Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer

OBJECTIVES: To determine the sensitivity and specificity of elevated serum IgG4 level for the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer, its main differential diagnosis. METHODS: We measured serum IgG4 levels (normal 8-140 mg/dL) in 510 patients including 45 with AIP, 135 with pancreatic cancer, 62 with no pancreatic disease, and 268 with other pancreatic diseases. RESULTS: Sensitivity, specificity, and positive predictive values for elevated serum IgG4 (>140 mg/dL) for diagnosis of AIP were 76%, 93%, and 36%, respectively, and 53%, 99%, and 75%, respectively, for IgG4 of >280 mg/dL. Among subjects with elevated IgG4, non-AIP subjects (N = 32) differed from AIP subjects (N = 34) in that they were more likely to be female (45%vs 9%, P < 0.001), less likely to have serum IgG4 >280 mg/dL (13%vs 71%, P < 0.001), or elevation of total IgG (16%vs 56%, P < 0.001). Serum IgG4 levels were elevated in 13/135 (10%) pancreatic cancer patients; however, only 1% had IgG4 levels >280 mg/dL compared with 53% of AIP. Compared with AIP, pancreatic cancer patients were more likely to have CA19-9 levels of >100 U/mL (71%vs 9%, P < 0.001). CONCLUSION: Elevated serum IgG4 levels are characteristic of AIP. However, mild (<2-fold) elevations in serum IgG4 are seen in up to 10% of subjects without AIP including pancreatic cancer and cannot be used alone to distinguish AIP from pancreatic cancer. Because AIP is uncommon, IgG4 elevations in patients with low pretest probability of having AIP are likely to represent false positives.     

A proposal of a diagnostic algorithm with validation of International Consensus Diagnostic Criteria for autoimmune pancreatitis in a Japanese cohort

BackgroundAmong many diagnostic criteria for autoimmune pancreatitis (AIP), the International Consensus Diagnostic Criteria (ICDC) first enabled us to diagnose and compare type 1 and type 2 AIP, which permitted tailoring individual diagnostic algorithms depending on local expertise. We compared them and validated ICDC with special reference to levels 1 and 2, and proposed a diagnostic algorithm for AIP in Japan.MethodsThe diagnostic sensitivity of 5 major criteria (ICDC, Korean, Japanese-2011, Asian, and HISORt criteria) was compared, using 61 patients with AIP. Fifty six patients with pancreatic cancer served as a control. Pancreas imaging on computed tomography (CT) and endoscopic retrograde pancreatography (ERP) were independently evaluated by 3 pancreatologists (5, 10, and 20 years of career experience) and each diagnostic criterion of ICDC was validated with special reference to levels 1 and 2.ResultsThe sensitivities of 5 major criteria were 95.1% (ICDC), 90.2% (Korean), 86.9% (Japanese), 83.6% (Asian), and 83.6% (HISORt) with 100% of specificity in each. In the evaluation of pancreas imaging, diagnostic sensitivities of combination with CT and ERP in segmental/focal type AIP were significantly higher than single imaging (26% in CT (P < 0.01) or 35% in ERP (P < 0.05) vs 63% in CT + ERP), but not significantly different in the diffuse type.ConclusionsOf the 5 criteria, ICDC is the most sensitive and useful for diagnosing AIP. We have proposed a diagnostic algorithm with CT for the diffuse type of AIP, and combination with CT + ERP followed by EUS-FNA for the segmental/focal type.     

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: A coincidental association

Background/aimsCoexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates.MethodsSerum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant.ResultsSerum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN.ConclusionsIn a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.     

Serum free light chain assessment in type 1 autoimmune pancreatitis

Background/Object: Some patients with type 1 autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease, have normal serum IgG4. The aim of this study is to investigate the diagnostic value of measuring serum free light chains (FLCs) in type 1 AIP.Materials and methodsThirty-seven patients with type 1 AIP, and 21 healthy, 17 alcoholic chronic pancreatitis (ACP), 21 idiopathic chronic pancreatitis (ICP) and 20 pancreatic cancer (PC) patients were enrolled. Serum IgG4 and FLC concentrations were measured using sFLC Freelite assays on a nephelometric analyzer.ResultsActive AIP patients have significantly higher serum levels of κ (median 30.97 (12.3–227.0) mg/L) and λFLC (median 20.53 (12.36–102.7) mg/L)) than healthy controls (κFLC; median 12.5 (3.1–52.1) mg/L), λFLC: median 12.45 (5.4–39.5) mg/L) (p < 0.05) correlating with raised serum IgG4, and significantly higher summated FLCs (∑) (median 53.09 (25.0–218.0) mg/L) than ICP patients (median 26.77 (15.0–89.2) mg/L) and healthy controls (median 24.43 (8.5–91.6) mg/L) (p < 0.05). AIP patients (median 1.43 (0.84–3.24)) showed significantly higher κ/λ ratios than ACP (median 0.83 (0.42–1.18)), ICP (median 0.87 (0.47–2.16)), PC patients (median 0.90 (0.48–1.27)) and healthy controls (median 0.963 (0.51–1.32)). There was a correlation between increased κ and λ FLCs levels and the number of affected organs involved in IgG4 related disease.ConclusionPatients with type 1 AIP have increased serum k and λ FLC concentrations, Σ FLC, and κ/λ ratios. These novel biomarkers may be useful in the diagnosis of type 1 AIP and in monitoring disease activity.     

The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: A systematic review and meta-analysis

BackgroundThe diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP.MethodsA comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy.ResultsThe meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70–80.75); sensitivity 0.64 (95% CI, 0.59–0.69); specificity 0.93 (95% CI, 0.91–0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla).ConclusionsCurrent data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.     

Autoimmunpankreatitis – „the new kid on the block“

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis which is characterized by diffuse or focal pancreatic enlargement, a lymphoplasmacytic infiltrate with a storiform fibrosis and a dramatic response to steroid treatment. AIP can be classified into three subtypes: lymphoplasmacytic sclerosing pancreatitis (LPSP; AIP type 1), idiopathic duct centric pancreatitis (IDCP; AIP type 2), and not otherwise specified (NOS). AIP type 1 is the pancreatic manifestation of IgG4-related disease which also involves other organs; AIP type 2 is a pancreas-specific, IgG4-negative disorder and is associated with inflammatory bowel disease. Epidemiological studies from Japan estimate an incidence of approximately 0.82 per 100,000 inhabitants; in Europe 5–6% of all patients with chronic pancreatitis are diagnosed with AIP. The pathomechanism of AIP remains enigmatic, but a mulitfactorial etiology with genetic predisposition and environmental influences has been proposed. Clinically, patients can present with jaundice, epigastric pain, weight loss and new-onset diabetes, thus, raising suspicion for pancreatic malignancy. A combination of the HISORt (Histology, Imaging, IgG4 Serology, other Organ involvement and Response to steroid therapy) criteria can be used to definitively diagnose AIP in most cases. The greatest challenge is to differentiate AIP from pancreatic cancer and cholangiocarcinoma, since it often presents with a pancreatic mass, lymphadenopathy and bile duct obstruction. The prognosis of AIP is usually favorable; in over 90% of cases remission can be induced by steroid treatment.     

The relationship between pancreatic atrophy after steroid therapy and diabetes mellitus in patients with autoimmune pancreatitis

Background/objectivesMany patients with autoimmune pancreatitis (AIP) have an association with diabetes mellitus. It has not been clarified whether steroid therapy for AIP improves or worsens the condition of diabetes mellitus. The aim of this study was thus to investigate the relationship between pancreatic atrophy after steroid therapy and the clinical course of diabetes.MethodsThirty-one AIP patients, who were treated by steroid therapy, were included in this study during December 2005 to March 2013. Pancreatic atrophy 6 months after the beginning of steroid therapy was defined to be present when the width of the pancreatic body was less than 10 mm. The relationships between pancreatic atrophy and patient characteristics as well as the course of diabetes were examined.ResultsSteroid therapy was effective in all treated patients. Pancreatic atrophy was observed in 12 patients and not in 19 patients after the steroid therapy. AIP patients with pancreatic atrophy showed higher incidences of diabetes mellitus (p = 0.001, 9/12 vs. 2/19), diabetes control worsening (p = 0.007, 7/12 vs. 2/17), and new onset of diabetes (p = 0.02, 5/7 vs. 1/18) than those without atrophy. It was not associated with gender, other organ involvement, pattern of pancreas swelling (diffuse/focal), serum IgG4 level, alcohol intake, and pancreatic calcification on CT. Patients with new onset of diabetes needed insulin therapy, even in the maintenance therapy of AIP.ConclusionsAIP patients with pancreatic atrophy after steroid therapy have a high incidence of diabetes mellitus. New onset of diabetes is closely associated with pancreatic atrophy after steroid therapy.     

Autoimmune pancreatitis associated with a large pancreatic pseudocyst

INTRODUCTIONAutoimmune pancreatitis (AIP) is a benign disease that responds well to steroid treatment. Characteristics in-clude radiological evidence of an irregular narrowing of the pancreatic main duct and a diffuse enlargement of the pancreas, together…     

Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience.

BACKGROUND & AIMS: The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. METHODS: We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. RESULTS: Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with > or =1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. CONCLUSIONS: AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.     

Cell-free DNA promoter hypermethylation as a diagnostic marker for pancreatic ductal adenocarcinoma – An external validation study

BackgroundWe recently identified a diagnostic prediction model based on promoter hypermethylation of eight selected genes in plasma cell-free (cf) DNA, which showed promising results as a diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to validate this biomarker profile in an external patient cohort and examine any additional effect of serum CA 19-9.MethodsPatients with PDAC (n = 346, stage I-IV) and chronic pancreatitis (n = 25) were included. Methylation-specific PCR of a 28-gene panel was performed on serum cfDNA samples. The previously developed diagnostic prediction model (age>65 years, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) was validated alone and in combination with serum CA 19-9 in this external patient cohort.ResultsPatients with PDAC had a higher number of hypermethylated genes (mean 8.11, 95% CI 7.70–8.52) than patients with chronic pancreatitis (mean 5.60, 95% CI 4.42–6.78, p = 0.011). Validation of the diagnostic prediction model yielded an AUC of 0.77 (95% CI 0.69–0.84). The combination of serum CA 19-9 and our test had an AUC of 0.93 (95% CI 0.89–0.96) in the primary study and 0.85 (95% CI 0.79–0.91) in the validation study.ConclusionIn this validation study, PDAC was associated with a higher number of hypermethylated genes in serum cfDNA than chronic pancreatitis. Our diagnostic test was superior to the predictive value of serum CA 19-9 alone in both the primary and the validation study. The combination of our test with CA 19-9 may serve as a clinically useful diagnostic biomarker for PDAC.     

Autoimmune pancreatitis

Abstract

Background. Autoimmune pancreatitis (AIP) is a relatively newly recognized type of pancreatitis that is characterized by diffuse or focal swelling of the pancreas due to lymphoplasmacytic infiltration and fibrosis of the pancreatic parenchyma. Material and methods. A PubMed literature search was performed using the keywords “autoimmune pancreatitis”. Sometimes, bibliographies were cross-referenced and related article searches were performed once an article of interest was identified. Results. Pathologically, AIP shows narrowing of the pancreatic ducts and the intrapancreatic portion of the common bile duct. Obstructive jaundice is a common symptom at presentation, and pancreatic cancer represents an important clinical differential diagnosis. In late stages of the disease, the normal pancreatic parenchyma is often replaced by large amounts of fibrosis. Histologically, there seem to be two subtypes of the disease–one showing infiltration with IgG4-positive plasma cells but lacking granulocytic epithelial lesions (GELs), the other showing GELs but lacking strong IgG4 positivity. AIP is in at least some instances the pancreatic manifestation of a clinicopathological entity of IgG4-related systemic sclerosing disease. On the basis of pancreatic imaging, together with serological measurement of IgG4 and evaluation of other organ involvement, many AIP patients can be identified. The remaining patients require further diagnostic work-up. In these patients, pancreatic core needle biopsy and, as AIP responds to steroid treatment, also a trial with steroids, can help to differentiate AIP from pancreatic cancer. Outlook and discussion. This review presents the pathological, radiologic and laboratory findings of AIP. Moreover, the treatment and pathogenesis are discussed.     

Endoscopic retrograde cholangiopancreatography-related adverse events in patients with type 1 autoimmune pancreatitis

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) is frequently performed for the diagnosis and treatment of type 1 autoimmune pancreatitis (AIP). However, the prevalence of ERCP-related adverse events in patients with type 1 AIP has not been evaluated. We aimed to clarify the feasibility of ERCP in patients with type 1 AIP.MethodsWe retrospectively reviewed 82 consecutive ERCP procedures performed in patients with type 1 AIP from 2004 to 2014 in one university hospital and three tertiary-care referral centers. One hundred four ERCP procedures in chronic pancreatitis and 1123 in non-AIP cohort were enrolled as control groups. We compared the incidence of post-ERCP pancreatitis (PEP) between type 1 AIP and control groups. We evaluated the incidence of ERCP-related adverse events and various predictive factors for hyperamylasemia after ERCP.ResultsPancreatography and cholangiography by ERCP were obtained in 78 (95.1%) and 76 (92.7%) patients, respectively. The incidence of PEP, cholangitis, and bleeding was 1.2% (1/82), 0%, and 1.2%, respectively. PEP occurred in type 1 AIP patient with diffuse parenchymal imaging, and the severity was mild. The incidences of PEP were 2.9% (3/104) and 5.4% (61/1123) in chronic pancreatitis and normal cohort, respectively. The incidence of PEP was slightly lower in type 1 AIP than non-AIP cohort (1.2% vs 5.8%, p = 0.119). There were no significant predictive factors for hyperamylasemia after ERCP in type 1 AIP.ConclusionsThe incidence of ERCP-related adverse events is low in patients with type 1 AIP. ERCP-related procedures are feasible in the diagnosis and treatment of AIP.     

自身免疫性胰腺炎不同诊断标准间诊断率的差异及其主要影响因素分析

目的 探讨自身免疫性胰腺炎(AIP)不同诊断标准间诊断情况的差异及其主要影响因素,为AIP临床诊治提供指导.方法 回顾性分析解放军总医院2008年6月-2013年1月收治的561例慢性胰腺炎住院患者的临床资料,对比以美国HISORt标准及亚洲标准诊断AIP的情况,分析两者AIP诊断率差异的产生原因.结果 符合2006年美国HISORt标准的AIP患者共34例,其中满足组织学诊断标准、胰腺典型影像学表现+血清IgG4升高诊断标准、激素治疗有效+血清IgG4升高诊断标准的病例数分别为5、10和26例,同时符合后两组标准者7例.符合2008年亚洲诊断标准的AIP患者共15例,其中满足两条必备影像学标准者10例,满足手术切除后病理为淋巴浆细胞硬化性胰腺炎标准者5例.结论 AIP是一种以自身免疫性炎症为特征的特殊类型的慢性胰腺炎,临床上易误诊为胰腺癌、胆管癌等.不同诊断标准相继推出,2008年亚洲诊断标准更适合我国临床实践,在血清学指标、病理结果及试验性糖皮质激素治疗等诊断方法基础上,应充分重视影像学检查对AIP诊断的重要性.     

Diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis(AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to Ig G4(lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion(idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum Ig G4 and positive serum autoantibodies, abundant infiltration of Ig G4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology(IAP).     

Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases

IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.     

Autoimmune pancreatitis: Multimodality non-invasive imaging diagnosis

Autoimmune pancreatitis(AIP)is characterized by obstructive jaundice,a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate,with or without a pancreatic mass.Type 1AIP is the pancreatic manifestation of an Ig G4-related systemic disease and is characterized by elevated Ig G4serum levels,infiltration of Ig G4-positive plasma cells and extrapancreatic lesions.Type 2 AIP usually has none or very few Ig G4-positive plasma cells,no serum Ig G4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement.AIP is diagnosed in approximately 2%-6%of patients that undergo pancreatic resection for suspected pancreatic cancer.There are three patterns of autoimmune pancreatitis:diffuse disease is the most common type,with a diffuse,“sausage-like”pancreatic enlargement with sharp margins and loss of the lobular contours;focal disease is less common and manifests as a focal mass,often within the pancreatic head,mimicking a pancreatic malignancy.Multifocal involvement can also occur.In this paper we describe the features of AIP at ultrasonography,computed tomography,magnetic resonanceand positron emission tomography/computed tomography imaging,focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma.It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients.Non-invasive imaging plays also an important role in therapy monitoring,in follow-up and in early identification of disease recurrence.     

The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma

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.

Serum IgG4-negative autoimmune pancreatitis

Background  

Autoimmune pancreatitis (AIP) is considered to be a pancreatic lesion of IgG4-related systemic disease, but about 20% of AIP patients do not have elevated serum IgG4 levels. This study aimed to clarify the pathophysiology of AIP patients without elevated serum IgG4 levels.     

Pancreatic Juice 90K and Serum CA 19–9 Combined Determination Can Discriminate between Pancreatic Cancer and Chronic Pancreatitis

Objectives: Differential diagnosis of pancreatic cancer versus chronic pancreatitis may be difficult. The aim of this study is to determine whether a group of tumor-associated antigens could differentiate between the two pathologies. Methods: CA 19–9, TAG–72, CAR–3, and a newly discovered antigen termed "90K" were determined in the serum and in the pancreatic juice of 19 patients with pancreatic cancer, 20 patients with chronic pancreatitis, and seven controls with lithiasis of extrapancreatic bile ducts. Results: The serum antigen levels of all three markers except 90K were significantly higher in pancreatic cancer than in chronic pancreatitis. High correlations were found between serum CA 19–9 and both TAG–72 and CAR–3. 90K did not correlate with other markers. In pancreatic juice, only 90K values were significantly higher in chronic pancreatitis than in pancreatic cancer, and only 90K and CA 19–9 were significantly correlated. At the stepwise discriminant analysis, serum CA 19–9 and pancreatic juice 90K had independent diagnostic roles. Used in combination, they correctly identified 84.2% of pancreatic cancer and 90% of chronic pancreatitis. Conclusions: These data suggest that pancreatic juice 90K and serum CA 19–9 can discriminate between chronic pancreatitis and pancreatic cancer. The data further support the complementary use of tumor-associated antigens along with other diagnostic tools.     

Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: A systematic literature review and meta-analysis

High circulating serum immunoglobulin G4 (IgG4) levels have been proposed as a marker of autoimmune pancreatitis (AIP). The aim of the present study was to review the data existing in the English literature on the usefulness of the IgG4 serum levels in the diagnosis and follow up of patients with AIP. A total of 159 patients with AIP and 1099 controls were described in seven selected papers reporting the usefulness of serum IgG4 in diagnosing AIP. In total, 304 controls had pancreatic cancer, 96 had autoimmune diseases, and the remaining 699 had other conditions. The summary receiver–operating characteristic curve analysis was carried out by means of Meta-DiSc open-access software. Serum IgG4 showed good accuracy in distinguishing between AIP and the overall controls, pancreatic cancer and other autoimmune diseases (area under the curve [± SE]: 0.920 ± 0.073, 0.914 ± 0.191, and 0.949 ± 0.024, respectively). The studies analyzed showed significantly heterogeneous specificity values in each of the three analyses performed. The analysis of the four studies comparing AIP and pancreatic cancers also showed significantly heterogeneous values of sensitivities and odds ratios. Regarding the usefulness of IgG4 as a marker of efficacy of steroid treatment, a decrease in the serum concentrations of IgG4 was found in the four available studies. The serum IgG4 subclass is a good marker of AIP, and its determination should be included in the diagnostic workup of this disease. However, the heterogeneity of the studies published until now means that more studies are necessary in order to better evaluate the true accuracy of IgG4 in discriminating AIP versus other autoimmune diseases.