The molecular basis of type 1 autoimmune pancreatitis (AIP) remains unclear. Recent attention on the role of extracellular vesicles microRNA (EV miRNA) in immune homeostasis has prompted us to perform an extensive miRNA screening of serum-derived EV in AIP. EV miRNA expression was analyzed using microarrays in AIP, chronic pancreatitis (CP), and healthy adult (HC) samples (n = 10 from each group). Differences in signals, > 3 or <1/3 times, represented significant differences in expression. Another cohort of AIP (n = 14), CP (n = 10), and HC (n = 10) samples of EV miRNA was analyzed using reverse-transcription polymerase chain reaction (RT-PCR). miRNA expression in pancreatic tissues was evaluated using in situ hybridization (ISH) in three additional subjects from each group. Signals of eight miRNAs (miR-659-3p, -27a-3p, -99a-5p, -21-5p, -205-5p, -100-5p, -29c-3p, and -125b-1-3p) were significantly higher, while those of two miRNAs (miR-4252 and -5004-5p) were significantly lower in AIP than in HC. EV miR-21-5p was significantly up-regulated in AIP than in HC (P = 0.035) and CP (P = 0.048). The number of miR-21-5p positive inflammatory cells was significantly elevated in AIP than in CP (P = 0.014). Circulating EVs exhibited altered miRNA expression patterns with elevated miR-21-5p in AIP when compared with those in HC and CP. miR-21-5p was highly expressed in pancreatic inflammatory cells in AIP. Our data suggests that miR-21-5p may be involved in the regulation of effector pathways in the pathophysiology of AIP, thus differentiating AIP from CP.

Some patients with IgG4-related disease (IgG4-RD) exhibit elevated serum interleukin (IL)-6 with excessive inflammatory reactions or with repeating relapse. To date few reports pertaining to clinical implications of elevated serum IL-6 in IgG4-RD patients have been published. The aims of the current retrospective study were to investigate the clinical implications of elevated serum IL-6 in IgG4-RD patients, and to examine whether IL-6 can predict the activity and/or relapse of the disease. We examined the clinical picture at the onset of 43 patients who were diagnosed with IgG4-RD in our hospital and were able to measure serum IL-6 before steroid treatment. The median level of serum IL-6 was 2.2 pg/mL. There was a significant correlation between IL-6 and C-reactive protein (CRP) level (r = 0.397, p = 0.008), hemoglobin level (r = -0.390, p = 0.010) and albumin level (r = -0.556, p < 0.001). When 43 patients were divided into two groups by using a cut-off IL-6 of 4 pg/mL, the high IL-6 group showed higher age, lower albumin, higher CRP and higher aspartate aminotransferase (AST) (age p = 0.014, albumin p = 0.006, CRP p <0.001, AST p = 0.009). Hepatic swelling and splenomegaly were significantly more prevalent in the high IL-6 group than it was in the low IL-6 group (liver p < 0.001, spleen p = 0.020). Biliary tract involvement tended to admit more in the high IL-6 group (p = 0.060). Serum IL-6 level at the onset of IgG4-RD may be significantly correlated with clinical inflammatory parameters and it may also be associated with involvement of the bile duct, liver, and spleen.

Pancreatic metastases (PMs) account for 1% to 2% of pancreatic tumors, and their prognostic significance is poorly defined. We evaluated the incidence and clinical characteristics of primary tumors and defined prognostic factors. This retrospective study of 39 Japanese tertiary referral hospitals (January 2005 to August 2015) analyzed patient and tumor characteristics and survival time. Kaplan-Meier analysis and Cox proportional hazards models were applied to evaluate overall survival and prognostic factors, respectively. We enrolled 159 patients with a pathologic diagnosis of PM. The most common primary tumor was renal cell carcinoma (38.4%), followed by lung cancer (24.5%), colorectal cancer (11.3%), and sarcoma (6.3%). Eight patients were lost during follow-up, and 151 patients were included for statistical analysis. Median overall survival was 43.0 months, and the 5-year survival rate was 42.6%. Multivariate analysis identified 3 independent prognostic factors: extrapancreatic metastasis (hazard ratio, 2.13; 95% confidence interval, 1.11–4.07; P = 0.02), tumor-related symptoms at diagnosis (hazard ratio, 5.39; 95% confidence interval, 2.92–9.91; P < 0.001), and pathologic diagnosis of primary tumors (P < 0.001). Treatment strategies and prognoses for PMs completely differ according to the primary tumor type. A definitive pathologic diagnosis of PMs is essential for selecting the appropriate treatment.