Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy.

BACKGROUND: A high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. METHODS: Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as 'improvement' and 'non-improvement' (including 'no change' and 'exacerbation'). RESULTS: Among 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. CONCLUSIONS: Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Triple A syndrome-related achalasia treated by per-oral endoscopic myotomy: Three case reports.

BACKGROUND: Triple A syndrome is a rare autosomal recessive disease characterized by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima and achalasia. In the last 5 years, per-oral endoscopic myotomy (POEM) has proved highly successful in treating primary achalasia over the long term, but its long-term performance has not been certified by achalasia related to Triple A syndrome. CASE SUMMARY: Triple A syndrome is a rare autosomal recessive disease characterized by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima and achalasia. In the past 5 years, POEM has proved highly successful in treating primary achalasia over the long term, but its long-term performance has not been certified by achalasia related to Triple A syndrome. Eckardt scores and esophageal manometry improved significantly during the 2 years following POEM; however, grade-A reflux esophagitis recurred in 66.7% of patients in 12 mo post-procedure. CONCLUSION: Based on these case studies, POEM is efficacious and safe for a treatment of achalasia associated with Triple A syndrome.

The genomic landscape of Cronkhite-Canada syndrome: Possible clues for pathogenesis.

OBJECTIVES: Cronkhite-Canada syndrome (CCS) is a rare hamartomatous polyposis syndrome with a proposed association with chronic autoimmune inflammation. To date, genetic background of patients with CCS remains less investigated. In this study we aimed to explore the genomic landscape of CCS. METHODS: Whole exome sequencing was performed on peripheral blood samples extracted from 18 patients with CCS. Potential function-impacting germline variants were filtered by R software. Through systematic data analysis, a number of genetic variants were identified. Enrichment analysis was performed using the R package ClusterProfiler. RESULTS: Overall, 3960 low-frequency (<0.05 or not reported in the Exome Aggregation Consortium East Asian, 1000 Genomes, or ESP6500 database) potentially function-impacting germline variants were identified, with 18 genes (FDFT1, LOC400863, MUC3A, MUC4, ZNF806, GXYLT1, MUC6, PABPC3, PSPH, ZFPM1, CIC, LOC283710, ARSD, GOLGA6L2, LOC388282, SLC25A5, TMEM247, WDR89) involved over half the patients. Functional enrichment of these genes revealed several biological processes in relation to innate immune responses and glycosylation. Only one likely pathogenic germline variant of an hamartomatous polyposis syndrome-associated gene, PTCH1, was detected in one patient. CONCLUSIONS: CCS has genomic alteration patterns completely distinct from those of traditional hamartomatous polyposis syndrome. The germline mutation landscape indicates potential roles of innate immune responses and glycosylation in the pathogenesis of CCS.

Endoscopic ultrasound features of autoimmune pancreatitis: The typical findings and chronic pancreatitis changes.

BACKGROUND: Few studies have fully described endoscopic ultrasound (EUS) features of newly diagnosed autoimmune pancreatitis (AIP) involving both typical findings and chronic pancreatitis (CP) features. The typical EUS findings are prevalent in the diffuse type AIP but may not be as common for the focal type, and the differences between the diffuse and focal AIP need to be specified. AIM: To demonstrate the EUS features of newly diagnosed AIP and the difference between diffuse and focal AIP. METHODS: This retrospective single center study included 285 patients of newly diagnosed type 1 AIP following the international consensus diagnostic criteria, with the EUS procedures accomplished before corticosteroid initiation. We explored the EUS features and compared the typical AIP and CP features between the diffuse and focal AIP cases. The Rosemont criteria were employed for CP features definition and CP change level comparison. RESULTS: For the typical AIP features, there were significantly more patients in the diffuse group with bile duct wall thickening (158 of 214 cases, 73.4% vs 37 of 71 cases, 52.1%, P = 0.001) and peripancreatic hypoechoic margin (76 of 214 cases, 35.5% vs 5 of 71 cases, 7.0%, P < 0.001). For the CP features, there were significantly more patients in the focal group with main pancreatic duct dilation (30 of 214 cases, 14.0% vs 18 of 71 cases, 25.3%, P = 0.03). The cholangitis-like changes were more prevalent in the focal cases with pancreatic head involvement. The CP change level was relatively limited for newly diagnosed AIP cases in both groups. CONCLUSION: This study demonstrated the difference in the typical AIP and CP features between diffuse and focal AIP and indicated the limited CP change level in newly diagnosed AIP.

Factors contributing to diagnostic delay of Caroli syndrome: a single-center, retrospective study.

BACKGROUND: Caroli syndrome (CS) is a rare congenital disorder without pathognomonic clinical symptoms or laboratory findings; therefore, the diagnosis is often delayed. The objective of this study was to investigate the diagnostic delay and associated risk factors in CS patients. METHODS: This was a retrospective analysis of 16 CS patients admitted to a single tertiary medical center on mainland China. The diagnostic timelines of CS patients were reviewed to demonstrate the initial findings of CS at diagnosis, the risk factors associated with diagnostic delay, and potential clues leading to early diagnosis. RESULTS: The median diagnostic delay was 1.75 years (range: 1 month to 29 years, interquartile range: 6.2 years) in 16 enrolled CS patients. Sex, age, and initial symptoms were not associated with diagnostic delay. 87.5% of CS patients were diagnosed by imaging, and the accuracies of ultrasonography, computed tomography (CT), and magnetic resonance cholangiopancreatography were 25, 69.2, and 83.3%, respectively. The median diagnostic delays for patients with or without CT performed at the first hospital visited according to physician and radiologist suspicion of the diagnosis were 7.4 months and 6 years, respectively (p = 0.021). Hepatic cysts with splenomegaly were detected by ultrasound in over half of CS patients. CONCLUSIONS: The majority of CS patients were not diagnosed until complications of portal hypertension had already developed. Recognition and early suspicion of the disease were important factors influencing diagnostic delay of CS. Hepatic cysts plus splenomegaly detected by US might raise the clinical suspicion to include CS in the differential diagnosis.

Short- and Long-term Therapeutic Efficacies of Intravenous Transplantation of Bone Marrow Stem Cells on Cardiac Function in Rats with Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials.

Objective To investigate the short- and long-term therapeutic efficacies of intravenous trans- plantation of bone marrow stem cells (MSCs) in rats with experimental myocardial infarction by meta- analysis. Methods Randomized controlled trials were systematically searched from PubMed, Science Citation Index (SCI), Chinese journal full-text database (CJFD) up to December 2014. While the experimental groups (MSCs groups) were injected MSCs intravenously, the control groups were injected Delubecco's minimum essential medium (DMEM) or phosphate buffered saline (PBS). Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for outcome parameters including ejection fraction (EF) and fractional shortening (FS), which were measured by echocardiogram after intravenous injection and analyzed by RevMan 5.2 and STATA 12.0. Results Data from 9 studies (190 rats) were included in the meta-analysis. As compared to the control groups, the cardiac function of the experimental groups were not improved at day 7 (EF: WMD=0.08, 95%CI -1.32 to 1.16, P>0.01; FS: WMD=-0.12, 95%CI -0.90 to 0.65, P>0.01) until at day 14 after MSCs' transplantation (EF: WMD=10.79, 95%CI 9.16 to 12.42, P<0.01; FS: WMD=11.34, 95%CI 10.44 to 12.23, P<0.01), and it lasted 4 weeks or more after transplantation of MSCs (EF: WMD=13.94, 95%CI 12.24 to 15.64, P<0.01; FS: WMD=9.64, 95%CI 7.98 to 11.31, P<0.01). Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis.

Human cytomegalovirus (CMV) is a herpesvirus, which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However, CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis, portal hypertension-related ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation, and suggests that testing for CMV should be carried out, even in patients with normal immune status, presenting with severe liver damage or cholestasis.

[The clinical features of 16 cases of primary adenocarcinoma of the third portion of duodenum].

OBJECTIVE: To summarize the clinical features of the third portion of duodenum (PATD) for improving the understanding of PATD. METHODS: Sixteen cases with PATD in Peking Union Medical College Hospital(PUMCH) were retrospectively analyzed. RESULTS: The most common symptoms of PATD were upper abdominal pain (12/16) , vomiting (9/16) and distention (7/16).On average, the disease had progressed 5.5 months (including 2.5 months of diagnostic workup) before the diagnosis was established. Patients with pathologically poorly differentiated PATD had shorter course of disease (6.5 vs 16.6 months, P = 0.56) and lower chance of cancer-directed surgery (1/8 vs 6/8, P = 0.04) than those with well differentiated PATD. The diagnostic rate was 11/14 by CT scan while only 2/7 by upper gastrointestinal radiography. Three cases were misdiagnosed as superior mesenteric artery syndrome by barium examination. CONCLUSIONS: PATD should be considered in patients presenting upper abdominal symptoms with negative gastro endoscopy and barium examination.Overall, CT scan plays a pivotal role in diagnosing PATD. Making a correct diagnosis timely can improve the outcome of PATD patients, particularly, in those with poorly differentiated pathology.

[Progress in the study on the molecules in CD28 family].

CD28 family consists of CD28, ICOS, CTLA-4 and PD-1 molecules. The former two are activation receptors and the later two are inhibition receptors. They produce co-stimulatory signals combining with the relevant molecules in B7 family, which plays important role in T cell activation and homeostasis among T subsets. Although the mechanism of signaling by CD28 and CTLA-4 has been well studied, many questions still remain to be answered. Further investigations are required for substantiating the dual-signaling model.