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Woo J, Sano K, Oshio K, Suzuki A, Isayama H, Saiura A, Fukumura Y, Kamagata K, Kuwatsuru R, Aoki S. Differentiation of Autoimmune Pancreatitis From Pancreatic Ductal Adenocarcinoma by Diffusion-Weighted Magnetic Resonance Imaging With Weighted Diffusion Subtraction. Cureus 2025; 17:e81438. [PMID: 40303521 PMCID: PMC12037419 DOI: 10.7759/cureus.81438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/29/2025] [Indexed: 05/02/2025] Open
Abstract
Purpose Weighted diffusion subtraction (WDS) is a new imaging technique derived from a pair of diffusion-weighted images (DWIs) using low and high b values. This study assesses the diagnostic performance of WDS in distinguishing pancreatic ductal adenocarcinoma (PDAC) from autoimmune pancreatitis (AIP) by comparing the efficacy of DWI alone compared to DWI with WDS. Methods The patient cohort consisted of 10 patients diagnosed with AIP and 28 patients diagnosed with PDAC. Two blinded radiologists reviewed the MRI images and assessed their diagnostic accuracy and confidence levels. Differences between groups A (DWI alone) and B (DWI added WDS) were assessed, and a receiver operating characteristic (ROC) curve analysis was performed. Inter-reader agreement was analyzed using weighted κ statistics, and apparent diffusion coefficient (ADC) values were calculated for both AIP and PDAC. Results In diagnostic accuracy, Group B demonstrated significantly higher area under the curve (AUC) values than Group A for both readers. The inter-reader agreement was evaluated as "substantial" in both groups. The mean confidence scores for Group B were significantly higher than those for Group A for both readers. Conclusion The addition of WDS to DWI may enhance the visual differentiation between AIP and PDAC, potentially improving diagnostic accuracy and confidence.
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Affiliation(s)
- Jun Woo
- Department of Radiology, Jikei University School of Medicine, Tokyo, JPN
| | - Katsuhiro Sano
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Koichi Oshio
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Akiyoshi Suzuki
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Hiroyuki Isayama
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Koji Kamagata
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Ryohei Kuwatsuru
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, JPN
| | - Shigeki Aoki
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, JPN
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Tłustochowicz K, Krajewska A, Kowalik A, Małecka-Wojciesko E. Treatment Strategies for Chronic Pancreatitis (CP). Pharmaceuticals (Basel) 2025; 18:311. [PMID: 40143090 PMCID: PMC11945612 DOI: 10.3390/ph18030311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are diseases with overlapping features, both requiring complex management strategies. CP is characterized by pancreatic exocrine insufficiency (PEI) and pain, with treatment focused on symptom relief through pancreatic enzyme replacement therapy (PERT), pain control, and lifestyle and nutritional changes. However, the standard therapy does not address the underlying inflammation or fibrosis, which drives disease progression. AIP, on the other hand, presents with obstructive jaundice and fibrosis and is classified into two subtypes: Type 1 (AIP-1), linked to IgG4-related disease, and Type 2 (AIP-2), associated with inflammatory bowel disease. Treatment for AIP typically involves oral steroids. Immunomodulators and rituximab are used for recurrent or refractory cases. Novel therapies targeting the inflammation and fibrotic components of CP are being explored. A multidisciplinary approach is essential to optimize care and improve patients' outcomes.
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Affiliation(s)
| | | | | | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland; (K.T.); (A.K.)
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Zhu S, Cao X, Nabi G, Zhang F, Liu P, Zhang J, Guo C. Contrast-enhanced endoscopic ultrasound for differential diagnosis of autoimmune pancreatitis: a meta-analysis. Endosc Int Open 2024; 12:E1134-E1142. [PMID: 39398443 PMCID: PMC11466521 DOI: 10.1055/a-2409-5519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 04/25/2024] [Indexed: 10/15/2024] Open
Abstract
Background and study aims To assess the diagnostic value of contrast-enhanced endoscopic ultrasound (CE-EUS) for autoimmune pancreatitis and other solid pancreatic masses. Patients and methods A systematic search of PubMed, Embase, and Web of Science was performed from inception to October 2022. We calculated individual and pooled sensitivities and specificities to determine the diagnostic ability of CE-EUS. In addition, we calculated I 2 to test for heterogeneity and explored the source of heterogeneity by meta-regression analysis. Results A total of 472 patients from seven eligible studies were included. The mean sensitivity and specificity of the Bivariate analysis were 0.84 (95% CI 0.71-0.92) and 0.95 (95% CI 0.84-0.99), respectively. The diagnostic advantage ratio was 107.91 (95% confidence interval [CI] 22.22-524.13), and the area under the summary receiver operating characteristics curve was 0.91 (95% CI 0.88-0.93). The overall heterogeneity of the studies is negligible (I 2 =0, 95% CI 0-100). However, notable heterogeneity was observed in the combined specificity ( P <0.01, I 2 =74.82) and diagnostic odds ratio ( P =0.05, I 2 =51.54). The heterogeneity in these aspects could be elucidated through sensitivity analysis. Conclusions Our analysis showed that CE-EUS is useful in identifying autoimmune pancreatitis. However, further large sample size, multicenter, prospective studies are needed to demonstrate its utility.
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Affiliation(s)
- Shanshan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinguang Cao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ghulam Nabi
- ENdocrinology and Physiology, Institute of Nature Conservation PAS, Krakow, Poland
| | - Fangbin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ping Liu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jingwen Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Changqing Guo
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Karamya ZA, Kovács A, Illés D, Czakó B, Fazekas A, Farkas N, Hegyi P, Czakó L. Prevalence of autoimmune pancreatitis in pancreatic resection for suspected malignancy: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:278. [PMID: 39169289 PMCID: PMC11337777 DOI: 10.1186/s12876-024-03367-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 08/09/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND/OBJECTIVES Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer. METHODS A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles. RESULTS Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients). CONCLUSION Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.
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Affiliation(s)
- Zain A Karamya
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary
| | - Attila Kovács
- Department of Gastroenterology and Internal Medicine, Markusovszky Teaching Hospital, Szombathely, Hungary
| | - Dóra Illés
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary
| | - Bálint Czakó
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary
| | - Alíz Fazekas
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Nelli Farkas
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Division of Pancreatic Diseases, Heart and Vascular Centre, Semmelweis University, Budapest, Hungary
| | - László Czakó
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary.
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Datta D, Selvakumar B, Goel AD, Chhibber S, Varshney VK, Kumar R. Diagnostic performance of F-18 FDG PET/CT in differentiating autoimmune pancreatitis from pancreatic cancer: a systemic review and meta-analysis. Ann Nucl Med 2024; 38:619-629. [PMID: 38750330 DOI: 10.1007/s12149-024-01934-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 04/18/2024] [Indexed: 06/14/2024]
Abstract
OBJECTIVES This study aims to evaluate the utility of F-18 FDG PET/CT in the non-invasive diagnosis of autoimmune pancreatitis (AIP) and differentiating it from pancreatic cancer (CaP) based on the amount and pattern of FDG uptake, as well as involvement of extra-pancreatic sites. METHODS A systematic search was conducted using PubMed, Scopus, Cochrane Library and Google Scholar. Only those studies that compared the findings of F-18 FDG PET/CT in terms of SUVmax, pattern of FDG uptake and presence of FDG-avid extra-pancreatic sites in both AIP and CaP were included. Studies were qualitatively assessed for risk of bias and publication bias. The diagnostic performance of parameters on PET/CT was examined through pooled sensitivity, specificity, diagnostic odd's ratio (DOR) and summary receiver operator characteristic (SROC) curve analysis. RESULTS Six studies were included with a total of 580 patients. 178 patients had AIP (Age 18-90 years, male, M: female, F ratio-8.4:1) and 402 patients had CaP (Age 22-88 years, M:F ratio-1.5:1). Type of AIP was reported in only 3 studies, with the included cases predominantly being type 1 AIP. All studies were retrospective with heterogeneity and a risk on patient selection and index test. The FDG uptake, expressed as SUVmax, was lower in AIP with a weighted mean difference of -3.11 (95% confidence interval, CI: -5.28 to -0.94). To diagnose AIP, the pooled sensitivity, specificity and DOR of diffuse pattern of FDG uptake were 0.59 (95% CI: 0.51-0.66), 0.89 (95% CI: 0.86-0.92) and 21.07 (95% CI: 5.07-88.32), respectively, with an area under curve (AUC) of 0.717 on SROC analysis. The pooled sensitivity, specificity and DOR of FDG-avid extra pancreatic sites were 0.55 (95% CI: 0.45-0.65), 0.58 (95% CI: 0.52-0.64) and 2.33 (95% CI: 1.40-3.89), respectively, with an AUC of 0.632. CONCLUSION On F-18 FDG PET/CT, a pancreatic lesion of AIP has a lower SUVmax value than CaP. A diffuse pattern of FDG uptake and presence of an extra-pancreatic FDG-avid site are nearly 21 times and twice more likely in AIP than CaP, respectively.
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Affiliation(s)
- Deepanksha Datta
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - B Selvakumar
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Basni Industrial Area Phase 2, Jodhpur, Rajasthan, 342005, India.
| | - Akhil Dhanesh Goel
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | | | - Vaibhav Kumar Varshney
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Basni Industrial Area Phase 2, Jodhpur, Rajasthan, 342005, India
| | - Rajesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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Gallo C, Dispinzieri G, Zucchini N, Invernizzi P, Massironi S. Autoimmune pancreatitis: Cornerstones and future perspectives. World J Gastroenterol 2024; 30:817-832. [PMID: 38516247 PMCID: PMC10950636 DOI: 10.3748/wjg.v30.i8.817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/18/2023] [Accepted: 01/25/2024] [Indexed: 02/26/2024] Open
Abstract
Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.
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Affiliation(s)
- Camilla Gallo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Giulia Dispinzieri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Nicola Zucchini
- Department of Pathology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
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7
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Liu B, Tang N, Yao Y, Li H, Xu L, Zhou B, Liu B. Steroid treatment response combined with serological mark in differentiating type-1 autoimmune pancreatitis from pancreatic cancer. Medicine (Baltimore) 2022; 101:e31660. [PMID: 36397434 PMCID: PMC9666219 DOI: 10.1097/md.0000000000031660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 10/13/2022] [Indexed: 11/19/2022] Open
Abstract
Autoimmune pancreatitis (AIP) and pancreatic cancer (PC) are two different diseases. Their diagnosis, treatment, and prognosis are different, and it is difficult to differentiate them. This study aimed to explore the role of steroid treatment response combined with serological mark in distinguishing type-1 AIP from PC. Clinical data were collected and compared from 50 cases of AIP (group 1) and 100 cases of PC (group 2). The diagnostic value of serum IgG4, CA19-9, globulin, and eosinophil cell (EC) were evaluated. The response of steroid treatment of 28 patients with atypical imaging in group 1 was analyzed. After 2 weeks, the patients were classified as positive and negative steroid response according to the manifestations and/or the radiological changes. The positive response cases (n = 20) were confirmed as AIP, whereas negative ones (n = 8) were finally diagnosed as PC after complete resection. Serum globulin, IgG4, and EC levels in group 1 were significantly higher than those in group 2 (P < .01), and CA19-9 levels were distinctly lower in group 1 (P < .01). The level of serum IgG4 was related to the accuracy of diagnosis of AIP on the basis of the result of logistic regression analysis. Two-weeks steroid therapy response combined with serum IgG4 levels contribute to the differential diagnosis AIP and PC. However, regular and long-term follow-up were important for the differential diagnosis. There was an urgent need to explore the specific markers that distinguish these 2 entities.
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Affiliation(s)
- Bingqian Liu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Ning Tang
- Department of Nutrition, Weifang People’s Hospital, Shandong Province, China
| | - Yuan Yao
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Hua Li
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Lishan Xu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Bin Zhou
- Department of Biliary and Pancreatic Surgery, Department of Retroperitoneal Tumor Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Bin Liu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
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8
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Lee SC, Yang CH, Chang CT, Yu KH. Diagnostic Utility of Serum IgG4 in Autoimmune Pancreatitis: An Updated Comprehensive Systematic Review and Meta-analysis. J Clin Gastroenterol 2022; 56:810-817. [PMID: 34516462 DOI: 10.1097/mcg.0000000000001612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Despite many studies suggesting an association between serum immunoglobulin G4 (sIgG4) and autoimmune pancreatitis (AIP), the evidence of utility in differentiation between AIP and pancreatic cancer (PC) remain uncertain. METHODS The analysis based on published studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, diagnostic odds ratios (DOR), areas under summary receiver operating characteristic curves were calculated. RESULTS In the included thirteen studies, sIgG4 were measured in 594 patients with AIP and 958 patients with PC. The pooled sensitivity, specificity, DOR, and area under the curve were 0.72 [95% confidence interval (CI): 0.68-0.75], 0.93 (95% CI: 0.92-0.95), 51.37 (95% CI: 23.20-113.74), and 0.91 (95% CI: 0.87-0.95). Subgroup analyses of the DORs for region and year: Asia, (112.10; 95% CI: 27.72-453.32), non-Asia (26.01; 95% CI: 12.38-54.65), and year before 2011 (107.61; 95% CI: 39.30-294.68), year after 2011 (26.96; 95% CI: 9.78-74.32). Overall, sIgG4 was associated with AIP, the result revealed a moderate sensitivity 0.72 and high specificity 0.93. In the meta-analysis, the pooled DOR of sIgG4 levels of 2-fold upper limit 50.44 was similar with the DOR 51.37 when 1-fold cut-off value, but the summary receiver operating characteristic was 0.755 and 0.91. The higher specificity (from 93% to 98%) derived from the cut-off value (from 130-140 to 260-280 mg/dL) for sIgG4 occurred at a significant reduction in sensitivity (from 72% to 43%). CONCLUSIONS The study revealed sIgG4 is a good marker of AIP. Screening of sIgG4 may help clinicians differentiate between AIP and PC, and the best cut-off value should be 140 rather than 280 mg/dL.
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Affiliation(s)
- Shih-Ching Lee
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan
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Nadi A, Benhayoun Y, Cherkaoui R, Delsa H, Rouibaa F. Case Series of Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis. Cureus 2022; 14:e26657. [PMID: 35949783 PMCID: PMC9357350 DOI: 10.7759/cureus.26657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2022] [Indexed: 11/05/2022] Open
Abstract
IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease that can involve any organ. The involvement of the pancreas and biliary tract is the most common and well-studied in the literature. It is characterized by a non-specific presentation, mimicking a malignant process. The goal was to look at the different clinical and paraclinical aspects of this disease, as well as the challenges that come from its management. It was made up of three observations of patients with IgG4-RD involving the biliary tract and pancreas. The first observation concerned intrahepatic biliary cholangitis that was accompanied by porto-mesenteric thrombosis, which was discovered by cholestatic jaundice on the 15th day after an appendectomy, and the patient improved under corticosteroids and anticoagulants. The second observation concerned an acute revelation of the disease. It was an acute attack of chronic pancreatitis of IgG4-RD. The main symptoms were pancreatic pain and exocrine pancreatic insufficiency, and corticosteroid therapy allowed remission. The third observation was related to autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis, revealed by jaundice with cholestasis. The patient acquired corticosteroid resistance and an adverse progression to decompensated cirrhosis, and liver transplantation was indicated. The clinical presentation of IgG4-RD is heterogeneous, as evidenced by our three clinical observations. There are still significant gaps in our understanding, particularly in terms of pathogenesis and factors that influence therapy response. Further observational and interventional research is needed to better manage this disease.
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Affiliation(s)
- Anass Nadi
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Yassamin Benhayoun
- Gastroenterology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Reda Cherkaoui
- Radiology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Hanane Delsa
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Fedoua Rouibaa
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
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10
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Adam Z, Zeman D, Čermák A, Dastych M, Doubková M, Horváth T, Skorkovská Š, Adamová Z, Řehák Z, Koukalová R, Pour L, Štork M, Krejčí M, Sandecká V, Ševčíková S, Král Z. IgG4-related disease. Clinical manifestation differential diagnosis and recent International Diagnostic Criteria for IgG4-related disease. VNITRNI LEKARSTVI 2022; 68:4-19. [PMID: 36283812 DOI: 10.36290/vnl.2022.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder. Autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum, prostate and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD and in 2019 four Clinical phenotypes of IgG4-related disease were described. Diagnosis is based on morphological examination with typical findings of lymphoplasmocellular inflammation, storiform fibrosis and obliterative phlebitis in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. New diagnostic criteria for IgG4-RD have been published recently in 2019 and 2021. This review summarizes current knowledge on pathophysiology, clinical manifestations, diagnosis and differential diagnosis of IgG4-RD from the point of view 2022 and in next article brings overview of the IgG4-RD therapy.
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11
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Masood M. Autoimmune pancreatitis: What we know so far. JGH Open 2021; 6:3-10. [PMID: 35071782 PMCID: PMC8762623 DOI: 10.1002/jgh3.12688] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 11/12/2021] [Accepted: 11/20/2021] [Indexed: 12/19/2022]
Abstract
Autoimmune pancreatitis (AIP) is a rare, often‐missed disease that involves inflammation of the pancreas and strictures of the pancreatic duct. Its prevalence and incidence in the United States remain scarce. The disease has a varied presentation and often mimics pancreatic malignancy, which can make the diagnosis challenging. Most patients have an excellent response to corticosteroid therapy. Immunomodulators may be used in some cases. Rituximab is an effective, emerging treatment in steroid‐refractory cases. This study aims to review the two distinct types of AIP and provide a detailed analysis of the diagnostic approach and treatment modalities.
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Affiliation(s)
- Muaaz Masood
- Department of Internal Medicine Medical College of Georgia at Augusta University Augusta Georgia USA
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12
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Ziegelmayer S, Kaissis G, Harder F, Jungmann F, Müller T, Makowski M, Braren R. Deep Convolutional Neural Network-Assisted Feature Extraction for Diagnostic Discrimination and Feature Visualization in Pancreatic Ductal Adenocarcinoma (PDAC) versus Autoimmune Pancreatitis (AIP). J Clin Med 2020; 9:jcm9124013. [PMID: 33322559 PMCID: PMC7764649 DOI: 10.3390/jcm9124013] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 11/25/2020] [Accepted: 12/08/2020] [Indexed: 12/12/2022] Open
Abstract
The differentiation of autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC) poses a relevant diagnostic challenge and can lead to misdiagnosis and consequently poor patient outcome. Recent studies have shown that radiomics-based models can achieve high sensitivity and specificity in predicting both entities. However, radiomic features can only capture low level representations of the input image. In contrast, convolutional neural networks (CNNs) can learn and extract more complex representations which have been used for image classification to great success. In our retrospective observational study, we performed a deep learning-based feature extraction using CT-scans of both entities and compared the predictive value against traditional radiomic features. In total, 86 patients, 44 with AIP and 42 with PDACs, were analyzed. Whole pancreas segmentation was automatically performed on CT-scans during the portal venous phase. The segmentation masks were manually checked and corrected if necessary. In total, 1411 radiomic features were extracted using PyRadiomics and 256 features (deep features) were extracted using an intermediate layer of a convolutional neural network (CNN). After feature selection and normalization, an extremely randomized trees algorithm was trained and tested using a two-fold shuffle-split cross-validation with a test sample of 20% (n = 18) to discriminate between AIP or PDAC. Feature maps were plotted and visual difference was noted. The machine learning (ML) model achieved a sensitivity, specificity, and ROC-AUC of 0.89 ± 0.11, 0.83 ± 0.06, and 0.90 ± 0.02 for the deep features and 0.72 ± 0.11, 0.78 ± 0.06, and 0.80 ± 0.01 for the radiomic features. Visualization of feature maps indicated different activation patterns for AIP and PDAC. We successfully trained a machine learning model using deep feature extraction from CT-images to differentiate between AIP and PDAC. In comparison to traditional radiomic features, deep features achieved a higher sensitivity, specificity, and ROC-AUC. Visualization of deep features could further improve the diagnostic accuracy of non-invasive differentiation of AIP and PDAC.
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Affiliation(s)
- Sebastian Ziegelmayer
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
| | - Georgios Kaissis
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
- Department of Computing, Faculty of Engineering, Technology and Medicine, Imperial College of Science, London SW7 2BU, UK
| | - Felix Harder
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
| | - Friederike Jungmann
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
| | - Tamara Müller
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
| | - Marcus Makowski
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
| | - Rickmer Braren
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; (S.Z.); (G.K.); (F.H.); (F.J.); (T.M.); (M.M.)
- German Cancer Consortium, Partner Site Technical University of Munich, D-69120 Heidelberg, Germany
- Correspondence: ; Tel.: +49-89-4140-5627
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Pelaez-Luna M, Soriano-Rios A, Lira-Treviño AC, Uscanga-Domínguez L. Steroid-responsive pancreatitides. World J Clin Cases 2020; 8:3411-3430. [PMID: 32913848 PMCID: PMC7457102 DOI: 10.12998/wjcc.v8.i16.3411] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/03/2020] [Accepted: 07/30/2020] [Indexed: 02/05/2023] Open
Abstract
Autoimmune pancreatitis has received considerable attention, especially due to the marked effect of corticosteroid therapy on its clinical course. Knowledge, especially regarding type 1 autoimmune pancreatitis, has significantly increased over the last decades, and despite significant differences in pathophysiology and outcomes, both type 1 and 2 autoimmune pancreatitis are still considered different types of the same disease. Some have proposed a different nomenclature reflecting these differences. Although the term steroid-responsive pancreatitides may be interpreted as synonymous to type 1 and 2 autoimmune pancreatitis, these are not the only pancreatic conditions that show a response to steroid therapy. Acute pancreatitis caused by vasculitis and connective tissue diseases and acute pancreatitis secondary to checkpoint inhibitors or programmed cell death receptor antibody-mediated blockage cancer therapy may also benefit from steroid treatment. This review presents current concepts on these disorders, aiming to increase awareness, analyze similarities and differences, and propose a new nomenclature that reflects their specific particularities, clustering them under the term "steroid-responsive pancreatitides".
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Affiliation(s)
- Mario Pelaez-Luna
- Research Division School of Medicine, Universidad Nacional Autonoma de México, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Andrea Soriano-Rios
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Ana C Lira-Treviño
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Luis Uscanga-Domínguez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
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14
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Ghassem-Zadeh S, Hufnagel K, Bauer A, Frossard JL, Yoshida M, Kutsumi H, Acha-Orbea H, Neulinger-Muñoz M, Vey J, Eckert C, Strobel O, Hoheisel JD, Felix K. Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach. Int J Mol Sci 2020; 21:E2403. [PMID: 32244327 PMCID: PMC7177860 DOI: 10.3390/ijms21072403] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 03/27/2020] [Accepted: 03/30/2020] [Indexed: 12/13/2022] Open
Abstract
Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients' sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.
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Affiliation(s)
- Sahar Ghassem-Zadeh
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany; (S.G.-Z.); (M.N.-M.); (O.S.)
- Department of Biochemistry, University of Lausanne, 1066 Epalinges-Lausanne, Switzerland;
| | - Katrin Hufnagel
- Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
| | - Andrea Bauer
- Department of Functional Genomics, DKFZ, 69120 Heidelberg, Germany; (A.B.); (J.D.H.)
| | - Jean-Louis Frossard
- Department of Medical Specialties, Division of Gastroenterology, University Hospital of Geneva, 1205 Geneva, Switzerland;
| | - Masaru Yoshida
- Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan;
| | - Hiromu Kutsumi
- Center for Clinical Research and Advanced Medicine Shiga University of Medical Science Seta Tsukinowa-cho, Otsu 520-2192, Japan;
| | - Hans Acha-Orbea
- Department of Biochemistry, University of Lausanne, 1066 Epalinges-Lausanne, Switzerland;
| | - Matthias Neulinger-Muñoz
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany; (S.G.-Z.); (M.N.-M.); (O.S.)
| | - Johannes Vey
- Institute of Medical Biometry and Informatics, University Medical Center Ruprecht-Karls University Heidelberg, 69120 Heidelberg, Germany;
| | - Christoph Eckert
- Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany;
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany; (S.G.-Z.); (M.N.-M.); (O.S.)
| | - Jörg D. Hoheisel
- Department of Functional Genomics, DKFZ, 69120 Heidelberg, Germany; (A.B.); (J.D.H.)
| | - Klaus Felix
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany; (S.G.-Z.); (M.N.-M.); (O.S.)
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15
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Miyoshi H, Kano M, Kobayashi S, Ito T, Masuda M, Mitsuyama T, Nakayama S, Ikeura T, Shimatani M, Uchida K, Takaoka M, Okazaki K. Diffuse Pancreatic Cancer Mimicking Autoimmune Pancreatitis. Intern Med 2019; 58:2523-2527. [PMID: 31178502 PMCID: PMC6761344 DOI: 10.2169/internalmedicine.2689-19] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The characteristic finding of sausage-shaped pancreas or capsule-like rim facilitates the diagnosis of autoimmune pancreatitis. We herein report a case of a 67-year-old man showing a sausage-shaped, enlarged pancreas with a capsule-like rim on computed tomography. Furthermore, endoscopic retrograde cholangiopancreatography demonstrated diffuse narrowing of the main pancreatic duct, in addition to stenosis of the lower bile duct. Finally, we were able to diagnose pancreatic cancer in this patient by an endoscopic ultrasound-guided fine-needle aspiration biopsy following peroral cholangioscopy and bile cytology. This report emphasizes the significance of pathological confirmation before starting treatment, even in cases with diffuse pancreatic enlargement.
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Affiliation(s)
- Hideaki Miyoshi
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Masataka Kano
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Sanshiro Kobayashi
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Takashi Ito
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Masataka Masuda
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Toshiyuki Mitsuyama
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Shinji Nakayama
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Tsukasa Ikeura
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Masaaki Shimatani
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Kazushige Uchida
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Makoto Takaoka
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Kazuichi Okazaki
- Division of Gastroenterology and Hepatology, Kansai Medical University, Japan
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16
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Management of Autoimmune Pancreatitis. Clin Gastroenterol Hepatol 2019; 17:1937-1939. [PMID: 31042584 DOI: 10.1016/j.cgh.2019.04.052] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 04/16/2019] [Accepted: 04/19/2019] [Indexed: 02/07/2023]
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17
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Abstract
Type 1 autoimmune pancreatitis (AIP) is an IgG-4-related systemic disease that can manifest as a pancreatic disorder or another disorder of presumed autoimmune origin. Type 2 disease is typically characterized by absent IgG-4-positive cells. As patients often present with acute pancreatitis, obstructive jaundice, or pancreatic mass, it is imperative to exclude malignancy, a more common diagnosis. AIP may respond to corticosteroids, and has a strong association with other immune-mediated diseases. Recent literature suggests the benefit of immune-modulating therapy, including rituximab, although no consensus exists. This review covers the essentials of diagnosis, but focuses primarily on management of AIP.
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Affiliation(s)
- Kamraan Madhani
- Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Department of Medicine, Waterbury Internal Medicine Residency Program, Waterbury Hospital, Yale New Haven Hospital, Main 3, 64 Robbins Street, Waterbury, CT 06708, USA
| | - James J Farrell
- Section of Digestive Diseases, Yale University School of Medicine, Yale Center for Pancreatic Disease, Yale University, LMP 1080, 15 York Street, New Haven, CT 06510, USA.
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18
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Zhang J, Jia G, Zuo C, Jia N, Wang H. 18F- FDG PET/CT helps differentiate autoimmune pancreatitis from pancreatic cancer. BMC Cancer 2017; 17:695. [PMID: 29061130 PMCID: PMC5654006 DOI: 10.1186/s12885-017-3665-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 09/29/2017] [Indexed: 02/07/2023] Open
Abstract
Background 18F-FDG PET/CT could satisfactorily show pancreatic and extra-pancreatic lesions in AIP, which can be mistaken for pancreatic cancer (PC). This study aimed to identify 18F-FDG PET/CT findings that might differentiate AIP from PC. Methods FDG-PET/CT findings of 26 AIP and 40 PC patients were reviewed. Pancreatic and extra-pancreatic lesions related findings, including maximum standardized uptake values (SUVmax) and patterns of FDG uptake, were identified and compared. Results All 26 patients with AIP had increased pancreatic FDG uptake. Focal abnormal pancreatic FDG activities were found in 38/40 (95.00%) PC patients, while longitudinal were found in 18/26 (69.23%) AIP patients. SUVmax was significantly different between AIP and PC, both in early and delayed PET/CT scans (p < 0.05). AUCs were 0.700 (early SUVmax), 0.687 (delayed SUVmax), 0.683 (early lesions/liver SUVmax), and 0.715 (delayed lesion/liver SUVmax). Bile duct related abnormalities were found in 12/26 (46.15%) AIP and 10/40 (25.00%) PC patients, respectively. Incidentally, salivary and prostate gland SUVmax in AIP patients were higher compared with those of PC patients (p < 0.05). In males,an inverted “V” shaped high FDG uptake in the prostate was more frequent in AIP than PC patients (56.00%, 14/25 vs. 5.71%, 2/35). Increased FDG activity in extra-pancreatic bile duct was present in 4/26 of AIP patients, while was observed in none of the PC patients. Only in AIP patients, both diffuse pancreatic FDG accumulation and increased inverted “V” shaped FDG uptake in the prostate could be found simultaneously. Conclusions 18F-FDG PET/CT findings might help differentiate AIP from PC.
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Affiliation(s)
- Jian Zhang
- Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.,Department of Nuclear Medicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
| | - Guorong Jia
- Department of Nuclear Medicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
| | - Changjing Zuo
- Department of Nuclear Medicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200433, China
| | - Hui Wang
- Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
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Wallace ZS, Wallace CJ, Lu N, Choi HK, Stone JH. Association of IgG4-Related Disease With History of Malignancy. Arthritis Rheumatol 2017; 68:2283-9. [PMID: 27273903 DOI: 10.1002/art.39773] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Accepted: 05/26/2016] [Indexed: 12/24/2022]
Abstract
OBJECTIVE IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4-RD patients who have a history of malignancy preceding the clinical onset of IgG4-RD. This study was undertaken to characterize IgG4-RD in the setting of previous malignancy diagnosis. METHODS We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age- and sex-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls, using conditional logistic regression. RESULTS The mean ± SD age at IgG4-RD onset was 50.3 ± 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1-3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3-fold higher in IgG4-RD patients (95% CI 1.6-6.2). CONCLUSION Our findings suggest that, in a subset of patients with IgG4-RD, malignancy may be associated with subsequent IgG4-RD development. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment.
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Affiliation(s)
| | | | - Na Lu
- Massachusetts General Hospital, Boston
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20
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Yadlapati S, Verheyen E, Efthimiou P. IgG4-related disease: a complex under-diagnosed clinical entity. Rheumatol Int 2017; 38:169-177. [PMID: 28681251 DOI: 10.1007/s00296-017-3765-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 06/28/2017] [Indexed: 12/11/2022]
Abstract
IgG4-related disease (IgG4-RD) encompasses a spectrum of complex fibro-inflammatory disorders which are often under diagnosed due to unfamiliarity by clinicians. A challenging multitude of clinical manifestations makes the diagnosis cumbersome. The primary clinical feature in IgG4-RD entails a tumor-like presentation coupled with tissue-destructive lesions. Histopathological findings include lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. These findings, in combination with elevated serum immunoglobulin G4 levels, are diagnostic in the setting of single- or multi-organ involvement. A closer understanding of the role of T cells and B cells in the increased production of IgG4 has led to a notion that IgG4 can act as a pathogen, anti-inflammatory agent, or rheumatoid factor. Glucocorticoids are the primary treatment modality; however, relapse is common with prolonged therapy. Alternatively, immunomodulatory agents are being increasingly used as therapy. The aim of this article is to raise awareness of IgG4-RD and review the diagnostic algorithm, as IgG4-RD often mimics a wide array of clinical conditions. In addition, we summarize the pathogenesis and current treatment guidelines of IgG4-RD for clinicians. Awareness and accurate diagnosis are crucial in preventing progression to chronic diseases, thereby diminishing disease-related morbidity and mortality.
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Affiliation(s)
- Sujani Yadlapati
- Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA
| | - Elijah Verheyen
- Department of Internal Medicine, St. Luke's-Roosevelt Hospital Center, New York, NY, USA
| | - Petros Efthimiou
- Division of Rheumatology, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, USA.
- Weill Cornell Medical College, New York, NY, USA.
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21
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Ghassem-Zadeh S, Gaida MM, Szanyi S, Acha-Orbea H, Frossard JL, Hinz U, Hackert T, Strobel O, Felix K. Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma. J Transl Med 2017; 15:126. [PMID: 28578701 PMCID: PMC5457650 DOI: 10.1186/s12967-017-1227-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 05/27/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging. In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. The identification of differential cytokine profiles may help to prevent unnecessary surgical resection and allow optimal treatment of these pathologies. METHODS To compare the cytokine profiles of AIP, CP, and PDAC patients, serum and pancreatic tissue homogenates were subjected to multiplex analysis of 17 inflammatory mediators. In total, serum from 73 patients, composed of 29 AIP (14 AIP-1 and 15 AIP-2), 17 CP, and 27 PDAC, and pancreatic tissue from 36 patients, including 12 AIP (six AIP-1 and six AIP-2), 12 CP, and 12 PDAC, were analyzed. RESULTS Comparing AIP and PDAC patients' serum, significantly higher concentrations were found in AIP for interleukins IL-1β, IL-7, IL-13, and granulocyte colony-stimulating factor (G-CSF). G-CSF also allowed discrimination of AIP from CP. Furthermore, once AIP was divided into subtypes, significantly higher serum levels for IL-7 and G-CSF were measured in both subtypes of AIP and in AIP-2 for IL-1β when compared to PDAC. G-CSF and TNF-α were also significantly differentially expressed in tissue homogenates between AIP-2 and PDAC. CONCLUSIONS The cytokines IL-1β, IL-7, and G-CSF can be routinely measured in patients' serum, providing an elegant and non-invasive approach for differential diagnosis. G-CSF is a good candidate to supplement the currently known serum markers in predictive tests for AIP and represents a basis for a combined blood test to differentiate AIP and particularly AIP-2 from PDAC, enhancing the possibility of appropriate treatment.
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Affiliation(s)
- Sahar Ghassem-Zadeh
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
- Department of Biochemistry, University of Lausanne, Lausanne, Switzerland
| | - Matthias M. Gaida
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Szilard Szanyi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
| | - Hans Acha-Orbea
- Department of Biochemistry, University of Lausanne, Lausanne, Switzerland
| | - Jean-Louis Frossard
- Department of Medical Specialties, Gastroenterology and Hepatology Division, University Hospitals and Faculty of Medicine of Geneva, Geneva, Switzerland
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
| | - Klaus Felix
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
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de Pretis N, Amodio A, Bernardoni L, Campagnola P, Capuano F, Chari ST, Crinò S, Gabbrielli A, Massella A, Topazian M, Frulloni L. Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis. Clin Transl Gastroenterol 2017; 8:e90. [PMID: 28448071 PMCID: PMC5543465 DOI: 10.1038/ctg.2017.17] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 02/11/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Steroids are used to induce remission in autoimmune pancreatitis (AIP). Low-dosage steroid therapy or immunosuppressant (IMs) has been proposed as maintenance therapy to prevent AIP relapse. Few and conflicting data have been published on the efficacy of azathioprine (AZA) in preventing AIP relapse. The aim of this study was to evaluate the indication and efficacy of AZA as maintenance therapy to prevent disease relapse in AIP. METHODS Patients suffering from AIP diagnosed according to the ICDC in type 1, type 2, and not otherwise specified (NOS) were divided in those treated with AZA (AZA+ group) as maintenance therapy and not treated with maintenance therapy (AZA- group). Exclusion criteria were: previous pancreatic surgery, other autoimmune diseases as indication for AZA treatment, and use of IMs different from AZA. Drug safety, clinical and instrumental outcome of AZA+ patients were evaluated. RESULTS A total of 23 patients (18 Males and 5 Females, mean age 54±11 years) in AZA+ group and 97 (58 Males and 39 Females, mean age 45±18 years) in AZA- group were compared. In AZA+ group, patients were significantly older (P=0.043), type 1 AIP was more frequently diagnosed (87 vs. 51%, P=0.006), sIgG4 higher (758±625 vs. 311±409 mg/dl, P<0.001), other organ involvement (OOI) more frequently observed (83 vs. 48%, P=0.002), with higher frequency of relapse before AZA treatment (78 vs. 14%, P<0.001). Three patients in AZA+ group required drug discontinuation because of adverse events. Twenty patients were therefore evaluated for outcome. Six out of 20 patients (30%) relapsed after 24±15 months (5 in pancreas and 1 on biliary tract). They were retreated with steroids and continued AZA. Two out of 6 patients (33%) had a second relapse,after respectively 11 months (in pancreas and kidney) and 22 months (in kidney). CONCLUSIONS AZA is an effective and safe treatment to prevent AIP relapses.
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Affiliation(s)
- Nicolò de Pretis
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Antonio Amodio
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Pietro Campagnola
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Fabiana Capuano
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Suresh T Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Stefano Crinò
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Armando Gabbrielli
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Arianna Massella
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
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Yan T, Ke Y, Chen Y, Xu C, Yu C, Li Y. Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin. PLoS One 2017; 12:e0174735. [PMID: 28369140 PMCID: PMC5378371 DOI: 10.1371/journal.pone.0174735] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 03/14/2017] [Indexed: 12/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19-9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time.
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Affiliation(s)
- Tianlian Yan
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yini Ke
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Chen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chengfu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Boninsegna E, Manfredi R, Negrelli R, Avesani G, Mehrabi S, Pozzi Mucelli R. Pancreatic duct stenosis: Differential diagnosis between malignant and benign conditions at secretin-enhanced MRCP. Clin Imaging 2016; 41:137-143. [PMID: 27840266 DOI: 10.1016/j.clinimag.2016.10.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 10/20/2016] [Accepted: 10/27/2016] [Indexed: 12/26/2022]
Abstract
PURPOSE To define imaging criteria of benign and malignant nature in patients with main pancreatic duct (MPD) stenosis. MATERIALS-METHODS S-MRCPs of 35 patients with pancreatitis and 14 with adenocarcinoma were evaluated. RESULTS Adenocarcinoma caused higher prevalence of complete stenosis (14/14-100% vs 17/35-49%), dilated side-branches (14/14-100% vs 18/35-51%) and lower prevalence of duct-penetrating sign (0/14-0% vs 31/35-89%). The number of stenoses was higher in benign conditions (mean 1.4 Vs 1). Upstream MPD diameter was higher in cancer-induced stenoses (4.5 vs 2.9mm). CONCLUSIONS Single complete stenosis with dilated side branches, increased MPD caliber and absent duct-penetrating sign are suggestive of malignancy.
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Affiliation(s)
- Enrico Boninsegna
- Department of Radiology, Policlinico G.B. Rossi, University of Verona, Italy.
| | - Riccardo Manfredi
- Department of Radiology, Policlinico G.B. Rossi, University of Verona, Italy
| | - Riccardo Negrelli
- Department of Radiology, Policlinico G.B. Rossi, University of Verona, Italy
| | - Giacomo Avesani
- Department of Radiology, Policlinico G.B. Rossi, University of Verona, Italy
| | - Sara Mehrabi
- Department of Radiology, Policlinico G.B. Rossi, University of Verona, Italy
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25
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Kim M, Jang KM, Kim JH, Jeong WK, Kim SH, Kang TW, Kim YK, Cha DI, Kim K. Differentiation of mass-forming focal pancreatitis from pancreatic ductal adenocarcinoma: value of characterizing dynamic enhancement patterns on contrast-enhanced MR images by adding signal intensity color mapping. Eur Radiol 2016; 27:1722-1732. [PMID: 27510628 DOI: 10.1007/s00330-016-4522-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2016] [Revised: 07/18/2016] [Accepted: 07/20/2016] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To evaluate the value of dynamic enhancement patterns on contrast-enhanced MR images by adding signal intensity colour mapping (SICM) to differentiate mass-forming focal pancreatitis (MFFP) from pancreatic ductal adenocarcinoma (PDAC). METHODS Forty-one clinicopathologically proven MFFPs and 144 surgically confirmed PDACs were enrolled. Laboratory and MR imaging parameters were used to differentiate MFFP from PDAC. In particular, enhancement patterns on MR images adding SICM were evaluated. By using classification tree analysis (CTA), we determined the predictors for the differentiation of MFFP from PDAC. RESULTS In the CTA, with all parameters except enhancement pattern on SICM images, ductal obstruction grade and T1 hypointensity grade of the pancreatic lesion were the first and second splitting predictor for differentiation of MFFP from PDAC, in order. By adding an enhancement pattern on the SICM images to CTA, the enhancement pattern was the only splitting predictor to differentiate MFFP from PDAC. The CTA model including enhancement pattern on SICM images has sensitivity of 78.0 %, specificity of 99.3 %, and accuracy of 94.6 % for differentiating MFFP from PDAC. CONCLUSION The characterization of enhancement pattern for pancreatic lesions on contrast-enhanced MR images adding SICM would be helpful to differentiate MFFP from PDAC. KEY POINTS • SICM was useful to characterize enhancement pattern. • Enhancement pattern on SICM was the only splitting predictor on CTA. • This model may be useful for differentiating MFFP from PDAC.
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Affiliation(s)
- Mimi Kim
- Department of Radiology, Hanyang Medical Center, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Kyung Mi Jang
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. .,Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
| | - Jae-Hun Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seong Hyun Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae Wook Kang
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Kon Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Ik Cha
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyunga Kim
- Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
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Valero Liñán AS, Rueda Martínez JL, González Masiá JA, Miota de Llama JI, González Masegosa P. ¿Pancreatitis autoinmune o cáncer de páncreas? Cir Esp 2016; 94:415-7. [DOI: 10.1016/j.ciresp.2016.02.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 02/16/2016] [Accepted: 02/17/2016] [Indexed: 01/07/2023]
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Yamada R, Horiguchi SI, Yamashita T, Kamisawa T. IgG4-related mastitis, a rare disease, can radiologically and histologically mimic malignancy. BMJ Case Rep 2016; 2016:bcr-2016-214870. [PMID: 27009197 DOI: 10.1136/bcr-2016-214870] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary.
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Affiliation(s)
- Rin Yamada
- Department of Pathology, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Shin-ichiro Horiguchi
- Department of Pathology, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Toshinari Yamashita
- Department of Breast Surgery, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan
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Abstract
OBJECTIVES Eosinophil infiltration is a histological feature of autoimmune pancreatitis (AIP). However, little is known about the mechanisms underlying eosinophilic infiltration. In this study, we aimed to investigate the expression of the eosinophil chemotactic protein, eotaxin-3, in human pancreatic myofibroblasts. METHODS Enzyme-linked immunosorbent assays and quantitative polymerase chain reactions were used to quantify eotaxin-3 protein and messenger RNA levels, respectively. RESULTS Eotaxin-3 expression was induced by T helper type 2 cytokines, interleukin-4 (IL-4) and IL-13, in time- and dose-dependent manners. Both IL-4 and IL-13 induced the rapid phosphorylation of STAT6 (signal transducer and activator of transcription 6), and STAT6-specific small interfering RNA significantly blocked IL-4- and IL-13-induced eotaxin-3 expression, indicating involvement of STAT6 signaling pathways in eotaxin-3 induction. In contrast, SOCS (suppressor of cytokine signaling) protein-specific small interfering RNA experiments suggested that the SOCS family proteins are negative regulators of IL-4- and IL-13-induced eotaxin-3 expression in pancreatic myofibroblasts. Interferon-γ significantly inhibited IL-4- and IL-13-induced eotaxin-3 expression, and this response was mediated by STAT1 activation. CONCLUSIONS Pancreatic myofibroblasts may be a cellular source of eotaxin-3 in the pancreas. The T helper type 2 cytokines, IL-4 and IL-13, are critical factors for the induction of eotaxin-3 in the pancreas.
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Madhani K, Farrell JJ. Autoimmune Pancreatitis: An Update on Diagnosis and Management. Gastroenterol Clin North Am 2016; 45:29-43. [PMID: 26895679 DOI: 10.1016/j.gtc.2015.10.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
There is an evolving understanding that autoimmune pancreatitis (AIP) is an immunoglobulin (Ig) G4 systemic disease. It can manifest as primarily a pancreatic disorder or in association with other disorders of presumed autoimmune cause. Classic clinical characteristics include obstructive jaundice, abdominal pain, and acute pancreatitis. Thus, AIP can be difficult to distinguish from pancreatic malignancy. However, AIP may respond to therapy with corticosteroids, and has a strong association with other immune mediated diseases. Although primarily a pathologic diagnosis, attempts have been made to reliably diagnose AIP clinically. AIP can be classified as either type 1 or type 2.
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Affiliation(s)
- Kamraan Madhani
- Yale-Waterbury Internal Medicine Residency Program, Yale University School of Medicine, New Haven, CT 06510, USA
| | - James J Farrell
- Yale Center for Pancreatic Disease, Section of Digestive Disease, Yale University, LMP 1080, 15 York Street, New Haven, CT 06510, USA.
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30
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Chiu YH, Chan DC, Shih YL. Immunoglobulin G4-related disease with recurrent obstructive jaundice. ADVANCES IN DIGESTIVE MEDICINE 2016. [DOI: 10.1016/j.aidm.2014.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Rasch S, Phillip V, Schmid RM, Algül H. Epidemiology, clinical presentation, diagnosis and treatment of autoimmune pancreatitis: A retrospective analysis of 53 patients. Pancreatology 2015; 16:73-7. [PMID: 26694138 DOI: 10.1016/j.pan.2015.11.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 09/03/2015] [Accepted: 11/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Most of the data about epidemiology, clinical presentation and treatment of autoimmune pancreatitis (AIP) is based on case series or small study groups. We therefore analyzed all cases of AIP treated at our clinic retrospectively. METHODS We searched our clinical database for the diagnosis pancreatitis between January 2007 and June 2014, selected patients with AIP and entered all relevant information in a database for statistical analysis. RESULTS In total 53 patients with AIP were treated at our institution, 62% with type 1 and 23% with type 2 AIP. Gender distribution was male/female 3.1:1 for type 1 and 1:1.2 for type 2 AIP. The median age was 63.0 and 32.5 years for type 1 and type 2 AIP, respectively. The most common symptom is abdominal pain particular in patients with type 2 AIP whereas jaundice was only apparent in patients with type 1 AIP. The international diagnostic criteria seem to facilitate diagnosis of AIP as unnecessary pancreatic surgery in patients with AIP decreases. In 62.6% of the patients therapy was indicated and 84.8% showed a response to initial therapy with steroids. Recurring disease occurred in 28.3% of the cases but only 3.8% suffered a second relapse. Permanent maintenance therapy with steroids or additional therapy with immunomodulatory drugs is successful in recurring disease. CONCLUSION Our data further corroborate previous findings on epidemiology, clinical presentation and treatment of AIP. AIP is a well manageable autoimmune disease in most patients. Better biopsy techniques and simplified diagnostic criteria might further alleviate diagnosis of AIP.
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Affiliation(s)
- Sebastian Rasch
- II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
| | - Veit Phillip
- II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany
| | - Roland M Schmid
- II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany
| | - Hana Algül
- II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany
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32
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Jani N, Buxbaum J. Autoimmune pancreatitis and cholangitis. World J Gastrointest Pharmacol Ther 2015; 6:199-206. [PMID: 26558153 PMCID: PMC4635159 DOI: 10.4292/wjgpt.v6.i4.199] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 06/22/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.
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Fan RY, Sheng JQ. Immunoglobulin G4-related autoimmune pancreatitis and sialadenitis: A case report. World J Gastroenterol 2015; 21:9448-9452. [PMID: 26309373 PMCID: PMC4541399 DOI: 10.3748/wjg.v21.i31.9448] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/27/2015] [Accepted: 06/26/2015] [Indexed: 02/06/2023] Open
Abstract
Immunoglobulin G4 (IgG4)-related disease is a rare systemic diseases. A 67-year-old male presented at our institution with mild upper abdominal pain and jaundice for 20 d. Laboratory results revealed high levels of IgG4 (15.4 g/L, range: 0.08-1.4 g/L). Computed tomography (CT) showed significant enlargement of the entire pancreas and a capsule-like low-density rim surrounding the whole pancreas. Positron emission tomography/CT revealed increased uneven metabolism of the entire pancreas. Both magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed stenosis of the distal common bile duct and proximal main pancreatic duct, and dilation of the proximal common bile duct and extra- and intra-hepatic bile ducts. He was diagnosed with IgG4-related autoimmune pancreatitis. The patient was treated with prednisone for 14 mo. The patient responded well to prednisone but upon cessation of the corticosteroid developed enlargement of the submandibular gland. The patient’s serum IgG4 was elevated at 23.9 g/L. It is important to maintain treatment, so the patient was again treated with prednisone and had a good response. Follow-up of IgG4-related disease is thus necessary.
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Nononcologic applications of diffusion-weighted imaging in the gastrointestinal system. AJR Am J Roentgenol 2015; 204:758-67. [PMID: 25794064 DOI: 10.2214/ajr.14.12729] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The purpose of this article is to review infectious, inflammatory, and auto-immune-mediated processes in the gastrointestinal system where diffusion-weighted imaging can be helpful as well as pitfalls associated with its use. CONCLUSION Diffusion-weighted imaging has become an important and widely used tool in abdominal and pelvic MRI, but it has been used primarily for oncologic applications. As more body MRI protocols are routinely including diffusion-weighted imaging, this sequence can be useful in evaluating an increasing number of nononcologic processes.
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35
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Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas 2015; 44:557-60. [PMID: 25785724 DOI: 10.1097/mpa.0000000000000297] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Serum IgG4 (sIgG4) elevation, more common to autoimmune pancreatitis (AIP), occurs in some patients with pancreatic cancer (PaC). We investigated whether sIgG4 could differentiate AIP from PaC, its role in prognostication, and the concomitant occurrence of AIP and PaC. METHODS We identified all patients with PaC (n = 548) and with type 1 AIP (n = 99) with sIgG4 measurements from 2001 to 2011. We compared demographics and sIgG4 profiles in these groups. Among patients with PaC, we compared resectability and mortality with and without elevated sIgG4. We reviewed AIP and PaC tissue specimens to identify concomitant occurrence of both diseases. RESULTS Patients with AIP were more likely to have elevation in sIgG4 (65% vs 10.4%, P < 0.001) and sIgG4 more than 2 times upper limit of normal (40% vs 2.4%, P < 0.001). Patients with PaC with sIgG4 elevation were more commonly male compared with those with normal sIgG4 (81% vs 53%). Both groups were similarly aged with similar rates of resectability and mortality. No evidence of concurrent PaC and AIP was found. CONCLUSIONS Mild elevations in sIgG4 cannot distinguish AIP from PaC. Elevations more than 2 times upper limit of normal appear more commonly in AIP. Serum IgG4 elevation has no prognostic significance in PaC. We could not identify a relationship between AIP and PaC.
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Mallya V, Rathi KR, Sahai K, Jakhmola CK. Autoimmune pancreatitis - a case report. J Clin Diagn Res 2015; 9:ED01-2. [PMID: 25859461 DOI: 10.7860/jcdr/2015/8799.5504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 10/06/2014] [Indexed: 11/24/2022]
Abstract
Autoiommune pancreatitis (AIP) is a rare disease that has distinct histological, immunological, serological and radiological findings. It is characterised histologically by lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phelibitis and presence of IgG4 positive plasma cells and lymphocytes. Elevated serum levels of IgG4 are also noted. It is usually misdiagnosed preoperatively as pancreatic cancer. It may involve extrapancreatic sites also and responds well to steroid therapy. Here, we share our experience of AIP in a 52-year-old male.
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Affiliation(s)
- Varuna Mallya
- Assistant Professor, Department of Pathology, Army College of Medical Sciences & Base Hospital , New Delhi, India
| | - K R Rathi
- Advisor, Department Pathology & Neuropathology, Army College of Medical Sciences & Base Hospital , New Delhi, India
| | - Kavita Sahai
- Professor & HOD, Department of Pathology, Army College of Medical Sciences & Base Hospital , New Delhi, India
| | - C K Jakhmola
- Senior Advisor, Department of G I Surgery, Army College of Medical Sciences & Base Hospital , New Delhi, India
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Deciphering autoimmune pancreatitis, a great mimicker: case report and review of the literature. Case Rep Gastrointest Med 2015; 2015:924532. [PMID: 25705529 PMCID: PMC4326036 DOI: 10.1155/2015/924532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 12/21/2014] [Accepted: 12/23/2014] [Indexed: 11/17/2022] Open
Abstract
Background. Autoimmune pancreatitis (AIP) is an atypical chronic inflammatory pancreatic disease that appears to involve autoimmune mechanisms. In recent years, AIP has presented as a new clinical entity with its protean pancreaticobiliary and systemic presentations. Its unique pathology and overlap of clinical and radiological features and absence of serological markers foster the disease's unique position. We report a case of diffuse type 1 autoimmune pancreatitis with obstructive jaundice managed with biliary sphincterotomy, stent placement, and corticosteroids. A 50-year-old Caucasian woman presented to our hospital with epigastric pain, nausea, vomiting, and jaundice. Workup showed elevated liver function tests (LFT) suggestive of obstructive jaundice, MRCP done showed diffusely enlarged abnormal appearing pancreas with loss of normal lobulated contours, and IgG4 antibody level was 765 mg/dL. EUS revealed a diffusely hypoechoic and rounded pancreatic parenchyma with distal common bile duct (CBD) stricture and dilated proximal CBD and common hepatic duct (CHD). ERCP showed tight mid to distal CBD stricture that needed dilatation, sphincterotomy, and placement of stent that led to significant improvement in the symptoms and bilirubin level. Based on clinical, radiological, and immunological findings, a definitive diagnosis of AIP was made. Patient was started on prednisone 40 mg/day and she clinically responded in 4 weeks.
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Malik SM, Raina A, Hartman DJ. Immunoglobulin G4-related pseudotumor presenting as metastatic colon cancer. Clin Gastroenterol Hepatol 2015; 13:e1-2. [PMID: 25220937 DOI: 10.1016/j.cgh.2014.08.034] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 08/26/2014] [Accepted: 08/31/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Shahid M Malik
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Amit Raina
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, East Carolina University, Greenville, North Carolina
| | - Douglas J Hartman
- Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
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Pancreatic duct "Icicle sign" on MRI for distinguishing autoimmune pancreatitis from pancreatic ductal adenocarcinoma in the proximal pancreas. Eur Radiol 2014; 25:1551-60. [PMID: 25501271 DOI: 10.1007/s00330-014-3548-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 11/20/2014] [Accepted: 12/01/2014] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To determine reliable MRI features of autoimmune pancreatitis (AIP) in the proximal pancreas that could allow its differentiation from pancreatic ductal adenocarcinoma (PDAC). METHODS Twenty-three patients with AIP and 61 patients with PDAC in the proximal pancreas underwent MRI. Two observers analyzed MRI for lesion morphology, hypointensity degree on T1-weighted images, enhancement pattern during dynamic phases, capsule-like rim, presence of cysts and duct penetrating sign, morphology of bile duct, and icicle appearance and tortuosity of the upstream pancreatic duct. Sensitivity and specificity for the diagnosis of AIP were calculated for each category or combined. RESULTS When isointensity on the portal and late phase of MRI and/or the icicle sign of pancreatic duct are applied, 100 % sensitivity for the diagnosis of AIP in the proximal pancreas was achieved. Applying both mild T1 hypointensity similar to the spleen and the icicle sign enabled 100 % specificity for the diagnosis of AIP by differentiating it from PDAC. CONCLUSION The combination of the icicle sign in the upstream pancreatic duct and mild T1 hypointensity or isointensity on portal and late phase of dynamic MRI could be reliable MR features for the diagnosis of AIP in the proximal pancreas by allowing its differentiation from PDAC. KEY POINTS • The icicle sign of the pancreatic duct is useful for diagnosing AIP. • Mild T1 hypointensity similar to the spleen is useful for diagnosing AIP. • Isointensity on portal and late phases MRI is useful for diagnosing AIP.
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Franchello A, Gonella F, Campra D, Limerutti G, Bruno M, De Angelis C, Cassine D, Fronda G, Silvestri S. A rare case of IgG4-related systemic disease manifesting with pancreatic head mass mimicking borderline resectable cancer. Int J Surg Case Rep 2014; 5:1095-7. [PMID: 25460484 PMCID: PMC4275972 DOI: 10.1016/j.ijscr.2014.11.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Accepted: 11/06/2014] [Indexed: 01/02/2023] Open
Abstract
Diagnostic algorithm for pancreatic head mass. Differential diagnosis between pancreatic cancer and mass forming autoimmune pancreatitis. Diagnosis and treatment of IgG4-related systemic disease. INTRODUCTION Autoimmune pancreatitis (AIP) is a rare pancreatic disorder among chronic pancreatitis that can mimick pancreatic cancer (PC). Patients with type 1 AIP usually present obstructive jaundice associated with high level of IgG4 in serum and a pancreatic mass at radiological imaging; these disorders may be associated with other organs lesions presenting the same histopathological features, and in these cases AIP should be considered a pancreatic localization of an IgG4-related systemic disease. PRESENTATION OF CASE We report the case of a young man with initial suspect of PC to be treated with surgery, and final diagnosis of AIP in the context of an IgG4-related systemic disease. DISCUSSION Because of its similar features, several algorithms have been proposed for AIP diagnosis, based on combination of clinical/serological and radiological criteria. However, histology represents the only way to obtain definitive diagnosis, even if sometimes it is difficult to obtain biological samples. CONCLUSION IgG4-related systemic disease must be taken into account among differential diagnosis during the workup for PC, in order to avoid unnecessary surgery.
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Affiliation(s)
| | | | - Donata Campra
- Department of Surgery, Molinette Hospital, Turin, Italy
| | | | - Mauro Bruno
- Department of Gastroenterology, Molinette Hospital, Turin, Italy
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Saavedra-Perez D, Vaquero EC, Ayuso JR, Fernandez-Cruz L. Pancreatitis autoinmune: un dilema quirúrgico. Cir Esp 2014; 92:645-53. [DOI: 10.1016/j.ciresp.2014.01.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Accepted: 01/25/2014] [Indexed: 01/06/2023]
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Busireddy KK, AlObaidy M, Ramalho M, Kalubowila J, Baodong L, Santagostino I, Semelka RC. Pancreatitis-imaging approach. World J Gastrointest Pathophysiol 2014; 5:252-270. [PMID: 25133027 PMCID: PMC4133524 DOI: 10.4291/wjgp.v5.i3.252] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 02/13/2014] [Accepted: 05/16/2014] [Indexed: 02/06/2023] Open
Abstract
Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI.
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Pieringer H, Parzer I, Wöhrer A, Reis P, Oppl B, Zwerina J. IgG4- related disease: an orphan disease with many faces. Orphanet J Rare Dis 2014; 9:110. [PMID: 25026959 PMCID: PMC4223520 DOI: 10.1186/s13023-014-0110-z] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 07/03/2014] [Indexed: 02/07/2023] Open
Abstract
Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD.
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Comparative MRI analysis of morphologic patterns of bile duct disease in IgG4-related systemic disease versus primary sclerosing cholangitis. AJR Am J Roentgenol 2014; 202:536-43. [PMID: 24555589 DOI: 10.2214/ajr.12.10360] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The purpose of this study was to perform a retrospective MRI-based comparative analysis of the morphologic patterns of bile duct disease in IgG4-related systemic disease (ISD, also called autoimmune pancreatitis) compared with primary sclerosing cholangitis (PSC) and the autoimmune liver diseases autoimmune hepatitis and primary biliary cirrhosis. MATERIALS AND METHODS This study included 162 consecutively registered patients (47 with ISD, 73 with PSC, and 42 with autoimmune liver diseases). Two abdominal radiologists retrospectively reviewed MR images in consensus. Imaging findings on the bile ducts, liver, pancreas, and other organs were analyzed to establish disease patterns. RESULTS ISD was associated with contiguous thickening of intrahepatic and extrahepatic bile ducts (p<0.001), pancreatic parenchymal abnormalities (p<0.001), renal abnormalities (p<0.001), and gallbladder wall thickening (p<0.03). The severity of common bile duct wall thickness was significantly different in ISD (p<0.001). The mean single wall thickness in the ISD group was 3.00 (SD, 1.47) mm, in the PSC group was 1.89 (SD, 0.73) mm, and in the autoimmune liver disease group was 1.80 (SD, 0.67) mm. PSC was associated with liver parenchymal abnormalities (p<0.001). We did not find statistical significance between the three groups in location (p=0.220) or length (p=0.703) of extrahepatic bile duct strictures, enhancement of bile duct stricture (p=0.033), upper abdominal lymphadenopathy, or retroperitoneal fibrosis. Although presence of intrahepatic bile duct stricture was statistically significant when all three groups were compared, it was not useful for differentiating ISD from PSC. CONCLUSION The presence of continuous as opposed to skip disease in the bile ducts, gallbladder involvement, and single-wall common bile duct thickness greater than 2.5 mm supports a diagnosis of ISD over PSC. ISD and PSC could not be differentiated on the basis of location and length of common bile duct stricture.
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Should Steroid Therapy Be Necessarily Needed for Autoimmune Pancreatitis Patients with Lesion Resected due to Misdiagnosed or Suspected Malignancy? Gastroenterol Res Pract 2014; 2014:253471. [PMID: 24578705 PMCID: PMC3918699 DOI: 10.1155/2014/253471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 12/12/2013] [Accepted: 12/23/2013] [Indexed: 11/17/2022] Open
Abstract
To explore whether steroid therapy should be needed for autoimmune pancreatitis patients after operation, eight AIP patients receiving operation were enrolled in this study from January 2007 to July 2013. All patients underwent liver function, CA19-9, and contrast-enhanced CT and/or MRI. Tests of IgG and IgG4 were performed in some patients. Tests of serum TB/DB, γ -GT, and γ -globulin were undergone during the perioperative period. Six cases receiving resection were pathologically confirmed as AIP patients and two were confirmed by intraoperative biopsy. For seven patients, TB/DB level was transiently elevated 1 day or 4 days after operation but dropped below preoperative levels or to normal levels 7 days after operation, and serum γ -GT level presented a downward trend. Serum γ -globulin level exhibited a downward trend among six AIP patients after resection, while an upward trend was found in another two AIP patients receiving internal drainage. Steroid therapy was not given to all six AIP patients until two of them showed new lines of evidence of residual or extrapancreatic AIP lesion after operation, while another two cases without resection received steroid medication. Steroid therapy might not be recommended unless there are new lines of evidence of residual extrapancreatic AIP lesions after resection.
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Patel H, Khalili K, Kyoung KT, Yazdi L, Lee E, May G, Kortan P, Coltescu C, Hirschfield GM. IgG4 related disease - a retrospective descriptive study highlighting Canadian experiences in diagnosis and management. BMC Gastroenterol 2013; 13:168. [PMID: 24321047 PMCID: PMC3878912 DOI: 10.1186/1471-230x-13-168] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2012] [Accepted: 11/15/2013] [Indexed: 02/06/2023] Open
Abstract
Background Appreciating the utility of published diagnostic criteria for autoimmune pancreatitis, when compared to the characteristics of patients clinically managed as having disease, informs and refines ongoing clinical practice. Methods Comparative retrospective descriptive evaluation of patients with autoimmune pancreatitis including dedicated radiology review. Results 66 subjects with radiographic OR clinical features of autoimmune pancreatitis were initially identifiable (Male: n = 50), with 55 confirmed for evaluation. The most common presentation included pain (67%), weight loss (65%), and jaundice (62%). Diffuse enlargement of the pancreas was evident in 38%, whilst multifocal, focal, or atrophic changes were seen in 7%, 33% and 9% respectively. 13% had no pancreatic parenchymal involvement. Peripheral rim enhancement was seen in 23 patients (42%). Where discernible, disease was a) Sclerosing pancreatitis and cholangitis, n = 21; b) Sclerosing cholangitis, n = 9; c) Sclerosing pancreatitis, n = 4; d) Sclerosing pancreatitis and cholangitis with pancreatic pseudotumour, n = 7; e) Sclerosing cholangitis with hepatic pseudotumour, n = 3; f) Sclerosing pancreatitis with pancreatic pseudotumour, n = 1. 56% of the patients had systemic manifestations and the median serum IgG4 at diagnosis was 5.12 g/L. The Korean criteria identified most patients (82%) compared to HISORt (55%) or the Japan Pancreas Society (56%). The majority (HISORt 60%; Japan Pancreas Society 55%; Korean 58%) met diagnostic criterion by radiological findings and elevated serum IgG4. Treatment and response did not differ when stratified by diagnostic criteria. Conclusion Our descriptive and retrospective dataset confirms that in non-expert practice settings, autoimmune pancreatitis scoring systems with a focus on radiology and serology capture most patients who are clinically felt to have disease.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Gideon M Hirschfield
- Centre for Liver Research and NIHR Biomedical Research Unit, Institute of Biomedical Research, The Medical School, University of Birmingham, 5th Floor, Birmingham B15 2TT, UK.
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Limited efficacy of (18)F-FDG PET/CT for differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis. Clin Nucl Med 2013; 38:417-21. [PMID: 23486318 DOI: 10.1097/rlu.0b013e3182817d9d] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is important to avoid unnecessary operative procedures. This study was aimed at evaluating the efficacy of PET/CT with F-FDG (FDG PET/CT) for the differential diagnosis between them. PATIENTS AND METHODS FDG-PET/CT was performed in 47 study patients with pancreatic masses and without any detectable metastases, 33 of which cases were finally diagnosed as pancreatic cancer and the other 14 as pancreatitis, and the corresponding imaging data were evaluated retrospectively. The maximal SUV (SUVmax) within the masses were determined at 1 hour and mostly at 2 hours after intravenous injection of FDG. RESULTS SUVmax at 1 hour in pancreatic cancer was significantly higher than that in mass-forming pancreatitis, and the change in SUVmax from 1- to 2-hour time points was more consistent with pancreatic cancer than with mass-forming pancreatitis. However, there remained considerable overlapping between the SUVmax values of both diseases except either at the higher range for pancreatic cancer (> 7.7 at 1 hour or > 9.98 at 2 hours) or at the lower range for mass-forming pancreatitis (<3.37 at 1 hour or <3.53 at 2 hours). No obvious difference was found in the FDG uptake patterns of the mass areas between both diseases. CONCLUSIONS Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is difficult by FDG-PET/CT due to considerable overlapping between the SUVmax values of the two diseases, although the differential diagnosis may be possible either at the higher range of SUVmax (> 7.7 at 1 hour or > 9.98 at 2 hours) for pancreatic cancer or at the lower range of SUVmax (<3.37 at 1 hour or <3.53 at 2 hours) for mass-forming pancreatitis.
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Capability and limitations of recent diagnostic criteria for autoimmune pancreatitis. Int J Rheumatol 2013; 2013:465428. [PMID: 24288540 PMCID: PMC3833014 DOI: 10.1155/2013/465428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 09/04/2013] [Accepted: 09/08/2013] [Indexed: 12/24/2022] Open
Abstract
Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC.
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Lee YS, Lee SH, Lee MG, Lee SJ, Hwang JH, Shin E, Lee YJ. Immunoglobulin g4-related disease mimicking unresectable gallbladder cancer. Gut Liver 2013; 7:616-20. [PMID: 24073322 PMCID: PMC3782679 DOI: 10.5009/gnl.2013.7.5.616] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2013] [Revised: 04/05/2013] [Accepted: 04/07/2013] [Indexed: 12/24/2022] Open
Abstract
Immunoglobulin G4 (IgG4)-related disease is a novel disease entity that can involve diverse organs, causing specific diseases, including autoimmune pancreatitis, sclerosing cholangitis, cholecystitis, inflammatory aortic aneurysm, and inflammatory pseudotumor. IgG4-related disease is characterized by elevated serum IgG4 concentrations, abundant IgG4 lymphoplasmacytic infiltration, and dramatic steroid responses. It is clinically important to differentiate this rare disease from primary sclerosing cholangitis and cholangiocarcinoma, because the treatment and prognosis of these two diseases are completely different. However, the preoperative diagnosis is challenging, and the disease is frequently misdiagnosed. If the serum level of IgG4 is within the normal range, the diagnosis of IgG4-related disease is more difficult. This article reports on a 59-year-old man with IgG4-related disease mimicking unresectable gallbladder cancer with normal serum IgG4 concentrations.
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Affiliation(s)
- Yoon Suk Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Wu WC, Yao XZ, Jin DY, Wang DS, Lou WH, Qin XY. Clinical strategies for differentiating autoimmune pancreatitis from pancreatic malignancy to avoid unnecessary surgical resection. J Dig Dis 2013; 14:500-8. [PMID: 23692995 DOI: 10.1111/1751-2980.12075] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The study aimed to determine a practical strategy for differentiating between autoimmune pancreatitis (AIP) and pancreatic malignancy in order to avoid unnecessary surgical resection. METHODS Altogether, 19 patients with AIP or other pancreatic diseases underwent routine examinations including liver function test and carbohydrate antigen 19-9, computed tomography and/or magnetic resonance imaging. Serum immunoglobulin G (IgG) and/or IgG4 was determined in patients with clinically suspected or pathologically proven AIP. Patients with suspected AIP either received diagnostic steroid therapy or laparotomy (if malignant tumors could not be excluded). Surgery was not performed in patients with a definite diagnosis of AIP by fast intraoperative frozen biopsy. Those with confirmed AIP received steroid treatment. RESULTS In total, 15 cases were finally confirmed as AIP with eight diagnosed preoperatively, five confirmed by surgical pathology (preoperatively misdiagnosed) and two by intraoperative biopsy. Of these 15 patients with AIP and one without AIP, 14 had elevated serum γ-globulin levels. It was proven by subsequent antibody tests that serum IgG or IgG4 were simultaneously increased. CONCLUSIONS Elevated serum γ-globulin level can be used as a preoperative sentinel indicator for differentiating between IgG4-related AIP and pancreatic malignancy. Serum IgG or IgG4 tests should be further performed in those with elevated serum γ-globulin level, which helps to identify AIP in order to avoid unnecessary operation.
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Affiliation(s)
- Wen Chuan Wu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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