Gastroenterology
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Multicenter Study Comparative Study
Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection Is Associated With Increased Survival in Patients With a History of Hepatocellular Carcinoma.
There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. ⋯ In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.
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It is unclear if hepatocellular carcinoma (HCC) risk declines over time after hepatitis C virus (HCV) eradication. We analyzed changes in HCC annual incidence over time following HCV eradication and identified dynamic markers of HCC risk. ⋯ Patients with cirrhosis before an SVR to treatment for HCV infection continue to have a high risk for HCC (>2%/year) for many years, even if their FIB-4 score decreases, and should continue surveillance. Patients without cirrhosis but with FIB-4 scores ≥3.25 have a high enough risk to merit HCC surveillance, especially if FIB-4 remains ≥3.25 post-SVR.
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Randomized Controlled Trial Multicenter Study Comparative Study
Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn's Disease.
Although ustekinumab is an effective therapy for moderate to severe Crohn's disease (CD), its effects on the microscopic manifestations of CD are unknown. ⋯ In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo. The largest improvements occurred in patients who received ustekinumab maintenance therapy every 8 weeks. ClinicalTrials.gov nos. NCT01369329, NCT01369342, and NCT01369355.
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Randomized Controlled Trial Multicenter Study
Efficacy of Prophylactic Hemoclips in Prevention of Delayed Post-Polypectomy Bleeding in Patients With Large Colonic Polyps.
The efficacy of prophylactic placement of hemoclips to prevent delayed bleeding after removal of large colonic polyps has not been established. We conducted a randomized equivalence study to determine whether prophylactic placement of hemoclips affects incidence of delayed post-polypectomy bleeding (PPB). ⋯ In a randomized trial, we found that prophylactic placement of hemoclips after removal of large colon polyps does not affect the proportion of important delayed PPB events, compared with no hemoclip placement. These findings call into question the widespread, expensive practice of routinely placing prophylactic hemoclips after polypectomy. ClinicalTrials.gov ID: NCT01647581.
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Most pancreatic ductal adenocarcinomas (PDACs) express an activated form of KRAS, become hypoxic and dysplastic, and are refractory to chemo and radiation therapies. To survive in the hypoxic environment, PDAC cells upregulate enzymes and transporters involved in pH regulation, including the extracellular facing carbonic anhydrase 9 (CA9). We evaluated the effect of blocking CA9, in combination with administration of gemcitabine, in mouse models of pancreatic cancer. ⋯ In response to hypoxia, PDAC cells that express activated KRAS increase expression of CA9, via stabilization of HIF1A and HIF2A, to regulate pH and glycolysis. Disruption of this pathway slows growth of PDAC xenograft tumors in mice and might be developed for treatment of pancreatic cancer.