Salima Ismail

A Review of Integrated Staging Systems for Renal Cell Carcinoma

CONTEXT Several outstanding integrated staging systems (ISSs) have been devised for patients with renal cell carcinoma (RCC). OBJECTIVE To review the available literature on existing ISSs. EVIDENCE ACQUISITION A nonsystematic search was conducted using Medline and PubMed databases. Original articles, review articles, and editorials addressing the development and validation of ISSs in RCC published up to February 2012 were identified. The search was limited to the English language. Keywords included kidney cancer, renal cell carcinoma, nomogram, risk group, prognosis, predictive accuracy, external validation, and discrimination. Links to related articles and cross-reading of citations in related articles were surveyed. All articles with a pertinent level of evidence were included and represent the basis for the current review article. EVIDENCE SYNTHESIS In nephrectomy patients, a variety of models have been developed for prediction of recurrence and survival, both in the preoperative and postoperative settings. Several of those models relied on variables that are not routinely available in clinical practice. Not all tools were externally validated. In patients treated with systemic therapy, novel tools that were developed and validated in the targeted therapy era replaced tools devised during the cytokine era. CONCLUSIONS The development of ISSs for prediction of risk or prognosis in the context of RCC has evolved and improved. In the targeted therapy era, the urologic community should focus on direct comparisons of existing tools with the intent of identifying the optimal ISS for each specific end point.

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma

BACKGROUND To provide an updated review of adverse events associated with sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus and sorafenib and their management. MATERIALS AND METHODS We performed a PubMed and Cochrane-based review of side effects associated with the seven agents including product monographs to provide an outline of treatment measures aiming to reduce their toxicities. Subject and outcome of interest, design type, sample size, pertinence and quality, and detail of reporting were the indicators of manuscript quality. RESULTS All targeted therapies cause adverse events. Most adverse events may be prevented or tested before they escalate to severe levels. CONCLUSION Prevention, early recognition, and prompt management of side effects are of key importance and avoid unnecessary dose reductions, which may undermine treatment efficacy.

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population-based study.

Study Type – Therapy (cohort) Level of Evidence 2b

Lack of efficacy of phenytoin in children presenting with febrile status epilepticus.

BACKGROUND Fever is the most common precipitant of status epilepticus in children. Animal models suggest that only γ-aminobutyric acidic drugs are effective in the treatment of febrile seizures, but there is limited clinical evidence to support this. OBJECTIVE The aim of this study was to determine the efficacy of phenytoin, a sodium channel blocker, in the treatment of febrile status epilepticus in children. METHODS This study is a retrospective chart review of 56 children (62 episodes) who presented to our emergency department with febrile status epilepticus and received phenytoin. The clinical parameters were evaluated by reviewing the charts. The efficacy of phenytoin was classified into 3 categories: positive, negative, and nonevaluable response. RESULTS The primary outcome was to evaluate the efficacy rate of phenytoin; there were 9 (14.5%) of 62 episodes with a positive response, 25 (40.3%) with a negative response, and 28 (45.2%) with a nonevaluable response because phenytoin was given simultaneously with a γ-aminobutyric acidic (GABAergic) drug (P < .001). The secondary outcome was to measure the mean seizure duration for each treatment category, which were 52.8, 109.9, and 52.6 minutes, respectively (P < .01). CONCLUSION Phenytoin is rarely effective in controlling febrile status epilepticus. Children exposed to phenytoin have more prolonged febrile seizures, increasing the risk of brain injury.

Fournier’s gangrene: A retrospective analysis of 26 cases in a Canadian hospital and literature

We performed a systematic review of all cases of Fourniers Gangrene (FG) at our hospital over a 12-year period. A total of 26 cases were assessed. Our goal was to determine the mortality rate and to identify risk factors associated with FG. We also wanted to examine three potential prognostic factors in relation to patient survival, including the time delay from emergency room admission to surgery, the initial extent of the disease, and the impact of more than one debridement procedure under general anesthesia. The time between emergency room admission and the beginning of surgical debridement was not statistically different between survivors and non-survivors. The extent of surgical debridement was close to the margin of statistical significance (p = 0.07) and can be considered an index of the extent of the disease. FG extending to the thighs or to the abdominal wall carries a worse prognosis. The number of surgical debridement procedures done under anesthesia was statistically different between survivors and non-survivors. Patients were 4.8 times more at risk of dying if they are required to have more than one surgical debridement under general anesthesia. This presumably reflects persistent gangrene following initial surgical debridement, fluid resuscitation, and wide spectrum antibiotic treatment.

FG has no added value in prediction of mortality after partial and radical nephrectomy for chromophobe renal cell carcinoma patients

Our objective was to test whether FG (FG) is applicable in the context of chromophobe renal cell carcinoma patients treated with partial and radical nephrectomy. Patients (n=1862) with chromophobe renal cell carcinoma treated with partial and radical nephrectomy were identified within the Surveillance, Epidemiology, and End Results (1988–2008). Univariable and multivariable Cox regression analyses were fitted to predict cancer-specific mortality. Discriminant properties were assessed for the conventional four-tiered FG scheme. Additionally, discrimination of the three-tiered FG scheme (1–2 vs 3 vs 4) and the two-tiered FG scheme (1–2 vs 3–4) was also assessed. The statistical significance of the differences in accuracy estimates was compared using the Mantel–Haenszel test. A total of 65 of the 1862 died of the disease. The overall 5-year cancer-specific mortality-free survival rate was 94.8% (95% confidence interval: 93.5–96.2). In univariable analyses, none of the FG strata were significantly associated with cancer-specific mortality. Furthermore, FG was less informative (63%) than tumor size (72%) and tumor stage (69%), using measures of discrimination in univariable analyses. After accounting for all covariates, prediction of 5-year cancer-specific mortality was 79.0% vs 80.3% accurate, respectively, with vs without the consideration of FG (P=0.01). Similar discrimination estimates were obtained for the modified three-tiered FG scheme (78.5%; P=0.009) and the modified two-tiered FG scheme (79.5%; P=0.02). In conclusion, FG is not an informative predictor of prognosis, defined as cancer-specific mortality, after partial and radical nephrectomy for chromophobe renal cell carcinoma patients.

A critical appraisal of systemic treatment options for metastatic non-clear cell renal cell carcinoma

Current guidelines provide most support for the use of temsirolimus in first line therapy for metastatic non-clear cell renal cell carcinoma (nccRCC). However, this recommendation is based on scant level 2a evidence. The objective of this review is to examine the evidence supporting first line temsirolimus use in patients with metastatic nccRCC as well as alternative first line treatment options. Six studies, that assessed the efficacy of five agents qualified for inclusion. Among recognized treatment options for metastatic nccRCC, mean weighted progression free survival values of 7.9 months for temsirolimus vs. 7.3 for sunitinib vs. 8.5 months for sorafenib vs. ≈4.1 months for erlotinib were recorded based on data from 10, 74, 33 and 51 patients respectively. In conclusion, the data supporting first line temsirolimus for metastatic nccRCC are based on a small patient sample. Sunitinibs efficacy is similar to that of temsirolimus but is based on a bigger patient sample that originates from phase II studies.