Gavin J. Johnson

Presentation and Management of Post-treatment Relapse in Autoimmune Pancreatitis/Immunoglobulin G4-Associated Cholangitis

BACKGROUND & AIMS Autoimmune pancreatitis (AIP) is a multisystem disorder that often has extrapancreatic manifestations such as immunoglobulin G4-associated cholangitis (IAC). Patients respond rapidly to steroids but can relapse after therapy. We assessed the clinical management of relapse in a group of patients with AIP/IAC. METHODS We performed a prospective study of patients diagnosed with AIP from 2004-2007 who received steroids. Treatment outcome was defined clinically, radiologically, and biochemically as response to steroids, remission after steroids, failure to wean steroids, and relapse. Steroids +/- azathioprine (AZA) were used to treat patients who failed, relapsed, or could not be weaned from steroids. RESULTS Twenty-eight patients with AIP were studied; 23 (82%) had IAC. All patients responded within 6 weeks to prednisolone therapy. Twenty-three patients achieved remission after a median of 5 months of treatment (range, 1.5-17 months), whereas 5 patients (18%) could not be weaned because of a disease flare. Of the patients who achieved remission, 8 of 23 (35%) subsequently relapsed. Overall, 13 of 23 patients (57%) with AIP/IAC relapsed, compared with 0 of the 5 with isolated AIP (P = .04, Fisher exact test). Steroids were increased/restarted in all patients who relapsed; 10 also received AZA. Remission was achieved and maintained in 7 patients; they remain on AZA monotherapy at a median of 14 months (range, 1-27 months). CONCLUSIONS Relapse or failure to wean steroids occurred in 46% of patients with AIP. Patients with IAC are at particularly high risk of relapse. AZA appears to be effective in patients with post-treatment relapse or who cannot be weaned from steroids. To view this articles video abstract, go to the AGAs YouTube Channel.

Good questions, good answers: construct alignment improves the performance of workplace-based assessment scales

Medical Education 2011: 45: 560–569

Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicentre study

Background Characteristic pancreatic duct changes on endoscopic retrograde pancreatography (ERP) have been described in autoimmune pancreatitis (AIP). The performance characteristics of ERP to diagnose AIP were determined. Methods The study was done in two phases. In phase I, 21 physicians from four centres in Asia, Europe and the USA, unaware of the clinical data or diagnoses, reviewed 40 preselected ERPs of patients with AIP (n=20), chronic pancreatitis (n=10) and pancreatic cancer (n=10). Physicians noted the presence or absence of key pancreatographic features and ranked the diagnostic possibilities. For phase II, a teaching module was created based on features found most useful in the diagnosis of AIP by the four best performing physicians in phase I. After a washout period of 3 months, all physicians reviewed the teaching module and reanalysed the same set of ERPs, unaware of their performance in phase I. Results In phase I the sensitivity, specificity and interobserver agreement of ERP alone to diagnose AIP were 44, 92 and 0.23, respectively. The four key features of AIP identified in phase I were (i) long (>1/3 the length of the pancreatic duct) stricture; (ii) lack of upstream dilatation from the stricture (<5 mm); (iii) multiple strictures; and (iv) side branches arising from a strictured segment. In phase II the sensitivity (71%) of ERP significantly improved (p<0.05) without a significant decline in specificity (83%) (p>0.05); the interobserver agreement was fair (0.40). Conclusions The ability to diagnose AIP based on ERP features alone is limited but can be improved with knowledge of some key features.

Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort.

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.

Cholangiocarcinoma and dominant strictures in patients with primary sclerosing cholangitis: a 25-year single-centre experience.

Background Dominant biliary strictures occur commonly in patients with primary sclerosing cholangitis (PSC), who have a high risk of developing cholangiocarcinoma (CC). The natural history and optimal management of dominant strictures remain unclear, with some reports suggesting that endoscopic interventions improve outcome. Methods We describe a 25-year experience in patients with PSC-related dominant strictures at a single tertiary referral centre. Results A total of 128 patients with PSC (64% men, mean age at referral 49 years) were followed for a mean of 9.8 years. Eighty patients (62.5%) with dominant biliary strictures had a median of 3 (range 0–34) interventions, compared with 0 (0–7) in the 48 patients without dominant strictures (P<0.001). Endoscopic interventions included the following: (i) stenting alone (46%), (ii) dilatation alone (20%), (iii) dilatation and stenting (17%) and (iv) none or failed intervention (17%, of whom most required percutaneous transhepatic drainage). The major complication rate for endoscopic retrograde cholangiopancreatography was low (1%). The mean survival of those with dominant strictures (13.7 years) was worse than that for those without dominant strictures (23 years), with much of the survival difference related to a 26% risk of CC developing only in those with dominant strictures. Half of those with CC presented within 4 months of the diagnosis of PSC, highlighting the importance of a thorough evaluation of new dominant strictures. Conclusion Repeated endoscopic therapy in PSC patients is safe, but the prognosis remains worse in the subgroup with dominant strictures. In our series, dominant strictures were associated with a high risk of developing CC.

Endoscopic Retrograde Cholangiography Does Not Reliably Distinguish IgG4-Associated Cholangitis From Primary Sclerosing Cholangitis or Cholangiocarcinoma

BACKGROUND & AIMS Distinction of immunoglobulin G4-associated cholangitis (IAC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma is challenging. We aimed to assess the performance characteristics of endoscopic retrograde cholangiography (ERC) for the diagnosis of IAC. METHODS Seventeen physicians from centers in the United States, Japan, and the United Kingdom, unaware of clinical data, reviewed 40 preselected ERCs of patients with IAC (n = 20), PSC (n = 10), and cholangiocarcinoma (n = 10). The performance characteristics of ERC for IAC diagnosis as well as the κ statistic for intraobserver and interobserver agreement were calculated. RESULTS The overall specificity, sensitivity, and interobserver agreement for the diagnosis of IAC were 88%, 45%, and 0.18, respectively. Reviewer origin, specialty, or years of experience had no statistically significant effect on reporting success. The overall intraobserver agreement was fair (0.74). The operating characteristics of different ERC features for the diagnosis of IAC were poor. CONCLUSIONS Despite high specificity of ERC for diagnosing IAC, sensitivity is poor, suggesting that many patients with IAC may be misdiagnosed with PSC or cholangiocarcinoma. Additional diagnostic strategies are likely to be vital in distinguishing these diseases.

Cerebral involvement in IgG4-related disease

IgG4-related disease is a recently recognised multi-system disease. Common organ involvement includes the pancreas, biliary tree and salivary glands. Central nervous system involvement has been infrequently reported. In a single-centre cohort of 84 patients, we report cerebral involvement in three (4%) patients. Details of cerebral involvement in these patients are outlined, including pituitary involvement in two patients and a diffuse autoimmune-like encephalopathy in the other.

The Acute Care Assessment Tool: a new assessment in acute medicine

T he Royal College of Physicians has produced a new training programme for trainee doctors, consisting of two new competency-based curricula (JRCPTB 2007a, 2007b) and an electronic portfolio (e-portfolio). The General Internal Medicine (Acute) curriculum aims to train doctors to become competent in the delivery of effective care in the acute setting. The Generic curriculum aims to deliver doctors that are equipped with generic doctorly competencies, i.e. to practise within a sound moral, legal, ethical and professional framework, by the end of the specialist training.

Multicenter experience from the UK and Ireland of use of lumen-apposing metal stent for transluminal drainage of pancreatic fluid collections

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 %.

Pancreatoscopy-Directed Electrohydraulic Lithotripsy for Pancreatic Ductal Stones in Painful Chronic Pancreatitis Using SpyGlass.

Objective Painful chronic pancreatitis is often associated with main duct obstruction due to stones. Approaches to management are challenging, including surgery, extracorporeal shock wave lithotripsy, or endoscopic approaches. Here, we report our experience of pancreatoscopy + electrohydraulic lithotripsy (EHL) for pancreatic duct (PD) stones using SpyGlass. Methods We retrospectively audited the use of SpyGlass (Legacy and DS) + EHL. Indication, procedural details, and clinical outcomes were assessed. Results A total of 118 SpyGlass + EHL procedures for stones were performed, of which 8 (7%) for pancreatic stones, in 6 patients (3 female; mean [standard deviation] age, 45 [7] years). All patients had painful chronic pancreatitis, with radiological evidence of a dilated PD, and main duct stone disease. Surgical options had been considered in all cases. Stone fragmentation and PD decompression were achieved in 83% (n = 5) without complications. Two patients required 2 EHL procedures to achieve clearance. In 1 patient with failed clearance, pancreatoscopy revealed a stone in the adjacent parenchyma and not in PD. All patients with successful EHL had pain relief/marked improvement at clinical review (mean [standard deviation] follow-up, 2.7 [1.1] years). Conclusions Pancreatoscopy + EHL may have a valuable role in treating obstructing PD stones, possibly avoiding the need for surgery in some patients.