Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study.

OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

The levels of IL-1ß and soluble IL-1 receptors in patients with IgG4-related periaortitis/periarteritis.

PURPOSE: IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory and an immune-mediated disease characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system, and its pathogenesis and characteristics remain unclear. The inflammatory cytokine IL-1ß is involved in a variety of cellular activities including inflammation, fibrosis, and angiogenesis. The present study compared the levels of the inflammatory cytokine IL-1ß and two soluble IL-1 receptors, IL-1R1 and IL-1R2, between IgG4-RD patients with and without IgG4-related periaortitis/periarteritis. METHODS: The patients with IgG4-related periaortitis/periarteritis (n â€‹= â€‹38), those without (n â€‹= â€‹66) and healthy (n â€‹= â€‹33) were recruited to measure cytokines of IL-1ß and soluble receptors (sIL-1R1 and sIL-1R2) in sera by ELISA assay. RESULTS: Serum IgG4 was significantly higher in patients with periaortitis/periarteritis compared to non-periaortitis/periarteritis (p â€‹= â€‹0.0074), while serum IL-1ß was significantly lower in patients with periaortitis/periarteritis (p â€‹= â€‹0.00037). The three groups did not show significant difference in sIL1-R1, while sIL-1R2 in the periaortitis/periarteritis and healthy group was higher than in the group without periaortitis/periarteritis (p â€‹= â€‹0.00001). CONCLUSIONS: The characteristic changes in IL-1ß, sIL-1R1, and sIL-1R2 levels in IgG4-RD patients with and without IgG4-related periaortitis/periarteritis may indicate an active phase of the inflammatory process in these diseases.

Steroid therapy still plays a crucial role and could serve as a bridge to the next promising treatments in patients with IgG4-related sclerosing cholangitis: Results of a Japanese Nationwide Study.

OBJECTIVE: The acceptable duration of steroid therapy for patients with IgG4-sclerosing cholangitis (SC) has been under debate. Our aim is to clarify the feasible duration of steroid treatment. DESIGN: We retrospectively reviewed the data of patients with IgG4-SC and analyzed the following: biliary status during the steroid therapy, incidence of remission, relapse, relapse-free survival rate, and steroid-related complications (SRCs). RESULTS: Remission was achieved 99.5% (763/767) of patients who received steroid therapy, while remission rate dropped to 63.6% (78/129) of patients who didn't receive it. Relapse was noted in 19.7% (151/763) of the patients who received steroid. Besides, relapse rate went up 38.4% (30/78) of the counterpart. Normalization of the serum total bilirubin and serum alkaline phosphatase (ALP) levels were achieved at two weeks regardless of biliary drainage. Multivariate analysis identified younger onset, MST less than three years, immunosuppressant, and steroid cessation as independent risk factors for relapse. Steroid-free was achieved in the patients underwent MST only 3.4% over 54 months. SRCs were recorded in a total of 99 patients (12.9%) despite sufficient preemptive medications. Multivariate analysis identified history of malignancy and immunosuppressant as independent risk factors for SRCs. CONCLUSION: Steroid therapy should be continued for no less than three years to reduce the risk of relapse, with use of preemptive measures taken around five years. The biliary drainage might not be mandatory. Steroid as 1st line therapy could serve as a bridge to further promising treatments.

IL1R1 gene variants associate with disease susceptibility to IgG4-related periaortitis/periarteritis in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system. Since the genetic factors related to disease onset are unclear, we examined the genetic associations with IgG4-related periaortitis/periarteritis susceptibility. METHODS: A small scale of genome-wide association analysis identified that interleukin 1 receptor type 1 (IL1R1) gene variants were correlated with the development of IgG4-related periaortitis/periarteritis in 75 patients with IgG4-RD. Accordingly, 8 single nucleotide polymorphisms (SNPs) in the IL1R1 gene were selected and genotyped in 124 patients with IgG4-RD (43 with periaortitis/periarteritis and 81 without periaortitis/periarteritis) and 344 healthy subjects. RESULTS: The minor allele frequencies of 6 SNPs (rs2287049, rs3917273, rs2160227, rs951192, rs3917318, rs7582198) were significantly increased in IgG4-related periaortitis/periarteritis patients compared with those without periaortitis/periarteritis (corrected P < 0.05). In addition, the frequency of the AGAAA haplotype, comprised of 5 SNPs (rs3917273, rs2160227, rs951192, rs3917318, rs7582198), was significantly higher in patients with periaortitis/periarteritis (OR = 2.41, 95% CI:1.42-4.10). CONCLUSION: Our findings indicated that IL1R1 genetic polymorphisms contributed to IgG4-related periaortitis/periarteritis and the possibility of certain genetic factors influencing the risk of specific IgG4-RD manifestations.

Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020.

In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.

Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort.

BACKGROUND: The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. AIMS: To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. METHODS: We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. RESULTS: AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. CONCLUSIONS: The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020: (Revision of the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2012).

Several years have passed since the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2012 were published. New findings and knowledge have accumulated since then. The Research Committees for IgG4-related Diseases and for Intractable Diseases of the Liver and Biliary Tract, in association with the Ministry of Health, Labor, and Welfare of Japan and the Japan Biliary Association, have established a working group consisting of researchers specializing in IgG4-SC and have drawn up new clinical diagnostic criteria for IgG4-SC 2020. The diagnosis of IgG4-SC is based on a combination of the following six criteria: (a) narrowing of the intra- or extrahepatic bile duct; (b) thickening of the bile duct wall; (c) serological findings; (d) pathological findings; (e) other organ involvement; and (f) effectiveness of steroid therapy. These new diagnostic criteria for IgG4-SC are useful in practice for general physicians and other non-specialists.

The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.

Hypocomplementemia is related to elevated serum levels of IgG subclasses other than IgG4 in IgG4-related kidney disease.

OBJECTIVES: This study investigated the clinical features of IgG4-RKD patients with hypocomplementemia compared with those without it, so as to clarify the factors related to hypocomplementemia. METHODS: In this single-center retrospective study, we analyzed the clinical features of 25 patients with IgG4-RKD according to the presence/absence of hypocomplementemia. Additionally, we validated the results of a single-center study in a separate large multicenter cohort of 328 patients with IgG4-RD, and searched for factors related to hypocomplementemia. RESULTS: Serum IgG levels (p < .001), non-IgG4 IgG levels, calculated as the total IgG minus IgG4 (p < .001), serum IgG1 levels (p = .017), and the number of involved organs (p = .018) were significantly higher in the hypocomplementemia group. At relapse of renal lesions in four patients, all had serum IgG4 re-elevation, with the three with hypocomplementemia presenting worsening of hypocomplementemia and re-elevation of non-IgG4 IgG levels. In a validation cohort of 328 patients with IgG4-RD, multivariate logistic regression analysis indicated elevation of non-IgG4 IgG levels to be an independent factor related to hypocomplementemia in the patients with IgG4-RKD. CONCLUSION: The present study suggests that hypocomplementemia is associated with elevation of IgG subclasses other than IgG4 including IgG1 in IgG4-RKD.

Guidance for diagnosing autoimmune pancreatitis with biopsy tissues.

The biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.

Corticosteroids prevent the progression of autoimmune pancreatitis to chronic pancreatitis.

BACKGROUND/OBJECTIVES: Patients with autoimmune pancreatitis (AIP) sometimes progress to chronic pancreatitis (CP). We evaluated the ability of corticosteroids to prevent the progression to CP. METHODS: We defined patients with definitive findings of CP (stones in the main pancreatic duct [MPD] or multiple pancreatic calcifications) as having severe calcification (SC). A total of 145 AIP patients were enrolled. We measured the duration between AIP diagnosis and SC development and retrospectively compared the time to SC development between patients with and without steroids. Multivariate analysis for factors associated with SC were performed. RESULTS: Nineteen (13%) patients progressed to SC. Since 95 patients had pancreatic head swelling and SC was found in these patients only, our analysis focused mainly on these at-risk populations. In Kaplan-Meier analysis limited to patients with pancreatic head swelling, the incidence of SC was significantly lower in patients with steroids than in those without (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.07-0.52; p < 0.001). Multivariate testing of patients with pancreatic head swelling confirmed that steroid therapy was significantly associated with a lower incidence of SC (HR 0.11, 95% CI 0.03-0.34; p < 0.001), while MPD dilation at AIP diagnosis was related to a higher incidence of SC (HR 4.02, 95% CI 1.43-11.7; p = 0.009). CONCLUSIONS: Corticosteroids appeared to prevent progression to CP in AIP patients, especially in those with pancreatic head swelling. Patients with both pancreatic head swelling and MPD dilation at diagnosis have a higher incidence of progression to CP. Steroid therapy is suggested for these high-risk cases.

Efficacy and limitations of the histological diagnosis of type 1 autoimmune pancreatitis with endoscopic ultrasound-guided fine needle biopsy with large tissue amounts.

OBJECTIVES: We examined the efficacy and limitations of acquiring large specimens by endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for diagnosing type 1 autoimmune pancreatitis (AIP). METHODS: Patients from 12 institutions with non-neoplastic diseases or pancreatic ductal adenocarcinoma (PDAC) with large EUS-FNB specimens were investigated. Slides stained with hematoxylin-eosin, elastic, IgG4, and IgG stains were evaluated. The IgG4- and IgG-positive cell numbers were counted in three foci. The diagnoses were based on the Japan Pancreas Society 2011 (JPS 2011) criteria and the International Consensus Diagnostic Criteria (ICDC). RESULTS: We analyzed 85 non-neoplastic (definite type 1 AIP in 73/85 based on the ICDC) cases and 64 PDAC cases. IgG4-positive cells were numerous (>10 in 85.9%), and the IgG4/IgG ratios were high (>40% in 81.2%). Plasma cell crushing by an artifact caused unsuccessful immunostaining, notably in smaller samples. Tissue lengths were an important factor for the presence of storiform fibrosis and obliterative phlebitis, but storiform fibrosis was equivocal even in large tissues. A definite or possible histological diagnosis was achieved in 45.9% (39/85) and 41.2% (35/85), respectively, and contributed to the definite final diagnosis of type 1 AIP in 33.3% (ICDC) and 55.6% (JPS 2011) in cases with segmental/focal lesions. In the PDAC group, >10 IgG4-positive cells was rare (2/58), but elastic stains revealed fibrous venous occlusions in 10.3% (6/58). CONCLUSIONS: EUS-FNB with large tissue amounts was useful for diagnosing type 1 AIP, notably by facilitating successful IgG4 immunostaining, but definite diagnosis may not be achieved even in cases with large specimens.

Epidemiological features of immunoglobulin G4-related sclerosing cholangitis in Japan.

BACKGROUND/PURPOSE: Epidemiological data on immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are scarce. METHOD: We randomly selected healthcare facilities from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with IgG4-SC in 2018. Among responding facilities, we further inquired about the clinical characteristics of the patients with IgG4-SC. RESULTS: We selected 1180 departments from health centers across Japan. Of them, 532 (45.1%) responded to the questionnaires. The number of reported patients with IgG4-SC was 1045, and the estimated point prevalence was 2.18 (95% confidence interval, 2.13-2.23) per 100 000 population. In addition, we enrolled 1096 patients with IgG4-SC, combining data from previously and newly registered patients. Male patients comprised 79.5% of the population and patients aged 60-80 years had the highest risk for developing the disease. The follow-up period was 5.1 ± 4.0 years and the 5- and 10-year overall survival rates were 95.3% and 89.0%, respectively. CONCLUSIONS: The point prevalence of IgG4-SC was 2.18 per 100 000 population. The epidemiological features were similar to those observed in previous studies.

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis.

BACKGROUND.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS.: We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS.: Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION.: AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

Diagnostic imaging guide for autoimmune pancreatitis.

The International Consensus Diagnosis Criteria for autoimmune pancreatitis (AIP) has been published internationally for the diagnosis of AIP. However, since the revisions in 2006 and 2011, the Clinical Diagnostic Criteria for Autoimmune Pancreatitis 2018 have been published. The criteria were revised based the Clinical Diagnostic Criteria 2011, and included descriptions of characteristic imaging findings such as (1) pancreatic enlargement and (2) distinctive narrowing of the main pancreatic duct. In addition, pancreatic duct images obtained by magnetic resonance cholangiopancreatography as well as conventional endoscopic retrograde pancreatography were newly adopted. The guideline explains some characteristic imaging findings, but does not contain descriptions of the imaging methods, such as detailed imaging parameters and optimal timings of dynamic contrast-enhanced computed tomography/magnetic resonance imaging. It is a matter of concern that imaging methods can vary from hospital to hospital. Although other characteristic findings have been reported, these findings were not described in the guideline. The present paper describes the imaging methods for obtaining optimal images and the characteristic imaging findings with the aim of standardizing image quality and improving diagnostic accuracy when radiologists diagnose AIP in actual clinical settings.

A comparison of the features of fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) between IgG4-related disease with bilateral hilar lymphadenopathy and sarcoidosis.

We aimed to show the differentiation of the degree and distribution on Fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) between patients with immunoglobulin G4-related disease (IgG4-RD) and sarcoidosis, though both diseases frequently show bilateral hilar lymphadenopathy (BHL). The clinical records were retrospectively reviewed in 25 patients with IgG4-RD with BHL and 15 patients with sarcoidosis (stage I-II) diagnosed at Shinshu University Hospital. All patients underwent FDG-PET at Aizawa Hospital from January 2004 to December 2015. The FDG accumulation pattern and maximum standardized uptake value (SUVmax) of the hilar lymph nodes were compared between the two groups. The IgG4-RD group (21 men; median age 69 years) showed a significant male predominance and older age compared with the sarcoidosis group (3 men, median age 55.4 years). The IgG4-RD group showed a significantly higher incidence of FDG accumulation in the lachrymal gland, submandibular gland, pancreas, prostate and periurethral and periarterial regions compared with the sarcoidosis group. In contrast, the sarcoidosis group showed a significantly higher incidence of FDG accumulation in the supraclavicular and abdominal lymph nodes, muscle and soft tissues compared with the IgG4-RD group. Furthermore, the SUVmax of the hilar lymph nodes was significantly higher in the sarcoidosis group (median 7.20) than in the IgG4-RD group (median 4.20, p=0.002). In conclusion, significant differences were observed in the FDG accumulation patterns and SUVmax values of the hilar lymph nodes between IgG4-RD with BHL and sarcoidosis, although both diseases develop through the lymphatic routes of the lungs and are frequently associated with BHL.

Validity and safety of endoscopic biliary stenting for biliary stricture associated with IgG4-related pancreatobiliary disease during steroid therapy.

Background Patients with IgG4-related sclerosing cholangitis and autoimmune pancreatitis frequently develop obstructive jaundice, which requires endoscopic biliary stenting (EBS) during steroid therapy to prevent bile duct infection from cholestasis and adverse steroid effects. However, it is controversial whether EBS during steroid therapy is advisable, because the procedure itself carries a risk of cholangitis and procedure-related adverse events. This study aimed to clarify the validity and safety of EBS for patients with biliary stricture associated with IgG4-related pancreatobiliary disease (IgG4-PBD) during steroid therapy. Methods We enrolled 59 patients who presented with biliary stricture exhibiting jaundice or liver dysfunction and who were treated with EBS. The incidences of recurrent biliary obstruction and acute cholangitis were compared for EBS cases with and without steroid administration. Results EBS was present in 55 periods with steroid administration and 110 periods without. The incidence of recurrent biliary obstruction was significantly lower in cases with steroids than in those without (1-month no obstruction rate: 100 % vs. 82 %; log-rank test P  = 0.0015). The incidence of acute cholangitis related to stenting was significantly lower in cases with steroids than in those without (1-month no acute cholangitis rate: 100 % vs. 90 %; log-rank test P  = 0.0278). Biliary stents could be removed without acute cholangitis, liver dysfunction, or stent replacement in 96 % of patients who underwent endoscopic retrograde cholangiopancreatography 1 month after commencing steroid administration. Conclusions EBS during steroid administration was both valid and safe in patients with biliary stricture associated with IgG4-PBD. Stents could be safely removed 1 month after steroid initiation.

Effectiveness of steroid therapy for pancreatic cysts complicating autoimmune pancreatitis and management strategy for cyst-related complications.

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications. Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications. Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10 mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size. Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.