Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes. We searched for their noninvasive biomarkers.Approach and Results: Global RNA sequencing of liver tissue from 98 patients with biopsy-proven NAFLD was performed. Unsupervised hierarchical clustering well distinguished NASH from nonalcoholic fatty liver (NAFL), and NASH patients exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified proteins upregulated in NASH and/or advanced fibrosis (stage F3-4), including matricellular glycoprotein thrombospondin-2 (TSP-2), encoded by the thrombospondin 2 (THBS2) gene. The intrahepatic THBS2 expression level showed the highest areas under the receiver operating characteristic curves (AUROCs) of 0.915 and 0.957 for diagnosing NASH and advanced fibrosis, respectively. THBS2 positively correlated with inflammation and ballooning according to NAFLD activity score, serum aspartate aminotransferase and hyaluronic acid (HA) levels, and NAFLD Fibrosis Score (NFS). THBS2 was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase-mediated cleavage of cytoskeletal proteins, and immune cell infiltration. Serum TSP-2 expression was measured in 213 patients with biopsy-proven NAFLD, was significantly higher in NASH than in NAFL, and increased parallel to fibrosis stage. The AUROCs for predicting NASH and advanced fibrosis were 0.776 and 0.856, respectively, which were comparable to Fibrosis-4 index, serum HA level, and NFS in advanced fibrosis diagnosis. Serum TSP-2 level and platelet count were independent predictors of NASH and advanced
Accepted ArticleThis article is protected by copyright. All rights reserved fibrosis. Serum TSP-2 levels could stratify NAFLD patients according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events.Conclusions: TSP-2 may be a useful biomarker for NASH and advanced fibrosis diagnosis in NAFLD patients.
Good's syndrome is an immunodeficiency disease involving thymoma accompanied by hypogammaglobulinemia. We encountered a case of Good's syndrome accompanied by agranulocytosis that followed a rapid clinical course. A 72-year-old man visited our hospital with a two-week history of a sore throat. Candida albicans was detected in the pharynx, and hypogammaglobulinemia was detected in addition to granulocytopenia. The patient subsequently developed septic shock and followed a rapid clinical course which ended in death. Good's syndrome with agranulocytosis was diagnosed at autopsy. Good's syndrome accompanied by agranulocytosis can follow a rapid clinical course and some cases remain asymptomatic until old age. Its prompt treatment is crucial.
Objectives
Perihilar cholangiocarcinoma (PCC) is a complex disorder involving the hepatic hilum. Multiple endoscopic retrograde cholangiopancreatography sessions are necessary for diagnosis and treatment with underlying cholangitis risk. Our aim is to clarify the initial‐drainage‐related prognostic factors of PCC.
Methods
This study was a single‐center retrospective study. A total of 104 consecutive patients diagnosed with PCC from January 2010 to February 2020 were enrolled. We defined the diagnostic period as the time between the first biliary drainage attempt and the final drainage when treatment, including surgery or chemotherapy, was started. We focused on this initial period and analyzed the endoscopy‐related factors that affected mortality.
Results
Overall survival of all PCC patients was 599 days. Overall survival of surgically treated patients and unresectable patients were 893 days and 512 days, respectively. In 48 surgically treated patients, drainage‐related cholangitis within the diagnostic period, defined as new cholangitis that occurred after the first biliary drainage attempt, worsened overall survival from 1460 days to 607 days. Endoscopic sphincterotomy, the first drainage method other than endoscopic nasobiliary drainage, and four or more endoscopic retrograde cholangiopancreatography sessions were risk factors for drainage‐related cholangitis. Drainage‐related cholangitis increased pathological lymph node metastasis. Percutaneous transhepatic biliary drainage as final drainage was the only prognostic factor in unresectable chemotherapy‐treated patients.
Conclusions
Drainage‐related cholangitis worsened the prognosis in PCC patients who underwent surgery. Appropriate endoscopic retrograde cholangiopancreatography strategies, especially during the diagnostic period, are of great importance in PCC.
Focal pancreatic stenosis and focal pancreatic atrophy are features of early-stage pancreatic cancer including carcinoma in situ. We have performed endoscopic retrograde pancreatography (ERPs) on patients with focal pancreatic stenosis with no apparent tumor seen despite multiple imaging studies. Clinical data were collected from 36 patients over 37 sessions who underwent pathological examination by ERPs from January 2010 to December 2020. This included 18 males and 19 females, median age 74 years, and median observation period of 952 days. Of the 37 sessions, 12 were malignant, and 25 benign lesions. The sensitivity of ERP cytology was: pancreatic juice cytology 50%, brush cytology 57%, SPACE 50%, and whole ERP cytology 67%. The malignant group had less acute pancreatitis history, and more males, more stenosis length less than 5 mm, and more focal pancreatic atrophy compared to the benign group. Within the 4 malignant sessions that could not be diagnosed by ERP cytology, 2 were diagnosed with metastases within one year of the final ERP session. About 30% of focal pancreatic stenosis without tumor being detected was malignant, especially in patients with shorter length stenosis and with focal pancreatic atrophy. ERP cytology is a valuable method for detecting pancreatic cancer.
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