Poor quality of life in patients with urethral stricture treated with intermittent self-dilation.

PURPOSE: We assessed patient perceptions of regular intermittent self-dilation in men with urethral stricture. MATERIALS AND METHODS: We constructed and distributed a visual analog questionnaire to evaluate intermittent self-dilation via catheterization by men referred for urethral stricture management at a total of 4 institutions. Items assessed included patient duration, frequency, difficulty and pain associated with intermittent self-dilation as well as interference of intermittent self-dilation with daily activity. The primary outcome was patient perceived quality of life. Multivariate analysis was performed to assess factors that affected this outcome. RESULTS: Included in the study were 85 patients with a median age of 68 years, a median of 3.0 years on intermittent self-dilation and a median frequency of 1 dilation per day. On a 1 to 10 scale the median intermittent self-dilation difficulty was 5.0 ± 2.7, the median pain score was 3.0 ± 2.7 and median interference with daily life was 2.0 ± 1.3. Overall quality of life in patients with stricture was poor (median score 7.0 ± 2.6 with poor quality of life defined as 7 or greater). On univariate analysis younger age (p <0.01), interference (p = 0.03), pain (p <0.01) and difficulty performing intermittent self-dilation (p = 0.03) correlated with poor quality of life in a statistically significant manner. On multivariate analysis only difficulty catheterizing (p <0.01) and younger age (p = 0.05) were statistically significant predictors. Patients with stricture involving the posterior urethra had a statistically significant increase in difficulty and decrease in quality of life (each p = 0.04). CONCLUSIONS: Most patients with urethral stricture who are on intermittent self-dilation rate difficulty and pain as moderate, and inconvenience as low but report poor quality of life.

Risk stratification of pubertal children and postpubertal adolescents with clinical stage I testicular nonseminomatous germ cell tumors.

PURPOSE: The COG (Children's Oncology Group) currently recommends surveillance for all children and adolescents with clinical stage I testicular germ cell tumors. However, up to 30% of adults with clinical stage I testicular germ cell tumors harbor occult metastatic disease. In adults with clinical stage I nonseminoma some groups advocate a risk stratified approach. Occult metastases were noted in 50% of patients with features such as lymphovascular invasion or embryonal carcinoma predominance in the orchiectomy. However, to our knowledge there are no data on the impact of high risk features in such pubertal children and postpubertal adolescents. MATERIALS AND METHODS: We reviewed an institutional testis cancer database for pubertal children and postpubertal adolescents younger than 21 years. We tested the hypothesis that lymphovascular invasion, or 40% or greater embryonal carcinoma in the orchiectomy specimen, would increase the risk of occult metastases, ie relapse during surveillance or positive nodes on retroperitoneal lymph node dissection. RESULTS: We identified 23 patients with a median age of 18.6 years (range 7.1 to 20.9) at diagnosis. Of these patients 14 (60.9%) were on surveillance, 9 (39.1%) underwent primary retroperitoneal lymph node dissection and none received initial chemotherapy. Seven patients (30.4%) had occult metastatic disease. High risk pathological features were found in the orchiectomy specimen in 12 patients (52.2%), including all 12 (52.2%) with 40% or greater embryonal carcinoma and 3 (13.0%) with lymphovascular invasion. Seven patients (58.3%) with high risk features had occult metastatic disease vs none (0%) without high risk features (log rank p = 0.031). CONCLUSIONS: Approximately half of pubertal children and postpubertal adolescents with high risk clinical stage I testicular germ cell tumors harbor occult metastatic disease. These results may be useful when discussing prognosis and treatment with patients and families.

A comparison of pediatric, adolescent, and adult testicular germ cell malignancy.

BACKGROUND: Testicular germ cell tumors (T-GCTs) occur from infancy to adulthood, and are the most common solid tumor in adolescent and young adult males. Traditionally, pediatric T-GCTs were perceived as more indolent than adult T-GCTs. However, there are few studies comparing these groups and none that specifically evaluate adolescents. METHODS: An institutional database of T-GCT patients was reviewed and patients were categorized into Pediatric, aged 0-12 years, Adolescent, aged 13-19 years, and Adult, older than 20 years, cohorts. Demographics, tumor characteristics, disease stage, treatment, event-free survival (EFS), and overall survival (OS) were compared between groups. RESULTS: Overall, 413 patients (20 pediatric, 39 adolescent, 354 adult) met study criteria and were followed for a median of 2.0 years (0.1-23.6). Adolescents presented with more advanced stage than children (P = 0.018) or adults (P = 0.008). There was a higher rate of events in Adolescents (13, 33.3%) than in Adults (61, 17.2%) or Children (2, 10.0%). Three-year EFS was 87.2% in the Pediatric group, 59.9% in Adolescents and 80.0% in Adults (P = 0.011). In a multivariate analysis, controlling for stage, IGCCCG risk, and histology, the hazard ratio (HR) for an event was: 1 (Reference) for Adults, HR = 0.82 (95% CI 0.19-3.46; P = 0.33) for the Pediatric group, and HR = 2.22 (95% CI 1.21-4.07; P = 0.01) for Adolescents. Five-year OS was 100% in the Pediatric group, 84.8% in Adolescents, and 92.8% in Adults (P = 0.388). CONCLUSION: Lower EFS in adolescent T-GCT patients was observed than in either children or adults. Elucidating factors associated with inferior outcomes in adolescents is an important focus of future research.

Pathological review of Wilms tumor nephrectomy specimens and potential implications for nephron sparing surgery in Wilms tumor.

PURPOSE: Nephron sparing surgery is accepted as standard of care for children with bilateral Wilms tumor or Wilms tumor in a solitary kidney and some study protocols allow nephron sparing surgery in select cases of unilateral Wilms tumor. With the increasing use of nephron sparing surgery in Wilms tumor, we reviewed pathological features from Wilms tumor radical nephrectomy specimens to determine the potential efficacy of a nephron sparing approach. MATERIALS AND METHODS: Medical records of children undergoing pre-chemotherapy radical nephrectomy for unilateral Wilms tumor at our institution were reviewed. Ideal candidates for nephron sparing surgery were defined as those having a unifocal mass outside the renal hilum, sparing a third or more of the kidney, favorable histology, no signs of renal sinus or segmental vascular invasion, no metastatic lymph nodes or gross regional disease, and a distinct interface on pathological review between tumor and remaining parenchyma. RESULTS: A total of 78 children at a median age of 3.2 years (range 0.3 to 16.2) underwent pre-chemotherapy radical nephrectomy for unilateral Wilms tumor. Median tumor diameter was 11 cm (range 2.5 to 22). Of these children 36 (46.2%) had tumors sparing a third or more of the kidney and 70 (89.7%) had unifocal tumors. There were 73 specimens (94.6%) that showed favorable histology, and 56 (71.8%) of the specimens had a distinct border between tumor and remaining parenchyma. In total, 19 (24.4%) of the patients reviewed met all of our strict pathological criteria as ideal partial nephrectomy candidates. CONCLUSIONS: In a post hoc analysis using strict pathological criteria and accepted surgical oncologic principles, as many as 1 in 4 children undergoing pre-chemotherapy surgery for nonmetastatic, unilateral Wilms tumor have post-resection pathological tumor characteristics favorable for nephron sparing surgery.

Correlation between preoperative staging computerized tomography and pathological findings after nodal sampling in children with Wilms tumor.

PURPOSE: Guidelines for staging Wilms tumor mandate regional lymph node sampling at nephrectomy. However, the usefulness of preoperative computerized tomography in staging lymph nodes has not been rigorously investigated. Thus, we correlated preoperative computerized tomography and pathological lymph node findings to establish a radiological criterion for pathological lymph node enlargement. MATERIALS AND METHODS: We reviewed the medical records of children with Wilms tumor at our institution who underwent pre-chemotherapy surgery with lymph node sampling and had preoperative computerized tomography with contrast medium available for interpretation. Computerized tomography was independently reviewed by 2 radiologists blinded to the pathological findings. We collected data on the diameter of the largest regional lymph node identified and this measurement was correlated with the pathological results. RESULTS: A total of 52 children (25 male, 27 female) with a median age of 3.1 years (range 0.4 to 9.6) were identified. The median largest regional lymph node diameter was 6 mm (range 2 to 15). Of the children 10 (19.2%) had metastatic involvement of sampled lymph nodes. A radiological cutoff of 7 mm for lymph node positivity corresponded to a negative predictive value of 89.0%, a sensitivity of 70.0% and a specificity of 57.1%. A ROC curve was constructed with these data describing the prognostic ability of the diameter of the largest regional lymph node on preoperative computerized tomography to determine lymph node positivity in Wilms tumor, which revealed an AUC of 0.67 (95% CI 0.48-0.87, p = 0.09). CONCLUSIONS: By defining a radiological size cutoff for suspicious lymph nodes, preoperative computerized tomography for staging lymph nodes in Wilms tumor demonstrates potential clinical usefulness through risk stratification for therapy and future study design.

Survival among men with clinically localized prostate cancer treated with radical prostatectomy or radiation therapy in the prostate specific antigen era.

PURPOSE: Radical prostatectomy, external beam radiotherapy and brachytherapy are accepted treatments for localized prostate cancer. However, it is unknown if survival differences exist among treatments. We analyzed the survival of patients treated with these modalities according to contemporary standards. MATERIALS AND METHODS: A total of 10,429 consecutive patients with localized prostate cancer treated with radical prostatectomy (6,485), external beam radiotherapy (2,264) or brachytherapy (1,680) were identified. Multivariable regression analyses were used to model the disease (biopsy grade, clinical stage, prostate specific antigen) and patient specific (age, ethnicity, comorbidity) parameters for overall survival and prostate cancer specific mortality. Propensity score analysis was used to adjust for differences in observed background characteristics. RESULTS: The adjusted 10-year overall survival after radical prostatectomy, external beam radiotherapy and brachytherapy was 88.9%, 82.6% and 81.7%, respectively. Adjusted 10-year prostate cancer specific mortality was 1.8%, 2.9% and 2.3%, respectively. Using propensity score analysis, external beam radiotherapy was associated with decreased overall survival (HR 1.6, 95% CI 1.4-1.9, p<0.001) and increased prostate cancer specific mortality (HR 1.5, 95% CI 1.0-2.3, p=0.041) compared to radical prostatectomy. Brachytherapy was associated with decreased overall survival (HR 1.7, 95% CI 1.4-2.1, p<0.001) but not prostate cancer specific mortality (HR 1.3, 95% CI 0.7-2.4, p=0.5) compared to radical prostatectomy. CONCLUSIONS: After adjusting for major confounders, radical prostatectomy was associated with a small but statistically significant improvement in overall and cancer specific survival. These survival differences may arise from an imbalance of confounders, differences in treatment related mortality and/or improved cancer control when radical prostatectomy is performed as initial therapy.

Single-stage reconstruction of complex anterior urethral strictures using overlapping dorsal and ventral buccal mucosal grafts.

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? This technique has been reported to have an excellent success rate in the bulbar urethra, although no data exists for its use in the penile urethra. This is the first study to report successful use of the technique in the reconstruction of penile urethral strictures. OBJECTIVE: • To review our initial experience with single-stage overlapping dorsal and ventral buccal mucosa graft (BMG) urethroplasty for the reconstruction of complex anterior urethral strictures. PATIENTS AND METHODS: • Among 696 urethroplasties performed at two tertiary urethroplasty centres from October 2007 to September 2010, single-stage urethral reconstruction using urethral plate incision and/or excision and overlapping dorsal and ventral BMGs was used in 36 men (5%) with complex urethral strictures (mean length 4.5 cm). • Demographic and perioperative data was tabulated and outcomes were analysed. RESULTS: • Stricture location was bulbar (61%), penile (19%), or both bulbar and penile (20%). • Dorsal grafts, applied only within the most severely strictured segment, measured a mean 42% of the opposing ventral graft length. • At a mean follow-up of 15.7 months, 32 of the 36 cases were successful (89%). • Repeat urethroplasty was performed in all four recurrences, three of which were successful at a mean follow-up of 16 months. CONCLUSION: • Single-stage reconstruction of focally obliterative long urethral strictures using overlapping dorsal and ventral BMGs is safe and effective.

Oncologic outcomes of partial versus radical nephrectomy for unilateral Wilms tumor.

BACKGROUND: Radical nephrectomy (RN) is the recommended surgical management as part of multi-modality therapy for unilateral Wilms tumor (UWT). Based on recent data demonstrating that renal preserving surgery decreases the likelihood of chronic renal disease and associated co-morbidities, we analyzed oncologic outcomes of patients after partial nephrectomy (PN) for UWT. METHODS: We identified all published cases of PN for UWT. Cases of elective PN for UWT were analyzed for tumor stage, presence, timing and location of disease recurrence, and overall survival (OS). Eighty-two patients had adequate data for analysis. For comparison, these endpoints were collected on consecutive children undergoing RN for UWT from 1985 to 2010 at our institution. RESULTS: Of the 82 PN patients, tumor stage was: I-64, II-10, III-6, IV-2. Of the 121 RN patients, the staging was: I-24, II-45, III-29, IV-23. In the PN group, at a median of 48 months (3-372), the recurrence-free survival (RFS), local RFS and OS were 89.1%, 92.7%, and 95.1%, respectively. In the RN group, at a median of 69 months (0-214), the RFS, local RFS, and OS were 83.1%, 95.0%, and 95.0%, respectively. After controlling for stage, there were no statistically significant differences in the above oncologic outcomes between the groups. CONCLUSION: Based on reported data, the oncologic outcomes of PN for UWT in selected patients do not appear to differ from those of RN. PN for appropriately selected patients with UWT should be studied in prospective, co-operative group trials.

Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinoma.

BACKGROUND: Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS: We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS: The H allele was associated with a reduced risk of aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54-0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per allele) = 0.73; 95% CI: 0.50-1.07). CONCLUSION: These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype.

Effect of testicular germ cell tumor therapy on renal function.

OBJECTIVE: To assess the pre- and post-therapy glomerular filtration rate in patients with testicular germ cell tumors to determine its effect on the natural history of renal function. METHODS: We reviewed an institutional database of patients with testicular germ cell tumor, with pre- and post-therapy serum creatinine levels available. The renal function was estimated using a calculated glomerular filtration rate. We compared the patients treated without chemotherapy (orchiectomy with or without radiotherapy or retroperitoneal lymph node dissection) with those who received systemic chemotherapy. We analyzed the data for the outcome of new-onset chronic kidney disease (CKD) stage 3 between these groups. Kaplan-Meier curves were constructed and compared using a log-rank test. RESULTS: A total of 144 patients were reviewed. The testicular germ cell tumor stage distribution was stage I in 78 (54.2%), stage II in 28 (19.4%), and stage III in 38 (26.4%). Overall, the median creatinine and estimated glomerular filtration rate at diagnosis was 0.9 mg/dL (range 0.5-1.5) and 104.0 mL/min/1.73 m(2) (range 58.7-235), respectively. Of the 144 patients, 102 (70.8%) had CKD stage 0-1, 41 (28.5%) stage 2, and 1 (0.7%) stage 3. The median creatinine and estimated glomerular filtration rate at the last follow-up visit was 1.0 mg/dL (range 0.6-2.6) and 95.5 mL/min/1.73 m(2) (range 31.5-167.6), respectively. This difference between the pre- and post-therapy estimated glomerular filtration rate was significant (P < .01). A total of 81 patients (56.3%) received chemotherapy (median 4 cycles, range 1-12), and 63 (43.7%) were treated without chemotherapy. Of the 81 patients who received chemotherapy, 8 (9.9%) developed new-onset CKD 3 compared with none in the nonchemotherapy group (P = .01). CONCLUSION: Patients with testicular germ cell tumor receiving chemotherapy experienced a significant decrease in the estimated glomerular filtration rate and had a significantly increased risk of developing CKD stage 3 compared with those treated without chemotherapy. These findings offer insight into the long-term risks of testicular germ cell tumor survivorship and will be useful in counseling patients.