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- Grover, S, et al.
(författare)
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Clinicopathological strategies to identify contralateral prostate cancer involvement in potential candidates for focal therapy
- 2010
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Ingår i: International journal of surgical pathology. - : SAGE Publications. - 1940-2465 .- 1066-8969. ; 18:6, s. 499-507
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify the magnitude and possible predictors of contralateral lobe involvement and contralateral extraprostatic extension (EPE) in prostatic biopsy—defined localized unilateral cancers. Patients and Methods: Between January 2005 and August 2009, 1861 patients underwent robotic-assisted radical prostatectomy at the authors’ institution. A total of 1114 had unilateral disease on preoperative biopsy. Final histopathology reports of these patients were reviewed. Results: Of the 1114 patients with unilateral disease on biopsy, 867 (77.9%) had contralateral or bilateral disease on final histopathology. EPE was found in 132 patients (11.9%). Twenty patients (1.8%) had contralateral EPE involvement. High-grade prostatic intraepithelial neoplasm (HGPIN) on biopsy was the significant predictor of contralateral lobe involvement on both univariate ( P = .02; odds ratio [OR] = 1.791) and multivariate analysis ( P = .004; OR = 2.677). Clinical stage T2 was the significant predictor of contralateral EPE on both univariate ( P = .012; OR = 5.250) and multivariate analysis ( P = .007; OR = 8.656). Conclusion: HGPIN on biopsy significantly predicts for contralateral lobe involvement and should be considered an exclusion criterion for focal therapy in prostate cancer patients. Patients with palpable tumor on digital rectal examination should be advised in favor of radical treatment as these patients may harbor more aggressive tumors involving the contralateral side despite the biopsy findings.
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- Mudaliar, S., et al.
(författare)
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Efficacy and Safety of the Farnesoid X Receptor Agonist Obeticholic Acid in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
- 2013
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 145:3, s. 574-582
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Obeticholic acid (OCA; INT-747, 6 alpha-ethyl-chenodeoxycholic acid) is a semisynthetic derivative of the primary human bile acid chenodeoxycholic acid, the natural agonist of the farnesoid X receptor, which is a nuclear hormone receptor that regulates glucose and lipid metabolism. In animal models, OCA decreases insulin resistance and hepatic steatosis. METHODS: We performed a double-blind, placebocontrolled, proof-of-concept study to evaluate the effects of OCA on insulin sensitivity in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus. Patients were randomly assigned to groups given placebo (n = 23), 25 mg OCA (n = 20), or 50 mg OCA (n = 21) once daily for 6 weeks. A 2-stage hyperinsulinemiceuglycemic insulin clamp was used to measure insulin sensitivity before and after the 6-week treatment period. We also measured levels of liver enzymes, lipid analytes, fibroblast growth factor 19, 7 alpha-hydroxy-4-cholesten-3-one (a BA precursor), endogenous bile acids, and markers of liver fibrosis. RESULTS: When patients were given a low-dose insulin infusion, insulin sensitivity increased by 28.0% from baseline in the group treated with 25 mg OCA (P = .019) and 20.1% from baseline in the group treated with 50 mg OCA (P = .060). Insulin sensitivity increased by 24.5% (P = .011) in combined OCA groups, whereas it decreased by 5.5% in the placebo group. A similar pattern was observed in patients given a high-dose insulin infusion. The OCA groups had significant reductions in levels of gamma-glutamyltransferase and alanine aminotransferase and dose-related weight loss. They also had increased serum levels of low-density lipoprotein cholesterol and fibroblast growth factor 19, associated with decreased levels of 7 alpha-hydroxy-4-cholesten-3-one and endogenous bile acids, indicating activation of farnesoid X receptor. Markers of liver fibrosis decreased significantly in the group treated with 25 mg OCA. Adverse experiences were similar among groups. CONCLUSIONS: In this phase 2 trial, administration of 25 or 50 mg OCA for 6 weeks was well tolerated, increased insulin sensitivity, and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Longer and larger studies are warranted. ClinicalTrials.gov, Number: NCT00501592.
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