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.

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.

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.

CA19-9/DBil exhibited promising diagnostic performance in differentiating between CA19-9-elevated PH-AIP and PHC.

Type 1 autoimmune pancreatitis (AIP) frequently involves biliary lesions and poses diagnostic and therapeutic challenges. We aimed to evaluate the clinical features and long-term prognosis of type 1 AIP with a focus on the locations of bile duct lesions.

In this retrospective study, 159 patients with type 1 AIP were included. Patients were classified on the basis of the location of bile duct strictures, and clinical outcomes, including relapse rates and steroid dependency, were analyzed.

Eighty-nine (56%) patients had bile duct involvement. Forty-nine patients (30.8%) experienced relapse, with a significantly higher cumulative relapse rate in cases of stricture or wall thickening upstream of the intrapancreatic bile duct (3 years: 24% vs. 37.1%, p < .001). These patients also had a significantly higher rate of two or more relapses than did the patients without stricture or wall thickening (5.1% vs. 19.5%, p = .01). Two patients with stricture and dilation up to the intrahepatic bile ducts became steroid-dependent and were treated with azathioprine.

Patients with type 1 AIP with biliary lesions involving upstream strictures or wall thickening, especially those with stricture and dilation extending into the intrahepatic bile ducts, are at high risk of relapse and may become steroid dependent.

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.

The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan.

We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis.

The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex.

Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.

The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years.

In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor.

Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005).

Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.

Pancreatitis, encompassing acute and chronic forms, and pancreatic cancer pose significant challenges to the exocrine tissue of the pancreas. Recurrence rates and complications following acute pancreatitis episodes can lead to long-term risks, including diabetes mellitus. Chronic pancreatitis can develop in approximately 15% of cases, regardless of the initial episode's severity. Alcohol-induced pancreatitis, idiopathic causes, cigarette smoking, and hereditary pancreatitis contribute to the progression to chronic pancreatitis. Chronic pancreatitis is associated with an increased risk of pancreatic cancer, with older age at onset and smoking identified as risk factors. This scoping review aims to synthesise recent publications (2017-2022) on the diagnostic differentiation between pancreatitis and pancreatic cancer while identifying knowledge gaps in the field. The review focuses on biomarkers and imaging techniques in individuals with pancreatitis and pancreatic cancer. Promising biomarkers such as faecal elastase-1 and specific chemokines offer non-invasive ways to assess pancreatic insufficiency and detect early biomarkers for chronic pancreatitis. Imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), and positron emission tomography (PET), aid in differentiating between chronic pancreatitis and pancreatic cancer. However, accurately distinguishing between the two conditions remains a challenge, particularly when a mass is present in the head of the pancreas. Several knowledge gaps persist despite advancements in understanding the association between pancreatitis and pancreatic cancer, including the correlation between histopathological grading systems, non-invasive imaging techniques, and biomarkers in chronic pancreatitis to determine the risk of progression to pancreatic cancer, as well as differentiating between the two conditions. Further research is necessary to enhance our understanding of these aspects, which can ultimately improve the diagnosis and management of pancreatitis and pancreatic cancer.

IgG4-related digestive diseases encompass a group of chronic inflammatory disorders characterized by autoimmune reactions and fibrosis affecting multiple digestive organs. These diseases are identified by elevated serum levels of IgG4 and the presence of IgG4-positive plasma cell infiltration in the affected sites, along with storiform fibrosis, obliterative phlebitis, and eosinophilic infiltration. Although extensive research has been conducted, a comprehensive understanding of these conditions remains elusive. Current clinical diagnosis often relies on the application of integrated diagnostic criteria for IgG4-related diseases, combined with specific organ involvement criteria. Distinguishing them from malignancies poses considerable challenges. Moreover, further investigations are required to elucidate the underlying pathogenic mechanisms and explore potential therapeutic interventions. This review provides a systematic classification of IgG4-related digestive diseases while discussing their diagnostic strategies, clinical presentations, and treatment modalities. The comprehensive insights shared herein aim to guide clinicians in their practice and contribute to the advancement of knowledge in this field.

Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic fibroinflammatory condition potentially resulting in organ dysfunction. We aimed to evaluate imaging characteristics of disease relapse and complications in this cohort of patients.

This was a cohort study of IgG4-RD patients imaged between 2010 and 2020. Radiological manifestations of disease activity (remission/stability vs. relapse and complications) were correlated with clinical symptoms. Univariate analyses were performed with χ2, Fisher exact, and Mann-Whitney U tests. Times to relapse and organ atrophy were studied with Kaplan-Meier analyses.

A total of 69 patients had imaging surveillance over a median duration of 47 months. Radiological relapse occurred in 50.7% (35/69) with median time to relapse at 74 months (95% confidence interval, 45-122 months); 42.8% (15/35) of this cohort had different-site relapse with the following recognized primary-secondary patterns: pancreas-hepatobiliary (p = 0.005), hepatobiliary-pancreas (p = 0.013), and periaortitis-mesenteric (p = 0.006). Clinical symptoms were significantly associated with imaging characteristics (p < 0.001). Abdominal complications were detected in 52.2% (36/69) of patients, mostly solid organ atrophy (97.2% [35/36]). New-onset diabetes was more likely in pancreatic IgG4-RD (n = 51) when accompanied by gland atrophy (4/21 vs. 0/30 nonatrophy, p = 0.024).

Radiological relapse of IgG4-RD is common over prolonged imaging surveillance and is significantly associated with symptomatic relapse. A multisystem review to detect new/different sites of disease and abdominal complications may help predict future organ dysfunction.

There is conflicting evidence regarding autoimmune pancreatitis (AIP) association with pancreatic and non-pancreatic cancers. Literature lacks data on overall prevalence of malignancies in autoimmune pancreatitis.

Given the lack of definite evidence, we aimed to pool and summarize data from available literature regarding prevalence of different malignancies in AIP.

We conducted a systematic search of MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science through February 16, 2021, to include observational studies assessing the incidence of cancer in AIP. We used the DerSimonian-Laird method with random effects for meta-analysis. Pooled prevalence, 95% confidence interval (CI), and I² statistic are reported.

A total of 17 studies with 2746 patients were included assessing the prevalence of cancer in AIP. The overall prevalence of cancer in AIP was 9.6% [95% confidence interval (CI), 5.7-13.5%]. The cancers with the highest prevalence in AIP population were gastric and colorectal cancer, with prevalence of 1.3% (95% CI, 0.5-2.1%) and 1.2% (95% CI, 0.6-1.8%), respectively.

We demonstrate the prevalence of different cancers in AIP. Inflammatory surge in AIP and subsequent carcinogenesis is one explanation for this association. Moreover, AIP can be a paraneoplastic syndrome manifestation of malignancies.

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.

Inflammatory bowel disease (IBD) can involve multiple organ systems, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases is more frequent in patients with Crohn's disease and ulcerative colitis than in the general population. Pancreatic manifestations in IBD include a heterogeneous group of disorders and abnormalities ranging from mild, self-limited disorders to severe diseases. Asymptomatic elevation of amylase and/or lipase is common. The risk of acute pancreatitis in patients with IBD is increased due to the higher incidence of cholelithiasis and drug-induced pancreatitis in this population. Patients with IBD commonly have altered pancreatic histology and chronic pancreatic exocrine dysfunction. Diagnosing acute pancreatitis in patients with IBD is challenging. In this review, we discuss the manifestations and possible causes of pancreatic abnormalities in patients with IBD.

Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer, whereas such an association with autoimmune pancreatitis (AIP) is widely debated. Due to the rarity of the latter disorder, there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer, which do not seem to support it. However, these studies are affected by several limitations and, therefore, a link between AIP (and, specifically, type 1 AIP) and pancreatic cancer cannot be ruled out definitively on this basis. Moreover, several immunopathological aspects of type 1 AIP and, in general, immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression. In detail, Th2 immunological dominance, type 2 macrophage polarization and basophil infiltration observed in type 1 AIP, may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis, in addition to the immunosuppressive therapies that can be used in these patients.

We aimed to examine therapeutic efficacy and prognosis prediction of autoimmune pancreatitis (AIP) using shear wave elastography (SWE) and shear wave dispersion (SWD) in transabdominal ultrasound (US).

The subjects were 23 patients with diffuse type 1 AIP who underwent SWE and SWD, and 34 controls with a normal pancreas. Elasticity and dispersion were defined as the pancreatic elastic modulus (PEM) and dispersion slope, respectively. PEM and dispersion slope were compared between AIP and control cases, and the short-term therapeutic effect and long-term prognosis were examined.

PEM (30.9 vs. 6.6 kPa, P < 0.001) and dispersion slope (15.3 vs. 13.0 (m/sec)/kHz, P = 0.011) were significantly higher in AIP cases than in controls. Among the 17 AIP patients followed-up in two weeks after treatment, these parameters were 12.7 kPa and 10.5 (m/sec)/kHz with median decrease rate of 37.2% and 32.8%, respectively, which were significantly higher than the change in the size of pancreatic parenchyma (14.4%, P = 0.026). Fourteen of these subjects were followed up for >12 months, during which 2 had relapse; diabetes improved in 5 and worsened in 2; in 60% of cases, the pancreatic parenchyma was atrophied. The % change in PEM after two weeks was tended to be higher in non-atrophy cases.

SWE and SWD measurement in US may be useful for quantitative assessment of AIP and evaluation of short-term treatment efficacy.

The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy.

We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6-12 months vs. 12-36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated.

Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9-54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8-49.8%) for 6-12 months, 34.1% (95% CI, 28.6-39.7%) for 12-36 months, and 27.0% (95% CI, 23.4-30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5-34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8-52.4%). Adverse events were comparable between groups.

The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.