The incidence of kidney cancer has been rising over the last two decades, especially in cases where the disease is localized. Although rates of renal surgery parallel this trend, mortality rates have continued to rise. To investigate the basis of this "treatment disconnect" (i.e., increased rates of treatment accompanied by increased mortality rates), we analyzed patient data from nine registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. We assembled a cohort of 34,503 kidney cancer patients and derived incidence, treatment, and mortality trends for kidney cancer, overall and as a function of tumor size. From 1983 to 2002, the overall age-adjusted incidence rate for kidney cancer rose from 7.1 to 10.8 cases per 100,000 US population; tumors < or = 4 cm in size accounted for most of the increase. Adjusted rates of renal surgery increased concurrently, most notably for tumors < or = 4 cm (0.9-3.6 surgeries per 100,000 US population). However, among kidney cancer patients, all-cause mortality per 100,000 US population increased from 1.5 deaths in 1983 to 6.5 deaths in 2002, with the greatest absolute increase noted for patients with lesions > 7 cm. Our results demonstrate that the rising incidence of kidney cancer is largely attributable to an increase in small renal masses that are presumably curable. The fact that increased detection and treatment of small tumors is not reducing mortality argues for a reassessment of the current treatment paradigm.

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BackgroundAngioedema is a common presentation in the emergency department (ED). Airway angioedema can be fatal; therefore, prompt diagnosis and correct treatment are vital.Objective of the reviewBased on the findings of two expert panels attended by international experts in angioedema and emergency medicine, this review aims to provide practical guidance on the diagnosis, differentiation, and management of histamine- and bradykinin-mediated angioedema in the ED.ReviewThe most common pathophysiology underlying angioedema is mediated by histamine; however, ED staff must be alert for the less common bradykinin-mediated forms of angioedema. Crucially, bradykinin-mediated angioedema does not respond to the same treatment as histamine-mediated angioedema. Bradykinin-mediated angioedema can result from many causes, including hereditary defects in C1 esterase inhibitor (C1-INH), side effects of angiotensin-converting enzyme inhibitors (ACEis), or acquired deficiency in C1-INH. The increased use of ACEis in recent decades has resulted in more frequent encounters with ACEi-induced angioedema in the ED; however, surveys have shown that many ED staff may not know how to recognize or manage bradykinin-mediated angioedema, and hospitals may not have specific medications or protocols in place.ConclusionED physicians must be aware of the different pathophysiologic pathways that lead to angioedema in order to efficiently and effectively manage these potentially fatal conditions.

Despite more frequent application during the last 2 decades, nationwide use of PN remains relatively uncommon, even for the smallest renal masses. Recognizing the favorable outcomes associated with preservation of renal parenchyma, our findings identify a possible quality of care concern that should be addressed by the urological community.

Purpose Current therapies for male lower urinary tract symptoms secondary to prostate enlargement prevent hormonal effects on prostate growth and inhibit smooth muscle contraction to ease bladder neck and urethral pressure. However, lower urinary tract symptoms can be refractory to these therapies, suggesting that additional biological processes not addressed by them may also contribute to lower urinary tract symptoms. Aging associated fibrotic changes in tissue architecture contribute to dysfunction in multiple organ systems. Thus, we tested whether such changes potentially have a role in impaired urethral function and perhaps in male lower urinary tract symptoms. Materials and Methods Periurethral tissues were obtained from a whole prostate ex vivo and from 28 consecutive men treated with radical prostatectomy. Lower urinary tract symptoms were assessed using the American Urological Association symptom index. Prostate tissues were subjected to mechanical testing to assess rigidity and stiffness. Fixed sections of these tissues were evaluated for collagen and elastin content, and glandularity to assess fibrosis. Statistical analysis included the Student t test and calculation of Pearson correlation coefficients to compare groups. Results Periurethral prostate tissues demonstrated nonlinear viscoelastic mechanical behavior. Tissue from men with lower urinary tract symptoms was significantly stiffer (p = 0.0016) with significantly higher collagen content (p = 0.0038) and lower glandularity than that from men without lower urinary tract symptoms (American Urological Association symptom index 8 or greater vs 7 or less). Conclusions Findings show that extracellular matrix deposition and fibrosis characterize the periurethral prostate tissue of some men with lower urinary tract symptoms. They point to fibrosis as a factor contributing to lower urinary tract symptom etiology.

BACKGROUND.Kidney cancer's rising incidence is largely attributable to the increased detection of small renal masses. Although surgery rates have paralleled this incidence trend, mortality continues to rise, calling into question the necessity of surgery for all patients with renal masses. Using a population‐based cohort, a competing risk analysis was performed to estimate patient survival after surgery for kidney cancer, as a function of patient age and tumor size at diagnosis.METHODS.With data from the Surveillance, Epidemiology, and End Results Program (1983–2002), a cohort was assembled of 26,618 patients with surgically treated, local‐regional kidney cancer. Patients were sorted into 20 age‐tumor size categories and the numbers of patients that were alive, dead from kidney cancer, and dead from other causes were tabulated. Poisson regression models were fitted to obtain estimates of cancer‐specific and competing‐cause mortality.RESULTS.Age‐specific kidney cancer mortality was stable across all size strata but varied inversely with tumor size. Patients with the smallest tumors enjoyed the lowest cancer‐specific mortality (5% for masses ≤4 cm). Competing‐cause mortality rose with increasing patient age. The estimated 5‐year competing‐cause mortality for elderly subjects (≥70 years) was 28.2% (95% confidence interval [CI]: 25.9%–30.8%), irrespective of tumor size.CONCLUSIONS.Despite surgical therapy, competing‐cause mortality for patients with renal masses rises with increasing patient age. After 5 years, one‐third of elderly patients (≥70 years) will die from other causes, suggesting the need for prospective studies to evaluate the role of active surveillance as an initial therapeutic approach for some small renal masses. Cancer 2007. © 2007 American Cancer Society.

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P‐glycoprotein (P‐gp) is a plasma membrane glycoprotein that has been signaled as a primary cause of multidrug resistance (MDR) in tumors. We performed a yeast 2‐hybrid screen using the C‐terminal domain of P‐gp and identified 2 small GTPases involved in vesicular trafficking, Rab4 and Rab14, which complex with P‐gp. The overexpression of GFP‐Rab4, either transiently or stably, but not of Rab14, in K562ADR cells decreased the presence of P‐gp in the cell surface. As a result, expression of this GTPase reduced the MDR phenotype of K562ADR cells, by augmenting the intracellular accumulation of daunomycin (DNM). This effect was mimicked by the constitutively active Rab4Q72L mutant, but not by the dominant negative Rab4S27N mutant. Rab4 regulated excocytotic P‐gp trafficking to the plasma membrane from intracellular compartments, and this modulation required the interaction of both proteins and the GTPase activity. Noteworthy, K562ADR cells exhibited a significant reduction of Rab4 levels, but not of other Rab GTPases, as compared with the sensitive parental cell line, suggesting that the development of the MDR phenotype in these cells involves upregulation of P‐gp and a concomitant downregulation of proteins that regulate its surface expression. Attenuation of endogenous Rab4 levels in K562ADR by RNA interference enhanced the expression of P‐gp in the cell surface, and reduced the uptake of DNM. Accordingly, these findings substantiate the notion that modulation of the temporal and spatial distribution of P‐gp in cancer cells may be a valid therapeutic strategy to alleviate the MDR phenotype, and signal to Rab4 as a potential target.