Autoimmune Pancreatitis Not Otherwise Specified (AIP-NOS): The Importance of Gastroenterology Consultation When Clinical Findings Are Concerning for Pancreatic Cancer

Biliary plastic stent does not influence the accuracy of endoscopic ultrasound-guided sampling of pancreatic head masses performed with core biopsy needles

During the last decade, patients with steroid responsive sclerosing cholangitis have been described in a number of case reports and a few cases series. These patients meet diagnostic criteria for primary sclerosing cholangitis (PSC) but seem to have a better prognosis and are often, but not always, associated with autoimmune pancreatitis (AIP). Unlike biliary strictures in PSC, most PSC-like biliary strictures seen in association with AIP respond well to steroids and some have been shown to resolve after immunosuppressive treatment during prolonged follow-up. In addition, steroid-responsive dominant bile duct lesions, sometimes mimicking infiltrating hilar cholangiocarcinoma, without pancreatic abnormalities have also been reported. Here we review the literature on this emerging clinical entity and suggest that this condition of steroid responsive biliary strictures be named Immunoglobulin G4 (IgG4) Associated Cholangitis (IAC). We performed an electronic database search of MEDLINE for case reports and case series of sclerosing cholangitis with pancreatitis and/or pancreatic mass (1960–July 2006). Articles were limited to English and these case reports and cases series were reviewed and all references on the combination of sclerosing cholangitis and pancreatitis as well as IgG4 positive cholangitis without pancreatic involvement not identified by our original search were obtained. Terminology and Definition

EUS-guided FNA for diagnosing autoimmune pancreatitis: Doesit enhance existing consensus criteria?

Background: To determine the diagnostic performance of elevated serum Immunoglobulin G4 (IgG4) in the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer. Methods: We retrospectively analyzed serum IgG4 levels in 865 patients with suspected AIP. There were 57 patients with confirmed AIP, 146 with pancreatic cancer, 9 with idiopathic pancreatitis, 104 with acute pancreatitis, 106 with chronic pancreatic disease, and 443 with other pancreatic conditions, including benign enlargement of pancreas, abdominal pain, or obstructive jaundice. Results: The median serum IgG4 level was significantly greater in AIP patients than in patients with other pancreatic diseases (442.0 vs. 73.8 mg/dL, p＜0.001). Based on an IgG4 cutoff value of 132 mg/dL (determined by receiver operating curve analysis), the sensitivity, specificity, and positive predictive values in the differential diagnosis of AIP and pancreatic cancer were 94.7%, 78.8%, and 63.5% respectively. Use of an IgG4 cutoff of 132 mg/dL meant that 31 of 146 patients (21.2%) with pancreatic cancer had elevated serum IgG4, 3 of 57 patients with AIP (5.2%) did not have elevated serum IgG4, and the positive and negative predictive values for diagnosis of AIP were 63.5% and 97.5% respectively. Conclusion: Serum IgG4 concentrations were significantly greater in AIP patients than in patients with other pancreatic diseases. A serum concentration of IgG4 that is more than 2 times the upper limit of normal is highly suggestive of AIP, but does not totally rule out pancreatic cancer. Mild (＜2-fold) elevations in serum IgG4 were present in many subjects without AIP, including 16.4% of subjects with pancreatic cancer. IgG4 elevation in a patient with a low pretest probability of having AIP is likely to represent a false positive. However, the high predictive value and high positive likelihood ratio confirm the good performance of 2-fold cutoff value in the differential diagnosis of AIP and pancreatic cancer.Background: To determine the diagnostic performance of elevated serum Immunoglobulin G4 (IgG4) in the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer. Methods: We retrospectively analyzed serum IgG4 levels in 865 patients with suspected AIP. There were 57 patients with confirmed AIP, 146 with pancreatic cancer, 9 with idiopathic pancreatitis, 104 with acute pancreatitis, 106 with chronic pancreatic disease, and 443 with other pancreatic conditions, including benign enlargement of pancreas, abdominal pain, or obstructive jaundice. Results: The median serum IgG4 level was significantly greater in AIP patients than in patients with other pancreatic diseases (442.0 vs. 73.8 mg/dL, p＜0.001). Based on an IgG4 cutoff value of 132 mg/dL (determined by receiver operating curve analysis), the sensitivity, specificity, and positive predictive values in the differential diagnosis of AIP and pancreatic cancer were 94.7%, 78.8%, and 63.5% respectively. Use of an IgG4 cutoff of 132 mg/dL meant that 31 of 146 patients (21.2%) with pancreatic cancer had elevated serum IgG4, 3 of 57 patients with AIP (5.2%) did not have elevated serum IgG4, and the positive and negative predictive values for diagnosis of AIP were 63.5% and 97.5% respectively. Conclusion: Serum IgG4 concentrations were significantly greater in AIP patients than in patients with other pancreatic diseases. A serum concentration of IgG4 that is more than 2 times the upper limit of normal is highly suggestive of AIP, but does not totally rule out pancreatic cancer. Mild (＜2-fold) elevations in serum IgG4 were present in many subjects without AIP, including 16.4% of subjects with pancreatic cancer. IgG4 elevation in a patient with a low pretest probability of having AIP is likely to represent a false positive. However, the high predictive value and high positive likelihood ratio confirm the good performance of 2-fold cutoff value in the differential diagnosis of AIP and pancreatic cancer.

Background: Chronic pancreatitis (CP), pancreatic cancer (PCa), and autoimmune pancreatitis (AIP) often present as a pancreatic mass. Accurate diagnosis is not always possible; up to 8% of surgical procedures are performed in benign pancreatic masses presumed to be malignant. Objectives: We aimed to compare clinical and imaging characteristics of resected focal type 2 AIP, CP, and PCa and identify factors that could improve preoperative differential diagnosis. Methods: Charts from patients that underwent pancreatic resection under suspicion of PCa between 2000 and 2014 were reviewed. Clinical and imaging data were recorded. Subjects were grouped as type 2 AIP, CP, and PCa. Results: We included 79 cases; 41 men, mean age of 57.3 years/old ± 15.6 SD. Pathology report was type 2 AIP (20%), CP (10%), and PCa (70%). According to international consensus criteria for AIP 11 cases were deemed probable type 2 and 5 as unspecific pancreatic mass. A nondilated main pancreatic duct (MPD) was associated with AIP (OR 9.3; 95% CI 3.05–28.7), p < 0.001; obstructive jaundice (OR 28.5; 95% CI 8.18–79.5); and a dilated MPD (OR 5.21; 95% CI 1.9–14.6) suggested malignancy. Conclusions: In the setting of undetermined pancreatic focal mass, a nondilated MPD suggests the diagnosis of type 2 AIP.

Substitution of Aspartic Acid at Position 57 of the DQβ1 Affects Relapse of Autoimmune Pancreatitis

Best Practices in Endoscopic Ultrasound–Guided Fine-Needle Aspiration

Diagnosis of Autoimmune Pancreatitis: The Evolution of Diagnostic Criteria for a Rare Disease

Introduction: Autoimmune pancreatitis (AIP) is a chronic inflammatory condition typically presenting with abdominal pain, jaundice and weight loss. AIP is an uncommon cause of pancreatitis and diagnosis may be challenging, but it is highly responsive to corticosteroids. We present a case of painless obstructive jaundice complicated by a mass on the pancreatic head. Case Description/Methods: A 57-year-old Indian male with no past medical history presented with vague abdominal pain, pruritus, and clay colored stools. Vital signs were unremarkable and laboratory investigations revealed alkaline phosphatase 515 U/L, alanine transaminase 732 IU/L, and total bilirubin 7.6 mg/dL. The patient underwent a right upper quadrant ultrasound which showed an enlarged gallbladder and dilated common bile duct (1.9 cm) down to the level of the pancreatic head. An endoscopic ultrasound (EUS) revealed a 3.2 x 3.7 cm hypoechoic mass in the head of the pancreas obstructing the bile duct, 2 enlarged lymph nodes in the area near the bile duct, marked bile duct dilation, and an enlarged sludge-filled gallbladder. Of note, unlike most ductal tumors the pancreatic duct upstream of the mass was not dilated. Fine needle aspiration (FNA) was unsuccessful due to the obstruction by the lymph nodes. Endoscopic retrograde cholangiopancreatography (ERCP) showed stricture of bile duct consistent with a pancreatic head mass, and was stented. Abdominal and pelvic computed tomography (CT) confirmed a 3 cm pancreatic head mass. Pathology result from the attempted FNA was inconclusive. Further labs revealed normal IgG4 and CA 19-9 level of 194; indicative of possible pancreatic malignancy. The patient developed jaundice, scleral icterus and rapid weight loss. EUS with FNA with repeat biopsies revealed rare degenerated epithelial cells. The patient was treated with high dose steroids, with planned pancreaticoduodenectomy. Follow-up CT revealed resolution of the pancreatic mass and was confirmed by repeat EUS/ERCP and normal CA 19-9 level. Discussion: Although painless obstructive jaundice with a pancreatic mass is a typical presentation for a pancreatic neoplasm; it is not the only possible diagnosis. Despite biochemical and radiographic evidence suggesting a malignancy; if AIP remains in the differential, a trial of steroids may be warranted to avoid unnecessary surgical intervention and associated morbidity.

It is of utmost importance that autoimmune pancreatitis (AIP) be differentiated from pancreatic cancer (PC) because some AIP cases undergo unnecessary laparotomy or pancreatic resection on suspicion of PC. This study aimed to develop an appropriate strategy for differentiating between AIP and PC. Clinical, serological, and radiological features of 17 AIP patients forming a masslike lesion on pancreas head and 70 patients with pancreatic head cancer were compared. Numerous findings can be used to distinguish between AIP and PC, and the following are more likely in AIP: fluctuating jaundice; elevated serum IgG4 levels; delayed enhancement of the enlarged pancreas and a capsule-like low-density rim on computed tomography; long or skipped narrowed portion with side branches of the main pancreatic duct without upstream dilatation on endoscopic retrograde pancreatography, extrapancreatic lesions, such as stenosis of the intrahepatic bile duct, salivary gland swelling, and retroperitoneal mass; and responsiveness to steroid therapy. In elderly male patients presenting with obstructive jaundice and a pancreatic mass, AIP should be considered in the differential diagnosis. Based on a combination of clinical, serological, and radiological findings, AIP can be differentiated from PC. An algorithm for management of patients with a masslike lesion on pancreas head is presented.

Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist?

Autoimmune Chronic Pancreatitis

Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents: an evidence-based approach

Diagnostic criteria for autoimmune pancreatitis (AIP) have been proposed and used clinically because, despite its unique clinicopathological features, AIP does not have disease-specific serological tests for confirmation. However, diagnosis of a patient with pancreatic lesions mimicking cancer who deviates from these diagnostic criteria is still difficult. We present herein a patient with a variant form of AIP successfully diagnosed by fine-needle biopsy, whose response to steroid therapy was excellent. A 55-year-old Japanese man was admitted to hospital because of jaundice and pancreatic head mass. AIP was considered as one of the differential diagnoses; however, as the patient showed neither pancreatic duct narrowing nor immunological abnormalities, he did not meet the Japanese diagnostic criteria for AIP. Histopathology of the pancreatic mass demonstrated abundant infiltration by lymphocytes and interstitial fibrosis, which suggested AIP. Immunoreaction to IgG4, which is supposed to be specific to AIP, was not observed; however, response to subsequent prednisolone therapy was good, with dramatic pancreatic head mass regression. Aside from the pancreatic head mass, diffusely spreading small lesions were observed throughout the liver. The likelihood of a potential association with extrapancreatic lesions of AIP was considered and led us to carry out a liver biopsy, which revealed biliary hamartoma, also called von Meyenburg complex (VMC). As IgG4-positive plasma cell infiltration was not demonstrated in the hamartomatous regions, the hepatic condition was thought to have occurred incidentally; however, to the best of our knowledge, this is the first report in which the association between AIP and VMC was investigated and discussed.

Introduction: Presentation of autoimmune pancreatitis (AIP) can be similar to pancreatic adenocarcinoma (PAC) with a pancreatic mass that may cause obstructive jaundice. Chronic pancreatitis predisposes patients to PAC. The relationship between AIP and PAC is unknown. The aim of this systematic review is to determine the frequency of incident PAC in AIP, and secondarily to assess for prevalent PAC and AIP. Methods: A systematic search using PubMed, Embase, Scopus & Cochrane was performed. Search criteria included “autoimmune pancreatitis,” “pancreatic cancer,” “adenocarcinoma,” & “carcinoma” with all permutations. AIP was defined by international guidelines. Our inclusion criterion for incident PAC cases was a minimum of 1 year between AIP and PAC diagnoses to exclude prevalent cancers. The inclusion criterion for prevalent PAC cases was defined by presence of AIP and PAC within 1 year. The search yielded 636 results reviewed by 2 authors. 8 case reports and 4 retrospective studies with a total of 19 patients were included in the combined analyses. Results: There were 7 cases of incident PAC, with 4/7 (57.1%) men, mean age 67±14.1yrs (Range 39-80yrs) (Table 1). Mean time from AIP to PAC diagnosis was 78.1±60.9months (Range 12-186 months). 6/7 (85.7%) patients received prednisone therapy for AIP. 12 total cases of prevalent PAC with AIP were identified, all of which were men, mean age 61.4±5yrs (Range 53-70yrs) (Table 2). All prevalent cases of PAC with AIP were diagnosed simultaneously, with pathologic confirmation of both entities present on histology in 11/12 cases. Medical treatment of AIP was not reported for any prevalent PAC cases. Stage of PAC at diagnosis when reported was similar between incident & prevalent cases with most cases being unresectable (60% vs. 66.7%). Conclusion: Development of PAC in underlying AIP is exceedingly rare with only 7 total incident cases reported in the literature. The absolute risk remains unknown and was unable to be calculated based on included study types in this analysis. The number of prevalent cases of PAC concomitantly diagnosed with AIP should prompt a comprehensive investigation to exclude the presence of underlying malignancy and should be performed in cases of newly diagnosed AIP. Further prospective studies are warranted to determine overall risk of PAC in AIP.2733_A Figure 1. Study Characteristics of Autoimmune Pancreatitis Patients who Developed Incident Pancreatic Adenocarcinoma2733_B Figure 2. Study Characteristics of Autoimmune Pancreatitis Patients who had Prevalent Pancreatic Adenocarcinoma