Impact of the use of bowel for urinary diversion on perioperative complications and 90-day mortality in patients aged 75 years or older.

OBJECTIVE: A potential strategy to decrease the high complication rate of radical cystectomy (RC) in the elderly is to avoid the use of bowel for urinary diversion. The aim of this study was to address this issue in a multicentre study of patients aged ≥ 75 years. PATIENTS AND METHODS: We performed a retrospective, multicentre study of a consecutive series of patients aged ≥ 75 years who underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients (68% men, mean age 79.6 years) were analysed. 204 (80%) patients received a urinary diversion with use of bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0 vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007), while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe complications graded as Clavien III-V was significantly lower in the UC group (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1 vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30- and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9, 5.9 and 6.9% in the bowel cohort, respectively. CONCLUSION: UC following RC is associated with a lower complication rate in geriatric patients. The constantly increasing cohort of geriatric, multimorbid patients requiring cystectomy might justify reconsideration of this form of diversion.

Perioperative complications and 90-day mortality of radical cystectomy in the elderly (75+): a retrospective, multicentre study.

OBJECTIVE: To assess perioperative complications and 90-day mortality of radical cystectomy (RC) in elderly patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This is a retrospective, multicentre (n = 11) study of a consecutive series of patients ≥75 years who underwent RC for MIBC between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients with a mean age of 79.6 years (range 75.0-86.6) were analysed. Urinary diversion with the use of bowel was performed in 79.5% and ureterocutaneostomy in 20.5%, with a higher proportion in the ≥80 cohort (32.2 vs. 14%; p = 0.001). 41.4% of patients had an uneventful postoperative course (Clavien grade 0) and 26.6% developed severe complications (Clavien grade III-V). In a multivariable regression analysis, the Charlson comorbidity index (odds ratio 1.5 per unit increase; p < 0.001) and the body mass index (odds ratio 1.13 per kg/m(2) increase; p = 0.015) were predictors for the development of complications. The 90-day mortality rate was 9% and the independent correlates thereof were the development of severe medical complications (p = 0.004), the American Society of Anesthesiologists (ASA) score (p = 0.03) and age (p = 0.005). CONCLUSIONS: Morbidity and 90-day mortality of RC in the elderly remain substantial. The interrelation between comorbidity, complication rate and 90-day mortality underlines the need for a comprehensive geriatric assessment of elderly patients with MIBC in whom RC is indicated.

[Therapy of castration-resistant prostate cancer]. / Therapie des kastrationsrefraktären Prostatakarzinoms.

Within the last two years the therapy of castration resistant prostate cancer (CRPC) has made major advances. Both the COU-AA-301 phase III trial and the TROPIC trial showed a survival benefit for patients after docetaxel failure treated with abiraterone or cabazitaxel, respectively. With rising interest for chemotherapeutic options and novel drugs, our goal was to review within the context of a multidisciplinary team the available evidence and explore the standards for medical treatment of prostate cancer outside of clinical trials. From this background, we are carefully evaluating the current treatment recommendations, based on the available evidence, and highlight potential future treatment options but also discuss important clinical topics like treatment until progression versus the advantage of chemo holidays and definition of particular patient subgroups. Additionally, we focus on novel molecular entities, which will most likely be available in the near future, such as MDV3100 and Sipuleucel T. The role and importance of palliation with radiotherapy and proactive medical management of pain is also discussed, as well as new options for bone directed therapy. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists.

Sensory recovery after decompression of the distal pudendal nerve: anatomical review and quantitative neurosensory data of a prospective clinical study.

OBJECTIVES: Decompression of peripheral nerves at different anatomic sites leads to long-lasting improvement of nerve function. For the pudendal nerve such compression sites have also been described, however, indication for surgical decompression at the dorsal nerve canal, and outcome measures have not been presented. In the following work, we review the detailed anatomy of the pudendal nerve at its passage through the urogenital diaphragm into the base of the penis and present the results of our first five patients. METHODS: Normative neurosensory data of the penis of 20 normal individuals and 10 diabetics were obtained. Both One- and Two-Point Discrimination values were obtained. Five male patients were identified to have isolated distal pudendal nerve entrapment and a nerve release was performed. Both pre and postoperatively detailed neurosensory data was obtained, with a mean follow up of 18 months. RESULTS: Neurosensory evaluation revealed that classic two-point discrimination was an invalid parameter in penile sensation. However, one point pressure threshold testing was significantly higher in diabetics (25 +/- 14 gm/mm(2)) than in normal subjects (1.1 +/- 0.6 gm/mm(2)). Surgical exposure showed signs of nerve entrapment in two patients. All patients showed sensory improvement after decompression. CONCLUSIONS: The distal pudendal nerve is susceptible to compression at the passage from Alcocks canal to the dorsum of the penis. Diabetic patients with peripheral neuropathy can suffer from additional compression neuropathy with decreased penile sensibility and dysaesthesia. One-point pressure threshold testing proved to be a sensitive parameter in the diagnosis and finally, patients would benefit from decompression of the pudendal nerve.

[Chemotherapy for prostate cancer]. / Chemotherapie beim Prostatakarzinom.

For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists.

A prospective, open label, randomized phase II trial of weekly docetaxel versus weekly vinorelbine as first line chemotherapy in patients with androgen independent prostate cancer.

PURPOSE: In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in androgen independent prostate cancer. In the present trial we assessed the efficacy and tolerability of single agent low dose docetaxel vs vinorelbine in patients with advanced androgen independent prostate cancer. MATERIALS AND METHODS: A total of 40 chemotherapy naive patients with histologically proven androgen independent prostate cancer, adequate androgen ablation, and clinical and/or biochemical progression were randomly assigned to receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B) weekly. Treatment was continued until clinical and/or biochemical progression. In cases of progression patients switched to the alternative treatment arm. The primary end point was time to disease progression. Secondary end points included prostate specific antigen response rates in sequential treatment, analgesic response and toxicity. RESULTS: The current analysis showed a doubled risk of progression in treatment arm B. The median time to first disease progression was 14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a greater than 50% prostate specific antigen decrease on first line therapy was significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033). After progression to docetaxel second line vinorelbine yielded a greater than 50% prostate specific antigen response rate of 28.6% vs 62.5% for second line docetaxel. Clinically significant toxicity occurred more often in arm B with neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005) during the first treatment phase. CONCLUSIONS: While weekly application of both cytotoxic agents was well tolerated, this study demonstrates the superiority of docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent prostate cancer.

Penile cancer: review of the recent literature.

PURPOSE OF REVIEW: To review recent developments in the diagnosis and treatment of penile cancer, we reviewed the medical literature from 1 May 2002 to 1 June 2003 on the incidence, aetiology, staging, diagnosis and treatment of penile cancer by a Medline search. RECENT FINDINGS: The diagnostic tools and treatment modalities for penile cancer are still controversial. Recently developed diagnostic and therapeutic modalities should help urologists in the management of the disease. SUMMARY: Our review of the recent literature provides an update on diagnostic and therapeutic opinion on penile cancer.

Stage I testicular cancer.

PURPOSE OF REVIEW: To review current developments in the management of patients with testicular cancer, with special emphasis on risk factors for the primary tumour and treatment options for clinical stage I testicular germ cell tumours. RECENT FINDINGS: The management of patients with testicular cancer has substantially improved over the past 25 years. Current concepts for treating localized and regional disease have been influenced by effective systematic chemotherapy. At present, cure rates approach nearly 100% for low-stage disease and more than 80% for advanced disease. SUMMARY: Retroperitoneal lymph node dissection is still favoured as the therapy of choice for clinical stage I non-seminomatous germ cell tumours in many centres, but as risk factors for the primary tumour have become better understood, surveillance and risk-adapted therapy, including surveillance for low-risk patients and adjuvant chemotherapy for the high-risk group, is now being considered a therapeutic option particularly in European centres. Adjuvant radiotherapy is still the gold standard for the treatment of patients with clinical stage I seminoma, but the relapse rate of 19% and a 5-year overall survival of 97.7% make surveillance a possible therapeutic option. The results of phase II and III trials should soon provide additional information on carboplatin for single-agent adjuvant chemotherapy.

Low dose carboplatin combined with angiostatic agents prevents metastasis in human testicular germ cell tumor xenografts.

PURPOSE: Low dose chemotherapy combined with angiogenesis inhibitors has been shown to be more effective for experimental tumor treatment than chemotherapy alone. To our knowledge whether germ cell tumors could benefit from this treatment strategy remains to be evaluated. We examined the efficacy of angiostatic thrombospondin-1 (TSP-1), endostatin and combined angiostatic/low dose carboplatin in mice xenografted with human nonseminomatous germ cell tumor. MATERIALS AND METHODS: We monitored tumor progression and angiogenesis in the established model of human nonseminomatous germ cell tumor xenograft in 120 SCID mice using intravital video microscopy, immunocytochemistry and real-time polymerase chain reaction. Mice received TSP-1 (20 mg/kg daily) or endostatin (10 mg/kg daily) subcutaneously (via osmotic mini pumps) for 2 weeks starting 15 days after cancer cell grafting, carboplatin cycled twice (30 mg/kg intraperitoneally days 14 and 21 after cancer cell grafting), or a combination of carboplatin with TSP-1 or endostatin. Untreated, sham and tumor bearing mice treated with Ringer's solution served as controls. RESULTS: Primary tumor development was not affected in mice treated with TSP-1, endostatin or carboplatin alone. All animals had metastases at 6 months, while metastasis did not develop following the combination of carboplatin with TSP-1 or endostatin. This combined therapy suppressed tumor angiogenesis, enhanced apoptosis in tumor cells and decreased vascular endothelial growth factor-A tissue mRNA expression vs controls (p <0.05). CONCLUSIONS: These data indicate that angiostatic agents added to low dose carboplatin have the ability to suppress the progression of human germ cell tumor xenografts toward a metastatic phenotype. Therefore, this treatment strategy might be beneficial to prevent metastasis in germ cell tumors.

Efficient carboplatin single therapy in a mouse model of human testicular nonseminomatous germ cell tumor.

PURPOSE: Cisplatin based combination therapy has shown excellent clinical results in patients with testicular nonseminomatous germ cell tumor but chemotherapy induced morbidity and reduced patient compliance are limiting factors in this regimen. To decrease cisplatin based combination therapy induced morbidity we examined carboplatin versus etoposide single therapy in an animal model. MATERIALS AND METHODS: A total of 180 SCID mice bearing testicular nonseminomatous germ cell tumor xenografts received 120 mg./kg. carboplatin as a single cycle, 60 or 30 mg./kg. carboplatin cycled twice, 80, 50 or 30 mg./kg. etoposide cycled twice, or Ringer solution as the control. An additional 20 sham treated and 20 untreated mice also served as controls. Histological and immunocytochemical testing, in vivo microscopy, vascular corrosion casting, serum tumor markers, complete blood count and real-time polymerase chain reaction were used to monitor therapy efficacy. RESULTS: Carboplatin at 60 mg./kg. cycled twice eradicated the tumor and significantly reduced vascular density and vascular endothelial growth factor-A messenger RNA (p <0.05). Elevated tumor markers returned to baseline after carboplatin administration. Therapy was well tolerated, resulting thrombocytopenia disappeared 6 weeks after therapy and the animals were tumor-free 6 months after treatment. Although 120 mg./kg. carboplatin eradicated the tumor, it resulted in extensive mortality and morbidity. Single treatment 30, 50 and 80 mg./kg. etoposide failed. CONCLUSIONS: Carboplatin single therapy was highly effective in our nonseminomatous germ cell tumor model and it may be examined in future clinical trials in patients with high risk stage I nonseminomatous germ cell cancer for reducing cisplatin based combination therapy induced morbidity. Vascular density and vascular endothelial growth factor messenger RNA were elevated in our animal model and deserve further study in nonseminomatous germ cell tumor cases as potential risk factors.