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Capurso G, Pedica F, Palumbo D, Della-Torre E. IgG4-related autoimmune liver disease. Minerva Gastroenterol (Torino) 2023; 69:23-49. [PMID: 33267565 DOI: 10.23736/s2724-5895.20.02794-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
The term IgG4-related autoimmune liver disease (AILD) refers to hepato-biliary manifestations of Immunoglobin G4-related disease (IgG4-RD) including IgG4-related sclerosing cholangitis and IgG4-related pseudotumor. The association of some forms of autoimmune hepatitis to IgG4-RD remains controversial. Although autoimmune phenomena have not been clearly observed in IgG4-AILD, perturbation of the adaptive immune system and activation of the humoral response represent established pathophysiological hallmarks and potential therapeutic targets. Clinical manifestations of IgG4-AILD are virtually indistinguishable from bile duct cancer or primary sclerosing cholangitis and are due to mass forming lesions and thickening of the biliary tract that progressively lead to biliary ducts obstruction. There are no current reliable biomarkers for IgG4-AILD and diagnosis should rely on the integration of clinical, serological, radiological, and histological findings. In analogy to most IgG4-RD manifestations, and in contrast to its major mimickers, IgG4-AILD promptly responds to glucocorticoids but frequently relapses, thus requiring long-term maintenance therapy to avoid progressive fibrosclerotic disease and liver cirrhosis. Accumulating evidence on the efficacy of B-cell depletion therapy in patients with systemic IgG4-RD is gradually changing the treatment paradigm of IgG4-AILD and biologics will be increasingly used also for gastroenterological manifestations of IgG4-RD to spare glucocorticoids and traditional immunosuppressive agents. Looking ahead, identification of reliable biomarkers and of mini-invasive strategies to obtain informative biopsies from the biliary tree represent unavoidable priorities to optimize diagnosis and management of IgG4-AILD.
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Affiliation(s)
- Gabriele Capurso
- IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy -
- Division of Pancreato-Biliary Endoscopy and Endosonography, IRCCS San Raffaele Hospital, Milan, Italy -
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Hospital, Milan, Italy -
| | - Federica Pedica
- IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
- Unit of Pathology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Diego Palumbo
- IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
- Unit of Clinical and Experimental Radiology, Experimental Imaging Center, IRCCS San Raffaele Hospital, Milan, Italy
| | - Emanuel Della-Torre
- IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Hospital, Milan, Italy
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy
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Liu B, Tang N, Yao Y, Li H, Xu L, Zhou B, Liu B. Steroid treatment response combined with serological mark in differentiating type-1 autoimmune pancreatitis from pancreatic cancer. Medicine (Baltimore) 2022; 101:e31660. [PMID: 36397434 PMCID: PMC9666219 DOI: 10.1097/md.0000000000031660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 10/13/2022] [Indexed: 11/19/2022] Open
Abstract
Autoimmune pancreatitis (AIP) and pancreatic cancer (PC) are two different diseases. Their diagnosis, treatment, and prognosis are different, and it is difficult to differentiate them. This study aimed to explore the role of steroid treatment response combined with serological mark in distinguishing type-1 AIP from PC. Clinical data were collected and compared from 50 cases of AIP (group 1) and 100 cases of PC (group 2). The diagnostic value of serum IgG4, CA19-9, globulin, and eosinophil cell (EC) were evaluated. The response of steroid treatment of 28 patients with atypical imaging in group 1 was analyzed. After 2 weeks, the patients were classified as positive and negative steroid response according to the manifestations and/or the radiological changes. The positive response cases (n = 20) were confirmed as AIP, whereas negative ones (n = 8) were finally diagnosed as PC after complete resection. Serum globulin, IgG4, and EC levels in group 1 were significantly higher than those in group 2 (P < .01), and CA19-9 levels were distinctly lower in group 1 (P < .01). The level of serum IgG4 was related to the accuracy of diagnosis of AIP on the basis of the result of logistic regression analysis. Two-weeks steroid therapy response combined with serum IgG4 levels contribute to the differential diagnosis AIP and PC. However, regular and long-term follow-up were important for the differential diagnosis. There was an urgent need to explore the specific markers that distinguish these 2 entities.
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Affiliation(s)
- Bingqian Liu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Ning Tang
- Department of Nutrition, Weifang People’s Hospital, Shandong Province, China
| | - Yuan Yao
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Hua Li
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Lishan Xu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Bin Zhou
- Department of Biliary and Pancreatic Surgery, Department of Retroperitoneal Tumor Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Bin Liu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
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Miyagi A, Fujimoto D, Yoshikawa A, Okushi S, Miyagi J, Matsumoto R, Ogata S, Bando Y, Ogawa H, Tanahashi T. A rare case of fibrohistiocytic hepatic inflammatory pseudotumor with cholecystocholangitis showing positive IgG4 staining. Clin J Gastroenterol 2022; 15:975-980. [DOI: 10.1007/s12328-022-01663-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 06/12/2022] [Indexed: 11/29/2022]
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Clinical Characteristics and Potential Mechanisms in Patients with Abnormal Liver Function Indices and Elevated Serum IgG4. Can J Gastroenterol Hepatol 2022; 2022:7194826. [PMID: 36060522 PMCID: PMC9436615 DOI: 10.1155/2022/7194826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21. METHODS Clinical data (age, sex, past history, clinical manifestations, laboratory tests, imaging, diagnosis, and treatment) and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. RESULTS Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients (n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment. CONCLUSIONS Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease.
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Muto O, Tamakawa S, Takahashi K, Yokohama S, Takasoe A, Hirano F, Nishimura H, Saito H. IgG4-related Disease Manifesting as Gastroduodenal Ulcer Diagnosed by an Endoscopic Biopsy. Intern Med 2020; 59:2491-2497. [PMID: 32581158 PMCID: PMC7662039 DOI: 10.2169/internalmedicine.4483-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
A 26-year-old man was admitted to our hospital due to upper abdominal pain. He had previously been diagnosed with gastroduodenal ulcer at 23 and 25 years old and had been treated with proton-pump inhibitors. Endoscopic hemostasis and a biopsy were performed on the hemorrhagic gastroduodenal ulcers. Laboratory and pathologic examinations demonstrated elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into the gastroduodenal tissues. Based on the clinicopathologic findings and after excluding other causes, he was diagnosed with IgG4-related gastroduodenal ulcer. We herein report a rare case of IgG4-related disease manifesting as a gastroduodenal ulcer diagnosed by an endoscopic biopsy.
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Affiliation(s)
- Osamu Muto
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Susumu Tamakawa
- Department of Pathology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Kenji Takahashi
- Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Japan
| | - Shiro Yokohama
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Ai Takasoe
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Fuminori Hirano
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Hideo Nishimura
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Hiroki Saito
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
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Baenas DF, Miretti VS, Caeiro F, Paira S. Differential diagnosis between pancreatic involvement in IgG4-related disease and pancreatic cancer. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 44:144-155. [PMID: 32718841 DOI: 10.1016/j.gastrohep.2020.05.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/20/2020] [Accepted: 05/20/2020] [Indexed: 12/15/2022]
Abstract
IgG4-related disease is a systemic disorder characterised by diffuse or tumoural inflammatory lesions. It can mimic pancreatic cancer, leading to errors in diagnosis and treatment increasing rates of morbidity and mortality in patients. The aim of this review is to take a differential diagnostic approach to these two entities using epidemiology, clinical and laboratory findings, imaging and histopathology.
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Affiliation(s)
- Diego Federico Baenas
- Servicio de Reumatología, Hospital Privado Universitario de Córdoba, Córboba, Argentina; Grupo de estudio de enfermedad relacionada con IgG4 de la Sociedad Argentina de Reumatología (SAR), Argentina.
| | - Virginia Soledad Miretti
- Servicio de Oncología y Hematología, Hospital Privado Universitario de Córdoba, Córboba, Argentina
| | - Francisco Caeiro
- Servicio de Reumatología, Hospital Privado Universitario de Córdoba, Córboba, Argentina; Grupo de estudio de enfermedad relacionada con IgG4 de la Sociedad Argentina de Reumatología (SAR), Argentina
| | - Sergio Paira
- Grupo de estudio de enfermedad relacionada con IgG4 de la Sociedad Argentina de Reumatología (SAR), Argentina; Servicio de Reumatología, Hospital J.M. Cullen, Santa Fe, Argentina
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Matsubayashi H, Ishiwatari H, Imai K, Kishida Y, Ito S, Hotta K, Yabuuchi Y, Yoshida M, Kakushima N, Takizawa K, Kawata N, Ono H. Steroid Therapy and Steroid Response in Autoimmune Pancreatitis. Int J Mol Sci 2019; 21:E257. [PMID: 31905944 PMCID: PMC6981453 DOI: 10.3390/ijms21010257] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 12/18/2019] [Accepted: 12/25/2019] [Indexed: 12/11/2022] Open
Abstract
Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33-78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24-52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
- Genetic Medicine Promotion, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan
| | - Hirotoshi Ishiwatari
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Yoshihiro Kishida
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Sayo Ito
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Yohei Yabuuchi
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Naomi Kakushima
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
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Inaba H, Ariyasu H, Takeshima K, Iwakura H, Akamizu T. Comprehensive research on thyroid diseases associated with autoimmunity: autoimmune thyroid diseases, thyroid diseases during immune-checkpoint inhibitors therapy, and immunoglobulin-G4-associated thyroid diseases. Endocr J 2019; 66:843-852. [PMID: 31434818 DOI: 10.1507/endocrj.ej19-0234] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Various thyroid diseases are associated with autoimmunity. Major autoimmune thyroid diseases are Graves' disease (GD) and Hashimoto's thyroiditis (HT). Thyrotropin receptor is an autoantigen in GD, and its immunogenicity has been examined. Immune-checkpoint inhibitor (ICI) is recently widely used for treatment of malignant tumors, but cases of thyroid diseases during ICI treatment have been increasing. Thyroid diseases during ICI therapy have been investigated in immunological and clinical aspects, and their Japanese official diagnostic guidelines were established. In addition, serum and tissue immunoglobulin-G4 levels have been examined in association with clinicopathological characteristics in GD, HT, and Riedel's thyroiditis. We review these diseases associated with thyroid autoimmunity and comprehensively discuss their potential application in future research and therapeutic options.
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Affiliation(s)
- Hidefumi Inaba
- The First Department of Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan
| | - Hiroyuki Ariyasu
- The First Department of Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan
| | - Ken Takeshima
- The First Department of Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan
| | - Hiroshi Iwakura
- The First Department of Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan
| | - Takashi Akamizu
- The First Department of Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan
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Zaccari P, Cardinale V, Severi C, Pedica F, Carpino G, Gaudio E, Doglioni C, Petrone MC, Alvaro D, Arcidiacono PG, Capurso G. Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas. World J Gastroenterol 2019; 25:4343-4359. [PMID: 31496617 PMCID: PMC6710182 DOI: 10.3748/wjg.v25.i31.4343] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 07/13/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.
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Affiliation(s)
- Piera Zaccari
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00161 Rome, Italy
| | - Carola Severi
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Federica Pedica
- Pathology Department, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome 00161, Italy
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Division of Human Anatomy, Sapienza University of Rome, Rome 00161, Italy
| | - Claudio Doglioni
- Pathology Department, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Maria Chiara Petrone
- PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome 00161, Italy
| | - Paolo Giorgio Arcidiacono
- PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
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Abstract
Immunoglobuline G4-related disease (IgG4-RD) is a systemic disease that can involve virtually any organs including the biliary tract and liver. The biliary tract involvement of IgG4-RD is known as IgG4-sclerosing cholangitis (IgG4-SC) and may or may not present with an inflammatory pseudotumor. Large bile ducts such as extrahepatic, hilar, and perihilar ducts are typically affected and demonstrate marked bile duct wall thickening and develop strictures. Histologically, the involved ducts show transmural dense lymphoplasmacytic infiltrates with storiform fibrosis extending into peribiliary glands and periductal soft tissue. The luminal epithelium is usually preserved. Tissue eosinophilia and obliterative phlebitis are also frequently noted. Liver biopsy findings of IgG4-SC are heterogeneous and rather nonspecific, but two features specific to IgG4-SC have been described: >10 IgG4-positive plasma cell/HPF and small portal-based fibroinflammatory nodules. Secondary changes, due to downstream bile duct obstruction are often appreciated. When considering the differential diagnosis, primary sclerosing cholangitis and cholangiocarcinoma are great clinical and histologic mimics of IgG4-SC. Liver involvement in IgG4-RD has not been well characterized and includes IgG4-hepatopathy and IgG4-related autoimmune hepatitis (AIH). IgG4-hepatopathy is a generic term covering hepatic lesions related to IgG4-RD and /or IgG4-SC. It includes primary liver parenchymal changes inherent to IgG4-RD, liver parenchymal involvement of IgG4-SC, and secondary changes related to IgG4-SC. IgG4-related AIH is characterized by clinical and histologic features of classical AIH but with prominent (>10/HPF) IgG4-positive plasma cells. It is unclear whether this represents a hepatic manifestation of IgG4-RD or a subset of AIH with increased IgG4-positive plasma cells at the present time. Synchronous or metachronous involvement of other organs, offers a clue to make this distinction. IgG4 immunohistochemistry has an important role in diagnosing IgG4-RD. But the diagnosis cannot be made solely based on the number of IgG4-positive plasma cells, and results need to be interpreted with caution as increased IgG4-positive plasma cells can be seen in other inflammatory conditions or even in malignancy.
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Affiliation(s)
- Hee Eun Lee
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA
| | - Lizhi Zhang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.
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Ishigami K, Shitani M, Kimura Y, Hasegawa T, Masaki Y, Ito A, Akutsu N, Yamamoto M, Motoya M, Sasaki S, Takahashi H, Takemasa I, Nakase H. Ectopic relapse of IgG4-related disease presenting as IgG4-related sclerosing cholecystitis: A case report and review of literature. Medicine (Baltimore) 2018; 97:e13868. [PMID: 30593191 PMCID: PMC6314772 DOI: 10.1097/md.0000000000013868] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
RATIONALE Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a chronic inflammatory disorder characterized by high levels of serum IgG4, swollen organs with fibrosis and abundant infiltration of IgG4-positive plasmacytes. PATIENT CONCERNS An 82-year-old male visited our hospital for an evaluation of a pancreatic enlargement and a bilateral submandibular adenopathy. Further investigation revealed elevation of serum IgG4 and bilateral lacrimal submandibular adenopathy. We diagnosed him with IgG4-related disease (IgG4-RD) and started administration of corticosteroid (CS) therapy. Both pancreatic enlargement and adenopathy rapidly improved; however, there was a new occurrence of diffuse wall thickening of the gallbladder during CS treatment. DIAGNOSIS Radiological examination revealed diffuse wall thickening of the gallbladder, and its inner layer was smooth and homogenous. These findings suggested an inflammatory change, but the possibility of malignancy could not be excluded. INTERVENTIONS The patient underwent laparoscopic cholecystectomy for a pathological diagnosis. OUTCOMES Histological examination revealed a transmural infiltration of IgG4 positive plasma cells and dense fibrosis. The patient was pathologically diagnosed with IgG4 related cholecystitis presenting as an ectopic relapse. LESSONS There are 2 major types of IgG4-related cholecystitis, a diffuse wall thickening type and a mass formation type. It is sometimes difficult to differentiate IgG4-related cholecystitis with gallbladder cancer.Corticosteroid (CS) is effective for induction of remission; however, we sometimes encounter disease relapse after reduction of CS dose. We should be mindful that some patients may relapse with new organ involvements even if the primary site and serum IgG4 level are well controlled.
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Affiliation(s)
| | | | | | | | | | - Ayako Ito
- Department of Gastroenterology and Hepatology
| | | | - Motohisa Yamamoto
- Department of Rheumatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | | | | | - Hiroki Takahashi
- Department of Rheumatology, Sapporo Medical University School of Medicine, Sapporo, Japan
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12
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Systematic Investigation of Scutellariae Barbatae Herba for Treating Hepatocellular Carcinoma Based on Network Pharmacology. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:4365739. [PMID: 30584453 PMCID: PMC6280310 DOI: 10.1155/2018/4365739] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 10/30/2018] [Accepted: 11/08/2018] [Indexed: 12/14/2022]
Abstract
As the fifth most common type of malignant cancers globally, hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. As a long-time medicinal herb in Traditional Chinese Medicine (TCM), Scutellariae Barbatae Herba (SBH) has also been used for treating various cancers including HCC, but its underlying mechanisms have not been completely clarified. Presently, an innovative network-pharmacology platform was introduced to systematically elucidate the pharmacological mechanisms of SBH against HCC, adopting active ingredients prescreening, target fishing, and network analysis. The results revealed that SBH appeared to work on HCC probably through regulating 4 molecular functions, 20 biological processes, and hitting on 21 candidate targets involved in 40 pathways. By in-depth analysis of the first-ranked signaling pathway and hit genes, only TTR was highly and specially expressed in the liver tissue. TTR might play a crucial role in neutrophil degranulation pathway during SBH against HCC. Hence, TTR might become a therapeutic target of HCC. The study investigated the anti-hepatoma mechanisms of SBH from a holistic perspective, which provided a theoretical foundation for further experimental research and rational clinical application of SBH.
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13
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Masunaga A, Ishibashi F, Koh E, Oide T, Sekine Y, Hiroshima K. Possible relationship between fibrosis of IgG4-related thymitis and the profibrotic cytokines, transforming growth factor beta 1, interleukin 1 beta and interferon gamma: a case report. Diagn Pathol 2018; 13:6. [PMID: 29439708 PMCID: PMC5811959 DOI: 10.1186/s13000-018-0684-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 01/09/2018] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND IgG4-related disease often forms a mass and the affected lesion is clinically removed because the mass cannot be differentiated from a neoplasm. Affected lesions commonly occur in the pancreas, hepatobiliary tract, kidney, and retroperitoneum. However, the lesion rarely occurs in the thymus. A histological worldwide consensus of IgG4-related disease proposed that pathological diagnosis of IgG4-related disease should meet more than two of three major features: 1) dense lymphoplasmacytic infiltration with greater than 40% IgG4+/IgG+ plasma cells, 2) storiform fibrosis; and 3) obliterative phlebitis. Currently, fibrosis of IgG4-related disease is thought to be induced by profibrotic cytokines such as transforming growth factor beta 1 (TGFB1), interleukin 1 beta (IL1B) and interferon gamma (IFNG), which are secreted by regulatory T cells (Tregs) and CD4-positive cytotoxic T cells. However, it is unclear whether profibrotic cytokines are associated with the fibrosis seen in IgG4-related thymitis. Here we examined whether cytokines in the mass were increased compared with those in the surrounding thymus, and whether Tregs were present in the mass, using reverse transcription absolute quantitative polymerase chain reaction (RT-ab-qPCR) and immunohistochemistry. CASE PRESENTATION A 70-year-old Japanese man contracted IgG4-letated thymitis. Histological and immunohistochemical analyses demonstrated his mass had massive fibrosis with a focally storiform pattern and lymphoplasmacytic infiltration with 40% IgG4+/IgG+ plasma cells, but not obliterative phlebitis. The mass was surrounded by atrophic thymus. We diagnosed the mass as IgG4-related thymitis. Immunohistochemically, Tregs were scattered throughout the mass. RT-ab-qPCR showed that messenger RNA expressions of TGFB1, IL1B and IFNG in the mass were 270-, 158- and 5.5- fold higher than in the surrounding thymus. His serum IgG4 level after surgery was within the normal range (83.4 mg/dl soon after surgery, 89.3 mg/dl 2 weeks after surgery). CONCLUSIONS Our results suggested the profibrotic cytokines TGFB1, IL1B and IFNG induce fibrosis and that Tregs might produce some of these cytokines in IgG4-related thymitis as well as in the other affected lesions of IgG4-related disease.
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Affiliation(s)
- Atsuko Masunaga
- Department of Pathology, Tokyo Women’s Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524 Japan
- Respiratory Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa Japan
| | - Fumihiro Ishibashi
- Division of Thoracic Surgery, Department of Surgery, Tokyo Women’s Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan
| | - Eitetsu Koh
- Division of Thoracic Surgery, Department of Surgery, Tokyo Women’s Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan
| | - Takashi Oide
- Department of Pathology, Tokyo Women’s Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524 Japan
| | - Yasuo Sekine
- Division of Thoracic Surgery, Department of Surgery, Tokyo Women’s Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan
| | - Kenzo Hiroshima
- Department of Pathology, Tokyo Women’s Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524 Japan
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14
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Yan T, Ke Y, Chen Y, Xu C, Yu C, Li Y. Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin. PLoS One 2017; 12:e0174735. [PMID: 28369140 PMCID: PMC5378371 DOI: 10.1371/journal.pone.0174735] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 03/14/2017] [Indexed: 12/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19-9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time.
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Affiliation(s)
- Tianlian Yan
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yini Ke
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Chen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chengfu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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15
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Katabathina VS, Khalil S, Shin S, Lath N, Menias CO, Prasad SR. Immunoglobulin G4-Related Disease: Recent Advances in Pathogenesis and Imaging Findings. Radiol Clin North Am 2017; 54:535-51. [PMID: 27153787 DOI: 10.1016/j.rcl.2015.12.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a novel, immune-mediated, multisystem disease characterized by the development of tumefactive lesions in multiple organs. IgG4-RD encompasses many fibroinflammatory diseases that had been thought to be confined to single organs. Delayed diagnosis or misdiagnosis as malignancies leading to aggressive treatment may be averted by identification of the multisystem nature of IgG4-RD. Most cases show exquisite response to steroid therapy; steroid-resistant cases are being treated by novel therapeutic agents, including B-cell depleting agents such as rituximab. Cross-sectional imaging studies play a pivotal role in the initial diagnosis, assessing response to therapy and long-term surveillance.
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Affiliation(s)
- Venkata S Katabathina
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
| | - Suhare Khalil
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Sooyoung Shin
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Narayan Lath
- Department of Radiology, Singapore General Hospital, Outram road, Singapore 169608, Singapore
| | | | - Srinivasa R Prasad
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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16
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Bochatay L, Majno P, Giostra E, Frossard JL. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma. Case Rep Gastroenterol 2016; 10:512-517. [PMID: 27843427 PMCID: PMC5091269 DOI: 10.1159/000448989] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 08/09/2016] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy.
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Affiliation(s)
| | - Pietro Majno
- Geneva University Hospitals, Geneva, Switzerland
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17
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Matsubayashi H, Kishida Y, Iwai T, Murai K, Yoshida M, Imai K, Yamamoto Y, Kikuyama M, Ono H. Transpapillary biliary stenting is a risk factor for pancreatic stones in patients with autoimmune pancreatitis. Endosc Int Open 2016; 4:E912-7. [PMID: 27540582 PMCID: PMC4988851 DOI: 10.1055/s-0042-111201] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Accepted: 06/13/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND AND STUDY AIM Pancreatic stones occasionally develop in autoimmune pancreatitis (AIP), often worsen endocrine and exocrine functions, and occasionally cause pain attacks. However, the risks of pancreatic stones in AIP have been poorly studied. The aim of this study was to analyze the risk factors associated with pancreatic stone formation in cases of AIP. PATIENTS AND METHODS In total, 50 patients with AIP (39 males, 11 females; mean age 64.0 years), followed up for at least a year, were analyzed for their demographic and clinical findings and pancreatic stone occurrence. RESULTS In total, 50 patients were followed up for an average of 59.7 (12 - 120) months, with steroid treatment in 44 patients (88 %); pancreatic stones occurred in 14 (28 %) patients after the diagnosis of AIP and endoscopic treatment was needed in one patient with pain attack. The pancreatic stones appeared only in patients with long follow-up period (P < 0.001, 83.9 months vs. 49.6 months), biliary stenting (odds ratio [OR]: 8.40, P = 0.010), relapse (OR: 6.20, P = 0.023), jaundice (OR: 5.40, P = 0.019), and swelling of the duodenal major papilla (OR: 4.67, P = 0.040). Biliary stenting was placed for an average of 9.9 months in 27 patients. Multivariate analysis revealed a significant association only with biliary stenting (P = 0.011). The stones appeared relatively earlier in patients with stones in the main pancreatic duct or Santorini duct (22.1 months) than in patients where pancreatic stones developed elsewhere (53.4 months) (P = 0.018). CONCLUSIONS The risk of pancreatic stone development should be taken into account when a biliary stent is placed in patients with AIP.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan,Corresponding author Hiroyuki Matsubayashi, MD, PhD Division of EndoscopyShizuoka Cancer Center1007ShimonagakuboNagaizumiSuntogunShizuoka411-8777Japan+81-55-9895222
| | | | - Tomohiro Iwai
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuyuki Murai
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masataka Kikuyama
- Division of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
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18
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Abstract
Autoimmune pancreatitis (AIP) was recognized as a clinical entity, at least in the West little more than 10 years ago. Since then, studies globally, and international collaboration, have led to important advances in our understanding of its clinical features, disease course, and management, although the aetiopathogenesis of this curious disease remains to be fully elucidated. Types 1 and 2 AIP have been described, of which type 1 is the commonest form, and best defined. International consensus now recognizes it as one of the many clinical manifestations of IgG4-related disease, and is now termed IgG4-related pancreatitis (IgG4-RP). The disease is not confined to a particular race, gender, or age, but often presents after the fifth decade in men. A common presentation is with jaundice due to low bile duct obstruction related to diffuse pancreatic enlargement (historically often leading to a misdiagnosis of cancer). Acute pancreatitis is unusual. Other organ involvement is a particular feature, including biliary disease, retroperitoneal fibrosis, generalized lymphadenopathy, renal, and lung involvement. No single test makes the diagnosis, and diagnostic criteria for type 1 AIP/IgG4-RP, which incorporate clinical, laboratory, radiological, pathological, and therapeutic parameters should be applied. A particular attempt should be made to make a histological diagnosis, which is characterized by an IgG4-positive lymphoplasmacytic infiltrate. Management is not based on randomized studies, but corticosteroids are the mainstay of treatment, providing rapid clinical and radiological benefit. However, clinical relapse is common (particularly in type 1 AIP, and in those with associated other organ involvement). Additional immunosuppression may be required, including azathioprine, and rituximab may play an emerging role. The disease course is variable, but loss of organ function (especially pancreatic exocrine failure and pancreatic atrophy) may occur.
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Affiliation(s)
- George J Webster
- Pancreaticobiliary Medicine Unit, University College London Hospitals, London, UK
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19
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Minamino H, Inaba H, Ariyasu H, Furuta H, Nishi M, Yoshimasu T, Nishikawa A, Nakanishi M, Tsuchihashi S, Kojima F, Murata SI, Inoue G, Akamizu T. A novel immunopathological association of IgG4-RD and vasculitis with Hashimoto's thyroiditis. Endocrinol Diabetes Metab Case Rep 2016; 2016:160004. [PMID: 26966543 PMCID: PMC4785346 DOI: 10.1530/edm-16-0004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 02/19/2016] [Indexed: 11/08/2022] Open
Abstract
A 73-year-old man with Hashimoto's thyroiditis (HT) suffered from purpura on the lower legs. He was diagnosed with IgG4-related disease (IgG4-RD) with serum IgG4 elevation and dacryo-sialadenitis confirmed histologically. Serum Th2 and Treg cytokines, interleukin 7 (IL7), IL8 and Th2 chemokine levels were elevated, while skewed Th1 balance was seen in fluorescence-activated cell sorting (FACS). Therefore, preferential Th1 balance in HT appeared to be followed by IgG4-RD characterized with Th2 and Treg polarization. The commencement of steroid therapy dramatically exacerbated clinical manifestations including IgG4-RD-associated HT. The measurement of cytokine and chemokine levels as well as FACS analysis in the development of IgG4-RD seemed to be beneficial. In conclusion, an innovative association of HT, IgG4-RD and vasculitis was observed. This report also offers novel diagnostic and therapeutic approaches for IgG4-RD.
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Affiliation(s)
- Hiroto Minamino
- The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan; Department of Diabetes and Endocrinology, Wakayama Red Cross Hospital, Wakayama, Japan
| | - Hidefumi Inaba
- The First Department of Medicine, Wakayama Medical University , 811-1, Kimiidera, Wakayama, 641-8509 , Japan
| | - Hiroyuki Ariyasu
- The First Department of Medicine, Wakayama Medical University , 811-1, Kimiidera, Wakayama, 641-8509 , Japan
| | - Hiroto Furuta
- The First Department of Medicine, Wakayama Medical University , 811-1, Kimiidera, Wakayama, 641-8509 , Japan
| | - Masahiro Nishi
- The First Department of Medicine, Wakayama Medical University , 811-1, Kimiidera, Wakayama, 641-8509 , Japan
| | - Takashi Yoshimasu
- Department of Dermatology, Wakayama Medical University , Wakayama , Japan
| | - Akinori Nishikawa
- Department of Hematology, Wakayama Medical University , Wakayama , Japan
| | - Masanori Nakanishi
- Department of Respiratory Medicine & Medical Oncology, Wakayama Medical University , Wakayama , Japan
| | - Shigeki Tsuchihashi
- Department of Otolaryngology, Wakayama Medical University , Wakayama , Japan
| | - Fumiyoshi Kojima
- Department of Human Pathology, Wakayama Medical University , Wakayama , Japan
| | - Shin-Ichi Murata
- Department of Human Pathology, Wakayama Medical University , Wakayama , Japan
| | - Gen Inoue
- Department of Diabetes and Endocrinology, Wakayama Red Cross Hospital , Wakayama , Japan
| | - Takashi Akamizu
- The First Department of Medicine, Wakayama Medical University , 811-1, Kimiidera, Wakayama, 641-8509 , Japan
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20
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Katabathina VS, Flaherty EM, Dasyam AK, Menias CO, Riddle ND, Lath N, Kozaka K, Matsui O, Nakanuma Y, Prasad SR. "Biliary Diseases with Pancreatic Counterparts": Cross-sectional Imaging Findings. Radiographics 2016; 36:374-92. [PMID: 26824512 DOI: 10.1148/rg.2016150071] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
On the basis of the similarities in the histopathologic findings and the clinical-biologic behaviors of select biliary and pancreatic conditions, a new disease concept, "biliary diseases with pancreatic counterparts," has been proposed. Both nonneoplastic and neoplastic pathologic conditions of the biliary tract have their counterparts in the pancreas. Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is the biliary manifestation of IgG4-related sclerosing disease, and type 1 autoimmune pancreatitis is its pancreatic counterpart. People with chronic alcoholism can develop peribiliary cysts and fibrosis as well as pancreatic fibrosis and chronic pancreatitis simultaneously. Pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm are considered pancreatic counterparts for the biliary neoplasms of extrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the biliary tract, and hepatic mucinous cystic neoplasm, respectively. The anatomic proximity of the biliary tract and the pancreas, the nearly simultaneous development of both organs from the endoderm of the foregut, and the presence of pancreatic exocrine acini within the peribiliary glands surrounding the extrahepatic bile ducts are suggested as causative factors for these similarities. Interestingly, these diseases show "nearly" identical findings at cross-sectional imaging, an observation that further supports this new disease concept. New information obtained with regard to biliary diseases can be used for evaluation of pancreatic abnormalities, and vice versa. In addition, combined genetic and molecular studies may be performed to develop novel therapeutic targets. For both biliary and pancreatic diseases, imaging plays a pivotal role in initial diagnosis, evaluation of treatment response, efficacy testing of novel drugs, and long-term surveillance.
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Affiliation(s)
- Venkata S Katabathina
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Erin M Flaherty
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Anil K Dasyam
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Christine O Menias
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Nicole D Riddle
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Narayan Lath
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Kazuto Kozaka
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Osamu Matsui
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Yasuni Nakanuma
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
| | - Srinivasa R Prasad
- From the Departments of Radiology (V.S.K., E.M.F.) and Pathology (N.D.R.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, Mayo Clinic at Scottsdale, Scottsdale, Ariz (C.O.M.); Department of Radiology, Singapore General Hospital, Singapore (N.L.); Department of Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (K.K., O.M.); Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan (Y.N.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.)
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Sarkar A, Pitchumoni CS. The protean manifestations of IgG4-RD in gastrointestinal disorders. Dis Mon 2015; 61:493-515. [DOI: 10.1016/j.disamonth.2015.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Takahashi K, Ito H, Katsube T, Tsuboi A, Hashimoto M, Ota E, Mita K, Asakawa H, Hayashi T, Fujino K, Okamoto S. Immunoglobulin G4-related sclerosing cholecystitis presenting as gallbladder cancer: a case report. Surg Case Rep 2015; 1:120. [PMID: 26943444 PMCID: PMC4668245 DOI: 10.1186/s40792-015-0123-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 11/25/2015] [Indexed: 12/19/2022] Open
Abstract
Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic inflammatory syndrome, and an understanding of its characteristics is currently evolving. IgG4-related cholecystitis is a manifestation of IgG4-related sclerosing disease in the gallbladder. This case report describes the clinical, radiographic, and histopathological findings in a young male patient who presented with a synchronous mass in the gallbladder. Serum levels of IgG4 and the IgG4/IgG ratio were normal, and there was no associated autoimmune pancreatitis. Therefore, establishing a preoperative diagnosis of IgG4-related cholecystitis was very difficult, and a differential diagnosis of gallbladder cancer infiltrating the liver was suggested. Postoperative histopathological examination established a diagnosis of IgG4-related cholecystitis definitively. A preoperative diagnosis of IgG4-related cholecystitis, although possible, would have been highly challenging in this case. It is difficult to establish whether surgical intervention is necessary in IgG4-related cholecystitis. Because malignant tumors are frequently suspected with this clinical presentation, surgical intervention should be undertaken only after due deliberation.
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Affiliation(s)
- Kodai Takahashi
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Hideto Ito
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Toshio Katsube
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Ayaka Tsuboi
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Masatoshi Hashimoto
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Emi Ota
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Kazuhito Mita
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Hideki Asakawa
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Takashi Hayashi
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Keiichi Fujino
- Department of Surgery, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
| | - Sigeru Okamoto
- Department of Pathology, New Tokyo Hospital, 1271 Wanagaya, Matsudo City, Chiba, Japan.
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23
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Carpino G, Renzi A, Cardinale V, Franchitto A, Onori P, Overi D, Rossi M, Berloco PB, Alvaro D, Reid LM, Gaudio E. Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study. J Anat 2015; 228:474-86. [PMID: 26610370 DOI: 10.1111/joa.12418] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2015] [Indexed: 12/13/2022] Open
Abstract
Pancreatic duct glands (PDGs) are tubule-alveolar glands associated with the pancreatic duct system and can be considered the anatomical counterpart of peribiliary glands (PBGs) found within the biliary tree. Recently, we demonstrated that endodermal precursor niches exist fetally and postnatally and are composed functionally of stem cells and progenitors within PBGs and of committed progenitors within PDGs. Here we have characterized more extensively the anatomy of human PDGs as novel niches containing cells with multiple phenotypes of committed progenitors. Human pancreata (n = 15) were obtained from cadaveric adult donors. Specimens were processed for histology, immunohistochemistry and immunofluorescence. PDGs were found in the walls of larger pancreatic ducts (diameters > 300 μm) and constituted nearly 4% of the duct wall area. All of the cells identified were negative for nuclear expression of Oct4, a pluripotency gene, and so are presumably committed progenitors and not stem cells. In the main pancreatic duct and in large interlobular ducts, Sox9(+) cells represented 5-30% of the cells within PDGs and were located primarily at the bottom of PDGs, whereas rare and scattered Sox9(+) cells were present within the surface epithelium. The expression of PCNA, a marker of cell proliferation, paralleled the distribution of Sox9 expression. Sox9(+) PDG cells proved to be Pdx1(+) /Ngn3(+/-) /Oct4A(-) . Nearly 10% of PDG cells were positive for insulin or glucagon. Intercalated ducts contained Sox9(+) /Pdx1(+) /Ngn3(+) cells, a phenotype that is presumptive of committed endocrine progenitors. Some intercalated ducts appeared in continuity with clusters of insulin-positive cells organized in small pancreatic islet-like structures. In summary, PDGs represent niches of a population of Sox9(+) cells exhibiting a pattern of phenotypic traits implicating a radial axis of maturation from the bottoms of the PDGs to the surface of pancreatic ducts. Our results complete the anatomical background that links biliary and pancreatic tracts and could have important implications for the common patho-physiology of biliary tract and pancreas.
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Affiliation(s)
- Guido Carpino
- Division of Health Sciences, Department of Movement, Human and Health Sciences, University of Rome 'Foro Italico', Rome, Italy
| | - Anastasia Renzi
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy
| | - Antonio Franchitto
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Paolo Onori
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Massimo Rossi
- Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | | | - Domenico Alvaro
- Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy
| | - Lola M Reid
- Department of Cell Biology and Physiology, Program in Molecular Biology and Biotechnology, Lineberger Comprehensive Cancer Center, UNC School of Medicine, Chapel Hill, NC, USA
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
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Martínez-de-Alegría A, Baleato-González S, García-Figueiras R, Bermúdez-Naveira A, Abdulkader-Nallib I, Díaz-Peromingo JA, Villalba-Martín C. IgG4-related Disease from Head to Toe. Radiographics 2015; 35:2007-25. [DOI: 10.1148/rg.357150066] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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25
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Inoue T, Okumura F, Mizushima T, Nishie H, Iwasaki H, Anbe K, Ozeki T, Kachi K, Fukusada S, Suzuki Y, Watanabe K, Sano H. Localized IgG4-related Cholecystitis Mimicking Gallbladder Cancer. Intern Med 2015; 54:1869-74. [PMID: 26234227 DOI: 10.2169/internalmedicine.54.4383] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We encountered a case of localized IgG4-cholecystitis mimicking gallbladder cancer with focal/segmental type1 autoimmune pancreatitis (AIP). In this case, we were unable to exclude a diagnosis of gallbladder cancer and thus performed radical cholecystectomy. Type1 AIP is often associated with gallbladder lesions, accompanied by generally diffuse, circumferential thickening of the gallbladder wall. Although localized IgG4-related cholecystitis is extremely rare, differentiating this condition from gallbladder cancer is often very difficult.
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Affiliation(s)
- Tadahisa Inoue
- Department of Gastroenterology, Gifu Prefectural Tajimi Hospital, Japan
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