Renal Effect of NSAIDs in Cirrhosis
Short-term use of celecoxib did not affect renal function in patients with decompensated liver cirrhosis and ascites who participated in a small randomized trial.
In the double-blind study of 28 patients conducted by Joan Clària, Ph.D., of the University of Barcelona (Spain) and his colleagues, the glomerular filtration rate, renal plasma flow, and serum creatine levels worsened significantly in patients who received five therapeutic doses of naproxen during a 3-day period, compared with baseline values. None of these changes occurred in patients who received five therapeutic doses of celecoxib (Celebrex) or placebo during the same time interval (Hepatology 2005;41:579-87).
Naproxen significantly inhibited platelet aggregation and ex vivo thromboxane B2 synthesis and decreased urinary excretion of prostaglandin E2. Naproxen patients had significantly reduced diuretic and natriuretic responses to furosemide, which normally increases urine volume and urinary sodium excretion. Short-term celecoxib therapy does not reduce platelet or renal function, or response to diuretic drugs, in patients with decompensated cirrhosis, the authors concluded.
Ablating Colorectal Ca Liver Metastases
Small size of colorectal cancer liver metastases may indicate a good prognosis after radiofrequency thermal ablation, reported Eren Berber, M.D., and colleagues at the Cleveland Clinic Foundation, Cleveland.
In their prospective study, the presence of a liver tumor larger than 5 cm decreased the likelihood of overall survival by a factor of 2.5 in a multivariate analysis of 135 patients with colorectal cancer liver metastases. Factors that were significant in cutting overall survival in univariate, but not multivariate, analyses included more than three liver lesions, a size of 3-5 cm for the largest liver lesion, and a serum carcinoembryonic antigen level of more than 200 ng/mL. Although 30% of the patients had minor extrahepatic metastases, this was not a prognostic factor for survival (J. Clin. Oncol. 2005;23:1358-64).
Before enrollment in 1997-2002, 80% of patients had intrahepatic tumor progression despite prior chemotherapy with fluorouracil and leucovorin or irinotecan and/or oxaliplatin; 14% had had liver resection before radiofrequency thermal ablation (RFA). Median survival was 29 months after RFA, similar to survival reported after chemotherapy alone.
Detecting Colorectal Ca Mutations
Conversion analysis detects many of the mismatch repair mutations and clinically important information that genomic DNA sequencing misses in colorectal cancer patients, reported Graham Casey, Ph.D., of the Cleveland Clinic Lerner College of Medicine, Cleveland, and his associates.
In 89 patients with colorectal cancer, conversion analysis (which separates alleles in hybrids prior to mutation screening) detected all 28 likely mutations detected with conventional genomic DNA sequence analysis, plus 14 additional likely pathogenic mutations in the mismatch repair genes MLH1, MSH2, or MSH6. Conversion analysis detected a likely pathogenic role for an additional 21 mutations that could not be interpreted with genomic DNA sequencing alone. All patients were suspected to have mutations in the mismatch repair genes MLH1, MSH2, or MSH6 based on tumor microsatellite instability status and loss of MLH1 or MSH2 staining (JAMA 2005;293:799-809).
Conversion analysis increased the diagnostic yield of clinically relevant mutations by 56% (35 of 63), compared with genomic DNA sequencing. The researchers detected likely deleterious mutations in 49 of 64 patients with hereditary nonpolyposis colorectal cancer (HNPCC), 7 of 8 patients with HNPCC-like colorectal cancer, and 7 of 17 patients with colorectal cancer diagnosed before age 50 years.
Nonhepatic Ca in Hepatitis C Patients
Patients with chronic hepatitis C infection have an increased risk of developing non-Hodgkin's lymphoma and multiple myeloma, based on findings from a study of all notifications of chronic hepatitis C cases sent to the Swedish Institute for Infectious Disease Control during 1990-2000.
Patients with chronic hepatitis C virus (HCV) for more than 15 years were 1.89 times as likely to have non-Hodgkin's lymphoma and 2.54 times as likely to have multiple myeloma, compared with age-, sex-, and calendar year-specific incidence rates. The significant increase in risk for non-Hodgkin's lymphoma disappeared when four patients with HIV infection and non-Hodgkin's lymphoma were dropped from the analysis, said Ann-Sofi Duberg, M.D., of Örebro (Sweden) University Hospital, and her associates (Hepatology 2005;41:652-9).
The study included 26,686 persons with an observation time of 122,272 person-years, not including patients with a cancer diagnosis before or within 3 months of notification of HCV infection.