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Sakurai Y, Yokoyama K, Kanno A, Tanaka A, Ikeda E, Ando K, Taguchi M, Sasanuma H, Sata N, Sano N, Fukushima N, Yamamoto H. Pancreatic Ductal Adenocarcinoma with Autoimmune Pancreatitis: A Case Report and Literature Review. Intern Med 2025; 64:1525-1533. [PMID: 39462595 DOI: 10.2169/internalmedicine.4361-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/29/2024] Open
Abstract
A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.
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Affiliation(s)
- Yusuke Sakurai
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Kensuke Yokoyama
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Atsushi Kanno
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Akitsugu Tanaka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Eriko Ikeda
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
- Department of Pathology, Jichi Medical University, Japan
| | - Kozue Ando
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Masanobu Taguchi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Japan
| | - Hideki Sasanuma
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Japan
| | - Naohiro Sata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Japan
| | - Naoki Sano
- Department of Pathology, Jichi Medical University, Japan
| | | | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
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2
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Kim SH, Lee YC, Chon HK. Challenges for clinicians treating autoimmune pancreatitis: Current perspectives. World J Clin Cases 2023; 11:30-46. [PMID: 36687190 PMCID: PMC9846983 DOI: 10.12998/wjcc.v11.i1.30] [Citation(s) in RCA: 1] [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: 09/12/2022] [Revised: 10/31/2022] [Accepted: 12/19/2022] [Indexed: 01/04/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease clinically characterized by obstructive jaundice, unintentional weight loss, acute pancreatitis, focal pancreatic mass, and diabetes. AIP is classified into two subtypes - type 1 and type 2 - according to pathological findings, clinical features, and serology test results, but some cases may be defined as type not otherwise in the absence of pathological findings and inflammatory bowel disease. To address the differences in diagnostic criteria by country, standard diagnostic criteria for AIP were proposed in 2011 by an international consensus of expert opinions. Differential diagnosis of AIP from pancreatic ductal adenocarcinoma is important but remains challenging for clinicians. Fortunately, all subtypes of AIP show dramatic response to steroid treatment. This review discusses the current perspectives on the diagnosis and management of AIP in clinical practice.
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Affiliation(s)
- Seong-Hun Kim
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Yun Chae Lee
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Hyung Ku Chon
- Department of Internal Medicine, Institution of Wonkwang Medical Science, Wonkwang University School of Medicine and Hospital, Iksan 54538, South Korea
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3
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Macinga P, Bajer L, Del Chiaro M, Chari ST, Dite P, Frulloni L, Ikeura T, Kamisawa T, Kubota K, Naitoh I, Okazaki K, Pezzilli R, Vujasinovic M, Spicak J, Hucl T, Lӧhr M. Pancreatic cancer in patients with autoimmune pancreatitis: A scoping review. Pancreatology 2021; 21:928-937. [PMID: 33775564 DOI: 10.1016/j.pan.2021.03.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/25/2021] [Accepted: 03/11/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP). OBJECTIVE The aim of our study was to identify and analyse all published cases of AIP and PDAC co-occurrence, focusing on the interval between the diagnoses and the cancer site within the pancreas. METHODS Relevant studies were identified through automatic searches of the MEDLINE, EMBASE, Scopus, and Web of Science databases, and supplemented by manual checks of reference lists in all retrieved articles. Missing/unpublished data were obtained from the authors of relevant publications in the form of pre-prepared questionnaires. RESULTS A total of 45 cases of PDAC in AIP patients were identified, of which 12 were excluded from the analysis due to suspicions of duplicity or lack of sufficient data. Thirty-one patients (94%) had type 1 AIP. Synchronous occurrence of PDAC and AIP was reported in 11 patients (33%), metachronous in 22 patients (67%). In the metachronous group, the median period between diagnoses was 66.5 months (2-186) and a majority of cancers (86%) occurred more than two years after AIP diagnosis. In most patients (70%), the cancer originated in the part of the pancreas affected by AIP. CONCLUSIONS In the literature, there are reports on numerous cases of PDAC in AIP patients. PDAC is more frequent in AIP type 1 patients, typically metachronous in character, and generally found in the part of the pancreas affected by AIP.
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Affiliation(s)
- Peter Macinga
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Lukas Bajer
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - Suresh T Chari
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Petr Dite
- Clinic of Internal Medicine, University Hospital Ostrava, Ostrava, Czech Republic
| | - Luca Frulloni
- Gastroenterology Unit, Pancreas Center, University of Verona, Verona, Italy
| | - Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kensuke Kubota
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kazuichi Okazaki
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | | | - Miroslav Vujasinovic
- Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden; Department for Upper Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Julius Spicak
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Tomas Hucl
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
| | - Matthias Lӧhr
- CLINTEC, Karolinska Institute, Stockholm, Sweden; Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
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4
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Lee KW, Chang JH, Kim J, Kim TH, Kim CW, Kim JK, Han SW. Metachronous Development of Peritoneal Carcinomatosis in a Patient with Autoimmune Pancreatitis. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 75:356-361. [PMID: 32581208 DOI: 10.4166/kjg.2020.75.6.356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 04/08/2020] [Accepted: 04/08/2020] [Indexed: 11/03/2022]
Abstract
Autoimmune pancreatitis (AIP) is a rare and unique type of chronic pancreatitis. The prognosis of AIP, particularly when associated with pancreatic cancer or a related malignancy, is not known. Only a few cases, where metachronous pancreas-related cancer developed during follow-up, have been reported. Most of these patients either underwent surgery or steroid therapy. This paper reports a case of a 66-year-old woman with untreated type I AIP who developed peritoneal carcinomatosis more than 2 years later. Initially, the patient had a markedly elevated serum IgG4 level and a diffuse, infiltrative mass-like lesion in the pancreatic head, in which the biopsy results were consistent with type I AIP. The patient was not treated with steroids because of a cerebellar infarction. Twenty-eight months after the diagnosis of AIP, peritoneal carcinomatosis developed without noticeable changes in the pancreas from the initial findings.
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Affiliation(s)
- Kyu Won Lee
- Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Hyuck Chang
- Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeana Kim
- Departments of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Ho Kim
- Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chang Whan Kim
- Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Kwang Kim
- Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sok Won Han
- Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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5
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Goyal S, Sakhuja P. Autoimmune pancreatitis: Current perspectives. INDIAN J PATHOL MICR 2021; 64:S149-S159. [PMID: 34135159 DOI: 10.4103/ijpm.ijpm_59_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Over the last two decades, our knowledge and understanding regarding the pathogenesis and biology of autoimmune pancreatitis (AIP) have improved tremendously. Type 1 AIP or IgG4-related pancreatitis (IgG4-RP) is now believed to be the prototype of the multisystemic IgG4-related disease. In view of clinical features like obstructive jaundice and mass-forming lesions in the pancreas in elderly men, type 1 AIP often mimics pancreatic cancer. IgG4-related sclerosing cholangitis concomitantly involving the extrahepatic and intrahepatic biliary tree is the most common extrapancreatic involvement seen in up to 80% of these patients, which needs to distinguish from cholangiocarcinoma. Histology is characterised by lymphoplasmacytic inflammation, abundant IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. Apart from histology, high serum IgG4 levels, pancreatic parenchymal and duct imaging findings and other organ involvement aid in diagnosis especially in cases where definitive histology is not evident. Also, these parameters lay the foundation of various diagnostic criteria proposed over last few years. On the contrary, histology alone is the mainstay for establishing diagnosis of idiopathic duct-centric pancreatitis (IDCP) as it lacks any specific serological marker or imaging. Since both types of AIP respond dramatically to corticosteroid treatment, a biopsy is crucial to establish the preoperative diagnosis and to exclude malignancy so as to avoid unnecessary surgery. This review discusses the morphologic spectrum, treatment and prognosis of IgG4-RP and IDCP with an emphasis on approach to diagnosis with relevant histologic features, differential diagnoses and the challenges faced during biopsy interpretation.
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Affiliation(s)
- Surbhi Goyal
- Department of Pathology, GIPMER, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, GIPMER, New Delhi, India
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6
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Pattabathula K, Waters PS, Hwang J, Bettington M, Singh M, Bryant RD, Cavallucci DJ, O'Rourke N. Diagnostic and therapeutic considerations in biopsy-proven type 2 autoimmune pancreatitis: comparative analysis with biopsy-proven type 1 autoimmune pancreatitis. ANZ J Surg 2020; 91:907-914. [PMID: 33369858 DOI: 10.1111/ans.16445] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/26/2020] [Accepted: 11/03/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Autoimmune processes are now an increasingly recognized cause of acute and chronic pancreatitis. Autoimmune pancreatitis is a rare, benign pathology with two distinct clinicopathologic subtypes. The aim of this study was to compare the presentation, diagnostic considerations and outcomes of patients with biopsy-proven type 1 and 2 autoimmune pancreatitis (AIP). METHODS A retrospective review of the Queensland Health pathology database of histologically proven AIP was conducted. Parameters compared included demographics, diagnostic criterion and post-treatment outcomes. RESULTS Twenty-three patients had a confirmed histological diagnosis of AIP (type 1 = 13, type 2 = 10). Patients with type 2 AIP were younger (median age 49 versus 59 years, P < 0.05). There was no significant difference in gender distribution of disease at presentation. Type 2 AIP presented with significant increased focal pancreatic changes on cross-sectional imaging (80% versus 54%, P < 0.05). Serum IgG4 levels were raised (>1.40 g/L) in 69% of patients with type 1 AIP and not detected in type 2 (P < 0.01). Concurrent underlying inflammatory bowel disease was present in a higher proportion of type 2 AIP (40% versus 15%, P < 0.05). A significantly increased proportion of patients with type 2 AIP underwent surgical resection (70% versus 30%, P < 0.05). Conservative management was utilized in more patients with type 1 disease (54% versus 30%). On follow-up, two patients have experienced symptomatic relapse at 6-18 months. CONCLUSIONS Diagnostic challenges do exist and clinicians must suspect 2 type AIP in young, serum IgG4-negative inflammatory bowel disease patients with recurrent pancreatitis.
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Affiliation(s)
- Krishna Pattabathula
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Peadar S Waters
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Jason Hwang
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Mark Bettington
- Department of Histopathology, Envoi Pathology, Brisbane, Queensland, Australia
| | - Mahendra Singh
- Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Richard D Bryant
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - David J Cavallucci
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Department of Surgery, Wesley Hospital, Brisbane, Queensland, Australia
| | - Nicholas O'Rourke
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Department of Surgery, Wesley Hospital, Brisbane, Queensland, Australia
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7
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Sun W, Ren Y, Lu Z, Zhao X. The potential roles of exosomes in pancreatic cancer initiation and metastasis. Mol Cancer 2020; 19:135. [PMID: 32878635 PMCID: PMC7466807 DOI: 10.1186/s12943-020-01255-w] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 08/25/2020] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PaCa) is an insidious and highly metastatic malignancy, with a 5-year survival rate of less than 5%. So far, the pathogenesis and progression mechanisms of PaCa have been poorly characterized. Exosomes correspond to a class of extracellular nanovesicles, produced by a broad range of human somatic and cancerous cells. These particular nanovesicles are mainly composed by proteins, genetic substances and lipids, which mediate signal transduction and material transport. A large number of studies have indicated that exosomes may play decisive roles in the occurrence and metastatic progression of PaCa. This article summarizes the specific functions of exosomes and their underlying molecular mechanisms in mediating the initiation and metastatic capability of PaCa.
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Affiliation(s)
- Wei Sun
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China
| | - Ying Ren
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China
| | - Zaiming Lu
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China
| | - Xiangxuan Zhao
- Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.
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8
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Sugimoto M, Takagi T, Suzuki R, Konno N, Asama H, Watanabe K, Nakamura J, Kikuchi H, Waragai Y, Takasumi M, Sato Y, Hikichi T, Ohira H. Endoscopic Ultrasonography-Guided Fine Needle Aspiration Can Be Used to Rule Out Malignancy in Autoimmune Pancreatitis Patients. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2017; 36:2237-2244. [PMID: 28670760 DOI: 10.1002/jum.14265] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 02/06/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES The aim of this study was to review the suitability of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for ruling out malignancy in autoimmune pancreatitis patients. METHODS We retrospectively reviewed 40 autoimmune pancreatitis patients (type 1:37 patients; type 2: two patients; possible autoimmune pancreatitis: one patient) who received EUS-FNA. Among the 40 autoimmune pancreatitis patients, 34 were not histopathologically diagnosed with autoimmune pancreatitis by EUS-FNA, and they were followed up for more than 6 months in our hospital. Moreover, 14 pancreatic cancer patients who were not diagnosed by EUS-FNA were selected as a control group. These 14 patients constituted 3.9% of the 360 pancreatic cancer patients who received EUS-FNA. We evaluated the prognoses of the 34 autoimmune pancreatitis patients and the clinical differences between these 34 autoimmune pancreatitis patients and the 14 pancreatic cancer patients. RESULTS All 34 autoimmune pancreatitis patients showed reduced pancreatic swelling. The main pancreatic duct dilation ( > 3 mm), the diameter of the main pancreatic duct, the capsule-like rim sign, and serum CA19-9 levels were significantly different between the autoimmune pancreatitis and pancreatic cancer patients (2.9% versus 69.2%, P < .01; 1.7 ± 1.6 mm versus 6.8 ± 5.0 mm, P < .01; 79.4% versus 0%, P < .01; 41.4 ± 79.0 U/mL versus 2079.1 ± 275.3 U/mL, P = .02). CONCLUSIONS Almost all pancreatic cancers can be diagnosed by EUS-FNA. Furthermore, other clinical characteristics of pancreatic cancer undiagnosed by EUS-FNA were different from autoimmune pancreatitis undiagnosed by EUS-FNA. Endoscopic ultrasonography-guided FNA can be used to rule out malignancy in autoimmune pancreatitis patients.
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Affiliation(s)
- Mitsuru Sugimoto
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Tadayuki Takagi
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Rei Suzuki
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Naoki Konno
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Hiroyuki Asama
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Ko Watanabe
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Jun Nakamura
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Hitomi Kikuchi
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Yuichi Waragai
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Mika Takasumi
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Yuki Sato
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
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9
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Bennett AE, Fenske NA, Rodriguez-Waitkus P, Messina JL. IgG4-related skin disease may have distinct systemic manifestations: a systematic review. Int J Dermatol 2017; 55:1184-1195. [PMID: 27419384 DOI: 10.1111/ijd.13369] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 02/20/2016] [Accepted: 04/15/2016] [Indexed: 12/24/2022]
Abstract
IgG4-related disease (IgG4-RD) is an increasingly prevalent protean multisystem disorder characterized by single or multi-organ infiltration of IgG4-bearing plasma cells. Skin involvement has been recognized and is relevant to proper diagnosis. A systematic literature review of 50 cases involving the skin reveals that patients with IgG4-related skin disease show predominant involvement of the head and neck and have a distinct pattern of systemic involvement, also favoring the head and neck - lymphatics, orbit, salivary, and lacrimal glands - but generally lacking pancreaticobiliary involvement (16% of cases), which by contrast is a predominant manifestation in systemic IgG4-RD (60% with pancreaticobiliary involvement). We summarize clinical and pathologic descriptive data from this systematic review. We review differential diagnosis and propose a diagnostic scheme for stratifying probability of disease based upon comprehensive integration of clinical, histopathologic, and laboratory data. Plasmacyte infiltration and storiform fibrosis are prominent in IgG4-related skin disease, but obliterative venulitis is less common than in the prototypical IgG4-related disease manifestation of autoimmune pancreatitis. IgG4 tissue and serum values, with a mean (±95% CI) in the reviewed cases of 132.8 ± 32.6 IgG4-positive plasma cells per high-power field and 580 ± 183.8 mg/dl, respectively, are incorporated into the suggested criteria. The distinct set of manifestations identified by this systematic review and the proposed diagnostic considerations, while requiring further validation in prospective studies, highlight the need to consider that IgG4-related skin disease defines a unique systemic disease complex along the spectrum of IgG4-RD.
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Affiliation(s)
- Adam E Bennett
- Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
| | - Neil A Fenske
- Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Paul Rodriguez-Waitkus
- Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA.,Department of Pathology and Cell Biology, University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Jane L Messina
- Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA.,Department of Pathology and Cell Biology, University of South Florida Morsani College of Medicine, Tampa, FL, USA.,Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
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10
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Macinga P, Pulkertova A, Bajer L, Maluskova J, Oliverius M, Smejkal M, Heczkova M, Spicak J, Hucl T. Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass. World J Gastroenterol 2017; 23:2185-2193. [PMID: 28405146 PMCID: PMC5374130 DOI: 10.3748/wjg.v23.i12.2185] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 01/31/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the occurrence of autoimmune pancreatitis (AIP) in pancreatic resections performed for focal pancreatic enlargement.
METHODS We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria.
RESULTS Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients (5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma (PC) was also present in six patients with AIP (40%), all six were men. Patients with AIP + PC were significantly older (60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes (67% vs 11%, P = 0.09), and had experienced greater weight loss (15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case.
CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.
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11
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Koopman KE, Bloemena E, Kazemier G, Klemt-Kropp M. Immunoglobulin G4-mediated sclerosing cholangitis as a risk factor for cholangiocarcinoma: A case report. Mol Clin Oncol 2016; 5:786-788. [PMID: 28105357 DOI: 10.3892/mco.2016.1040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 08/08/2016] [Indexed: 02/07/2023] Open
Abstract
Immunoglobulin (Ig)G4-mediated disease is a systemic autoimmune disease, which occasionally presents solely as sclerosing cholangitis (SC). IgG4-mediated SC is challenging to diagnose, as it may mimic cholangiocarcinoma radiologically, and carcinoma cells may produce IgG4. The diagnosis of IgG4-mediated disease is based on histological consensus criteria and response to corticosteroids. In addition to the radiological and histological overlap between IgG4-mediated SC and cholangiocarcinoma, IgG4-mediated SC may be considered as a risk factor for the development of cholangiocarcinoma. We herein present the case of a patient in whom cholangiocarcinoma developed in two lesions previously characterized as IgG4-mediated SC, including a suggested mechanism underlying the contribution of IgG4-mediated SC to the development of cholangiocarcinoma.
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Affiliation(s)
- Karin E Koopman
- Department of Gastroenterology, Northwest Clinics, 1815 JD Alkmaar, The Netherlands
| | - Elisabeth Bloemena
- Department of Pathology, VU University Medical Center (VUMC), 1081 HV Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, VU University Medical Center (VUMC), 1081 HV Amsterdam, The Netherlands
| | - Michael Klemt-Kropp
- Department of Gastroenterology, Northwest Clinics, 1815 JD Alkmaar, The Netherlands
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12
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Ikeura T, Miyoshi H, Shimatani M, Uchida K, Takaoka M, Okazaki K. Long-term outcomes of autoimmune pancreatitis. World J Gastroenterol 2016; 22:7760-7766. [PMID: 27678359 PMCID: PMC5016376 DOI: 10.3748/wjg.v22.i34.7760] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/04/2016] [Accepted: 06/29/2016] [Indexed: 02/06/2023] Open
Abstract
Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.
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Yamabe A, Irisawa A, Notohara K, Shibukawa G, Fujisawa M, Sato A, Yoshida Y, Arakawa N, Ikeda T, Igarashi R, Maki T, Yamamoto S. A case of autoimmune pancreatitis effectively treated with an immunosuppressant (azathioprine). Clin J Gastroenterol 2016; 9:324-8. [PMID: 27450404 DOI: 10.1007/s12328-016-0673-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 07/10/2016] [Indexed: 10/21/2022]
Abstract
The patient was a 42-year-old man who presented at our hospital with obstructive jaundice. Although antinuclear antibody test results were negative, and immunoglobulin G4 (IgG4) was not elevated, endoscopic ultrasound revealed a mixed internal hyperechoic and diffuse hypoechoic pattern, a finding consistent with autoimmune pancreatitis. Endoscopic retrograde cholangiopancreatography further revealed irregular narrowing of the main pancreatic duct and sclerosing cholangitis with distal biliary stricture. In addition, endoscopic ultrasound with fine needle aspiration cytology resulted in a diagnosis of type 1 autoimmune pancreatitis. Oral prednisolone treatment was initiated at 30 mg/day, and the dosage was gradually decreased. However, in accordance with the patient's wishes, maintenance treatment was discontinued once dosage reached 5 mg/day. Despite this, relapse of obstructive jaundice occurred 1 month post discontinuation, and was treated with methyl-prednisolone pulse therapy (500 mg/day) followed by oral prednisolone. However, computed tomography, magnetic resonance imaging, and endoscopic ultrasound did not reveal sufficient improvement after 6 months of treatment. Therefore, an immunosuppressant (azathioprine) was introduced. Subsequent imaging analyses and endoscopic ultrasound fine needle aspiration revealed clear improvements in pathology.
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Affiliation(s)
- Akane Yamabe
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan.
| | - Atsushi Irisawa
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Kenji Notohara
- Department of Pathology, Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki, 710-8602, Japan
| | - Goro Shibukawa
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Mariko Fujisawa
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Ai Sato
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Yoshitsugu Yoshida
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Noriyuki Arakawa
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Tsunehiko Ikeda
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Ryo Igarashi
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Takumi Maki
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
| | - Shogo Yamamoto
- Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, 21-2, Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, 969-3492, Japan
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Yonenaga Y, Kushihata F, Watanabe J, Tohyama T, Inoue H, Sugita A, Takada Y. Localized 18F-fluorodeoxyglucose uptake at the pancreatic head during remission phase of autoimmune pancreatitis: A case report. Oncol Lett 2016; 12:1801-1805. [PMID: 27602112 PMCID: PMC4998295 DOI: 10.3892/ol.2016.4815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Accepted: 03/15/2016] [Indexed: 01/14/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a unique form of pancreatitis, histopathologically characterized by dense lymphoplasmacytic infiltration and fibrosis of the pancreas with obliterative phlebitis. AIP is associated with a good response to steroid therapy. Differentiation between AIP and pancreatic cancer to determine a preoperative diagnosis is often challenging, despite the use of various diagnostic modalities, including computed tomography (CT), magnetic resonance imaging and endoscopic retrograde cholangiopancreatography. It has been reported that 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/CT may be a useful tool for distinguishing between the two diseases. In the present case report, a 71-year-old male patient presented with a well-circumscribed, solitary, nodular and homogenous 18F-FDG uptake at the pancreatic head, while receiving maintenance steroid therapy in the remission phase of AIP; preoperatively, the patient had been strongly suspected of having pancreatic cancer. Pathological examination revealed post-treatment relapse of AIP. The present case highlights the diagnostic and management difficulties with AIP in the remission phase. In certain cases, it remains challenging to differentiate the two diseases, even using the latest modalities.
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Affiliation(s)
- Yoshikuni Yonenaga
- Department of Hepatobiliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; Department of Surgery, Nagahama City Hospital, Nagahama, Shiga 526-8580, Japan
| | - Fumiki Kushihata
- Department of Hepatobiliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Jota Watanabe
- Department of Hepatobiliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Taiji Tohyama
- Department of Hepatobiliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Hitoshi Inoue
- Department of Hepatobiliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Atsuro Sugita
- Pathology Division, Ehime University Hospital, Toon, Ehime 791-0295, Japan
| | - Yasutsugu Takada
- Department of Hepatobiliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
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A case of concurrent pancreatic intraepithelial neoplasia and type 1 autoimmune pancreatitis with marked pancreatic duct dilatation. Clin J Gastroenterol 2016; 9:266-71. [DOI: 10.1007/s12328-016-0666-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 06/17/2016] [Indexed: 12/31/2022]
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JOURNAL CLUB: Use of MDCT to Differentiate Autoimmune Pancreatitis From Ductal Adenocarcinoma and Interstitial Pancreatitis. AJR Am J Roentgenol 2015; 205:2-9. [DOI: 10.2214/ajr.14.14059] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Watanabe R, Yasuno T, Hisano S, Sasatomi Y, Nakashima H. Distinct cytokine mRNA expression pattern in immunoglobulin G4-related kidney disease associated with renal cell carcinoma. Clin Kidney J 2015; 7:269-74. [PMID: 25852888 PMCID: PMC4377746 DOI: 10.1093/ckj/sfu024] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 02/21/2014] [Indexed: 12/24/2022] Open
Abstract
We treated a 61-year-old man with immunoglobulin (Ig)G4-related kidney disease (IgG4-RKD). He had a history of allergic diseases and an allergic reaction and had received a diagnosis of autoimmune pancreatitis (AIP). He had also received a diagnosis of renal cell carcinoma (RCC) and had undergone segmental resection of the left kidney at 59 years of age. His serum amylase level and number of peripheral eosinophils increased after RCC development. We hypothesized that the RCC may have induced AIP and IgG4-RKD and we therefore examined the excised RCC tissue; typical findings of IgG4-RKD associated with RCC were recognized. We next evaluated the mRNA expression of cytokines in the excised tissues of this case and ten other ordinary RCC cases. In all cases, notable levels of IL-10 mRNA and high levels of TGF-β mRNA were seen. Although prominent differences were not observed in the mRNA expression of Th1, Th17 and Treg cytokines in all cases, the present case alone showed increased production of the Th2 cytokines IL-4 and IL-5, which were not detected in ordinary RCC cases. Although the mechanism underlying IgG4-RKD development has not yet been determined, Th2 and Treg cells are thought to play a prominent role in the pathogenesis. It is therefore likely that in this case, the association of these two diseases was not coincidental, and a distinct immune response against RCC may trigger IgG4-RKD development.
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Affiliation(s)
- Renya Watanabe
- Division of Nephrology and Rheumatology, Department of Internal Medicine , Fukuoka University , Fukuoka , Japan
| | - Tetsuhiko Yasuno
- Division of Nephrology and Rheumatology, Department of Internal Medicine , Fukuoka University , Fukuoka , Japan
| | - Satoshi Hisano
- Department of Pathology, Faculty of Medicine , Fukuoka University , Fukuoka , Japan
| | - Yoshie Sasatomi
- Division of Nephrology and Rheumatology, Department of Internal Medicine , Fukuoka University , Fukuoka , Japan
| | - Hitoshi Nakashima
- Division of Nephrology and Rheumatology, Department of Internal Medicine , Fukuoka University , Fukuoka , Japan
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Immunoglobulin G4 related chronic sclerosing sialadenitis. The Journal of Laryngology & Otology 2015; 129:226-31. [DOI: 10.1017/s0022215115000195] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AbstractBackground:ENT surgeons may be the first specialists to encounter and diagnose patients with salivary gland disease. A new entity involving the salivary glands has recently been described of which ENT surgeons need to be aware: immunoglobulin G4 related chronic sclerosing sialadenitis.Method:A literature search of Medline, Embase and Cochrane Library databases was performed, using the search terms ‘IgG4’, ‘hyperIgG4 syndrome’ and ‘IgG4 related chronic sclerosing sialadenitis’.Results:Knowledge concerning immunoglobulin G4 related chronic sclerosing sialadenitis is rapidly increasing. This new entity is part of a fibro-inflammatory corticosteroid-responsive systemic disease (immunoglobulin G4 related disease) and has been described in almost every organ. Biopsy of the submandibular gland can be diagnostic. However, the diagnosis can easily be overlooked if: clinical suspicion is not high, one is unaware of the classical morphology and/or immunoglobulin G4 staining is not performed. This paper presents a summary of the current understanding of the disease and its management.Conclusion:ENT surgeons should be aware of this new disease entity. Patients with systemic disease should be managed under a multidisciplinary team, with input from clinicians who have an interest in such diseases (such as gastroenterologists and rheumatologists), and input from histopathologists and radiologists.
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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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Huggett MT, Culver E, Kumar M, Hurst J, Rodriguez-Justo M, Chapman M, Johnson G, Pereira S, Chapman R, Webster GJ, Barnes E. Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort. Am J Gastroenterol 2014; 109:1675-1683. [PMID: 25155229 PMCID: PMC4552254 DOI: 10.1038/ajg.2014.223] [Citation(s) in RCA: 178] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 07/25/2014] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1-107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P<0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02). CONCLUSIONS Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.
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Affiliation(s)
- Matthew T. Huggett
- UCL Institute for Liver and Digestive Health, University College London, London, UK
- Department of Gastroenterology and Hepatology, University College Hospital, London, UK
| | - E.L. Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
- NDM Oxford University, Oxford Martin School, Oxford University, Oxford, UK
| | - M. Kumar
- Department of Gastroenterology and Hepatology, University College Hospital, London, UK
| | - J.M. Hurst
- Institute of Emerging Diseases, Oxford Martin School, Oxford University, Oxford, UK
| | | | - M.H. Chapman
- Department of Gastroenterology and Hepatology, University College Hospital, London, UK
| | - G.J. Johnson
- Department of Gastroenterology and Hepatology, University College Hospital, London, UK
| | - S.P. Pereira
- UCL Institute for Liver and Digestive Health, University College London, London, UK
- Department of Gastroenterology and Hepatology, University College Hospital, London, UK
| | - R.W. Chapman
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
- NDM Oxford University, Oxford Martin School, Oxford University, Oxford, UK
| | - George J.M. Webster
- Department of Gastroenterology and Hepatology, University College Hospital, London, UK
| | - E. Barnes
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
- NDM Oxford University, Oxford Martin School, Oxford University, Oxford, UK
- Oxford NIHR BRC, Oxford University, Oxford, UK
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21
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Kamisawa T, Okazaki K, Kawa S, Ito T, Inui K, Irie H, Nishino T, Notohara K, Nishimori I, Tanaka S, Nishiyama T, Suda K, Shiratori K, Tanaka M, Shimosegawa T. Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis. J Gastroenterol 2014; 49:961-70. [PMID: 24639058 DOI: 10.1007/s00535-014-0945-z] [Citation(s) in RCA: 144] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 02/06/2014] [Indexed: 02/04/2023]
Abstract
The standard treatment for autoimmune pancreatitis (AIP) is steroid therapy, although some patients improve spontaneously. Indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, back pain, and the presence of symptomatic extrapancreatic lesions. Prior to steroid therapy, obstructive jaundice should be managed by biliary drainage, and blood glucose levels should be controlled in patients with diabetes mellitus. The recommended initial oral prednisolone dose for induction of remission is 0.6 mg/kg/day, which is administered for 2-4 weeks. The dose is then tapered by 5 mg every 1-2 weeks, based on changes in clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5-5 mg/day) over a period of 2-3 months. Cessation of steroid therapy should be based on the disease activity in each case. Termination of maintenance therapy should be planned within 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapse. Application of immunomodulatory drugs is considered for AIP patients who prove resistant to steroid therapy. The prognosis of AIP appears to be good over the short-term with steroid therapy. The long-term outcome is less clear, as there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan,
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Ikeura T, Miyoshi H, Uchida K, Fukui T, Shimatani M, Fukui Y, Sumimoto K, Matsushita M, Takaoka M, Okazaki K. Relationship between autoimmune pancreatitis and pancreatic cancer: a single-center experience. Pancreatology 2014; 14:373-9. [PMID: 25278307 DOI: 10.1016/j.pan.2014.04.029] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 04/09/2014] [Accepted: 04/11/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Ordinary chronic pancreatitis (CP), such as alcoholic CP, is well established to have the increased risk for pancreatic cancer (PaC), nevertheless an association between autoimmune pancreatitis (AIP) and PaC is still unknown. The aims of this study are to examine the frequency of patients who developed PaC during follow-up after being diagnosed with type 1 AIP and to compare the incidence rate of PaC between patients with type 1 AIP and CP. METHODS Sixty-three patients with type 1 AIP and 41 patients with CP were enrolled. We examined development of PaC during follow-up from their clinical records. RESULTS The mean follow-up period was 62.4 months in AIP group and 49.2 months in CP group. The occurrence of PaC was observed in 3 patients with AIP during the mean follow-up period of 94.7 months (range, 31-186), whereas a single CP patient developed PaC 38 months after CP diagnosis. The incident rate of PaC during follow-up was comparable between the 2 groups [4.8% (3/63) in type 1 AIP group vs. 2.4% (1/41) in CP group]. In all of 3 AIP patients who developed accompanying PaC, the clinical remission of AIP was achieved with maintenance steroid therapy, when tumors were discovered. In the histological examination of one surgical patient with PaC, lymphoplasmacytic infiltration in storiform fibrosis with abundant IgG4-positive cell infiltration was observed around the PaC area. CONCLUSIONS Similar to patients with ordinary CP, surveillance for development of PaC is needed at regular interval during follow-up in AIP patients.
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Affiliation(s)
- Tsukasa Ikeura
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
| | - Hideaki Miyoshi
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Kazushige Uchida
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Toshiro Fukui
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masaaki Shimatani
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Yuri Fukui
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Kimi Sumimoto
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Mitsunobu Matsushita
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Makoto Takaoka
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Kazuichi Okazaki
- The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
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A case of pancreatic cancer in the setting of autoimmune pancreatitis with nondiagnostic serum markers. Case Rep Surg 2013; 2013:809023. [PMID: 23781378 PMCID: PMC3679691 DOI: 10.1155/2013/809023] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Accepted: 05/15/2013] [Indexed: 12/21/2022] Open
Abstract
Background. Autoimmune pancreatitis (AIP) often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS-) guided fine-needle aspiration (FNA) of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP.
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Yoneda M, Inada H, Kanayama K, Shiraishi T. A case of pancreatic ductal adenocarcinoma with marked infiltration with IgG4-positive cells. J Cytol 2013; 30:46-8. [PMID: 23661941 PMCID: PMC3643362 DOI: 10.4103/0970-9371.107513] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
A 75-year-old man was diagnosed as having pancreatic ductal carcinoma containing remarkable lymphocytic and plasma cell infiltration, as revealed by the cytological examination of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) specimen. The EUS-FNA specimen showed small amounts of atypical epithelium with noticeable lymphocytes and plasma cells. A pancreatic resection was performed, and the histopathological features showed an invasive pancreatic ductal carcinoma with autoimmune pancreatitis (AIP) lymphoplasmacytic sclerosing pancreatitis (LPSP)-like lesions. Most of the plasma cells were immunoreactive to anti-IgG4 antibody. EUS-FNA may be necessary for the differential diagnosis of AIP and pancreatic cancer, and close attention should be given to the presence of marked lymphoplasmacytic cells in EUS-FNA specimens while making the diagnosis.
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Affiliation(s)
- M Yoneda
- Department of Pathologic Oncology, Institute of Molecular and Experimental Medicine, Faculty of Medicine, Mie University Graduate School of Medicine, Japan
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25
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Does autoimmune pancreatitis increase the risk of pancreatic carcinoma?: a retrospective analysis of pancreatic resections. Pancreas 2013; 42:506-10. [PMID: 23271394 DOI: 10.1097/mpa.0b013e31826bef91] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES To estimate the risk of malignancy in autoimmune pancreatitis (AIP). METHODS We examined resected pancreata to compare the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP and 30 cases of chronic pancreatitis not otherwise specified (CP-NOS). We also reviewed a cohort of 84 AIP cases. RESULTS The mean age of the AIP cohort (57 years) was significantly higher than that of the cohort of CP-NOS (47 years) (P = 0.01). Twenty-three cases (82%) of AIP showed PanIN, and 7 cases (25%) showed grade 2 PanIN. Grade 3 PanIN was identified in one case of AIP. There was no statistically significant difference in the number of cases with high-grade PanIN lesions between the cases of type 1 as opposed to type 2 AIP. In comparison to CP-NOS, a comparable percentage of patients with AIP had PanIN (82% of AIP cases vs 63% of CP-NOS cases) (P = NS) and PanIN 2 (25% AIP vs 20% CP-NOS) (P = NS). Of the 84 AIP cases at our institution (mean follow-up, 49 months), 2 cases of pancreatic carcinoma were identified 6 and 10 years after the diagnoses of AIP. CONCLUSIONS These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.
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Sah RP, Chari ST. Autoimmune pancreatitis: an update on classification, diagnosis, natural history and management. Curr Gastroenterol Rep 2012; 14:95-105. [PMID: 22350841 DOI: 10.1007/s11894-012-0246-8] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Autoimmune Pancreatitis (AIP) is a recently recognized chronic fibro-inflammatory disease of the pancreas. Although rare, its recognition continues to increase worldwide. Patients often present with painless obstructive jaundice mimicking pancreatic cancer. Two subtypes of AIP are known-type 1 is a multi-organ disease associated with IgG4; type 2 appears to be a pancreas-specific disorder. Dramatic response to steroid treatment is characteristic of both forms. A non-invasive diagnosis of type 1 AIP may be possible using diagnostic criteria (in ~70% cases) while diagnosis of type 2 requires histology. These subtypes differ in natural history- type 1 often relapses while initial reports suggest that type 2 does not. Long term complications include endocrine and exocrine insufficiency and in case of type 1, disease relapses and complications from extra-pancreatic involvement. Neither form affects long term survival. The treatment and follow-up guidelines continue to evolve with our increasing experience in AIP.
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Affiliation(s)
- Raghuwansh P Sah
- Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN 55905, USA
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Herreros-Villanueva M, Hijona E, Cosme A, Bujanda L. Spontaneous regression of pancreatic cancer: real or a misdiagnosis? World J Gastroenterol 2012; 18:2902-2908. [PMID: 22736913 PMCID: PMC3380317 DOI: 10.3748/wjg.v18.i23.2902] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2012] [Revised: 03/04/2012] [Accepted: 03/20/2012] [Indexed: 02/06/2023] Open
Abstract
Spontaneous tumor regression has been subject of numerous studies and speculations for many years. This phenomenon is exceptional, but well reported, in some types of tumors, but not in pancreatic cancer. Pancreatic cancer has the worst five-year survival rate of any cancer. Despite numerous molecular studies and clinical approaches, using several mouse models, this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive. Although pancreatic cancer tumors seldom undergo spontaneous regression, and some authors take that with skepticism, there are some cases reported in the literature. However, the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis. Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential. Diseases such as pancreatic benign tumors, insulinomas, or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer. Here we review different cases reported, their clinical characteristics, and possible mechanisms leading to spontaneous regression of pancreatic cancer. We also discuss the possibilities of misdiagnosis.
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Treatment of autoimmune pancreatitis with the anecdotes of the first report. Int J Rheumatol 2012; 2012:597643. [PMID: 22548071 PMCID: PMC3323841 DOI: 10.1155/2012/597643] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Accepted: 02/04/2012] [Indexed: 12/23/2022] Open
Abstract
The first case that led researchers to put forward a new concept of autoimmune pancreatitis (AIP) was treated with steroids by gastroenterologists in Tokyo Women's Medical University. It is important to differentiate AIP from pancreatic cancer before treatment with steroids is started. Today, steroids are standard therapy for AIP worldwide. In the Japanese consensus guidelines, steroid therapy is indicated for symptomatic AIP. After management of glucose levels and obstructive jaundice, oral prednisolone is initiated at 0.6 mg/kg/day for 2-4 weeks and is gradually tapered to a maintenance dose of 2.5-5 mg/day over 2-3 months. To prevent relapse, maintenance therapy with low-dose prednisolone is used. For relapsed AIP, readministration or increased doses of steroids are effective. The presence of proximal bile duct stenosis and elevated serum IgG4 levels may be predictive of relapse of AIP. It is necessary to verify the validity of the Japanese regimen of steroid therapy for AIP. The necessity, drugs, and duration of maintenance therapy for AIP need to be clarified by prospective studies.
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Itokawa N, Atsukawa M, Nishino T, Kondo C, Fukuda T, Matsushita Y, Kidokoro H, Katakura T, Narahara Y, Tanaka S, Nakatsuka K, Oaki Y, Sakamoto C. A case of IgG4-related disease with rectal cancer. Clin J Gastroenterol 2011; 4:374-380. [PMID: 26189739 DOI: 10.1007/s12328-011-0253-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2011] [Accepted: 07/14/2011] [Indexed: 12/15/2022]
Abstract
A 72-year-old male with liver dysfunction and an increase in serum total protein/albumin (TP/Alb) ratio was referred to our hospital. There was a marked increase in serum immunoglobulin (Ig) G4 level (IgG/IgG4: 3,485/2,860 mg/dl). Diagnostic imaging did not reveal any enlargement of the pancreas or narrowing of the pancreatic duct. However, bilateral submaxillary gland swelling, sclerosing cholangitis, and retroperitoneal fibrosis were noted, suggesting multifocal fibrosclerosis. Histological examination of the submaxillary gland showed the infiltration of IgG4-positive plasma cells, although there was no narrowing of the pancreatic duct, leading to a diagnosis of IgG4-related disease with various extrapancreatic lesions. Systemic investigation before the introduction of steroid therapy revealed rectal cancer. After low-position anterior resection, steroid therapy was introduced, reducing the lesions. Recent studies have reported autoimmune pancreatitis/IgG4-related disease with malignant tumors. However, the association and pathogenesis remain to be clarified. Malignant tumors are detected before or after the treatment of autoimmune pancreatitis/IgG4-related disease; pretreatment diagnosis and post-treatment follow-up should be carefully performed, bearing in mind the concomitant development of malignant tumors.
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Affiliation(s)
- Norio Itokawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, 270-1694, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, 270-1694, Japan.
| | - Takayoshi Nishino
- Division of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, 270-1694, Japan
| | - Takeshi Fukuda
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoko Matsushita
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Hideko Kidokoro
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tamaki Katakura
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoshiyuki Narahara
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Shu Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Katsuhisa Nakatsuka
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoshiharu Oaki
- Department of Pathology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Choitsu Sakamoto
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
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Yamamoto M, Takahashi H, Tabeya T, Suzuki C, Naishiro Y, Ishigami K, Yajima H, Shimizu Y, Obara M, Yamamoto H, Himi T, Imai K, Shinomura Y. Risk of malignancies in IgG4-related disease. Mod Rheumatol 2011; 22:414-8. [PMID: 21894525 DOI: 10.1007/s10165-011-0520-x] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Accepted: 08/16/2011] [Indexed: 12/19/2022]
Abstract
IgG4-related disease (IgG4-RD) is considered a systemic, chronic, and inflammatory disorder that is characterized by the enlargement of involved organs, elevated levels of IgG4, and abundant infiltration of plasmacytes with IgG4 and fibrosis in involved organs. It is necessary to differentiate IgG4-RD from malignant tumors. Recently we have looked at case reports of IgG4-RD with malignancy that was discovered at systemic screening. In this study, we analyzed the relationship between IgG4-RD and malignancies. The study subjects were 106 patients with IgG4-RD who had been referred to our hospital since April 1997. We analyzed the clinical characteristics of IgG4-RD patients who had cancer that was observed upon the initial diagnosis of IgG4-RD or that occurred during an average follow-up period of 3.1 years. Using data from national cancer registries that monitor cancer incidence in Japan, we evaluated the standardized incidence ratio (SIR) for malignancies in IgG4-RD. Malignancies were observed in 11 of the IgG4-RD patients (10.4%). The malignancies were all different and included lung cancer, colon cancer, and lymphoma. With the exception of the age at which the IgG4-RD diagnosis was made, there were no common features in patients with cancer and those without. The SIR for these malignancies in IgG4-RD was 383.0, which was higher than that for the general population. We should be cognizant of the possible existence of malignancies in patients with IgG4-RD at the time of diagnosis and during follow-up care.
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Affiliation(s)
- Motohisa Yamamoto
- First Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1-West 16, Chuo-ku, Sapporo, Hokkaido 0608543, Japan.
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Pezzilli R, Vecchiarelli S, Di Marco MC, Serra C, Santini D, Calculli L, Fabbri D, Rojas Mena B, Imbrogno A. Pancreatic ductal adenocarcinoma associated with autoimmune pancreatitis. Case Rep Gastroenterol 2011; 5:378-85. [PMID: 21769291 PMCID: PMC3134062 DOI: 10.1159/000330291] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Autoimmune pancreatitis (AIP), in contrast to other benign chronic pancreatic diseases, can be cured with immunosuppressant drugs, thus the differentiation of AIP from pancreatic cancer is of particular interest in clinical practice. There is the possibility that some patients with AIP may develop pancreatic cancer, and this possibility contributes to increasing our difficulties in differentiating AIP from pancreatic cancer. We herein report the case of a 70-year-old man in whom pancreatic adenocarcinoma and AIP were detected simultaneously. We must carefully monitor AIP patients for the simultaneous presence of pancreatic cancer, even when a diagnosis of AIP is confirmed.
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Affiliation(s)
- Raffaele Pezzilli
- Pancreas Unit, Department of Digestive Diseases and Internal Medicine, University of Bologna, Bologna, Italy
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Kamisawa T, Takuma K, Hara S, Tabata T, Kuruma S, Inaba Y, Gopalakrishna R, Egawa N, Itokawa F, Itoi T. Management strategies for autoimmune pancreatitis. Expert Opin Pharmacother 2011; 12:2149-59. [PMID: 21711086 DOI: 10.1517/14656566.2011.595710] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. AREAS COVERED The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. EXPERT OPINION AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.
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Affiliation(s)
- Terumi Kamisawa
- Tokyo Metropolitan Komagome Hospital, Department of Internal Medicine, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan.
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33
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Autoimmune pancreatitis complicated by carcinoma of the pancreatobiliary system: a case report and review of the literature. Pancreas 2011; 40:151-4. [PMID: 21160372 DOI: 10.1097/mpa.0b013e3181f74a13] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
We present the case of a 67-year-old woman who developed a metastatic adenocarcinoma of the pancreatobiliary system shortly after the histologically confirmed diagnosis of autoimmune pancreatitis (AIP). This case highlights the need for increased alertness not only in differentiating AIP from pancreatic cancer at the time of diagnosis, but also to exclude concomitant malignancies of the pancreatobiliary system in the management of histologically confirmed AIP.
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Hayashi M, Arisaka Y, Takeshita A, Tominaga Y, Ki T, Masuda D, Hirokawa F, Egashira Y, Tsuji M, Yamamoto K, Higuchi K, Tanigawa N. Differential Diagnosis of Pancreatobiliary Carcinoma from Autoimmune Pancreatitis-Related Diseases: A Report of Three Cases. J Gastrointest Cancer 2010; 42:241-51. [DOI: 10.1007/s12029-010-9209-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Kamisawa T, Horiguchi SI, Hayashi Y, Yun X, Yamaguchi T, Tsuruta K, Sasaki T. K-ras mutation in the major duodenal papilla and gastric and colonic mucosa in patients with autoimmune pancreatitis. J Gastroenterol 2010; 45:771-8. [PMID: 20157749 DOI: 10.1007/s00535-010-0211-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2009] [Accepted: 01/15/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pancreatic cancer occurs in some patients with autoimmune pancreatitis (AIP). Significant K-ras mutations are frequently detected in the pancreas of AIP patients. AIP may be a pancreatic lesion of IgG4-related systemic disease. Gastric and colonic cancer can occur during the follow up of AIP patients. We examined K-ras mutations in the major duodenal papilla and gastric and colonic mucosa of AIP patients. METHODS K-ras analysis and/or immunohistochemical study was performed on the tissues of the major duodenal papilla (n = 8), gastric mucosa (n = 5), colonic mucosa (n = 3), pancreas (n = 5), common bile duct (n = 5), and gallbladder (n = 4) of 12 AIP patients. RESULTS Significant K-ras mutations were detected in the major duodenal papilla of 4 of 8 cases [GAT (n = 4)], in the gastric mucosa of 2 of 4 cases [AGT (n = 2)], and in the colonic mucosa of 2 of 3 cases [GAT (n = 2)]. Significant K-ras mutations were detected in the pancreas of all 5 cases [GAT (n = 5), in the common bile duct of 4 cases (GAT (n = 2), TGT (n = 1), and GCT/TGT (n = 1)], and in the gallbladder epithelium of 3 cases [GAT (n = 1), GCT (n = 1), and GTT (n = 1)]. K-ras mutations were detected in the organs associated with IgG4-related fibroinflammation with abundant infiltration of T lymphocytes and forkhead box P3-positive cells. CONCLUSIONS Significant K-ras mutations were frequently detected in the major duodenal papilla and gastric and colonic mucosa of AIP patients. AIP patients may have risk factors for gastric and colonic cancer, but the mechanisms of K-ras mutation and its clinical implications are not clear.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
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Sah RP, Chari ST, Pannala R, Sugumar A, Clain JE, Levy MJ, Pearson RK, Smyrk TC, Petersen BT, Topazian MD, Takahashi N, Farnell MB, Vege SS. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology 2010; 139:140-8; quiz e12-3. [PMID: 20353791 DOI: 10.1053/j.gastro.2010.03.054] [Citation(s) in RCA: 297] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2009] [Revised: 03/10/2010] [Accepted: 03/22/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP. METHODS We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP. RESULTS At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P < .0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P < .0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid-treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population. CONCLUSIONS Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival.
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Affiliation(s)
- Raghuwansh P Sah
- Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA
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Kamisawa T, Okazaki K, Kawa S, Shimosegawa T, Tanaka M. Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol 2010; 45:471-7. [PMID: 20213336 DOI: 10.1007/s00535-010-0221-9] [Citation(s) in RCA: 181] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2010] [Accepted: 02/04/2010] [Indexed: 02/04/2023]
Abstract
Steroid therapy appeared to be a standard treatment for autoimmune pancreatitis (AIP), although some AIP patients improve spontaneously. The indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, and back pain, and the presence of symptomatic extrapancreatic lesions. Before steroid therapy, jaundice should be managed by biliary drainage in patients with obstructive jaundice, and blood glucose levels should be controlled in patients with diabetes mellitus. For the initial oral prednisolone dose for induction of remission, 0.6 mg/kg/day is recommended. The initial dose is administered for 2-4 weeks, and the dose is tapered by 5 mg every 1-2 weeks, based on changes in the clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5-5 mg/day) over a period of 2-3 months. Steroid therapy should be stopped based on the disease activity in each case. Stopping of maintenance therapy should be planned within at least 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapses. The prognosis of AIP appears to be good over the short-term with steroid therapy. It is unclear whether the long-term outcome is good because there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan.
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Motosugi U, Ichikawa T, Yamaguchi H, Nakazawa T, Katoh R, Itakura J, Fujii H, Sato T, Araki T, Shimizu M. Small invasive ductal adenocarcinoma of the pancreas associated with lymphoplasmacytic sclerosing pancreatitis. Pathol Int 2009; 59:744-7. [PMID: 19788620 DOI: 10.1111/j.1440-1827.2009.02437.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
An asymptomatic 59-year-old man underwent pancreatoduodenectomy for a pancreatic mass that was discovered during a health check-up. Histopathology indicated typical features of lymphoplasmacytic sclerosing pancreatitis (LPSP) or autoimmune pancreatitis along with the presence of abundant IgG4-positive plasma cells throughout the mass. A small invasive ductal adenocarcinoma was observed in the center of the area affected by LPSP. The present case suggests that LPSP may be closely related to carcinogenesis of the pancreas.
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Affiliation(s)
- Utaroh Motosugi
- Department of Radiology, University of Yamanashi, Chuo, Japan.
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Frequent and significant K-ras mutation in the pancreas, the bile duct, and the gallbladder in autoimmune pancreatitis. Pancreas 2009; 38:890-5. [PMID: 19752775 DOI: 10.1097/mpa.0b013e3181b65a1c] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To assess the relationship between autoimmune pancreatitis (AIP) and pancreatic cancer, we analyzed K-ras mutation in the pancreatobiliary tissues of patients with AIP. METHODS An analysis of K-ras mutation and an immunohistochemical study were performed on the pancreas of 8 patients with AIP and 10 patients with chronic alcoholic pancreatitis and on the common bile duct and the gallbladder of 9 patients with AIP. K-ras mutation was analyzed in the pure pancreatic juice from 3 patients with AIP. RESULTS High-frequency K-ras mutation (2+ or 3+) was detected in the pancreas of all the 8 patients and in the pancreatic juice of the other 2 patients. The mutation in codon 12 of the ras gene was GAT in all the 10 patients. High-frequency K-ras mutation was detected in the common bile duct of 5 patients with AIP and in the gallbladder epithelium of 4 patients with AIP. The K-ras mutation was detected in the fibroinflammatory pancreas, the bile duct, and the gallbladder, with abundant infiltrating IgG4-positive plasma and Foxp3-positive cells of patients with AIP with elevated serum IgG4 levels. CONCLUSIONS Significant K-ras mutation occurs most frequently in the pancreatobiliary regions of patients with AIP. Autoimmune pancreatitis may be a risk factor of pancreatobiliary cancer.
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Long-term follow-up of autoimmune pancreatitis: characteristics of chronic disease and recurrence. Clin Gastroenterol Hepatol 2009; 7:S18-22. [PMID: 19896092 DOI: 10.1016/j.cgh.2009.07.041] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2009] [Revised: 07/21/2009] [Accepted: 07/23/2009] [Indexed: 02/07/2023]
Abstract
Autoimmune pancreatitis is a unique disease, characterized by lymphoplasmacytic inflammation in the acute stages. However, the active clinical features are unlikely to persist for long periods. Through long-term follow-up, we investigated the disease course in 51 patients with autoimmune pancreatitis. We found recurrence in 21 (41%) patients and pancreatic stone formation in 9 (18%) patients. Pancreatic stone formation was significantly more frequent in the recurrence group (7/21, 33%), compared with the nonrecurrence group (2/30, 7%). Moreover, we found high serum immunoglobulin G4 concentrations in 13 of 175 (7.4%) patients with ordinary chronic pancreatitis. This suggested that pancreatic stone formation is closely associated with recurrence and that autoimmune pancreatitis might transform into ordinary chronic pancreatitis after several recurrences. We found that the immune complex level, with a cutoff value of 10 microg/dL, served as a good predictor of recurrence, with high sensitivity (61.9%), specificity (70.0%), and efficacy (66.7%). We also confirmed that HLA and cytotoxic T-lymphocyte antigen-4 polymorphisms were useful predictors for AIP recurrence.
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Abstract
OBJECTIVES As the patients with autoimmune pancreatitis (AIP) are increasing in Japan, the practical guideline for managing AIP is required to be established. METHODS Three committees (the professional committee for making clinical questions [CQs] and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Fifteen specialists for AIP extracted the specific clinical statements from a total of 871 literatures by PubMed search (approximately 1963-2008) and from a secondary database and made the CQs and statements. The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. RESULTS The professional committee made 13, 6, 6, and 11 CQs and statements for the concept and diagnosis, extrapancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. CONCLUSIONS After evaluation by the moderators, the Japanese clinical guideline for AIP has been established. Further studies for the international guideline are needed after international consensus for diagnosis and treatment.
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Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) is a particular type of chronic pancreatitis that can be classified into diffuse and focal forms. The aim of this study was to analyze clinical and instrumental features of patients suffering from the diffuse and focal forms of AIP. METHODS AIP patients diagnosed between 1995-2008 were studied. RESULTS A total of 87 AIP patients (54 male and 33 female patients, mean age 43.4+/-15.3 years) were studied. Focal-type AIP was diagnosed in 63% and diffuse-type in 37%. Association with autoimmune diseases was observed in 53% of cases, the most common being ulcerative colitis (30%). Serum levels of IgG4 exceeded the upper normal limits (135 mg/dl) in 66% of focal AIP and in 27% of diffuse AIP (P=0.006). All patients responded to steroids. At recurrence non-steroid immunosuppressive drugs were successfully used in six patients. Recurrences were observed in 25% of cases, and were more frequent in focal AIP (33%) than in diffuse AIP (12%) (P=0.043), in smokers than in non-smokers (41% vs. 15%; P=0.011), and in patients with pathological serum levels of IgG4 compared to those with normal serum levels (50% vs. 12%; P=0.009). In all, 23% of the patients underwent pancreatic resections. Among patients with focal AIP, recurrences were observed in 30% of operated and in 34% of not operated patients. CONCLUSIONS Focal-type and diffuse-type AIP differ as regards clinical symptoms and signs. Recurrences occur more frequently in focal AIP than in diffuse AIP. The use of non-steroid immunosuppressants may be a therapeutic option in relapsing AIP.
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Shimosegawa T, Kanno A. Autoimmune pancreatitis in Japan: overview and perspective. J Gastroenterol 2009; 44:503-17. [PMID: 19377842 DOI: 10.1007/s00535-009-0054-6] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2009] [Accepted: 02/26/2009] [Indexed: 02/06/2023]
Abstract
Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.
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Affiliation(s)
- Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
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Possible association between IgG4-associated systemic disease with or without autoimmune pancreatitis and non-Hodgkin lymphoma. Pancreas 2009; 38:523-6. [PMID: 19258916 DOI: 10.1097/mpa.0b013e31819d73ca] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES IgG4-associated systemic disease (ISD) is a multiorgan fibroinflammatory disorder whose pancreatic manifestation is called autoimmune pancreatitis (AIP). We describe 3 patients who developed non-Hodgkin lymphoma during the follow-up of ISD. METHODS At our institution's pancreas clinic, we have prospectively and retrospectively examined patients with ISD with (n = 101) or without (n = 10) AIP (mean age, 59 years; 90 males and 21 females). We reviewed the medical records of all 111 patients to identify patients who developed non-Hodgkin lymphoma during the follow-up since their first presentation of ISD. Standardized incidence rate was calculated. RESULTS The 111 patients with ISD with or without AIP had 331 patient-years of observation during which 3 patients had a diagnosis of non-Hodgkin lymphoma 3 to 5 years after the diagnosis of ISD. In these patients who later developed lymphoma, ISD involved the pancreas (AIP) in 2 and salivary gland in 1. Non-Hodgkin lymphoma had extranodal involvement in all patients (liver [n = 2], adrenal glands [n=1], kidney [n= 1], and lung [n = 1]). Standardized incidence rate was 16.0 (95% confidence interval, 3.3-45.5). CONCLUSIONS We report 3 cases of non-Hodgkin lymphoma that developed during the follow-up of ISD suggesting that patients with ISD may be at an increased risk of developing non-Hodgkin lymphoma.
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Milne RL, Greenhalf W, Murta-Nascimento C, Real FX, Malats N. The inherited genetic component of sporadic pancreatic adenocarcinoma. Pancreatology 2009; 9:206-14. [PMID: 19352090 DOI: 10.1159/000210261] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pancreatic cancer, like many other complex diseases, has genetic and environmental components to its etiology. It is likely that relatively common genetic variants with modest effects on pancreatic cancer risk play an important role in both familial and sporadic forms of the disease, either individually or in interaction with environmental factors. The relatively high frequency of such variants means that they could potentially explain a substantial portion of disease risk. Here we summarize the findings published to date from genetic association studies. In general, very few low-penetrance variants have been identified and those that have require replication in independent studies. Possible gene-environment interactions arising from these studies also require replication. More comprehensive approaches are needed to make progress, including global analyses of biologically sound pathways and genome-wide association studies. Large sample sizes are required to do this appropriately and multi-study consortia make this possible. A number of consortia of pre-existing studies have already been formed, and these will facilitate the identification of further low-penetrance variants and gene-environment interaction. However, these approaches do not substitute for the design of novel, sufficiently powered studies that apply uniform criteria to case selection, the acquisition of environmental exposure information, and to biological sample collection.
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Affiliation(s)
- R L Milne
- Spanish National Cancer Research Centre, Madrid, Spain
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Zamboni G, Capelli P, Scarpa A, Bogina G, Pesci A, Brunello E, Klöppel G. Nonneoplastic mimickers of pancreatic neoplasms. Arch Pathol Lab Med 2009; 133:439-53. [PMID: 19260749 DOI: 10.5858/133.3.439] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2008] [Indexed: 11/06/2022]
Abstract
CONTEXT A variety of nonneoplastic conditions may form pancreatic masses that mimic carcinoma. Approximately 5% to 10% of pancreatectomies performed with the clinical diagnosis of pancreatic cancer prove on microscopic evaluation to be pseudotumors. OBJECTIVES To illustrate the clinical and pathologic characteristics of the 2 most frequent pseudotumoral inflammatory conditions, autoimmune pancreatitis and paraduodenal pancreatitis, and describe the criteria that may be useful in the differential diagnosis versus pancreatic carcinoma. DATA SOURCES Recent literature and the authors' experience with the clinical and pathologic characteristics of autoimmune pancreatitis and paraduodenal pancreatitis. CONCLUSIONS The knowledge of the clinical, radiologic, and pathologic findings in both autoimmune pancreatitis and paraduodenal pancreatitis is crucial in making the correct preoperative diagnosis. Autoimmune pancreatitis, which occurs in isolated or syndromic forms, is characterized by a distinctive fibroinflammatory process that can either be limited to the pancreas or extend to the biliary tree. Its correct preoperative identification on biopsy material with ancillary immunohistochemical detection of dense immunoglobulin G4-positive plasma cell infiltration is possible and crucial to prevent major surgery and to treat these patients with steroid therapy. Paraduodenal pancreatitis is a special form of chronic pancreatitis that affects young males with a history of alcohol abuse and predominantly involves the duodenal wall in the region of the minor papilla. Pathogenetically, the anatomical and/or functional obstruction of the papilla minor, resulting from an incomplete involution of the intraduodenal dorsal pancreas, associated with alcohol abuse represents the key factor. Endoscopic drainage of the papilla minor, with decompression of the intraduodenal and dorsal pancreas, might be considered in these patients.
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Affiliation(s)
- Giuseppe Zamboni
- Department of Pathology, University of Verona, Ospedale Sacro Cuore-Don Calabria, Via don Sempreboni 5, 37024 Negrar-Verona, Italy.
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Abstract
OBJECTIVES It is of utmost importance that autoimmune pancreatitis (AIP) be differentiated from pancreatic cancer (PC) because some AIP cases undergo unnecessary laparotomy or pancreatic resection on suspicion of PC. This study aimed to develop an appropriate strategy for differentiating between AIP and PC. METHODS Clinical, serological, and radiological features of 17 AIP patients forming a masslike lesion on pancreas head and 70 patients with pancreatic head cancer were compared. RESULTS Numerous findings can be used to distinguish between AIP and PC, and the following are more likely in AIP: fluctuating jaundice; elevated serum IgG4 levels; delayed enhancement of the enlarged pancreas and a capsule-like low-density rim on computed tomography; long or skipped narrowed portion with side branches of the main pancreatic duct without upstream dilatation on endoscopic retrograde pancreatography, extrapancreatic lesions, such as stenosis of the intrahepatic bile duct, salivary gland swelling, and retroperitoneal mass; and responsiveness to steroid therapy. CONCLUSIONS In elderly male patients presenting with obstructive jaundice and a pancreatic mass, AIP should be considered in the differential diagnosis. Based on a combination of clinical, serological, and radiological findings, AIP can be differentiated from PC. An algorithm for management of patients with a masslike lesion on pancreas head is presented.
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Abstract
PURPOSE OF REVIEW Autoimmune pancreatitis (AIP) is an increasingly recognized clinical condition. Our objective is to provide a concise review of the advances in the past year in our understanding of AIP. RECENT FINDINGS In a hospital survey from Japan, the prevalence of AIP was estimated at 0.82 per 100,000 individuals. The pathogenesis of AIP remains unclear but a recent report noted that T helper type 2 and T regulatory cells predominantly mediate the immune reaction in AIP. Genetic associations that may predispose to relapse of AIP were reported. Multiple case series further described the clinical profile of AIP and its extrapancreatic manifestations. A large series on immunoglobulin G4 (IgG4)-associated cholangitis noted that patients with IgG4-associated cholangitis presented with obstructive jaundice and had increased serum IgG4 levels and IgG4-positive cells in bile duct biopsy specimens. Tissue IgG4 staining is likely to be a useful adjunct to serological diagnosis. AIP is steroid-responsive but maintaining remission continues to remain challenging. Presently low-dose steroids or immunomodulators are being used but efficacy of these medications remains to be determined. SUMMARY There has been significant progress in understanding the clinical profile of AIP but knowledge of pathogenesis remains limited. Treatment practices vary widely and management of refractory disease continues to be challenging.
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Moon SH, Kim MH, Park DH. Treatment and relapse of autoimmune pancreatitis. Gut Liver 2008; 2:1-7. [PMID: 20485603 PMCID: PMC2871571 DOI: 10.5009/gnl.2008.2.1.1] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2008] [Accepted: 04/24/2008] [Indexed: 12/20/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a peculiar type of chronic pancreatitis whose pathogenesis involves autoimmune mechanisms. The steroid responsiveness has a significant impact on the diagnosis of AIP because patients with AIP and pancreatic cancer share many clinical features. This review focuses on the treatment and relapse of AIP. The goal of AIP treatment is remission of symptoms, serology, radiologic changes, or histology, which also applies to relapse. Although it is generally agreed that steroids should be offered to AIP patients with active disease, there is no standardized steroid regimen for AIP and no consensus on the dose and duration of steroid induction and tapering schedule, and optimal duration and dose of maintenance therapy. Obtaining a consensus on the optimal treatment regimen is very important to reducing the relapse rate. In this review, we discuss the treatment regimens used in many centers.
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Affiliation(s)
- Sung-Hoon Moon
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Myung-Hwan Kim
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Do Hyun Park
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Ghazale AH, Chari ST, Vege SS. Update on the diagnosis and treatment of autoimmune pancreatitis. Curr Gastroenterol Rep 2008; 10:115-121. [PMID: 18462596 DOI: 10.1007/s11894-008-0031-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic fibroinflammatory disease (IgG4-related systemic disease) in which affected organs demonstrate dense lymphoplasmacytic infiltration with abundant IgG4-positive cells. The diagnosis of AIP and its differentiation from pancreatic cancer, its main differential diagnosis, remains a clinical challenge. The five cardinal features of AIP are characteristic histology, imaging, and serology; other organ involvement; and response to steroid therapy. Recent advances in our understanding of these features have resulted in enhanced recognition and diagnosis of this benign disease. This in turn has resulted in the avoidance of unnecessary surgical procedures for suspected malignancy. This article reviews recent updates in the diagnosis and treatment of autoimmune pancreatitis.
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Affiliation(s)
- Amaar H Ghazale
- Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
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