Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Identification of "Digital Sarcopenia" Can Aid the Detection of Pancreatic Exocrine Insufficiency and Malnutrition Assessment in Patients with Suspected Pancreatic Pathology.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) and subsequent malnutrition can be difficult to diagnose but lead to sarcopenia and increased mortality and morbidity even in benign disease. Digital skeletal muscle analysis has been increasingly recognised as a tool to diagnose sarcopenia. OBJECTIVE: The aim of the study was to assess the prevalence of sarcopenia in patients with PEI secondary to benign disease using novel skeletal muscle recognition software. METHODS: Prospective recruitment of patients referred for endoscopic ultrasound (EUS) with suspected pancreatic pathology. Patients with suspected pancreatic cancer on initial computed tomography (CT) were excluded. The diagnosis of chronic pancreatitis (CP) was based on CT and EUS findings. PEI was assessed with faecal elastase-1. Digital measurement of skeletal muscle mass identified sarcopenia, with demographic and comorbidity data also collected. RESULTS: PEI was identified in 45.1% (46/102) of patients recruited, and 29.4% (30/102) had changes of CP. Sarcopenia was significantly more prevalent in PEI 67.4% (31/46) than no-PEI 37.5% (21/56) (37.5%), regardless of CP changes (p < 0.003). The prevalence of sarcopenia (67% vs. 35%; p = 0.02) and sarcopenic obesity (68.4% vs. 25%; p = 0.003) was significantly higher when PEI was present without a radiological diagnosis of CP. Multivariate analysis identified sarcopenia and diabetes to be independently associated with PEI (odds ratio 4.8 and 13.8, respectively, p < 0.05). CONCLUSION: Sarcopenia was strongly associated with PEI in patients undergoing assessment for suspected benign pancreatic pathology. Digital skeletal muscle assessment can be used as a tool to aid identification of sarcopenia in patients undergoing CT scan for pancreatic symptoms.

Experiences of using vedolizumab in the treatment of inflammatory bowel disease in the East Midlands UK - a retrospective observational study.

PURPOSE: Clinical trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn's disease (CD). Further real-world data is needed to inform clinical practice. The primary outcome was to assess corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers, concomitant drug use, endoscopic remission, surgical intervention, hospital admissions and adverse events. MATERIALS AND METHODS: A multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across seven UK hospitals 1/11/14-30/11/16. Clinical disease activity was assessed using the partial Mayo Scores (pMS) and Harvey Bradshaw Index (HBI). Clinical remission was defined as HBI ≤4 or pMS <2 with a combined stool frequency and rectal bleeding sub score of ≤1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI. RESULTS: One hundred ninety-two patients were included in the final analysis. 45% of UC and 10% of CD patients were anti-TNF naive. Over the observation period corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Time to corticosteroid free remission for UC and CD was 17.6 [IQR: 8.7-29.6] and 14.1 [QR: 6.0-21.7] weeks, respectively. Time to clinical response for UC was 9.4 [IQR: 5.7-15.4] and CD was 9.5 [IQR: 6.1-18.2] weeks. There was a substantial decrease in the concomitant use of immunomodulators and a similar decrease in concomitant corticosteroid use over the study period. CONCLUSIONS: Results in this predominately anti-TNF experienced population mirror other published real-world data, demonstrating good clinical effectiveness and a comparable safety profile.

A case report of pancreatic exocrine insufficiency in a patient with Parkinson's disease: A coincidence or is there more to it than meets the eye?

Pancreatic exocrine insufficiency (PEI) is an under-diagnosed condition. Untreated PEI can result in developing gastrointestinal symptoms and long-term complications including weight loss, nutrient deficiencies, sarcopenia and osteoporosis. Current best practice recommends testing for PEI in certain disorders including chronic pancreatitis, cystic fibrosis, pancreatic cancer and post-pancreatic surgery. However, there is increasing evidence that PEI is associated with a number of conditions in addition to the aforementioned diseases. These 'at-risk' conditions are a heterogeneous group of diseases, for example, diabetes mellitus, people living with human immunodeficiency virus, high alcohol intake, and coeliac disease. The pathophysiology of some of 'at-risk' conditions is becoming increasingly recognised; therefore, the list of associated conditions are in evolving process. We present a case of a 60-year-old male with Parkinson's disease and persistent abdominal pain who was found to have low faecal elastase levels indicative of severe PEI. His past medical history included none of the known risk factors for PEI. After examining the literature, we report a similar pathophysiological process underlying the development of pancreatitis and Parkinson's disease which is dysfunction of the Unfolded Protein Response. We suggest further research to assess the prevalence of PEI in the population of patients with Parkinson's disease.

What is the clinical significance of low serum amylase? Systematic review of the conditions associated with low serum amylase.

Objective: Most studies have assessed the impact of elevated serum amylase levels in clinical practice, but only a few have investigated the significance of low serum amylase. We therefore, aimed to review the literature to understand the conditions associated with low serum amylase and its clinical relevance. Method: This systematic review was performed in accordance with the criteria established in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted on Medline and Embase databases until November 2022. After identifying relevant titles, abstracts were read and data of eligible articles retrieved. The conditions associated with low serum amylase were evaluated. The quality of the studies was assessed using the Newcastle-Ottawa Score. Results: Our search strategy identified 19 studies including a total of 15 097 patients for systematic review. All the studies were observational including two studies which used secretin-induced test. The main conditions associated with low serum amylase were diabetes mellitus (n=9), metabolic syndrome (n=3), chronic pancreatitis (CP) (n=3), non-alcoholic fatty liver disease (n=2) and obesity (n=1). Low serum amylase showed a high specificity (94%) with low sensitivity (38.7%-59%) in diagnosing chronic pancreatitis. Conclusion: This systematic review revealed a unique insight into the relevance of low serum amylase in clinical practice. Low serum amylase can be a useful adjunct test in the assessment of patients with CP, pancreatic exocrine insufficiency, diabetes mellitus and metabolic syndrome.

Chronic atrophic gastritis - An overlooked association with severe vitamin B12 deficiency: A case report and rapid review of literature.

Current guidelines recommend surveillance for gastric adenocarcinoma in patients with extensive chronic atrophic gastritis (CAG), which is considered a premalignant condition. Although the association between vitamin B12 deficiency and CAG is well described, the indication for endoscopic investigation is only advised in patients with pernicious anaemia. Our case did not have evidence of autoimmune or H. pylori infection but despite this she had CAG. We suggest considering gastroscopy for severe, unexplained vitamin B12 deficiency, particularly in this patient group.

Endoscopic removal of common bile duct stones in nonagenarians: a tertiary centre experience.

BACKGROUND/AIMS: There are few studies assessed the efficacy and mortality of endoscopic retrograde cholangiopancreatography (ERCP) for the removal of common bile duct (CBD) stones in the elderly aged ≥90 years. We aimed to assess the safety and efficacy of endoscopic removal of CBD stones in nonagenarians. METHODS: We retrospectively reviewed ERCP reports for CBD stone removal. The endoscopic and therapeutic outcomes were collected. The length of stay (LOS), the total number of adverse events, and mortality rate were compared between groups. RESULTS: A total of 125 nonagenarians were compared with 1,370 controls (65-89 years old individuals). The mean LOS for nonagenarians was significantly higher than in controls (13.6 days vs. 6.5 days). Completed intended treatment was similar in the nonagenarians and controls (89.8% and 89.5%, respectively). The overall complication rate did not differ between the groups. However, nonagenarians had a higher incidence of post-ERCP pneumonia (3.9%). None of the nonagenarians were readmitted to the hospital within 7 days. Four nonagenarians (3.2%) and 25 (1.8%) controls died within 30 days. CONCLUSION: Advanced age alone did not affect the decision to perform the procedure. However, prompt diagnosis and treatment of post-ERCP pneumonia in nonagenarians could improve the outcomes and reduce mortality.

Are we missing pancreatic exocrine insufficiency in 'at-risk' groups? Prospective assessment of the current practice and yield of faecal elastase testing in patients with diabetes mellitus, HIV and/or high alcohol intake.

There is cumulative evidence that pancreatic exocrine insufficiency (PEI) is under-recognised and can occur in patients with 'at-risk' conditions. Thus, we aimed to assess the current practice and yield of requesting faecal elastase (FEL-1), an indicator of PEI, in patients with 'at-risk' conditions. We prospectively recruited patients attending secondary care clinics with diabetes mellitus (DM), people living with HIV (PLHIV) and inpatients admitted to hospital with high alcohol intake (HAI). All patients underwent testing with FEL-1. Those patients with PEI (FEL-1 <200 µg/g) were contacted and offered a follow-up review in gastroenterology clinic. In total, 188 patients were recruited (HAI, n=78; DM, n=64; and PLHIV, n=46). Previous FEL-1 testing had not been performed in any of the patients. The return rate of samples was 67.9% for patients with HAI, 76.6% for those with DM and 56.5% for those with PLHIV. The presence of PEI was shown in 20.4% of patients with DM, 15.4% of patients with PLHIV and 22.6% in those with HAI. Diarrhoea and bloating were the most reported symptoms in followed-up patients with low FEL-1 (31.8% and 22.7% of patients, respectively). Follow-up computed tomography (CT) scans in those patients with PEI identified chronic pancreatitis changes in 13.6% and pancreatic atrophy in 31.8% of patients. These results suggest that there is a lack of testing for PEI in 'at-risk' groups. Our findings also suggest that using FEL-1 to test for PEI in patients with DM, PLHIV and HAI has a significant impact, although further studies are required to validate these findings.

Body composition parameters predict survival in pancreatic cancer-A retrospective multicenter analysis.

BACKGROUND: Parameters to adapt individual treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) are urgently needed. The present study aimed to evaluate body composition parameters as predictors of overall survival (OS) in PDAC patients. METHODS: Measurements of body composition parameters were performed on computed tomography scans at diagnosis. Height-standardized and Body Mass Index- and sex-adjusted regression formulas deriving cut-offs from a healthy population were used. The Kaplan-Meier method with the log-rank test was performed for survival analysis. Independent prognostic factors were identified with uni- and multivariable Cox regression analyses. RESULTS: In total, 354 patients were analyzed. In a multivariable Cox model, besides tumor stage and resection status, only myosteatosis (HR 1.53; 95% CI 1.10-2.14, p = 0.01) was an independent prognostic factor of OS among body composition parameters. Subgroup analyses revealed that the prognostic impact of myosteatosis was higher in patients ≤68 years of age, with advanced tumor stages and patients without curative intended resection. CONCLUSIONS: The analysis of one of the largest Caucasian cohorts to date, demonstrated myosteatosis to be an independent prognostic factor of OS in PDAC. To improve outcomes, prospective trials aiming to investigate the utility of an early assessment of myosteatosis with subsequent intervention by dieticians, sports medicine physicians, and physiotherapists are warranted.

Does reverse mentoring work in the NHS: a feasibility study of clinicians in practice.

OBJECTIVE: To assess the risks and benefits of reverse mentoring of consultants by junior doctors. DESIGN: A feasibility study divided into two phases: first a semistructured interview where performance of participating consultants was assessed by junior doctors and then a second phase allowing for feedback to be given on a one-to-one basis. Data collected through questionnaires with free text questions and Likert scores. SETTING: Tertiary teaching hospital in the UK. PARTICIPANTS: Six junior doctors (66.6% male, age range 31-40 years) and five consultants (80% male, age range 35-65 years and consultants for 5-20 years). INTERVENTION: Reverse mentoring session. MAIN OUTCOME MEASURE: The concerns and/or benefits of the process of reverse mentoring. Confidence was assessed in 7 domains: clinical practice, approach to juniors, approachability, use of technology, time management, strengths and areas for improvement using Likert scales giving a total out of 35. RESULTS: The most common concerns cited were overcoming the hierarchical difference and a selection bias in both mentors and mentees. However, no participant experienced this hierarchical difference through the reverse mentoring process and no relationships were negatively affected. Mentors became more confident in feeding back to seniors (23 vs 29 out of 35, p=0.04) most evident in clinical practice and areas to improve (3 vs 4 out of 5, p=0.041 and 3 vs 5 out of 5, p=0.041, respectively). CONCLUSION: We present the first study of reverse mentoring in an NHS clinical setting. Initial concerns with regard to damaged relationships and hierarchical gradients were not experienced and all participants perceived that they benefited from the process. Reverse mentoring can play a role in engaging and training future leaders at junior stages and provide a means for consultants to receive valuable feedback from junior colleagues.

The Imbalance in Medico-Legal Cover Awareness and Uptake Between Overseas Junior Doctors and Local Graduates in the NHS.

Background Recent reports showed that overseas doctors were more likely than UK graduates to be referred by their employers to the General Medical Council (GMC). We investigated the trend of medico-legal insurance awareness and uptake of medical defence organisations (MDOs) by junior doctors and to examine if there is a difference between overseas and UK graduates. Methods Online questionnaire survey sent to junior doctors within the Yorkshire and Humber Deanery. Data regarding year of graduation, country of origin of primary medical qualification, year of starting work in the National Health Service (NHS) and date of joining an MDO were collected. Participant-identifiable information was not collected. Results A total of 202 junior doctors completed the survey: 153 (76%) UK graduates and 49 (24%) overseas. Overseas doctors were less likely to know about MDO compared to UK graduates prior to working in the NHS (13 [26.5%] vs. 146 [95.4%]; p < 0.0001). At the time of starting practice, MDO uptake was still significantly lower amongst overseas graduates (4 [8.2%] vs. 144 [94.1%]; p < 0.0001). Uptake by overseas doctors increased after starting work to 33 (67.3%). However, despite improvement in MDO uptake, a significant number of overseas doctors still did not have independent cover compared with UK graduates (16 [32.7%] vs. 3 [2%]; p < 0.0001). Conclusions Overseas graduates joining the NHS are still less likely to be aware of the requirement of adequate medico-legal cover and are less likely to join an MDO compared with UK graduates. Healthcare providers and regulators should work to decrease the existing gap and increase awareness amongst newly arrived overseas doctors.

Computed Tomographic Sarcopenia in Pancreatic Cancer: Further Utilization to Plan Patient Management.

PURPOSE: The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting 'computed tomographic sarcopenia' is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC). METHODS: Patients diagnosed with LAPC referred for endoscopic ultrasound-guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) were noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. RESULTS: In total, 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received best supportive care (BSC) only. The prevalence of sarcopenia (p = 0.0003), age ≥ 75 years old (p = 0.03), and ECOG-PS 2-3 (p = 0.01) were significantly higher in the patients receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. CONCLUSION: Our study has shown that computed tomographic skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

Yield of testing for micronutrient deficiencies associated with pancreatic exocrine insufficiency in a clinical setting: An observational study.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) can be difficult to diagnose and causes maldigestion symptoms and malabsorption. There has been a number of studies that have identified PEI associated micronutrient deficiencies (PEI-MD), however there is variation in both the frequency and type of PEI-MD reported, with the majority of studies including patients with PEI due to chronic pancreatitis (CP) or CP without PEI. There is a paucity of information regarding the prevalence of PEI-MD in patients with PEI without CP and the yield of testing for PEI-MD in a clinical setting in patients with suspected benign pancreatic diseases. AIM: To prospectively assess the yield and type of PEI-MD in patients with and without PEI secondary to benign pancreatic disease. METHODS: Patients investigated for maldigestion symptoms with Faecal Elastase-1 (FEL-1) and suspected or proven benign pancreatic disease were prospectively identified. At the time of FEL-1 testing, serum samples were taken for micronutrients identified by previous studies as PEI-MD: prealbumin, retinol binding protein, copper, zinc, selenium, magnesium and later in the study lipid adjusted vitamin E. FEL-1 was recorded, with a result < 200 µg/g considered diagnostic of PEI. Patients underwent computed tomography (CT) imaging when there was a clinical suspicion of CP, a new diagnosis of PEI recurrent, pancreatic type pain (epigastric abdominal pain radiating to back with or without previous acute pancreatitis attacks) or weight loss. RESULTS: After exclusions, 112 patients were recruited that underwent testing for FEL-1 and PEI-MD. PEI was identified in 41/112 (36.6%) patients and a pancreatic CT was performed in 82 patients. Overall a PEI-MD was identified in 21/112 (18.8%) patients. The yield of PEI-MD was 17/41 (41.5%) if PEI was present which was significantly higher than those without 4/71 (5.6%) (P = 0.0001). The yield of PEI-MD was significantly higher when PEI and CP were seen together 13/22 (59.1%) compared to CP without PEI and PEI without CP (P < 0.03). Individual micronutrient assessment showed a more frequent occurrence of prealbumin 8/41 (19.5%), selenium 6/41 (14.6%) and magnesium 5/41 (12.2%) deficiency when PEI was present (< 0.02). The accuracy of using the significant micronutrients identified in our cohort as a predictor of PEI showed a positive predictive value of 80%-85.7% [95% confidence interval (CI): 38%-100%] and a low sensitivity of 9.8%-19.5% [95% CI: 3.3%-34.9%]. CONCLUSION: Testing for PEI-MD in patients with suspected pancreatic disease has a high yield, specifically when PEI and CP are found together. PEI-MD testing should include selenium, magnesium and prealbumin.

Recent advances in the diagnosis and management of pancreatic neuroendocrine tumours.

The incidence of pancreatic neuroendocrine tumours (PNET) is rising mainly due to the increased use of cross-sectional imaging. Although many PNETs are asymptomatic and non-functioning, the overall 5-year survival is still less than 50%. In this article, we review the advances in diagnosis, classification and staging of PNET that have evolved with the development of new cross-sectional imaging methods and biopsy techniques. With accurate classification, evidence-based, individualised prognostic outcomes and treatments are able to be given which are also discussed.

Practical guide to the management of chronic pancreatitis.

Chronic pancreatitis (CP) is an irreversible fibroinflammatory disorder of the pancreas. It presents with relapsing, remitting upper abdominal pain accompanied by features of malabsorption due to pancreatic exocrine insufficiency and endocrine deficiency with the development of diabetes mellitus. The associated increased hospitalisation and high economic burden are related to CP often presenting at advanced stage with irreversible consequences. Diagnosing CP at an early stage is still challenging and therefore CP is believed to be under-reported. Our understanding of this disease has evolved over the last few years with attempts to redesign the definition of CP. Better recognition of the risk factors and conditions associated with CP can lead to an earlier diagnosis and coupled with a multidisciplinary approach to treatment, ultimately reduce complications. This article reviews the epidemiology, risk factors, diagnosis and management of CP.

INTERNATIONAL: Overseas doctors of the NHS: migration, transition, challenges and towards resolution.

Overseas doctors are playing an important role in the successful running of the NHS. They represent one-third of the total number of UK doctors and include doctors from the European Economic Area and international medical graduates. The main aim of this review is to explore the challenges that overseas doctors might face when they take up their first job in the UK. We conducted literature search using MEDLINE and EMBASE databases. The inclusion and exclusion criteria were designed to include published literature concerning overseas doctors in the UK and the NHS. Lack of information about the UK health system; language and communication challenges; clinical, educational and work-culture challenges; and discrimination challenges are some of the difficulties that overseas doctors might experience. Understanding these challenges and providing support are important steps in helping overseas doctors to make a smooth transition.