Retroperitoneal fibrosis associated with immunoglobulin G4-related disease

Retroperitoneal fibrosis is a rare disease characterized by the development of inflammation and fibrosis in the soft tissues of the retroperitoneum and other abdominal organs.Retroperitoneal fibrosis can be of 2 types:idiopathic and secondary.The recently advocated concept and diagnostic criteria of immunoglobulin G4(IgG4)-related disease,derived from research on autoimmune pancreatitis(AIP),has led to widespread recognition of retroperitoneal fibrosis as a condition caused by IgG4-related disease.We now know that previously diagnosed idiopathic retroperitoneal fibrosis includes IgG4-related disease;however,the actual prevalence is unclear.Conversely,some reports on AIP suggest that retroperitoneal fibrosis is concurrently found in about 10% of IgG4-related disease.Because retroperitoneal fibrosis has no specific symptoms,diagnosis is primarily based on diagnostic imaging(computed tomography and magnetic resonance imaging),which is also useful in evaluating the effect of therapy.Idiopathic retroperitoneal fibrosis can occur at different times with other lesions of IgG4-related disease including AIP.Thus,the IgG4 assay is recommended to diagnose idiopathic retroperitoneal fibrosis.High serum IgG4 levels should be treated and monitored as a symptom of IgG4-related disease.The first line of treatment for retroperitoneal fibrosis is steroid therapy regardless of its cause.For patients with concurrent AIP,i.e.,IgG4-related retroperitoneal fibrosis,the starting dose of steroid is usually 30-40 mg/d.The response to steroid therapy is generally favorable.In most cases,the pancreatic lesion and retroperitoneal fibrosis improve after the initial treatment.However,the epidemiology,treatment for recurring retroperitoneal fibrosis,and long-term prognosis are still largely unknown.Further analysis of such cases and research are necessary.

Endoscopic approach through the minor papilla for the management of pancreatic diseases

AIM:To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS:This study included 44 endoscopic retrograde cholangiopancreatography(ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012.We retrospectively evaluated the clinical profiles of the patients,the endoscopic interventions,short-term outcomes,and complications.RESULTS:Of 44 ERCPs,26 were diagnostic ERCP,and 18 were therapeutic ERCP.The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct.The overall success rate of minor papilla cannulation was 80%(35/44),which was significantly improved by wire-guided cannulation(P = 0.04).Endoscopic minor papillotomy(EMP) was performed in 17 of 34 patients(50%) using a needle-knife(13/17) or a pull-type papillotome(4/17).EMP with pancreatic stent placement,which was the main therapeutic option for patients with chronic pancreatitis,recurrent acute pancreatitis,and pancreatic pseudocyst,resulted in short-term clinical improvement in 83% of patients.Mild post-ERCP pancreatitis occurred as an early complication in 2 cases(4.5%).CONCLUSION:The endoscopic minor papilla approach is technically feasible,safe,and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.

Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.

Vasoactive Intestinal Peptide (VIP) and VIP Receptors-Elucidation of Structure and Function for Therapeutic Applications

Vasoactive intestinal peptide (VIP) is a 28-amino acid polypeptide first isolated from swine duodenum. VIP is a neurotransmitter that is extensively distributed in tissues. According to published reports, VPAC1 and VPAC2 act as VIP receptors and are widely present in the central nervous system and peripheral tissues. VIP exerts diverse actions on the cardiovascular system, pancreas, digestive tract, respiratory system, and urological system. Recent reports indicated that VIP has immunological and neuroprotective effects and also affects cell growth. While primary investigations for developing therapeutic applications for various pathological conditions and diseases are underway, the structure and function of VIP should be analyzed in more detail.

Single-cell analysis for identification of T-cell clonotypes associated with IgG4 production of autoimmune pancreatitis

Introduction Autoimmune pancreatitis(AIP)is one of the recently established immunoglobulin G4-related diseases(IgG4-RD)[1].The detailed pathogenic mechanisms have been an intensive research area for prophylactic and therapeutic purposes because aberrant immune activation and tissue fibrosis in AIP are the major factors that worsen the disease outcomes in these patients.