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Katz G, Harvey L, Hernandez-Barco YG, Wallace ZS, Fernandes AD, McMahon GA, Jha I, McMahon AE, Perugino CA, Stone JH. Defining pancreatic damage and symptom burden in IgG4-related autoimmune pancreatitis: A cross-sectional study of 118 patients from a single-center registry. Semin Arthritis Rheum 2025; 73:152742. [PMID: 40403524 PMCID: PMC12167670 DOI: 10.1016/j.semarthrit.2025.152742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 04/26/2025] [Accepted: 04/30/2025] [Indexed: 05/24/2025]
Abstract
OBJECTIVES Type 1 autoimmune pancreatitis is a common manifestation of IgG4-related disease (IgG4-RD). However, there is a paucity of literature characterizing pancreatic damage and symptom burden in IgG4-RD. METHODS We performed a cross-sectional analysis of patients who fulfilled the ACR/EULAR IgG4-RD Classification Criteria. Disease features and complications were collected by medical record review. A survey regarding symptoms and disease history was distributed to all patients. Characteristics were compared between patients with and without autoimmune pancreatitis. RESULTS Of 303 patients who fulfilled Classification Criteria at the time of the chart review, 118 (39 %) had evidence of autoimmune pancreatitis. Overt indicators of acute pancreatitis (e.g., abdominal pain, nausea/emesis, elevated serum lipase) each occurred in fewer than 50 % of patients with autoimmune pancreatitis. Diabetes mellitus (DM), exocrine pancreatic insufficiency (EPI), or both were present in 47 %, 48 %, and 21 % of the autoimmune pancreatitis patients, respectively. After encouraging all patients to have fecal elastase measured, 40/49 (82 %) stool samples had low elastase concentrations. 9/118 (8 %) had undergone pancreatic resections before the diagnosis was established. 162/325 (50 %) completed surveys (n = 81 [50 %] with autoimmune pancreatitis). Patients with autoimmune pancreatitis reported a higher burden of abdominal pain, weight loss, and changes in stool than those without (all p < 0.05). CONCLUSION Despite an often subclinical presentation, autoimmune pancreatitis is associated with EPI, DM, or both in a high percentage of patients with IgG4-RD. While symptomatic acute pancreatitis may not be common, patient-reported symptom burden due to IgG4-related autoimmune pancreatitis or its complications is greater than previously appreciated.
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Affiliation(s)
- Guy Katz
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA.
| | - Liam Harvey
- Frank H. Netter MD School of Medicine at Quinnipiac University, 370 Basset Rd, North Haven, CT, 06473, USA
| | - Yasmin G Hernandez-Barco
- Massachusetts General Hospital Division of Gastroenterology, 15 Parkman St, Wang 5, Boston, MA, 02114, USA
| | - Zachary S Wallace
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, 02114, USA
| | - Ana D Fernandes
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, 02114, USA
| | - Grace A McMahon
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, 02114, USA
| | - Isha Jha
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, 02114, USA
| | - Aubree E McMahon
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, USA
| | - Cory A Perugino
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, 02114, USA
| | - John H Stone
- Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology, 55 Fruit St, Yawkey 4B, Boston, MA, 02114, USA.
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Xi W, Liao W, Guo T, Jiang Q, Bai X, Wu X, Feng Y, Zhang S, Wu D, Wang Q, Yang A. CA19-9/DBil: a promising indicator to distinguish between CA19-9-elevated pancreatic head-type autoimmune pancreatitis and pancreatic head cancer. BMC Gastroenterol 2025; 25:306. [PMID: 40301736 PMCID: PMC12039079 DOI: 10.1186/s12876-025-03925-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 04/22/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND Pancreatic head-type autoimmune pancreatitis (PH-AIP) with elevated CA19-9 is sometimes difficult to distinguish from pancreatic head cancer (PHC) with elevated CA19-9. At times, IgG4 proves inadequate in offering assistance. The study aimed to elucidate the performance of CA19-9/DBil in distinguishing between the two conditions. METHODS This was a retrospective study. We collected serologic indicators from participants in PH-AIP and PHC Group. Three logistic regression equations were established ranging from non-adjustment (Model 1, only CA19-9/DBil included) to adjusting for sex, age, and CEA (Model 2 and Model 3) to explore the relationship between CA19-9/DBil and PH-AIP probability. ROC, Decision Curve Analysis (DCA), calibration curve were conducted. P for AUCs and net reclassification improvements (NRI) were computed to evaluate differences in discrimination and the improvement in risk reclassification between models. RESULTS The study included 90 PHC and 35 PH-AIP patients, all with elevated CA19-9. The ORs for CA19-9/DBil in three models were similar (0.915 to 0.921). ROC revealed that Model 1 had an AUC of 0.772. The sensitivity, specificity, and accuracy at the best threshold were all > 0.7. Model 1, although simple, was not inferior in its discriminative ability compared to complex models: the difference in discrimination between Model 1 and each of two adjusted models was not statistically significant (P > 0.05, both AUC and NRI). Additionally, calibration curve and DCA suggested that Model 1 had good calibration and clinical utility. CONCLUSIONS CA19-9/DBil exhibited promising diagnostic performance in differentiating between CA19-9-elevated PH-AIP and PHC.
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Affiliation(s)
- Wenfeng Xi
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wanying Liao
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Tao Guo
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
| | - Qingwei Jiang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaoyin Bai
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xi Wu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yunlu Feng
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Shengyu Zhang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Dongsheng Wu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Qiang Wang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Aiming Yang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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Paramythiotis D, Karlafti E, Siniosoglou K, Tsavdaris D, Deka IA, Raptou G, Mavropoulou XG, Psoma E, Panidis S, Michalopoulos A. Focal Autoimmune Pancreatitis Morphologically Mimicking Pancreatic Cancer: A Case Report and Literature Review. AMERICAN JOURNAL OF CASE REPORTS 2024; 25:e944286. [PMID: 39279197 PMCID: PMC11416134 DOI: 10.12659/ajcr.944286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 08/05/2024] [Accepted: 07/09/2024] [Indexed: 09/18/2024]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is identified as an outlier in the clinical practice of chronic pancreatitis caused by autoimmune system dysfunction. AIP is classified into 3 subtypes: AIP type 1 and AIP type 2, which are both sensitive to corticosteroids, and the recently introduced AIP type 3. CASE REPORT We present a case of a patient who presented with painless obstructive jaundice. Computed tomography (CT) revealed hyperdense gallbladder material, further dilatation of intrahepatic bile ducts, and distention of the bile duct (15 mm). Based on the available clinical data, which were strongly compatible with pancreatic cancer, Whipple surgery was selected as the treatment for this case. The consequent histopathological report revealed areas of pancreatic parenchyma with fibrous connective tissue development and dense inflammatory cell infiltration with lymphocytes and plasmacytes, which showcased IgG4 positivity. The clinical results suggested a diagnosis of AIP type 1, and the patient was referred to his treating physician for further treatment of AIP. Preoperative histological examination of the pancreas, along with evaluation of the radiological and serological features, could have aided in determining the diagnosis of AIP type 1 pancreatitis despite the unique abnormality of this particular case. CONCLUSIONS Given the aforementioned conditions, AIP, even as a rare clinical entity, emerges as a canonical ailment and should be considered a viable possibility in clinical practice since it can exclude the patient from an unnecessary surgery.
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Affiliation(s)
- Daniel Paramythiotis
- 1 Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Karlafti
- Department of Emergency, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
- 1 Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Krystallenia Siniosoglou
- 1 Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Tsavdaris
- 1 Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioanna Abba Deka
- Department of Pathology, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgia Raptou
- Department of Pathology, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Xanthippi G. Mavropoulou
- Department of Clinical Radiology, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Elizabeth Psoma
- Department of Clinical Radiology, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stavros Panidis
- 1 Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Antonios Michalopoulos
- 1 Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Karamya ZA, Kovács A, Illés D, Czakó B, Fazekas A, Farkas N, Hegyi P, Czakó L. Prevalence of autoimmune pancreatitis in pancreatic resection for suspected malignancy: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:278. [PMID: 39169289 PMCID: PMC11337777 DOI: 10.1186/s12876-024-03367-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 08/09/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND/OBJECTIVES Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer. METHODS A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles. RESULTS Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients). CONCLUSION Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.
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Affiliation(s)
- Zain A Karamya
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary
| | - Attila Kovács
- Department of Gastroenterology and Internal Medicine, Markusovszky Teaching Hospital, Szombathely, Hungary
| | - Dóra Illés
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary
| | - Bálint Czakó
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary
| | - Alíz Fazekas
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Nelli Farkas
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Division of Pancreatic Diseases, Heart and Vascular Centre, Semmelweis University, Budapest, Hungary
| | - László Czakó
- Division of Gastroenterology, Department of Medicine, University of Szeged, Pf.: 427, Szeged, H-6701, Hungary.
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Morão B, Ramos LR, Oliveira MH, Glória L. Malignancy and mass-forming phenotypes of IgG4-related disease: a challenging diagnosis. BMJ Case Rep 2024; 17:e257372. [PMID: 38960429 DOI: 10.1136/bcr-2023-257372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2024] Open
Abstract
Mass-forming phenotypes of IgG4-related disease (IgG4-RD) mimic malignancy and histological confirmation can be challenging. A woman in her 70s with HIV infection presented with painless obstructive jaundice and weight loss. Magnetic resonance imaging was suggestive of unresectable cholangiocarcinoma. Tumour markers and serum IgG4 were normal. Percutaneous liver biopsy was consistent with IgG4-RD inflammatory pseudotumour, with complete response to glucocorticoid therapy. Two years later, a new episode of obstructive jaundice occurred, with CT showing a solid lesion in the head of the pancreas with double duct sign and encasement of the portal vein. Re-induction therapy was tried without response. Fine-needle biopsy was consistent with pancreatic cancer. Supportive care was offered and the patient died 8 months later, with no signs of disease progression on subsequent imaging. We discuss the challenges of IgG4-RD diagnosis and treatment and the differential diagnosis between mass-forming phenotypes and malignancy, highlighting the difficulties in managing such patients.
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Affiliation(s)
- Bárbara Morão
- Gastroenterology, Hospital Beatriz Angelo, Loures, Lisboa, Portugal
| | | | | | - Luísa Glória
- Gastroenterology, Hospital Beatriz Angelo, Loures, Lisboa, Portugal
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Paramythiotis D, Karlafti E, Tsavdaris D, Arvanitakis K, Protopapas AA, Germanidis G, Kougias L, Hatzidakis A, Savopoulos C, Michalopoulos A. Comparative Assessment of Endoscopic Ultrasound-Guided Biopsies vs. Percutaneous Biopsies of Pancreatic Lesions: A Systematic Review and Meta-Analysis of Diagnostic Performance. J Clin Med 2024; 13:3108. [PMID: 38892819 PMCID: PMC11172871 DOI: 10.3390/jcm13113108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
Introduction: Pancreatic cancer ranks as the fourth deadliest form of cancer. However, it is essential to note that not all pancreatic masses signal primary malignancy. Therefore, it is imperative to establish the correct differential diagnosis, a process further supported by pre-operative biopsy procedures. This meta-analysis aims to compare the diagnostic performance of two minimally invasive biopsy approaches for pancreatic tissue sampling: percutaneous biopsies guided by computed tomography or ultrasound, and transduodenal biopsies guided by endoscopic ultrasound (EUS). Methods: A systematic literature search was conducted in the MEDLINE and Scopus databases. The included studies analyzed the diagnostic performance of the two biopsy methods, and they were assessed for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Statistical analysis was carried out using the RevMan and MetaDisc software packages. Results: The statistical analysis of the results demonstrated the superiority of the percutaneous approach. Specifically, the pooled sensitivity, specificity, LR+, LR-and DOR for the percutaneous approach were 0.896 [95% CI: 0.878-0.913], 0.949 [95% CI: 0.892-0.981], 9.70 [95% CI: 5.20-18.09], 0.20 [95% CI: 0.12-0.32] and 68.55 [95% CI: 32.63-143.98], respectively. The corresponding values for EUS-guided biopsies were 0.806 [95% CI: 0.775-0.834], 0.955 [95% CI: 0.926-0.974], 12.04 [95% CI: 2.67-54.17], 0.24 [95% CI: 0.15-0.39] and 52.56 [95% CI: 13.81-200.09], respectively. Nevertheless, it appears that this statistical superiority is also linked to the selection bias favoring larger and hence more readily accessible tumors during percutaneous biopsy procedures. Conclusions: Concisely, our meta-analysis indicates the statistical superiority of the percutaneous approach. However, selecting the optimal biopsy method is complex, influenced by factors like patient and tumor characteristics, clinical resources, and other relevant considerations.
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Affiliation(s)
- Daniel Paramythiotis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.M.)
| | - Eleni Karlafti
- Emergency Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.P.); (C.S.)
| | - Dimitrios Tsavdaris
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.M.)
| | - Konstantinos Arvanitakis
- First Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (K.A.); (G.G.)
| | - Adonis A. Protopapas
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.P.); (C.S.)
| | - Georgios Germanidis
- First Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (K.A.); (G.G.)
| | - Leonidas Kougias
- Department of Radiology, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (L.K.); (A.H.)
| | - Adam Hatzidakis
- Department of Radiology, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (L.K.); (A.H.)
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.P.); (C.S.)
| | - Antonios Michalopoulos
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.M.)
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Zhang BY, Liang MW, Zhang SX. Type one autoimmune pancreatitis based on clinical diagnosis: A case report. World J Clin Cases 2024; 12:2438-2444. [PMID: 38765756 PMCID: PMC11099416 DOI: 10.12998/wjcc.v12.i14.2438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 03/13/2024] [Accepted: 04/03/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION In patients with pancreatic swelling, the possibility of AIP should be considered.
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Affiliation(s)
- Bi-Yu Zhang
- Department of Gastroenterology, Guangzhou University of Chinese Medicine Shunde Hospital, Foshan 528300, Guangdong Province, China
- Department of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Mou-Wang Liang
- Department of Gastroenterology, Guangzhou University of Chinese Medicine Shunde Hospital, Foshan 528300, Guangdong Province, China
| | - Shuang-Xi Zhang
- Department of Gastroenterology, Guangzhou University of Chinese Medicine Shunde Hospital, Foshan 528300, Guangdong Province, China
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Gallo C, Dispinzieri G, Zucchini N, Invernizzi P, Massironi S. Autoimmune pancreatitis: Cornerstones and future perspectives. World J Gastroenterol 2024; 30:817-832. [PMID: 38516247 PMCID: PMC10950636 DOI: 10.3748/wjg.v30.i8.817] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/18/2023] [Accepted: 01/25/2024] [Indexed: 02/26/2024] Open
Abstract
Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.
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Affiliation(s)
- Camilla Gallo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Giulia Dispinzieri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Nicola Zucchini
- Department of Pathology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
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9
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Farrukh L, Akhtar MF, Waqar HH, Peredo-Wende R. Significant CA 19-9 elevation in IgG4-related autoimmune pancreatitis - A diagnostic dilemma. Am J Med Sci 2024; 367:67-71. [PMID: 37714269 DOI: 10.1016/j.amjms.2023.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 08/01/2023] [Accepted: 09/11/2023] [Indexed: 09/17/2023]
Abstract
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterized by dense infiltration of IgG4-positive plasma cells in the affected tissue along with characteristic storiform fibrosis that can lead to the development of tumefactive lesions in any organ. CA19-9 is a marker for pancreato-biliary malignancy, however mild to moderate elevation of CA 19-9 can also be observed in IgG4-RD autoimmune pancreatitis (AIP) and sclerosing cholangitis (IgG4-SC). Therefore, it becomes difficult to differentiate between these entities. We describe the case of a 65-year-old male with history of IgG4-RD, presenting with jaundice and abdominal pain. He was found to have a pancreatic mass with significantly elevated IgG4 162 (2-96 mg/dL and CA19-9 levels 2830 (0-35 U/ml). Patient underwent ERCP and biopsy, which ruled out pancreatic cancer and cholangiocarcinoma. He was diagnosed with IgG4-RD autoimmune pancreatitis (AIP) and sclerosing cholangitis. Treatment with steroids and rituximab resulted in significant improvement in the bilirubin and a dramatic decrease in CA19-9 levels.
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Affiliation(s)
- Larabe Farrukh
- Department of Medicine, Albany Medical Center, Albany, NY, USA.
| | | | | | - Ruben Peredo-Wende
- Department of Rheumatology, Albany Stratton VA Medical Center, Albany, NY, USA
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10
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Wang HX, Li YL, Huang JC, Ma YW, Lang R, Lyu SC. Clinical Value of Mean Platelet Volume to Platelet Ratio (MPR) in Distinguishing Mass-Forming Chronic Pancreatitis and Pancreatic Cancer. Diagnostics (Basel) 2023; 13:3126. [PMID: 37835869 PMCID: PMC10572152 DOI: 10.3390/diagnostics13193126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/30/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.
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Affiliation(s)
| | | | | | | | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
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11
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Caba O, Diéguez-Castillo C, Martínez-Galán J, González-Cebrián I, Jiménez-Luna C. Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma. World J Gastrointest Oncol 2023; 15:268-275. [PMID: 36908319 PMCID: PMC9994052 DOI: 10.4251/wjgo.v15.i2.268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/29/2022] [Accepted: 01/17/2023] [Indexed: 02/14/2023] Open
Abstract
Autoimmune pancreatitis (AIP), a chronic inflammation caused by the immune system attacking the pancreas, usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma (PDAC). Serum biomarkers, substances that quantitatively change in sera during disease development, are a promising non-invasive tool with high utility for differentiating between these diseases. In this way, the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4 (IgG4) antibody are elevated. However, this approach has some drawbacks. Notably, IgG4 antibody concentrations are also elevated in sera from some patients with PDAC. This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC, evaluating the usefulness of immunoglobulins, autoantibodies, chemokines, and cytokines. The proposed serum biomarkers have proven useful, although most studies had a small sample size, did not examine their presence in patients with PDAC, or did not test them in humans. In addition, current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity, either alone or in combination with clinical data and/or radiological images.
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Affiliation(s)
- Octavio Caba
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18016, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain
| | | | - Joaquina Martínez-Galán
- Department of Medical Oncology, Virgen de las Nieves University Hospital, Granada 18014, Spain. Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain
| | | | - Cristina Jiménez-Luna
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18016, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain
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12
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Zavrtanik H, Tomažič A. Is Surgery in Autoimmune Pancreatitis Always a Failure? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:193. [PMID: 36837395 PMCID: PMC9961097 DOI: 10.3390/medicina59020193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/14/2023] [Accepted: 01/15/2023] [Indexed: 01/21/2023]
Abstract
Autoimmune pancreatitis is a rare form of chronic pancreatitis of presumed autoimmune etiology. Due to significant overlap in clinical and imaging characteristics, misdiagnosis as a pancreatic malignancy is common. As a result, a significant number of patients undergo a major pancreatic resection, associated with considerable morbidity, for a disease process that generally responds well to corticosteroid therapy. In the past ten years, important advances have been made in understanding the disease. Several diagnostic criteria have been developed to aid in diagnosis. Despite this, pancreatic resection may still be required in a subset of patients to reliably exclude pancreatic malignancy and establish a definite diagnosis of autoimmune pancreatitis. This article aimed to define the role of surgery in autoimmune pancreatitis, if any. For this purpose, published case series of patients with a diagnosis of autoimmune pancreatitis, based on the histopathological examination of surgical specimens, were reviewed and patients' clinical, radiological and serological details were assessed. At the end, histopathologic examinations of patients who underwent pancreatic resection at our department in the last 10 years were retrospectively reviewed in order to identify patients with autoimmune pancreatitis and assess their clinical characteristics.
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Affiliation(s)
| | - Aleš Tomažič
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška Cesta 7, 1000 Ljubljana, Slovenia
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13
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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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14
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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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15
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Lee SC, Yang CH, Chang CT, Yu KH. Diagnostic Utility of Serum IgG4 in Autoimmune Pancreatitis: An Updated Comprehensive Systematic Review and Meta-analysis. J Clin Gastroenterol 2022; 56:810-817. [PMID: 34516462 DOI: 10.1097/mcg.0000000000001612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Despite many studies suggesting an association between serum immunoglobulin G4 (sIgG4) and autoimmune pancreatitis (AIP), the evidence of utility in differentiation between AIP and pancreatic cancer (PC) remain uncertain. METHODS The analysis based on published studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, diagnostic odds ratios (DOR), areas under summary receiver operating characteristic curves were calculated. RESULTS In the included thirteen studies, sIgG4 were measured in 594 patients with AIP and 958 patients with PC. The pooled sensitivity, specificity, DOR, and area under the curve were 0.72 [95% confidence interval (CI): 0.68-0.75], 0.93 (95% CI: 0.92-0.95), 51.37 (95% CI: 23.20-113.74), and 0.91 (95% CI: 0.87-0.95). Subgroup analyses of the DORs for region and year: Asia, (112.10; 95% CI: 27.72-453.32), non-Asia (26.01; 95% CI: 12.38-54.65), and year before 2011 (107.61; 95% CI: 39.30-294.68), year after 2011 (26.96; 95% CI: 9.78-74.32). Overall, sIgG4 was associated with AIP, the result revealed a moderate sensitivity 0.72 and high specificity 0.93. In the meta-analysis, the pooled DOR of sIgG4 levels of 2-fold upper limit 50.44 was similar with the DOR 51.37 when 1-fold cut-off value, but the summary receiver operating characteristic was 0.755 and 0.91. The higher specificity (from 93% to 98%) derived from the cut-off value (from 130-140 to 260-280 mg/dL) for sIgG4 occurred at a significant reduction in sensitivity (from 72% to 43%). CONCLUSIONS The study revealed sIgG4 is a good marker of AIP. Screening of sIgG4 may help clinicians differentiate between AIP and PC, and the best cut-off value should be 140 rather than 280 mg/dL.
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Affiliation(s)
- Shih-Ching Lee
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan
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de Pretis N, Amodio A, De Marchi G, Marconato E, Ciccocioppo R, Frulloni L. The role of serological biomarkers in the diagnosis and management of autoimmune pancreatitis. Expert Rev Clin Immunol 2022; 18:1119-1124. [PMID: 36125384 DOI: 10.1080/1744666x.2022.2125379] [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]
Abstract
INTRODUCTION Autoimmune pancreatitis (AIP) is a fibroinflammatory disease of the pancreas. Type 1 AIP is the pancreatic manifestation of a systemic IgG4-related disease and is associated with serum elevation of IgG4, tissue infiltration of IgG4-positive plasma cells, and multiorgan involvement. Although serum IgG4 elevation is considered a useful diagnostic tool, the concomitant presence of more diagnostic criteria is needed to achieve diagnosis. No other biomarkers have been approved in clinical practice in type 1 AIP. Type 2 AIP is a pancreatic-specific disease associated with inflammatory bowel disease. No specific biomarkers for type 2 AIP have been identified. AREAS COVERED The role of serum IgG4 in the diagnosis, management and follow-up of patients with type 1 AIP. Moreover, data on other emerging biomarkers for type 1 and 2 AIP have been reported. EXPERT OPINION The diagnosis of AIP is challenging in clinical practice, especially for focal forms without multiorgan involvement, where distinction from pancreatic cancer can be difficult. Despite the strong association with type 1 AIP, serum IgG4 should only be measured when the suspicion for the disease is high, considering its limited sensitivity. New biomarkers with high diagnostic yield for both type 1 and type 2 AIP are needed.
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Affiliation(s)
- Nicolò de Pretis
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Antonio Amodio
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Giulia De Marchi
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Eugenio Marconato
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Luca Frulloni
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
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17
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Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2022; 34:891-904. [PMID: 35913776 DOI: 10.1097/meg.0000000000002415] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker for detecting pancreatic cancer (PC). Since early diagnosis is important for improving PC prognosis, a comprehensive understanding of the diagnostic performance of CA19-9 is critical. This study focused on comprehensive evaluation of the efficacy of CA19-9 in PC diagnosis. Literature research was based on the seven databases. Studies released from January 2002 to January 2022 focused on the efficacy of CA19-9 in the detection of PC were included. Summarized sensitivity, specificity, and sROC/accuracy of discrimination (AUC) were estimated. Potential publication bias was measured with Funnel plot and Egger's test. Meta-regression was performed to detect possible causes of heterogeneity. Subgroup analysis was used to assess the diagnostic efficacy of CA19-9 under different conditions. The study is registered on PROSPERO (CRD42021253861). Seventy-nine studies containing 20 991 participants who met the criteria were included. The pooled sensitivity, specificity, and AUC of CA19-9 in diagnose PC were 72% (95% CI, 71-73%), 86% (95% CI, 85-86%), and 0.8474 (95% CI, 0.8272-0.8676). Subgroup analysis suggested that the diagnostic efficiency of CA19-9 in studies with healthy controls was the highest, followed by intraductal papillary mucinous neoplasm, in pancreatitis and diabetes were consistent with the overall result. Our analysis showed that serum CA19-9 had high and stable diagnostic efficacy for PC (not affected by diabetes). Subgroup analysis showed that serum CA19-9 yielded highest effectiveness in the diagnosis of pancreatic precancerous lesions, which indicated an irreplaceable clinical value in the early detection and warning value for PC.
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Affiliation(s)
- Boqiang Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- The First School of Clinical Medicine, Xi'an, China
| | - Boyue Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
| | - Fangyao Chen
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
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18
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Dugic A, Verdejo Gil C, Mellenthin C, Vujasinovic M, Löhr JM, Mühldorfer S. The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review. Biomedicines 2022; 10:1511. [PMID: 35884816 PMCID: PMC9312496 DOI: 10.3390/biomedicines10071511] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
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Affiliation(s)
- Ana Dugic
- Department of Gastroenterology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Medizincampus Oberfranken, 95445 Bayreuth, Germany;
- Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany
| | - Cristina Verdejo Gil
- Department of Gastroenterology, Hospital Universitario Fundación de Alcorcón, 28922 Madrid, Spain;
| | | | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, 14186 Stockholm, Sweden;
- Department of Medicine, Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden;
| | - J.-Matthias Löhr
- Department of Medicine, Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden;
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 14186 Stockholm, Sweden
| | - Steffen Mühldorfer
- Department of Gastroenterology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Medizincampus Oberfranken, 95445 Bayreuth, Germany;
- Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany
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Hall C, McLaren M, Mosse C. A pancreatic mass and extreme elevation of CA 19-9: a benign masquerade of cholangiocarcinoma. J Surg Case Rep 2022; 2022:rjac018. [PMID: 35186252 PMCID: PMC8849326 DOI: 10.1093/jscr/rjac018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 01/09/2022] [Indexed: 11/23/2022] Open
Abstract
Carbohydrate antigen 19–9 (CA 19–9) is a specific tumour marker for pancreato-biliary malignancy. Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition in which IgG4 deposits infiltrate various organs, including the biliary tract manifesting IgG4 sclerosing cholangitis and pseudotumours. An 83-year-old woman presented with severe obstructive jaundice, weight loss and an extreme elevation of CA 19–9 level of 3295 kU/L. Magnetic resonance cholangiopancreatography (MRCP) revealed a pancreatic mass amputating the biliary tree. Liver function tests revealed a cholestatic pattern and severe hyperbilirubinaemia (289umol/L). IgG4 level was found to be high at 7.97 g/L. After treatment with high-dose corticosteroids, repeat MRCP 2 months later revealed disappearance of the pancreatic mass. There was also normalization of the bilirubin and a dramatic decrease of CA 19–9. This case reports the highest published benign elevation of Ca19.9 level in the setting of IgG4 disease. Differentiation between cholangiocarcinoma and IgG4-RD is important, as the treatment is vastly different.
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Affiliation(s)
- Catherine Hall
- Division of Surgery, The Canberra Hospital, Garran, Australia
| | - Mairi McLaren
- Division of Surgery, The Canberra Hospital, Garran, Australia
| | - Charles Mosse
- Division of Surgery, The Canberra Hospital, Garran, Australia
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20
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A Transient Treatable Tumor of the Pancreas. Dig Dis Sci 2022; 67:76-80. [PMID: 34623577 DOI: 10.1007/s10620-021-07261-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2021] [Indexed: 12/09/2022]
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21
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Jearth V, Giri S, Sundaram S. Approach to management of pancreatic strictures: the gastroenterologist's perspective. Clin J Gastroenterol 2021; 14:1587-1597. [PMID: 34405382 DOI: 10.1007/s12328-021-01503-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 08/13/2021] [Indexed: 12/15/2022]
Abstract
Pancreatic strictures represent a complex clinical problem which often requires multidisciplinary management with a team of gastroenterologists, surgeons and radiologists. Dominant strictures are largely due to inflammatory processes of the pancreas like chronic pancreatitis. However, differentiating benign from malignant processes of the pancreas, leading to strictures is imperative and remains a challenge. With advances in endoscopic management, options for therapy include endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound-guided pancreatic drainage (EUS-PD) in situations where ERCP is not feasible or fails. However, endoscopic therapy is suited for a select group of patients and surgery remains key to management in many patients. In this narrative review, we look at the gastroenterologist's perspective and approach to pancreatic ductal strictures, including endoscopic and surgical management.
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Affiliation(s)
- Vaneet Jearth
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Suprabhat Giri
- Department of Gastroenterology, Seth GS Medical College and King Edward Memorial Hospital, Mumbai, India
| | - Sridhar Sundaram
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400012, India.
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22
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Zhang D, Mao S, Lan S, Zhou C, Liu X. CT Image Changes of Severe Acute Pancreatitis Based on Smart Electronic Medical Augmented Reality in Nursing Practice. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:5522492. [PMID: 33995982 PMCID: PMC8096576 DOI: 10.1155/2021/5522492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 04/03/2021] [Accepted: 04/15/2021] [Indexed: 01/11/2023]
Abstract
Severe acute pancreatitis (SAP) is traditionally treated with chemical analysis. Faced with the increasing maturity of CT imaging technology, it is necessary to use more advantageous CT imaging to treat SAP. In this article, 72 SAP patients admitted to the Affiliated Hospital of Southwest Medical University were selected for study, of which 62 were severely ill, 8 were exacerbated, and 2 changed from severe to mild. This article combines the patient's case records and related CT images during treatment from the perspective of nursing and conducts nursing research on the application of CT image changes in severe acute pancreatitis in nursing practice. CT image processing uses CT imaging system workstation (DICOM). The results of the study showed that, in the care of patients, 21 cases had recurrence after internal drainage, and the cure rate was 91.1%. Internal drainage is an effective way to treat SAP. The higher the incidence of pancreatitis, the more likely it is to relapse after SAP internal drainage, which may be related to repeated episodes of pancreatitis and repeated inflammation of the pancreas and pancreatic duct damage. 4 of the relapsed cases in this article are postchronic pancreatitis SAP, and the relapsed cases account for 50% of the chronic pancreatic cases. This may be due to chronic fibrosis of the branched and main pancreatic ducts, continuous abnormal pancreatic juice drainage. Therefore, it is necessary to further explore the prognosis of different causes of SAP. In terms of complication care, the overall complication rate was 16.6%. One patient died of postoperative hemorrhage. Analysis of the causes of cyst recurrence and complications may be closely related to the mechanism of the occurrence and development of SAP. The initiating factor of SAP is that the pancreatic tissue is damaged due to inflammation, trauma, or microcirculation disorder, and then the pancreatic juice leaks out of the pancreas, wrapping the pancreatic juice; it takes a certain time for the capsule of fibrous knot tissue to form and strengthen.
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Affiliation(s)
- Defen Zhang
- Emergency Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Shifang Mao
- Emergency Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Siyou Lan
- Department 1 of Respiratory and Critical Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Chengli Zhou
- Emergency Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Xiaoyan Liu
- Emergency Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
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Monroy-Iglesias MJ, Dolly S, Sarker D, Thillai K, Van Hemelrijck M, Santaolalla A. Pancreatic Cancer Exposome Profile to Aid Early Detection and Inform Prevention Strategies. J Clin Med 2021; 10:1665. [PMID: 33924591 PMCID: PMC8069449 DOI: 10.3390/jcm10081665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/19/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa.
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Affiliation(s)
- Maria J. Monroy-Iglesias
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Saoirse Dolly
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Debashis Sarker
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
- School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK
| | - Kiruthikah Thillai
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Mieke Van Hemelrijck
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Aida Santaolalla
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
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Focal Autoimmune Pancreatitis: A Simple Flow Chart for a Challenging Diagnosis. Ultrasound Int Open 2021; 6:E67-E75. [PMID: 33490857 PMCID: PMC7815440 DOI: 10.1055/a-1323-4906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 11/25/2020] [Indexed: 12/11/2022] Open
Abstract
Autoimmune pancreatitis is a chronic fibroinflammatory autoimmune mediated
disease of the pancreas. Clinically, obstructive painless jaundice and upper
abdominal pain are the main symptoms. Focal AIP is characterized by
segmental involvement of pancreatic parenchyma and it is often
radiologically represented by a pancreatic mass. In these cases, the
diagnosis can be very challenging, since it may be easily confused with
pancreatic cancer. Therefore, we suggest a combined approach of imaging
tests as the diagnostic workup. EUS study combined with CEUS and
elastography, if available, increases the accuracy of the method to rule out
cancer. Moreover, the lesion should always be sampled under EUS guidance to
obtain a cyto/histological diagnosis. The diagnostic workup should
also include the use of diagnostic clinical criteria (extrapancreatic
lesions, steroid response) and laboratory findings (CA 19.9 and IgG4
evaluations).
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25
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Hedenström P, Lindkvist B. EUS-guided fine needle biopsy sampling in autoimmune pancreatitis: Is needle tip design more important than needle size? Endosc Int Open 2020; 8:E1862-E1864. [PMID: 33270812 PMCID: PMC7695517 DOI: 10.1055/a-1293-7890] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Affiliation(s)
- Per Hedenström
- Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden,Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Björn Lindkvist
- Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden,Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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26
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Blaho M, Dítě P, Kunovský L, Kianička B. Autoimmune pancreatitis - An ongoing challenge. Adv Med Sci 2020; 65:403-408. [PMID: 32805624 DOI: 10.1016/j.advms.2020.07.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/15/2020] [Accepted: 07/13/2020] [Indexed: 02/07/2023]
Abstract
Autoimmune pancreatitis is a rare form of chronic pancreatitis. The first descriptions of the disease date back to the 1990s. Etiology is multifactorial, with the use of genetic, environmental and complex immunological mechanisms. It is classified into two subtypes. Type 1 is part of a group of diseases called IgG4-related disease. Clinically is autoimmune pancreatitis manifested by icterus and abdominal discomfort. It can rarely present as acute pancreatitis. There is also a completely asymptomatic form of the disease. The diagnosis is based on abnormalities in histology, imaging methods, serology, the involvement of other organs in relation to IgG4-related disease, and a significant positive response to corticosteroid therapy. Differential diagnosis between the focal form of autoimmune pancreatitis and pancreatic cancer can be complicated, with endosonography playing an important role. In the treatment, we use corticosteroids and other immunosuppressants including biological therapy. Patients with the asymptomatic disease should also be treated to prevent late complications and exocrine and endocrine insufficiency. In addition to drug treatment, endoscopic and/or surgical treatment may be necessary. Even after recovery, the disease can relapse. The relationship between autoimmune pancreatitis and malignancies has not been clearly confirmed. The goal of this review is to provide a comprehensive look at autoimmune pancreatitis and translate latest scientific knowledge into clinical practice.
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Affiliation(s)
- Martin Blaho
- Department of Internal Medicine, Department of Gastroenterology, University Hospital Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine, Palacký University Olomouc and University Hospital, Olomouc, Czech Republic
| | - Petr Dítě
- Department of Internal Medicine, Department of Gastroenterology, University Hospital Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Lumír Kunovský
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Brno, Czech Republic; Department of Surgery, University Hospital Brno, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Bohuslav Kianička
- Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2nd Department of Internal Medicine, Department of Gastroenterology, St. Anne's University Hospital, Brno, Czech Republic.
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27
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Löhr JM, Beuers U, Vujasinovic M, Alvaro D, Frøkjær JB, Buttgereit F, Capurso G, Culver EL, de-Madaria E, Della-Torre E, Detlefsen S, Dominguez-Muñoz E, Czubkowski P, Ewald N, Frulloni L, Gubergrits N, Duman DG, Hackert T, Iglesias-Garcia J, Kartalis N, Laghi A, Lammert F, Lindgren F, Okhlobystin A, Oracz G, Parniczky A, Mucelli RMP, Rebours V, Rosendahl J, Schleinitz N, Schneider A, van Bommel EFH, Verbeke CS, Vullierme MP, Witt H, the UEG guideline working group. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J 2020; 8:637-666. [PMID: 32552502 PMCID: PMC7437085 DOI: 10.1177/2050640620934911] [Citation(s) in RCA: 133] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 05/04/2020] [Indexed: 12/12/2022] Open
Abstract
The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.
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Affiliation(s)
- J-Matthias Löhr
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
| | - Miroslav Vujasinovic
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Frank Buttgereit
- Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division Pancreas Translational and Clinical Research Center IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, ISABIAL, Alicante, Spain
| | - Emanuel Della-Torre
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Disease (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Nils Ewald
- Institute of Endocrinology, Diabetology and Metabolism, Johannes Wesling University hospital, Minden, Germany and Justus Liebig University Giessen, Giessen, Germany
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman, Ukraine
| | - Deniz Guney Duman
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Nikolaos Kartalis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Andrea Laghi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, Sant’Andrea Hospital, Rome, Italy
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Fredrik Lindgren
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden
| | | | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Andrea Parniczky
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Insitute of Pediatrics, Budapest, Hungary
| | | | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, Clichy, Université de Paris, France
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - Nicolas Schleinitz
- Département de Médicine Interne Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France
| | - Alexander Schneider
- Department of Gastroenterology and Hepatology, Klinikum Bad Hersfeld, Bad Hersfeld, Germany
| | - Eric FH van Bommel
- Department of Internal Medicine, Dutch National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer hospital, Dordrecht, the Netherlands
| | | | | | - Heiko Witt
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Paediatric Nutritional Medicine, Technische Universität München, Freising, Germany
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28
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Sundaram S, Gupta DK. Raised CA19-9 in Autoimmune Pancreatitis. JOURNAL OF DIGESTIVE ENDOSCOPY 2020. [DOI: 10.1055/s-0039-3400709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
AbstractAutoimmune pancreatitis (AIP) is a known autoimmune disorder of the pancreas, with a clinical presentation similar to that of carcinoma of the pancreas. CA19-9 levels can be the distinguishing feature between the two disorders. In rare instances, CA19-9 may be elevated in AIP. Elevation of levels of more than 1,000 U/mL has been reported in only one case series previously. Here we report a rare instance of CA19-9 more than 1,000 U/mL in a case of AIP and its subsequent management.
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Affiliation(s)
- Sridhar Sundaram
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College, King Edward Memorial Hospital, Mumbai, Maharashtra, India
| | - Deepak Kumar Gupta
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College, King Edward Memorial Hospital, Mumbai, Maharashtra, India
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29
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Lopes Vendrami C, Shin JS, Hammond NA, Kothari K, Mittal PK, Miller FH. Differentiation of focal autoimmune pancreatitis from pancreatic ductal adenocarcinoma. Abdom Radiol (NY) 2020; 45:1371-1386. [PMID: 31493022 DOI: 10.1007/s00261-019-02210-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Autoimmune pancreatitis (AIP) is an inflammatory process of the pancreas that occurs most commonly in elderly males and clinically can mimic pancreatic adenocarcinoma and present with jaundice, weight loss, and abdominal pain. Mass-forming lesions in the pancreas are seen in the focal form of AIP and both clinical and imaging findings can overlap those of pancreatic cancer. The accurate distinction of AIP from pancreatic cancer is of utmost importance as it means avoiding unnecessary surgery in AIP cases or inaccurate steroid treatment in patients with pancreatic cancer. Imaging concomitantly with serological examinations (IgG4 and Ca 19-9) plays an important role in the distinction between these entities. Characteristic extra-pancreatic manifestations as well as favorable good response to treatment with steroids are characteristic of AIP. This paper will review current diagnostic parameters useful in differentiating between focal AIP and pancreatic adenocarcinoma.
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Affiliation(s)
- Camila Lopes Vendrami
- Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Joon Soo Shin
- Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Nancy A Hammond
- Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Kunal Kothari
- Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Pardeep K Mittal
- Department of Radiology and Imaging, Medical College of Georgia, 1120 15th Street BA-1411, Augusta, GA, 30912, USA
| | - Frank H Miller
- Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
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30
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Fernandez Y Viesca M, Arvanitakis M. Early Diagnosis And Management Of Malignant Distal Biliary Obstruction: A Review On Current Recommendations And Guidelines. Clin Exp Gastroenterol 2019; 12:415-432. [PMID: 31807048 PMCID: PMC6842280 DOI: 10.2147/ceg.s195714] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 10/23/2019] [Indexed: 12/13/2022] Open
Abstract
Malignant biliary obstruction is a challenging condition, requiring a multimodal approach for both diagnosis and treatment. Pancreatic adenocarcinoma and cholangiocarcinoma are the leading causes of malignant distal biliary obstruction. Early diagnosis is difficult to establish as biliary obstruction can be the first presentation of the underlying disease, which can already be at an advanced stage. Consequently, the majority of patients (70%) with malignant distal biliary obstruction are unresectable at the time of diagnosis. The association of clinical findings, laboratory tests, imaging, and endoscopic modalities may help in identifying the underlying cause. Novel endoscopic techniques such as cholangioscopy, intraductal ultrasonography, or confocal laser endomicroscopy have been developed with promising results, but are not used in routine clinical practice. As the number of patients with malignant distal biliary obstruction who will undergo curative surgery is limited, endoscopy has a crucial role in palliation, to relieve biliary obstruction. According to the last European guidelines published in the management of biliary obstruction, self-expandable metal stents have a central place in biliary drainage compared to plastic stents. Endoscopic ultrasound has evolved impressively in the last decades. When standard techniques of biliary cannulation by endoscopic retrograde cholangiopancreatography fail, endoscopic ultrasound-guided biliary drainage is a good option compared to percutaneous drainage.
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Affiliation(s)
- Michael Fernandez Y Viesca
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Univertié Libre de Bruxelles (ULB), Brussels, Belgium
| | - Marianna Arvanitakis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Univertié Libre de Bruxelles (ULB), Brussels, Belgium
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31
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High accuracy differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma by immunoglobulin G glycosylation. Clin Proteomics 2019; 16:1. [PMID: 30622446 PMCID: PMC6317216 DOI: 10.1186/s12014-018-9221-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 12/26/2018] [Indexed: 02/06/2023] Open
Abstract
Background Misdiagnosis of autoimmune pancreatitis (AIP) as pancreatic cancer (PDAC) or vice versa can cause dismal patents’ outcomes. Changes in IgG glycosylation are associated with cancers and autoimmune diseases. This study investigated the IgG glycosylation profiles as diagnostic and prognostic biomarkers in PDAC and AIP. Methods Serum IgG-glycosylation profiles from 86 AIP patients, 115 PDAC patients, and 57 controls were analyzed using liquid chromatography–electrospray ionization mass spectrometry. Classification and regression tree (CART) analysis was applied to build a decision tree for discriminating PDAC from AIP. The result was validated in an independent cohort. Results Compared with AIP patients and controls, PDAC patients had significantly higher agalactosylation, lower fucosylation, and sialylation of IgG1, a higher agalactosylation ratio of IgG1 and a higher agalactosylation ratio of IgG2. AIP patients had significantly higher fucosylation of IgG1 and a higher sialylation ratio of IgG subclasses 1, 2 and 4. Using the CART analysis of agalactosylation and sialylation ratios in the IgG to discriminate AIP from PDAC, the diagnostic accuracy of the glycan markers was 93.8% with 94.6% sensitivity and 92.9% specificity. There were no statistically significant difference of IgG-glycosylation profiles between diffuse type and focal type AIP. Conclusions AIP and PDAC patients have distinct IgG-glycosylation profilings. IgG-glycosylation could different PDAC from AIP with high accuracy. Electronic supplementary material The online version of this article (10.1186/s12014-018-9221-1) contains supplementary material, which is available to authorized users.
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Liu M, Hao M. Unique properties of IgG4 antibody and its clinical application in autoimmune pancreatitis. Scand J Gastroenterol 2018; 53:1121-1131. [PMID: 30175675 DOI: 10.1080/00365521.2018.1476915] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is defined as a unique form of chronic pancreatitis characterized by clinical presentation with obstructive jaundice, a dense lymphoplasmacytic infiltrate and fibrosis histologically, and a dramatic response to steroids therapeutically. The possible role of IgG4 in driving the pathology of AIP is a controversial subject that has not been addressed satisfactorily. Objective: The purpose of this review is to discuss the unique biology of IgG4 that are important for its role and the clinical applications for serologic detection. METHODS Review of current literature about IgG4 antibody in the clinical application in AIP. RESULTS High serum levels of IgG4 are an important biomarker and broadly used for diagnosis, differentiation from diseases especially pancreatic cancer, and as a parameter to indicate disease activity, extra-pancreatic lesions, and treatment monitoring. However, some controversial studies show it has a limited specificity and sensitivity in these conditions. Conclusion: Although increasing studies have promoted our understanding of the structure and function of IgG4, there is still dilemma between the beneficial and the adverse aspect of IgG4 in the pathogenesis of AIP.
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Affiliation(s)
- Min Liu
- a Department of Clinical Laboratory , Jinan Dermatosis Prevention and Control Hospital , Jinan , People's Republic of China
| | - Mingju Hao
- b Department of Clinical Laboratory , Qianfo Mountain Hospital of Shandong University , Jinan , People's Republic of China
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Detlefsen S, de Vos JD, Tanassi JT, Heegaard NHH, Fristrup C, Schaffalitzky de Muckadell OB. Value of anti-plasminogen binding peptide, anti-carbonic anhydrase II, immunoglobulin G4, and other serological markers for the differentiation of autoimmune pancreatitis and pancreatic cancer. Medicine (Baltimore) 2018; 97:e11641. [PMID: 30075546 PMCID: PMC6081052 DOI: 10.1097/md.0000000000011641] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The diagnosis of autoimmune pancreatitis (AIP) and its differential diagnosis from pancreatic cancer (PC) can be challenging. In this retrospective study, we aimed to evaluate the value of anti-plasminogen binding peptide (a-PBP), immunoglobulin G4 (IgG4), and anti-carbonic anhydrase-II (a-CA-II), together with other serological markers whose value is not fully elucidated.The serum levels of a-PBP, IgG4, IgG, anti-nuclear antibodies (ANA), anti-lactoferrin (a-LF), a-CA-II, and rheumatoid factor (RF) were evaluated in patients with AIP (n = 29), PC (n = 17), pancreatic neuroendocrine neoplasm (P-NEN, n = 12), and alcoholic chronic pancreatitis (ACP, n = 41). ANCA were measured in the AIP patients.There was no statistically significant difference in mean a-PBP values in AIP compared with PC. A ROC curve showed that, when using a cut-off of 38.3 U, low values of a-PBP had a sensitivity and specificity of 45% and 71% for differentiating AIP from PC. The sensitivity and specificity of IgG4 (cut-off 1.4 g/L) for differentiating AIP from PC was 45% and 88%, but rose to 52% and 88% when using a cut-off of 1.09 g/L. When using this cut-off, the sensitivity and specificity for differentiating type 1 AIP from PC was 68% and 88%. None of the other markers were significantly changed in AIP versus PC. For differentiation of type 1 and type 2 AIP, the only significant differences were IgG4 in type 1 AIP (P < .01), with a sensitivity of 68% and a specificity of 80%, and c-ANCA elevations found in some type 2 AIP patients (P < .05).The only serological marker for which we found a statistically significant difference in mean values between AIP and PC was IgG4. However, the value of IgG4 for the distinction of AIP from PC was limited, probably in part due to the relatively high number of type 2 AIP patients in our study. In accord with recent publications, our data do not support a role of increased serum a-PBP for the diagnosis of AIP.
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Affiliation(s)
- Sönke Detlefsen
- Department of Pathology
- Odense Pancreas Center (OPAC), Odense University Hospital
- Institute of Clinical Research, University of Southern Denmark
| | - Jesper D. de Vos
- Institute of Clinical Research, University of Southern Denmark
- Department of Medical Gastroenterology, Odense University Hospital, Odense
| | - Julia T. Tanassi
- Department of Autoimmunology and Biomarkers, Statens Serum Institute, Copenhagen
| | - Niels H. H. Heegaard
- Department of Autoimmunology and Biomarkers, Statens Serum Institute, Copenhagen
- Department of Clinical Biochemistry and Pharmacology
| | - Claus Fristrup
- Odense Pancreas Center (OPAC), Odense University Hospital
- Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Ove B. Schaffalitzky de Muckadell
- Institute of Clinical Research, University of Southern Denmark
- Department of Medical Gastroenterology, Odense University Hospital, Odense
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Dai C, Cao Q, Jiang M, Sun MJ. Serum Immunoglobulin G4 in Discriminating Autoimmune Pancreatitis From Pancreatic Cancer: A Diagnostic Meta-analysis. Pancreas 2018; 47:280-284. [PMID: 29351121 DOI: 10.1097/mpa.0000000000000994] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Differentiation between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) is a clinical challenge. Emerging published data on the accuracy of serum immunoglobulin G4 (IgG4) for the differential diagnosis between AIP and PC are inconsistent. The objective of our study was to perform a meta-analysis evaluating the clinical utility of serum IgG4 in the differential diagnosis between AIP and PC. METHODS We performed a systematic literature search of multiple electronic databases. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. Random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy. RESULTS Eleven studies comprising 523 AIP patients and 771 PC patients were included in the meta-analysis. The summary estimates for serum IgG4 in distinguishing AIP from PC were as follows: diagnostic odds ratio, 57.30 (95% confidence interval [CI], 23.17-141.67); sensitivity, 0.72 (95% CI, 0.68-0.76); specificity, 0.93 (95% CI, 0.91-0.94). The area under the curve of serum IgG4 in distinguishing AIP from PC was 0.9200. CONCLUSIONS Our meta-analysis found that serum IgG4 has high specificity and relatively low sensitivity in the differential diagnosis between AIP and PC. Therefore, serum IgG4 is useful in distinguishing AIP from PC.
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Affiliation(s)
- Cong Dai
- From the Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China
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Clinical Utility of FDG PET/CT in Patients with Autoimmune Pancreatitis: a Case-Control Study. Sci Rep 2018; 8:3651. [PMID: 29483544 PMCID: PMC5827761 DOI: 10.1038/s41598-018-21996-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 02/15/2018] [Indexed: 12/24/2022] Open
Abstract
Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.
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Pak LM, Schattner MA, Balachandran V, D’Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ. The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma. HPB (Oxford) 2018; 20:182-187. [PMID: 29033025 PMCID: PMC7362973 DOI: 10.1016/j.hpb.2017.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 08/08/2017] [Accepted: 09/06/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Elevation in the serum immunoglobulin-G4 (IgG4) level has been used as a diagnostic marker to distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), but its true utility is ill-defined. This study evaluates the clinical utility of IgG4 in differentiating AIP from PDAC. METHODS All patients evaluated in the hepatopancreaticobiliary surgery clinics with measured serum IgG4 were included. Patients were divided into normal IgG4 (<135 mg/dL) and elevated IgG4 (≥135 mg/dL) groups. The final diagnosis was determined by operative pathology when available or by clinical outcome. The sensitivity, specificity, PPV, and NPV of IgG4 for diagnosing AIP was assessed. RESULTS Between 1997 and 2015, 298 patients were identified. Normal IgG4 levels were present in 85% of patients (254/298), while 15% (44/298) were elevated. The overall prevalence of AIP was 17% (52/298). The sensitivity and specificity of IgG4 for AIP was 67% and 96%, respectively; however, the PPV was only 80%, including a 9% occurrence of PDAC in patients with an elevated IgG4. CONCLUSION In this study of selected patients who underwent IgG4 testing, 9% of elevated IgG4 patients had PDAC. The overreliance on IgG4 as diagnostic for AIP may lead to mis-diagnosis and delayed treatment for PDAC.
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Affiliation(s)
- Linda M. Pak
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - Mark A. Schattner
- Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - Vinod Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - Michael I. D’Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - Ronald P. DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - William R. Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
| | - Peter J. Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York, USA
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Abstract
CLINICAL ISSUE IgG4-related diseases are rare but the incidence is continuously increasing. The pathophysiology is only incompletely understood. Multiorgan involvement correlates with high relapse rates, high serum IgG4 levels and an aggressive disease course, which is why diagnostics and therapy must be carried out rapidly and efficiently according to international guidelines despite all the difficulties. STANDARD TREATMENT Currently the therapeutic standard is initial therapy (induction therapy) with glucocorticosteroids over a longer period of time and if necessary followed by low-dose maintenance therapy. Steroids are also the first choice therapy for management of relapses. Refractory disease courses are a rare but relevant problem. TREATMENT INNOVATIONS The B‑cell depleting antibody rituximab has shown excellent results in terms of remission induction and also maintenance therapy. The good effectiveness profile is likely to change the current treatment regimen for IgG4-related diseases in the future. DIAGNOSTIC WORK-UP The current diagnostic algorithms applicable for several organ systems are based on four major pillars: (i) patient history and physical examination, (ii) serological diagnostics, (iii) organ swelling in the appropriately selected imaging procedure and (iv) the histological picture as gold standard. PERFORMANCE The currently used algorithms allow a diagnosis to be made in most cases. ACHIEVEMENTS IgG4-related diseases are a relevant differential diagnosis, particularly of malignant diseases. It is often a diagnosis by exclusion. An interdisciplinary approach is essential for rapid diagnostics and induction of therapy. PRACTICAL RECOMMENDATIONS In Europe IgG4 serum levels are just one of several diagnostic criteria. Imaging studies should be chosen according to the organ and disease manifestations.
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Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma. Int J Mol Sci 2017; 18:ijms18030667. [PMID: 28335509 PMCID: PMC5372679 DOI: 10.3390/ijms18030667] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/07/2017] [Accepted: 03/10/2017] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker. When combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125), CA 19-9 can help predict the outcome of patients to surgery and chemotherapy. A slew of novel serum markers including multimarker panels as well as genetic and epigenetic materials have potential for early detection of pancreatic cancer, although these remain to be validated in larger trials. Imaging studies may not correlate with elevated serum markers. Critical features for determining PDAC include the presence of a mass, dilated pancreatic duct, and a duct cut-off sign. Features that are indicative of early metastasis includes neurovascular bundle involvement, duodenal invasion, and greater post contrast enhancement. 18-F-fluorodeoxyglucose (18-FDG) radiotracer uptake and changes following treatment may predict patient overall survival following treatment. Similarly, pretreatment apparent diffusion coefficient (ADC) values may predict prognosis with lower ADC lesions having worse outcome. Although these markers have provided significant improvement in the care of pancreatic cancer patients, further advancements can be made with perhaps better combination of markers or discovery of unique marker(s) to pancreatic cancer.
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De Marchi G, Paiella S, Luchini C, Capelli P, Bassi C, Frulloni L. Very high serum levels of CA 19-9 in autoimmune pancreatitis: Report of four cases and brief review of literature. J Dig Dis 2016; 17:697-702. [PMID: 27579898 DOI: 10.1111/1751-2980.12403] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 08/09/2016] [Accepted: 08/24/2016] [Indexed: 02/06/2023]
Affiliation(s)
- Giulia De Marchi
- Department of Gastroenterology B, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Unit of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, University of Verona Hospital Trust, Verona, Italy
- ARC-NET Research Center, University of Verona Hospital Trust, Verona, Italy
| | - Paola Capelli
- Department of Diagnostics and Public Health, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Luca Frulloni
- Department of Gastroenterology B, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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Serum IgG4 and IgG for the diagnosis of autoimmune pancreatitis: A systematic review with meta-analysis. Clin Res Hepatol Gastroenterol 2016; 40:99-109. [PMID: 26160477 DOI: 10.1016/j.clinre.2015.06.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 05/09/2015] [Accepted: 06/01/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE The correct diagnosis of autoimmune pancreatitis (AIP) is a clinical challenge. Emerging published data on the accuracy of serum IgG4 and IgG for diagnosing AIP are inconsistent. This study was performed to better elucidate the accuracy of serum IgG4 and IgG in diagnosing AIP. METHODS A comprehensive literature search of PubMed, Web of Science, EMBASE, the Cochrane Library and some other databases was conducted before October 2014. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Random-effects model was used to summarize the sensitivity, specificity and other measures of accuracy. RESULTS Fifteen studies on IgG4 and 8 studies on IgG were included. The summary estimates for serum IgG4 in distinguishing AIP from the overall controls, pancreatic cancer and ordinary chronic pancreatitis were as follows: sensitivity 0.74 (0.70-0.77), 0.73 (0.69-0.77) and 0.76 (0.72-0.80), respectively, specificity, 0.94 (0.93-0.95), 0.93 (0.91-0.95) and 0.96 (0.95-0.97), respectively. The summary estimates for serum IgG in distinguishing AIP from the overall controls and pancreatic cancer were as follows: sensitivity, 0.53 (0.47-0.59) and 0.51 (0.44-0.57), respectively, specificity, 0.87 (0.85-0.89) and 0.94 (0.91-0.96), respectively. The area under the curve (AUC) of serum IgG in distinguishing AIP from ordinary chronic pancreatitis was 0.657. CONCLUSIONS Both serum IgG4 and IgG have high specificity and relatively low sensitivity for diagnosing AIP. Besides, they are useful for distinguishing AIP from pancreatic cancer and ordinary chronic pancreatitis. To better elucidate the usefulness of serum IgG4 and IgG, further studies are needed.
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Wu L, Huang P, Wang F, Li D, Xie E, Zhang Y, Pan S. Relationship between serum CA19-9 and CEA levels and prognosis of pancreatic cancer. ANNALS OF TRANSLATIONAL MEDICINE 2016; 3:328. [PMID: 26734638 DOI: 10.3978/j.issn.2305-5839.2015.11.17] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND To explore the relationship between preoperative serum CA19-9 and CEA levels and prognosis of pancreatic cancer (PC). METHODS The clinicopathological data of 128 patients with pancreatic adenocarcinoma who were treated in our center between January 2012 and December 2013 were retrospectively analyzed. The relationships between serum CA19-9 and CEA levels and survival were analyzed using Kaplan-Meier method, log-rank test, and Cox regression analysis. The cut-off values for serum CA19-9 and CEA levels were 39 U/mL and 4.7 ng/mL, respectively. RESULTS Among these 128 patients, the mean age was 62 years, and median survival was 12.2 days. The positive rate of CA19-9 and CEA was 78.1% and 37.5%, respectively. Patients with increased CA19-9 or CEA level suffered a poorer prognosis than those with normal CA19-9 or CEA level (CA19-9: P=0.027; CEA: P=0.036). Cox logistic analysis revealed that lymphatic metastasis, CA19-9 >39 U/mL, and CEA >4.7 ng/mL were independent prognostic factors in patients with pancreatic carcinoma. CONCLUSIONS Preoperative serum CA19-9 and CEA level are closely related with survival time in PC patients and therefore may be used for evaluating the prognosis for PC.
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Affiliation(s)
- Lei Wu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Peijun Huang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Fang Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Daqian Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Erfu Xie
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yan Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Shiyang Pan
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
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Abstract
PURPOSE OF REVIEW There are two distinct steroid responsive chronic fibro-inflammatory diseases of the pancreas, called type 1 and type 2 autoimmune pancreatitis (AIP). We review recent progress in this field. RECENT FINDINGS It has recently been suggested that the term AIP be used to describe type 1 AIP and the term idiopathic duct-centric chronic pancreatitis (IDCP) be used for type 2 AIP. Clinical features and long-term outcomes of AIP and IDCP are well characterized and prognosis of both diseases is excellent. Diagnostic strategies tailored to regional practice patterns have emerged with the application of International Consensus Diagnostic Criteria for AIP. Although corticosteroids remain the mainstay of treatment, management of relapses and strategies for preventing multiple relapses are better understood, including the role of maintenance therapy and B-cell depletion therapy with rituximab. Association studies with malignancies have yielded conflicting results regarding risk of cancer in AIP. SUMMARY The treatment, follow-up guidelines and associations continue to evolve with our increasing experience with both AIP and IDCP. In AIP, rituximab can be used for both induction and maintenance of remission. IDCP responds to steroids without need for maintenance therapy. Both AIP and IDCP have excellent prognosis.
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Zhang R, Shen J, Hu Z. Focal mass-like autoimmune pancreatitis complicated by obviously elevated CA19-9: Efficacy of follow-up imaging. Pancreatology 2015; 15:308-9. [PMID: 26120823 DOI: 10.1016/j.pan.2015.01.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Revised: 01/14/2015] [Accepted: 01/25/2015] [Indexed: 12/11/2022]
Affiliation(s)
- Ruiguo Zhang
- Department of Nuclear Medicine, Tianjin First Center Hospital, No. 24, Fukang Road, Nankai District, Tianjin 300192, China.
| | - Jie Shen
- Department of Nuclear Medicine, Tianjin First Center Hospital, No. 24, Fukang Road, Nankai District, Tianjin 300192, China.
| | - Zhandong Hu
- Department of Pathology, Tianjin First Center Hospital, Tianjin, China.
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