Anna Orsola

Conservative treatment of phimosis in children using a topical steroid

OBJECTIVES From 1997 through 1998, we conducted a prospective study to evaluate the long-term outcome of using topical steroids in the treatment of childhood phimosis. METHODS Both the parents and their children were instructed to apply 0.05% betamethasone cream topically twice a day for 1 month and to retract the prepuce after the fifth day of treatment. Results were evaluated at the end of the treatment and 6 months later. RESULTS One hundred thirty-seven boys were evaluated. The median age was 5.4 years. At initial presentation, 61 boys had a phimotic but retractable prepuce, 37 had a nonretractable phimotic ring, and 39 had a pinpoint opening. Patients with a history of previous forcible foreskin retractions were considered to have secondary phimosis. By 6 months following treatment, 90% (124 children) had an easily retractable prepuce without a phimotic ring. No differences were seen in the response rate between those with primary and secondary phimosis. In all cases, the treatment was well tolerated without local or systemic side effects. All the patients with persistent or recurrent phimosis were found to be noncompliant with the suggested daily foreskin care. CONCLUSIONS Topical steroid for the treatment of phimosis is a safe, simple, and inexpensive procedure that avoids surgery and its associated risks. It is effective both in primary and in secondary phimosis. We emphasize the importance of proper and regular foreskin care and hypothesize on the mechanism of action of the steroids.

Bone Mineral Density Changes in Patients With Prostate Cancer During the First 2 Years of Androgen Suppression

PURPOSE We characterized bone mineral density changes in patients with prostate cancer on androgen deprivation therapy during the first 2 years of uninterrupted therapy, and identified which location most reflects bone mass loss. MATERIALS AND METHODS Using dual energy x-ray absorptiometry, bone mineral density was prospectively assessed in patients with nonmetastatic prostate cancer at the lumbar spine and femoral neck, Wards triangle, trochanter and total hip. Measurements were performed at baseline and yearly thereafter in patients on ADT, and at baseline and 1 year in controls (age matched patients with prostate cancer, free of biochemical progression after radical prostatectomy). RESULTS A total of 62 patients were included in the study, 31 in each group. Median age (70 and 69 years, respectively), mean Gleason score and mean baseline serum testosterone did not significantly differ. Patients receiving ADT experienced a significant bone mass loss at 12 months in all locations, ranging from 2.29% to 5.55% (p <0.001). In contrast, bone mineral density did not change significantly (0.64% to 1.68%) in patients not receiving ADT. In the 20 patients on ADT after 24 months, the second year decrease was not as severe, nor was it significant compared to first year values. The major bone mass loss occurred in Wards triangle, with decreases of 5.55% at 12 months and 7.05% at 24 months. CONCLUSIONS Bone mineral density decreases during the first 24 months of androgen suppression with the most relevant effect occurring in the first year. Wards triangle is the axial skeletal site that reflects the major bone mass loss. Because the deleterious impact of long-term androgen suppression on bone mineral density is inversely related to fracture risk and indirectly related to survival in patients with prostate cancer, early diagnosis and prevention of bone mass loss are warranted in these patients.

Improving Selection Criteria for Early Cystectomy in High-Grade T1 Bladder Cancer: A Meta-Analysis of 15,215 Patients

PURPOSE High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer, with highly variable prognosis, poorly understood risk factors, and considerable debate about the role of early cystectomy. We aimed to address these questions through a meta-analysis of outcomes and prognostic factors. METHODS PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology abstracts were searched for cohort studies in HGT1. We pooled data on recurrence, progression, and cancer-specific survival from 73 studies. RESULTS Five-year rates of recurrence, progression, and cancer-specific survival were 42% (95% CI, 39% to 45%), 21% (95% CI, 18% to 23%), and 87% (95% CI, 85% to 89%), respectively (56 studies, n = 15,215). In the prognostic factor meta-analysis (33 studies, n = 8,880), the highest impact risk factor was depth of invasion (T1b/c) into lamina propria (progression: hazard ratio [HR], 3.34; P < .001; cancer-specific survival: HR, 2.02; P = .001). Several other previously proposed factors also predicted progression and cancer-specific survival (lymphovascular invasion, associated carcinoma in situ, nonuse of bacillus Calmette-Guérin, tumor size > 3 cm, and older age; HRs for progression between 1.32 and 2.88, P ≤ .002; HRs for cancer-specific survival between 1.28 and 2.08, P ≤ .02). CONCLUSION In this large analysis of outcomes and prognostic factors in HGT1 bladder cancer, deep lamina propria invasion had the largest negative impact, and other previously proposed prognostic factors were also confirmed. These factors should be used for prognostication and patient stratification in future clinical trials, and depth of invasion should be considered for inclusion in TNM staging criteria. This meta-analysis can also help define selection criteria for early cystectomy in HGT1 bladder cancer, particularly for patients with deep lamina propria invasion combined with other risk factors.

Present strategies in the treatment of metastatic renal cell carcinoma: an update on molecular targeting agents.

The understanding of cellular processes underlying tumour biology has allowed the development of novel molecular‐targeted drugs with optimistic results in renal cell carcinoma (RCC). Mutations in the von Hippel‐Lindau gene are found in 75% of sporadic RCCs, which results in upregulation of several genes involved in angiogenesis, e.g. vascular endothelial growth factor and platelet‐derived growth factor. Other activated pathways in RCC are the epidermal growth factor receptor and the mTOR pathway, which regulate survival and cell growth. In addition to temsirolimus (an mTOR inhibitor) two different strategies have been studied to inhibit these targets: monoclonal antibodies, e.g. bevacizumab, and small molecule tyrosine‐kinase inhibitors such as sorafenib, sunitinib and AG 013736. Phase II studies with these drugs reported substantial clinical activity in advanced RCC. Survival benefit was reported with temsirolimus, sunitinib and sorafenib in randomized trials, which led to the accelerated approval of sorafenib and sunitinib for advanced RCC by regulatory authorities in the USA and Europe. Nevertheless, as new therapies develop, new challenges arise for the optimum use of these targeted drugs. We discuss the rationale and the clinical development of these novel molecular‐targeted agents, with special emphasis on updated information presented at recent meetings because of the relevance of the data reported and the potential future impact in the management of patients with RCC.

Heparin-Binding EGF-Like Growth Factor Is Up-Regulated in the Obstructed Kidney in a Cell- and Region-Specific Manner and Acts to Inhibit Apoptosis

The expression of certain growth factors in the epidermal growth factor (EGF) family is altered in response to renal injury. Recent studies have demonstrated that heparin binding EGF-like growth factor (HB-EGF) expression may be cytoprotective in response to apoptotic signals. The purpose of this study was to investigate the potential role of HB-EGF in the upper urinary tract following unilateral ureteral obstruction. We present evidence that: i) ureteral obstruction induced cell-specific but transient activation of HB-EGF gene expression; ii) HB-EGF expression in renal epithelial cells increased under conditions where mechanical deformation, such as that caused by hydronephrotic distension, induces apoptosis, but HB-EGF expression did not increase in renal pelvis smooth muscle cells under identical conditions; and iii) enforced expression of HB-EGF served to protect renal epithelial cells from stretch-induced apoptosis. These results suggest a potential mechanism by which the kidney protects itself from apoptosis triggered by urinary tract obstruction.

STAGHORN CALCULI IN CHILDREN: TREATMENT WITH MONOTHERAPY EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY

PURPOSE We evaluated the effectiveness of monotherapy extracorporeal shock wave lithotripsy (ESWLT) for treating children with staghorn calculi. MATERIALS AND METHODS From February 1992 to December 1997, 11 boys and 4 girls 14 months to 13 years old (median age 4 years) presented to our institution with staghorn calculi. In these patients ESWL was performed using a Siemens Lithostar-ULTRA with ultrasound stone localization and with intravenous sedation or without anesthesia. Using the Puigvert method the frequency and energy of the shock waves delivered were increased progressively to desensitize cutaneous nerve receptors, making the procedure less painful and improving stone fragmentation. RESULTS Overall stones resolved in 11 of the 15 patients (73.3%) after an average of 2 ESWL sessions. Of the 11 patients 7 were stone-free after only 1 session, 2 with fragments less than 5 mm. required no further intervention, and 2 required additional surgery, including percutaneous nephrolithotomy to remove large residual stone fragments in 1 and open renal surgery to remove a cystine staghorn calculus in 1. Ureteral stents were not required in any patients. One case of post-ESWL fever resolved promptly with antibiotics. CONCLUSIONS ESWL using the Siemens Lithostar-ULTRA is simple, effective and safe primary treatment in children with staghorn calculi.

The relationship between daily calcium intake and bone mineral density in men with prostate cancer.

To analyse the relationship between daily calcium intake (DCI) and bone mineral density (BMD) in patients with prostate cancer, and to assess if DCI is a risk factor for osteoporosis in this group of patients.

Controlled release of therapeutic agents: slow delivery and cell encapsulation

Abstract Some of the most promising systems for the controlled release of bioactive agents, i.e., peptides or hormones, involve the encapsulation or entrapment of hormones or peptides in biocompatible polymeric devices that enable their continuous release over prolonged periods. In urology, two major pathologic conditions, androgen deficiency and prostate cancer, currently benefit from treatments based on controlled delivery. Leuprolide acetate depot (Lupron-depot) was one of the first controlled-delivery systems used for the treatment of prostate cancer. Clinical studies indicate that patients with prostate cancer who undergo therapy with leuprolide acetate depot can benefit from this treatment. Currently available androgen-replacement therapies include the oral administration of testosterone tablets or capsules, depot injections, sublingual treatment, and skin patches. However, side effects such as metabolic inactivation of testosterone on oral administration; fluctuations in levels of the hormone; and burning, rash, and skin necrosis during the use of skin patches may occur. These side effects may be avoided through the application of encapsulated Leydig cells, which produce testosterone. Studies in our laboratory have shown that Leydig cells encapsulated in alginate/poly-l-lysine/alginate microspheres are capable of secreting testosterone in culture and in vivo. Microencapsulated Leydig cells delivered intraperitoneally into castrated rats maintained a testosterone level of 0.51 ng/ml for more than 3 months without any human chorionic gonadotropin stimulation. Similar studies are also being conducted in our laboratory on encapsulation of ovarian cells for the secretion of progesterone and estrogen in culture and in vivo using microencapsulation techniques.

Alendronate decreases the fracture risk in patients with prostate cancer on androgen-deprivation therapy and with severe osteopenia or osteoporosis

To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen‐deprivation therapy (ADT) and with a basal T‐score of >−2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture.

Risk factors for positive findings in patients with high-grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette-Guérin therapy and the decision for a repeat TUR

Study Type – Therapy (case series)