International Consensus Diagnostic Criteria Research Articles

Diagnosis, treatment and long-term outcomes of autoimmune pancreatitis in Spain based on the International Consensus DiagnosticCriteria: A multi-centre study.

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that has been reported worldwide for the last two decades. The aim of this study is to analyse the clinical profile of patients from Spain with AIP, as well as treatments, relapses and long-term outcomes. Data from 59 patients with suspected AIP that had been diagnosed in 15 institutions are retrospectively analysed. Subjects are classified according to the International Consensus Diagnostic Criteria (ICDC). Patients with type 1 AIP (AIP1) and type 2 AIP (AIP2) are compared. Kaplan-Meier methodology is used to estimate the overall survival without relapses. Fifty-two patients met ICDC, 45 patients were AIP1 (86.5%). Common manifestations included abdominal pain (65.4%) and obstructive jaundice (51.9%). Diffuse enlargement of pancreas was present in 51.0%; other organ involvement was present in 61.5%. Serum IgG4 increased in 76.7% of AIP1 patients vs. 20.0% in AIP2 (p=0.028). Tissue specimens were obtained in 76.9%. Initial successful treatment with steroids or surgery was achieved in 79.8% and 17.3%, respectively. Maintenance treatment was given in 59.6%. Relapses were present in 40.4% of AIP1, with a median of 483 days. Successful long-term remission was achieved in 86.4%. AIP1 is the most frequent form of AIP in Spain in our dataset. Regularly, ICDC allows AIP diagnosis without the need for surgery. Steroid and chirurgic treatments were effective and safe in most patients with AIP, although maintenance was required many times because of their tendency to relapse. Long-term serious consequences were uncommon.

Clinical and pathophysiological issues associated with type 1 autoimmune pancreatitis.

In 1995, Yoshida and colleagues proposed the concept of 'autoimmune pancreatitis' (AIP). Recently, it is accepted that the existence of two subtypes of AIP-type 1, which involves immunoglobulin G4 (IgG4) as the pancreatic manifestation of IgG4-related disease (IgG4-RD), and type 2, which is characterized by granulocytic epithelial lesions. Type 2 AIP is thought to be rare in Japan. In 2011, the International Consensus Diagnostic Criteria (ICDC) for autoimmune pancreatitis was proposed. In Japan, the clinical diagnostic criteria of AIP 2011 was proposed by the Japan Pancreas Society (JPS) and the Research Committee of Intractable Diseases of the Pancreas. The JPS 2011 is based on ICDC and a simplified checklist of items to diagnose type 1 AIP. Although recent progress in type 1 AIP has resolved clinical features, diagnosis, treatment, and pathogenesis, many clinical and basic issues still remain unclear. Here, we provide an overview of the recent clinical and basic issues associated with type 1 AIP.

Prospective multicenter study on the usefulness of EUS-guided FNA biopsy for the diagnosis of autoimmune pancreatitis

In the International Consensus Diagnostic Criteria (ICDC), autoimmune pancreatitis (AIP) is classified into types 1 and 2, and its definite histopathology diagnosis can be made based only on surgical or core biopsy specimens. Although EUS-guided FNA (EUS-FNA) biopsy is a safe technique for the collection of pancreatic tissue, no consensus viewpoint has been reached with regard to the role of EUS-FNA biopsy in the diagnosis of AIP. This study investigated the utility of pancreatic tissue collected by EUS-FNA biopsy by using a standard 22-gauge aspiration needle in the diagnosis of AIP. Patients with suspected AIP were prospectively enrolled in Nagoya University Hospital and Nagoya University-affiliated institutions. Pancreatic tissue was collected from each by EUS-FNA biopsy with a standard 22-gauge aspiration needle. Fifty patients were registered, including 45 with a final diagnosis of AIP. Lymphoplasmacytic infiltration and abundant immunoglobulin G4-positive plasmacyte infiltration (>10/high-power field) were detected in 36(72%) and 27 (54%) patients, respectively. Obliterative phlebitis and storiform fibrosis were not detected in our study. Granulocytic epithelial lesions (GEL) were observed in 3 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA biopsy to definitively diagnose AIP were 7.9% (3/38), 100% (12/12), 100% (3/3), and 25.5% (12/47), respectively. Pathology evaluation of pancreatic tissue collected by EUS-FNA biopsy improved the diagnostic accuracy in 8 (16%) of the 50 patients. In this study, EUS-FNA biopsy by using a standard 22-gauge aspiration needle is not an effective diagnostic method for most patients with AIP. The combination of level 2 histology diagnosis of AIP with other findings specified in the ICDC slightly improved the diagnostic accuracy, although it still remains insufficiently accurate forroutine clinical use.( 000006297.).

Autoimmune Pancreatitis: The Past, Present, and Future.

Before the immunoglobulin G4 (IgG4) era, autoimmune pancreatitis was proposed as a single clinical entity of autoimmune disease. In the IgG4 era, the following 2 subtypes have been proposed: type 1 is the pancreatic manifestation of IgG4-related disease and type 2 presents with granulocytic epithelial lesions. The characteristic features of type 1 are increased serum IgG4, lymphoplasmacytic sclerosing pancreatitis (abundant infiltration of IgG4+ plasmacytes and lymphocytes, storiform fibrosis, and obliterative phlebitis), other organ involvements (eg, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis), and responsiveness to steroid. Diagnosis of both types can be made using the International Consensus Diagnostic Criteria. Different from type 2, approximately half of type 1 shows a relapse within 1 year after remission. Despite consensus for the initial steroid treatment, steroid maintenance and treatment for relapses are controversial. In the long term, approximately 10% of type 1 may develop chronic pancreatitis or pancreatic stone formation. It is controversial whether autoimmune pancreatitis is a risk factor for malignancy. Although the pathogenic mechanism remains unclear, multiple factors such as genetic background and abnormal immunity may be involved. Future studies should be conducted to identify more specific and novel biomarkers for each subtype, alternative treatment options for relapse, and the precise pathogenic mechanism.

Unnecessary Procedures and Surgery in Autoimmune Pancreatitis

Background/Aims: To identify the number and potential causes of unnecessary diagnostic procedures in a cohort of patients with autoimmune pancreatitis (AIP). Methods: All AIP cases at our centre between April 2006 and April 2013 were collected and followed up. Diagnosis was established by the International Consensus Diagnostic Criteria (ICDC). Demographic, clinical, radiological, serological data, the number of diagnostic procedures and the reason for referral were recorded. Possible risk factors for a delayed diagnosis of AIP were analysed. Results: A total of 29 patients (median age 60 years; 22 males and 7 females) were diagnosed with AIP using ICDC. Twenty-five patients were diagnosed with definite, 2 with possible type 1 AIP and 2 with type 2 AIP. In 29 patients, 50 ERCPs and 18 EUS were carried out; based on ICDC recommendations, a total of 20 ERCPs and 4 EUS were unnecessary diagnostic procedures. Eight patients (23.0%) were referred for unnecessary surgery. Jaundice was shown to be a significant risk factor for unnecessary endoscopic investigations (OR 11.00, 95% CI 1.14-106.43, p = 0.04). Conclusion: Diagnosis of AIP still remains a challenge. Patients with jaundice are at particular risk of being subjected to unnecessary endoscopic procedures. Use of ICDC would help avoid unnecessary examinations or even major surgeries at times.

Autoimmune Pancreatitis: A Diagnostic Challenge for the Clinician.

Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis that poses a diagnostic challenge to the clinician in that it mimics pancreatic cancer and presents with painless obstructive jaundice. In this review, we discuss the two types of AIP: type 1, known as lymphoplasmacytic sclerosing pancreatitis and type 2, known as idiopathic duct centric pancreatitis. Type 1 AIP is considered as a pancreatic manifestation of immunoglobulin G4-related disease. The etiopathogenesis of AIP, particularly type 2 AIP, is largely unknown. Both types of AIP have unique pancreatic histological features; however, the radiological and clinical features may mimic those of pancreatic cancer. The most commonly used diagnostic criteria, including the Japan Pancreas Society criteria, the Mayo Clinic HISORt (histology, imaging serology, other organ involvement, and response to therapy) criteria, and the International Association of Pancreatology's international consensus diagnostic criteria, that help to differentiate AIP from pancreatic cancer are reviewed in this article. The treatment of choice for induction of remission for AIP is steroid therapy. Relapses are more common in type 1 AIP. In selected patients, immunomodulators such as azathioprine and rituximab are used to maintain remission.

Recent developments in steroid-responsive pancreatitides (autoimmune pancreatitis).

There are two distinct steroid responsive chronic fibro-inflammatory diseases of the pancreas, called type 1 and type 2 autoimmune pancreatitis (AIP). We review recent progress in this field. It has recently been suggested that the term AIP be used to describe type 1 AIP and the term idiopathic duct-centric chronic pancreatitis (IDCP) be used for type 2 AIP. Clinical features and long-term outcomes of AIP and IDCP are well characterized and prognosis of both diseases is excellent. Diagnostic strategies tailored to regional practice patterns have emerged with the application of International Consensus Diagnostic Criteria for AIP. Although corticosteroids remain the mainstay of treatment, management of relapses and strategies for preventing multiple relapses are better understood, including the role of maintenance therapy and B-cell depletion therapy with rituximab. Association studies with malignancies have yielded conflicting results regarding risk of cancer in AIP. The treatment, follow-up guidelines and associations continue to evolve with our increasing experience with both AIP and IDCP. In AIP, rituximab can be used for both induction and maintenance of remission. IDCP responds to steroids without need for maintenance therapy. Both AIP and IDCP have excellent prognosis.

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Clinical profiles and outcomes in idiopathic duct-centric chronic pancreatitis (type 2 autoimmune pancreatitis): the Mayo Clinic experience

Idiopathic duct-centric chronic pancreatitis (IDCP), also known as type 2 autoimmune pancreatitis (AIP), is an uncommon subtype of AIP. International Consensus Diagnostic Criteria for IDCP propose that the diagnosis requires pancreatic histology and/or concurrent IBD. We examined our experience with IDCP (type 2 AIP) to assess the appropriateness of these criteria, and identify unique characteristics in patients presenting with acute pancreatitis. We reviewed the Mayo Clinic AIP database through May 2014 to identify subjects with either definitive (n=31) or probable (n=12) IDCP. We compared demographic and clinical factors based on strength of diagnostic confidence (definitive versus probable), presence of IBD, and acute pancreatitis as the presenting manifestation. Relapse-free survival was determined using the Kaplan-Meier method. The clinical profiles were similar irrespective of the diagnostic criteria fulfilled. Common clinical presentations included acute pancreatitis (n=25, 58.1%, 12 of whom (27.9%) had recurrent pancreatitis) and pancreatic mass/obstructive jaundice (n=15, 34.9%). The cumulative relapse rate was 10.6% at 3 years (median follow-up 2.9 years). Relapse-free survival was similar for the different diagnostic categories, but was decreased in those initially presenting with acute pancreatitis (p=0.047) or treated with steroids (vs surgery, p=0.049). The current diagnostic classification of probable IDCP and the inclusion of IBD as a supportive criterion appear valid, because patients have similar clinical profiles and disease-related outcomes to those with definitive IDCP. Concurrent IBD, especially in young patients, may suggest when IDCP is the underlying cause of recurrent acute pancreatitis, but additional studies are needed for validation.

Tu1650 Feasibility and Diagnostic Yield of a New EUS Guided Histology 20-Gauge Needle in the Evaluation of Intraintestinal and Extraintestinal Lesions

Tu1650 Feasibility and Diagnostic Yield of a New EUS Guided Histology 20-Gauge Needle in the Evaluation of Intraintestinal and Extraintestinal Lesions

IgG4-related disease: dataset of 235 consecutive patients.

Immunoglobulin G4-related disease (IgG4-RD) is a recently discovered systemic condition, in which various organ manifestations are linked by a similar histological appearance. Our knowledge of this condition is still fragmented, as most studies have examined only a few dozen patients or focused on a particular organ manifestation. This study was conducted to learn the demography and patient characteristics of IgG4-RD using a large cohort. A total of 235 consecutive patients with IgG4-RD, diagnosed in 8 general hospitals in the same medical district, were identified by searching the institutions’ radiology database. Inclusion criteria were histology-proven IgG4-RD according to the Pathology Consensus Statement and/or definitive type 1 autoimmune pancreatitis meeting the International Consensus Diagnostic Criteria. Clinical notes and images of selected patients were retrospectively reviewed. All patients were adults (M/F = 4/1). The median age was 67 years (range 35–86). Nine tenths were diagnosed in their 50s to 70s. Among 486 manifestations identified in total, the most common was pancreatitis diagnosed in 142 patients (60%), followed by sialadenitis (34%), tubulointerstitial nephritis (23%), dacryoadenitis (23%), and periaortitis (20%). The majority of patients (95%) had at least 1 of the 5 most common manifestations. Male and female patients differed in their organ manifestations (periaortitis more common in males and sialodacryoadenitis more common in females). Serum IgG4 (normal ≤135 mg/dL) was elevated to >135 mg/dL in 208 patients (88%) and >270 mg/dL in 167 (71%). The IgG4 value was significantly higher in patients with multiorgan involvement than in those with a single manifestation (median 629 mg/dL vs 299 mg/dL, P < 0.01). Of 218 patients, for whom both IgG4 and IgG values were available, the IgG4/IgG ratio was raised to >10% in 194 (89%). Corticosteroids were effective, but the relapse rate was estimated to be 24% in the study period (median 37 months). During the follow-up, 15 malignant diseases were diagnosed in 13 patients (6%). This figure is similar to the incidence (12.9 cancers) expected from the Japanese nationwide study for cancer epidemiology (standardized incidence ratio 1.16). In conclusion, this reliable dataset could improve the characterization of IgG4-RD, particularly its unique demography and the frequency of each organ manifestation.

Prevalence and clinicopathological features of autoimmune pancreatitis in Japanese patients with inflammatory bowel disease.

The purpose of this study was to clarify the clinicopathological characteristics of autoimmune pancreatitis (AIP) in Japanese patients with inflammatory bowel disease (IBD). The clinicopathological findings of 7 patients with IBD whose definite AIP was diagnosed in our hospital according to the International Consensus Diagnostic Criteria were reviewed. Five (0.5%) of 961 patients with ulcerative colitis (UC) and 2 (0.3%) of 790 patients with Crohn disease had AIP. All of 7 patients whose AIP was diagnosed were type 2. The rate of elevated values of serum immunoglobulin G4 was 0%. Most patients with the diagnosis of IBD preceded that of AIP, and disease activity of IBD were active. Granulocyte epithelial lesion is similar to the cryptitis seen in colonic tissue of UC. All of 7 patients were given corticosteroids, immunomodulators, and/or biological agents for IBD. One patient had a recurrence. The frequency of AIP in Japanese patients with IBD was low. All cases were type 2 and responded well to corticosteroids, immunomodulators, and biological agents. Autoimmune pancreatitis in UC patients may be an extraintestinal manifestation of UC.

IgG4-related disease of the breast: a systemic disease whose mammary manifestations mimic breast cancer

IgG4-related disease is a newly identified disease entity that has begun to attract attention, and international consensus diagnostic criteria for the condition have recently been proposed. The characteristic features of IgG4-related disease are lymphoplasmacytic infiltration involving a high proportion of IgG4-positive cells, fibrosis exhibiting a storiform pattern, and obliterative phlebitis. It can affect various organs, including the breast (in rare cases). IgG4-related disease has previously been referred to as inflammatory myofibroblastic tumor, plasma cell granuloma, or pseudolymphoma. We have experienced a case of IgG-related disease of the breast. Clinically and cytologically, the lesion was somewhat similar to a malignant tumor. An immunohistochemical examination of a core needle biopsy sample resulted in a correct diagnosis. In addition, a review of the patient’s clinical history revealed that the disease had affected areas other than the breast. Clinicians should be aware that breast lesions can be a focal manifestation of systemic disease, and overdiagnosis should be avoided by performing appropriate pathological analysis.

Autoimmune pancreatitis with colonic stenosis: an unusual complication and atypical pancreatographic finding

BackgroundType 1 autoimmune pancreatitis (AIP) often accompanies various systematic disorders such as sclerosing cholangitis, sialoadenitis, retroperitoneal fibrosis, interstitial pneumonitis and nephritis. Although rarely reported in acute pancreatitis, colonic stenosis is an uncommon complication in cases with AIP.Case presentationA 69-year-old Japanese man complained of abdominal pain and continuous diarrhea, resistant to intake of antimuscarinic and probiotic agents. A colonoscopy demonstrated a stenosis at the splenic flexure. Computed tomography revealed a focal enlargement of the pancreatic tail with a capsule-like rim, contacting with the descending colon. Endoscopic retrograde pancreatography (ERP) was unable to visualize the main pancreatic duct (MPD) at the pancreatic tail, despite a full contrast injection. A high serum IgG4 level (1060 mg/dL) and exclusion of pancreatic cancer by endoscopic ultrasound guided-fine needle aspiration suggested AIP, but did not fulfill the diagnostic criteria, and steroid therapy was initiated. One month after starting steroid intake, pancreatic swelling was minimized and the MPD was visualized by ERP, fulfilling the international consensus diagnostic criteria (ICDC) of AIP. Colonic stenosis was relieved and the patient’s symptoms disappeared.ConclusionThe present case is the first report of AIP developing colonic stenosis by the inflammatory infiltration. In this case, steroid therapy was effective for the diagnosis and treatment of pancreatic mass involving the descending colon.

Recent advances in pancreatology.

Recent advances in pancreatology.

Autoimmune pancreatitis--treatment and pitfalls in diagnostics

Autoimmune pancreatitis (AIP) was first classified as a defined disease entity in 1995. It accounts for approximately 2 % of cases of chronic pancreatitis (western world prevalence 36-41/100,000 inhabitants) and AIP is diagnosed in 2.4 % of pancreas resection specimens. Presentation of strategies for diagnosis and treatment with focus on differentiation of AIP and pancreatic carcinoma. Selective literature research in PubMed regarding pathogenesis, diagnosis and treatment of AIP. Key characteristics of AIP are recurrent jaundice due to obstructed bile ducts, histological evidence of fibrosis, a lymphoplasmocytic or granulocytic infiltrate and the response to steroid therapy. There are two distinctive forms of AIP: type I or lymphoplasmocytic sclerosing pancreatitis and type II or idiopathic duct centric pancreatitis. The IgG4 positive AIP type I belongs to the group of IgG4-related systemic diseases. Diagnosis of AIP is established according to the international consensus diagnostic criteria (ICDC) or HISORt (mnemonic standing for histology, imaging, serology, other organ involvement and response to therapy) criteria. Differentiation from pancreatic adenocarcinoma can be challenging. The standard treatment consists of corticosteroids and in some cases azathioprine can be added. In refractory disease rituximab is a further option. Treatment is indicated in patients with jaundice, systemic manifestation or persistent pain. Although AIP is increasingly being identified, the differentiation from pancreatic adenocarcinoma still remains difficult and in cases of a suspicion of neoplasia, resection should be favored. It can successfully be treated conservatively with steroids and rituximab.

Comparison and validation of International Consensus Diagnostic Criteria for diagnosis of autoimmune pancreatitis from pancreatic cancer in a Taiwanese cohort

ObjectivesThe International Consensus Diagnostic Criteria (ICDC) designed to diagnosis autoimmune pancreatitis (AIP) has been proposed recently. The diagnostic performance of ICDC has not been previously evaluated in diffuse-type and focal-type...

Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels

Background/objectivesTo distinguish autoimmune pancreatitis (AIP), especially focal type, from pancreatic cancer, is a greatest challenge for clinician. The aim of the study is to compare the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of combined serum IgG4 and CA19-9 levels to differentiate AIP from pancreatic cancer by HISORt, Asian and international consensus diagnostic criteria. MethodsWe measured serum IgG4, CEA, and CA19-9 levels in 188 AIP patients, 86 non-AIP chronic pancreatitis patients, and 130 pancreatic cancer patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were compared with different diagnostic criteria. We also compared the diagnostic performance in patients with or without jaundice. ResultsThe serum level of IgG4 was significantly higher in AIP than those in non-AIP chronic pancreatitis and pancreatic cancer. The optimal cutoffs of IgG4 and CA19-9 to differentiate AIP from pancreatic cancer were 175 mg/dL and 85.0 U/ml based on ROC analysis. Combining IgG4 level over 280 mg/dL and CA19-9 below 85.0 U/ml could yield a best diagnostic accuracy (85.6%) to distinguishing AIP from pancreatic cancer in all of the HISORt, Asian and international consensus diagnostic criteria. With the combination of serological test, focal type AIP could be diagnosed with comparable accuracy as diffuse type AIP. ConclusionsOur study demonstrated that combined use of serum IgG4 (over 280 mg/dL) and CA19-9 9 (below 85.0 U/ml) together increases the diagnostic accuracy to distinguish AIP from pancreatic cancer non-invasively, especially in focal type autoimmune pancreatitis.

Retrospective Comparison Between Preoperative Diagnosis by International Consensus Diagnostic Criteria And Histological Diagnosis in Patients With Focal Autoimmune Pancreatitis Who Underwent Surgery With Suspicion of Cancer

The objective of this study was to compare the preoperative diagnosis by International Consensus Diagnostic Criteria (ICDC) with histological diagnosis in patients with focal autoimmune pancreatitis (AIP) who underwent surgery. Thirty patients (type 1 AIP in 23 and type 2 AIP in 7) with a diagnosis of AIP based on histology of surgical specimens were classified according to ICDC based on their preoperative data. Pancreatic core biopsies and diagnostic steroid trial were not preoperatively performed in any of the patients. Based on preoperative data, ICDC diagnosed 6 patients (20%) as having type 1 AIP and 24 (80%) as probable AIP. Assuming all patients had responded to a steroid trial preoperatively, ICDC would have diagnosed 8 patients (27%) as having type 1 AIP, 4 (13%) as type 2 AIP, 10 as AIP-not otherwise specified (33%), and 8 (27%) as probable AIP. In the hypothetical situation, 7 of 8 type 1 AIP patients and 3 of 3 type 2 AIP patients would have been classified into the correct subtype of AIP. A steroid trial enhances the possibility of correctly diagnosing AIP by ICDC despite the lack of histology. However, some patients cannot be diagnosed as having AIP or be classified into the correct subtype without histology.

Validation of international consensus diagnostic criteria for focal type autoimmune pancreatitis in a Taiwanese cohort

Peter Macinga , Adela Pulkertova , Jana Maluskova , Martin Oliverius , Julius Spicak , Tomas Hucl a a Institute for Clinical and Experimental Medicine, Department of Hepatogastroenterology, Czech Republic b Institute for Clinical and Experimental Medicine, Department of Clinical and Transplant Pathology, Czech Republic c Institute for Clinical and Experimental Medicine, Department of Transplant Surgery, Czech Republic