adenosquamous histology can be observed. This study assessed immunohistochemical p40 expression in fine needle biopsy (FNB) samples with PDAC and association with cytomorphological features of squamous differentiation and clinical data. 106 EUS FNBs with PDAC were assessed for eight cytomorphological features of squamous differentiation. P40 H-score (intensity 0-3 × percentage positive nuclei) was analysed for association with morphological features, patient age, gender, operability, chemotherapy and survival. P40 H-score in 14 paired FNBs and resections was compared. P40 h-score was 1-3 in 31%, 4-30 in 16% and > 30 in 13% of FNBs. It was significantly associated with intercellular bridges, elongated cell shape, sharp cell borders, angular nuclei with homogenous chromatin (p < 0.001) and dense cytoplasm (p = 0.002). Keratinisation was not seen. Inoperable patients (n = 81) had a shorter median survival for h-score > 30 (n = 9, 1.8 months) than for h-score ≤ 30 (n = 66, 6.7 months) not quite reaching statistical significance (p = 0.08). P40 was significantly associated with squamous morphology in FNBs with PDAC. P40 H-score > 30 showed a trend towards shorter survival in inoperable patients. Squamous differentiation may be a treatment target in PDAC.