Hazard ratios in cancer clinical trials--a primer

The increase and diversity of clinical trial data has resulted in a greater reliance on statistical analyses to discern value. Assessing differences between two similar survival curves can pose a challenge for those without formal training in statistical interpretation; therefore, there has been an increased reliance on hazard ratios often to the exclusion of more-traditional survival measures. However, because a hazard ratio lacks dimensions it can only inform the reader about the reliability and uniformity of the data. It does not provide practitioners with quantitative values they can use, nor does it provide information they can discuss with patients. Motivated by a non-scientific poll of oncologists in training and those with board certification that suggested only a limited understanding of the derivation of hazard ratios we undertook this presentation of hazard ratios: a measure of treatment efficacy that is increasingly used and often misused.     

Radiofrequency ablation of liver tumors: the role of microbubble ultrasound contrast agents

Radiofrequency ablation (RFA) is currently indicated for the treatment of primary and metastatic hepatic malignancies. Real-time ultrasound (US) is generally used during the procedure to guide electrode placement, but for evaluating the results of treatment, contrast-enhanced computed tomography and magnetic resonance imaging have traditionally been considered more effective. This view has changed, however, with the recent development of contrast-enhanced ultrasound (CEUS) (eg, using sulfur hexafluoride microbubbles), which can provide valuable information on the effects of RFA more rapidly and economically than computed tomography or magnetic resonance imaging without exposing the patient to ionizing radiation. In our center, CEUS is performed in patients with liver tumors before and immediately after RFA, in selected cases during the procedure as well, and in the follow-up. Between January 2003 and June 2005, we performed CEUS on 350 patients scheduled for RFA of primary or metastatic liver tumors. In 14 (13.4%) of the 96 patients whose disease was metastatic, CEUS revealed lesions that had been missed on the conventional US examination. In most of these cases, the result was a more complete treatment performed under CEUS guidance. In the remaining 2 (14%) of 14, the results of the examination allowed us to avoid subjecting the patient to useless treatment. In our experience, the use of CEUS also improved the management and follow-up of patients undergoing interstitial therapy.     

Risk of Preterm Delivery Associated with Prior Treatment of Cervical Precancerous Lesion according to the Depth of the Cone

The aim of this study was to evaluate the impact of the surgical excisional procedures for cervical intraepithelial neoplasia (CIN) treatment both on subsequent fertility (cervical factor) and pregnancy complication (risk of spontaneous preterm delivery). We retrospectively analyzed 236 fertile women who underwent conization for CIN. We included in the study 47 patients who carried on pregnancy and delivered a viable fetus. Patients were asked about postconization pregnancies, obstetrical outcomes, and a possible diagnosis of secondary infertility caused by cervical stenosis. We evaluated the depth of surgical excision, the timing between cervical conization and subsequent pregnancies, surgical technique, and maternal age at delivery. We recorded 47 deliveries, 10 cases of preterm delivery; 8 of them were spontaneous. The depth of surgical excision showed a statistically significant inverse correlation with gestational age at birth. The risk of spontaneous preterm delivery increased when conization depth exceeded a cut-off value of 1.5 cm. Our data do not demonstrated a relation between conization and infertility due to cervical stenosis.     

Asthma control can be maintained when fluticasone propionate/salmeterol in a single inhaler is stepped down

BACKGROUND: Asthma control is the goal of treatment, but little data exist to support treatment strategies for stepping down treatment once control has been achieved. OBJECTIVE: We assessed whether either the long-acting beta2-agonist or corticosteroid could be reduced without loss of asthma control once control had been attained with fluticasone propionate/salmeterol (FSC). METHODS: After 12 weeks of open-label treatment with FSC 250/50 microg twice daily, patients whose asthma was well controlled were randomized to FSC 100/50 microg twice daily or fluticasone propionate (FP) 250 microg twice daily. for 12 weeks. The primary endpoint was mean morning peak expiratory flow over the randomized study period. Secondary endpoints included symptom scores, rescue albuterol use, and asthma control. RESULTS: During open-label treatment, improvements from baseline were seen, and 435 of 641 patients (68%) achieved well controlled status during each of the last 4 weeks of this period. A total of 246 patients received FSC 100/50 microg twice daily and 238 FP 250 microg twice daily. The adjusted mean change in morning peak expiratory flow from the end of open-label treatment was -0.3 L/min for FSC and -13.2 L/min for FP (treatment difference, 12.9 L/min; 95% CI, 8.1-17.6; P<.001). Secondary efficacy endpoints also showed FSC 100/50 microg twice daily to be more effective than FP 250 microg twice daily alone. The majority of patients remained well controlled, but the proportion was higher with FSC. CONCLUSION: In patients achieving asthma control with FSC 250/50 microg twice daily, stepping treatment down to a lower dose of FSC 100/50 microg twice daily is more effective than switching to an inhaled corticosteroid alone.     

Symptoms in the lives of terminal cancer patients: which is the most important?

OBJECTIVES: Symptoms other than their primary disease can interfere in the lives of terminal cancer patients. We sought to identify which of these symptoms is most important. METHODS: We administered a questionnaire, including the M.D. Anderson Symptom Inventory (MDASI), to 142 terminal cancer patients at the National Cancer Center, Korea. The validity of the MDASI was tested by principal-axis factor analysis and Cronbach's alpha coefficient. Stepwise multiple regression analysis was used to determine the symptoms that interfered most in terminal cancer patients' lives. RESULTS: Factor analysis showed that it was composed of two factors (symptom and interference scales). Cronbach's alpha coefficients of symptom and interference scales were each >0.70. The patients had an average of 11 of 13 symptoms of the MDASI. Pain was the most common and severe, followed by feelings of distress and fatigue. Fatigue was the most highly correlated with interference sum. In stepwise multiple regression analysis, the most interfering symptom was fatigue. CONCLUSIONS: Although pain was the most common and severe symptom, fatigue was the most important symptom interfering in the lives of terminal cancer patients. In treating terminal cancer patients, healthcare providers should actively intervene to reduce both fatigue and pain.     

Statins in nephrotic syndrome: a new weapon against tissue injury

The nephrotic syndrome is characterized by metabolic disorders leading to an increase in circulating lipoproteins levels. Hypertriglyceridemia and hypercholesterolemia in this case may depend on a reduction in triglyceride-rich lipoproteins catabolism and on an increase in hepatic synthesis of Apo B-containing lipoproteins. These alterations are the starting point of a self-maintaining mechanism, which can accelerate the progression of chronic renal failure. Indeed, hyperlipidemia can affect renal function, increase proteinuria and speed glomerulosclerosis, thus determining a higher risk of progression to dialysis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in cholesterol synthesis from mevalonate and its inhibitors, or statins, can therefore interfere with the above-mentioned consequences of hyperlipidemia. Statins are already well known for their effectiveness on primary cardiovascular prevention, which cannot be explained only through their hypolipemic effect. As far as kidney diseases are concerned, statin therapy has been shown to prevent creatinine clearance decline and to slow renal function loss, particularly in case of proteinuria, and its favorable effect may depend only partially on the attenuation of hyperlipidemia. Statins may therefore confer tissue protection through lipid-independent mechanisms, which can be triggered by other mediators, such as angiotensin receptor blockers. Possible pathways for the protective action of statins, other than any hypocholesterolemic effect, are: cellular apoptosis/proliferation balance, inflammatory cytokines production, and signal transduction regulation. Statins also play a role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. In this study, we would like to provide scientific evidences for the pleiotropic effects of statins, which could be the starting point for the development of new therapeutical strategies in different clinical areas.     

Para-stomal hernias. Report of 3 cases

Three cases of stomal hernia are presented in this article; two females and one in male patient, the first two cases with colostomy and the remaining patient with ileostomy. One case was treated by replacing stoma and subsequent hernioplasty. The additional two were treated with Leslie technique. To date, there have been no recurrences. Patients were followed for a median of 2 years. Although this complication is infrequent we recommend careful planning prior to performing a stoma, as well as determining the best anatomic site and use good surgical technique.