Multicenter clinical experience with recombinant soluble thrombomodulin for disseminated intravascular coagulation associated with severe acute cholecystitis.

BACKGROUND: Severe acute cholecystitis (AC) is defined by the association of organ dysfunction, including hematological dysfunction, with AC. Severe AC is often complicated by disseminated intravascular coagulation (DIC), the diagnostic criteria of which overlap with AC-associated hematological dysfunction. Since the diagnosis of DIC often delays definitive surgical management of severe AC, treatment of DIC in this setting is clinically important. Recombinant human soluble thrombomodulin (rTM) is a new agent that has proven clinically useful for treating DIC. However, the relevance of rTM to sepsis-induced DIC caused by AC has not been clinically evaluated. This retrospective multicenter study aimed to determine the clinical impact of rTM on sepsis-induced DIC caused by AC. METHODS: This retrospective multicenter study initially included 68 consecutive patients and proceeded between July 2014 and December 2017. The inclusion criterion was sepsis-induced DIC caused by severe AC due to benign disease. Sixteen of the 68 patients were excluded in this study due to having advanced malignant tumors. Finally, 42 patients were enrolled in this study. We treated DIC with AC using Recomodulin® Injection (rTM) at doses of 130 or 380 U/kg/day. RESULTS: 17 and 25 patients were treated with and without rTM, respectively. Values on days 3 and 7 did not significantly differ between the groups for PT-INR (P = 0.38 and P = 0.16, respectively) and FDP (P = 0.06 and P = 0.08, respectively), and PLT was significantly increased in the rTM group at day 7 (P = 0.03). Resolution rates of DIC on day 7 were significantly higher in the group treated with, than without rTM (94.1% [16/17] vs. 68.0% [17/25], P = 0.04). Two patients in each group died of sepsis-induced DIC associated with severe AC, and thus mortality rates did not significantly differ. CONCLUSIONS: rTM can may be improve the resolution rate of sepsis-induced DIC due to severe AC. Future studies should include more patients to validate our findings.

Metabolomics-based search for therapeutic agents for non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver disease in developed countries. Non-alcoholic steatohepatitis (NASH), which represents advanced stage NAFLD, is increasingly being recognized as a major cause of liver-related morbidity and mortality. However, no effective drugs against NASH have yet been developed. Therefore, we searched for candidate therapeutic agents based on the changes in levels of hepatic metabolites via gas chromatography mass spectrometry (GC/MS)-based metabolome analysis of livers from methionine-choline deficient (MCD) diet-fed mice, a mouse model of NASH. METHODS: The metabolites were extracted from the livers of the MCD diet-fed mice and then analyzed using GC/MS. Subsequently, the MCD diet-fed mice were supplemented with hypotaurine, and the therapeutic effects of hypotaurine against steatohepatitis were evaluated. RESULTS: Ninety-nine metabolites were detected in the livers of the MCD diet-induced steatohepatitis model mice. Among these metabolites, hypotaurine exhibited the greatest decrease in its concentration in the mice. Supplementation with 2 mmol/kgBW hypotaurine attenuated liver injuries and fat accumulation caused by the MCD diet-induced steatohepatitis. Furthermore, 10 mmol/kgBW hypotaurine supplementation ameliorated fibrosis and oxidative stress induced by the MCD diet. CONCLUSION: The present metabolome analysis-based study demonstrated that hypotaurine is a novel candidate therapeutic agent for NASH.

[Marked effect of combination chemotherapy with tegafur-gimeracil-oteracil potassium and gemcitabine on a suspected case of pancreas cancer or gallbladder cancer metastasis to bone: further diagnosis of disseminated carcinomatosa of bone marrow recurrence after the 23 years of gastric cancer operation by autopsy findings].

A 70-year-old woman who underwent proximal gastrectomy for gastric cancer (poorly-differentiated adenocarcinoma) of Stage IIIB at age 46 visited our hospital April 2004 because of exacerbated pain by movement in the buttocks since November 2003. She showed multiple bone metastasis by CT (computerized tomography). Pancreas cancer or gallbladder cancer was suspected by CT, and a high tumor marker score (CA19-9 18,625 U/mL, DUPAN-II 15,000 U/ mL elevations were acknowledged). Although her symptoms were severe with performance status (PS) 4, she was administered combination chemotherapy with gemcitabine and cisplatin. After 2 cycle therapy, her PS was improved to 2, but the tumor markers had elevated. So we changed the chemotherapy menu to S-1 and gemcitabine. Her tumor markers lowered and PS was improved to 1. There was a remarkable response to this chemotherapy, and the result of CT and bone scintigraphy suggested that her bone metastasis was improved. Because of hematologic relapse due to DIC at 1 year after the first treatment, she was readmitted to our hospital and later died. The autopsical result revealed recurrence of gastric cancer 23 years post-operatively.