Patients' perception of surgical outcomes and quality of life after retroperitoneoscopic and open pyeloplasty.

PURPOSE: To report postoperative health-related quality of life (HRQoL) and patients' subjective evaluations of open pyeloplasty (OP) and retroperitoneoscopic pyeloplasty (RP) and influences on preoperative counselling. METHODS: 107 patients (age 16-80 years, mean 31.5) with symptomatic primary ureteropelvic junction obstruction who underwent OP (32) or RP (75) were evaluated prospectively. HRQoL was evaluated using Short Form 36 (SF-36) questionnaires with 1 year follow-up. Operative outcomes were evaluated using a self-designed questionnaire regarding cosmetic outcomes, objective postoperative/current pain, convalescence and return to work. RESULTS: The mean operative time was 174.4 vs. 161.4 min for RP versus OP, respectively, without intraoperative complications/conversions. There was an advantage for RP--except for two domains--without significance in any of the eight SF-36 domain scores. An advantage favouring RP in all aspects of the second questionnaire with significance in four aspects (cosmetic results, scar length, pain and convalescence) was found. Five weeks postoperatively, 58.7% (RP) vs. 25.8% (OP) were fully convalescent compared to 87.0% (RP) vs. 71.0% (OP) at 8 weeks. Similarly, 58.7 vs. 45.1% returned work 5 weeks postoperatively while 93.5 vs. 74.2% did so after 8 weeks, respectively. The small sample size, more questions on satisfaction/regret and mixed design are the main study limitations. CONCLUSION: RP provides the same functional results beside earlier convalescence, better HRQoL and patients' convenience with surgery, which favours its inclusion in preoperative counselling providing patients with realistic postoperative expectations.

In vitro investigations of repulsion during laser lithotripsy using a pendulum set-up.

Ureteroscopic laser lithotripsy is a commonly used technique to treat ureteral calculi.The type of energy source used is one of the main influences of retrograd calculi propulsion. Using a momentum pendulum under-water set-up the induced momentum and the initial velocity were investigated. Pulsed laser light from three different clinically available laser systems, including a Ho:YAG laser, a frequency-doubled double-pulse (second harmonic generation, SHG) Nd:YAG laser and a flash-lamp pumped dye (FLPD) laser, were transmitted via flexible fibres of different core diameter to the front of the pendulum sinker. Single pulses at variable pulse energy, according to the clinical laser parameter settings, were applied to the target sinker, thus causing a repulsion-induced deflection which was documented by video recording. The maximum deflection was determined. Solving the differential equation of a pendulum gives the initial velocity, the laser-induced momentum and the efficiency of momentum transfer. The induced deflection as well as the starting velocity of the two short-duration pulsed laser systems (SHG Nd:YAG, FLPD) were similar (s (max) = 2-3.6 cm and v (0) = 150-200 mm/s, respectively), whereas both values were lower using the Ho:YAG laser with a long pulse duration (s (max) = 0.9--1.6 cm and v (0) = 60-105 mm/s, respectively). The momentum I induced by the Ho:YAG laser was only 50% and its transfer efficacy η (Repuls) was reduced to less than 5% of the values of the two short-pulsed laser systems. This investigation clearly showed the variable parts and amounts of repulsion using different pulsed lasers in an objective and reproducible manner. The momentum transfer efficiency could be determined without any physical friction problems. Further investigations are needed to compare stone fragmentation techniques with respect to laser repulsion and its clinical impact.

Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma.

OBJECTIVE: • To analyse the safety and efficacy of simultaneous standard anti-angiogenic therapy and stereotactic radiosurgery (SRS) in patients with spinal and cerebral metastases from renal cell carcinoma. PATIENTS AND METHODS: • In all, 106 patients with spinal (n= 55) or cerebral (n= 51) metastatic lesions and an Eastern Cooperative Oncology Group status of 0 or 1 were treated with sorafenib or sunitinib and simultaneous SRS. • The primary endpoint was local control. • Secondary endpoints were toxicity and overall survival. RESULTS: • Median follow up was 14.7 months (range 1-42 months). Forty-five patients were treated with sunitinb and 61 patients with sorafenib. Two patients had asymptomatic tumour haemorrhage after SRS. • No skin toxicity, neurotoxicity or myelopathy occurred after SRS, and SRS did not alter the adverse effects of anti-angiogenic therapy. • Local tumour control 15 months after SRS was 98% (95% confidence interval 89-99%). The median pain score before SRS was 5 (range 1-8) and was lowered to 0 (range 0-2, P < 0.01) after SRS. There were no treatment-related deaths or late complications after SRS. • Overall survival was 17.4 months in patients with spinal lesions and 11.1 month in patients with cerebral lesions (P= 0.038). CONCLUSIONS: • Simultaneous systemic anti-angiogenic therapy and SRS for selected patients with renal cell carcinoma who have spinal and cerebral metastases is safe and effective. • Single-fraction delivery allows for efficacious integration of focal radiation treatment into oncological treatment concepts without additional toxicity. • Further studies are needed to determine the limits of SRS for renal cell carcinoma metastases outside the brain and spine.

DNA hypermethylation in papillary renal cell carcinoma.

OBJECTIVE: To investigate the pattern of DNA CpG island hypermethylation in papillary renal cell carcinoma (pRCC). MATERIAL AND METHODS: DNA from pRCC (n= 32) and adjacent normal tissue (n= 15) was isolated. A quantitative methylation-specific PCR was performed to analyse the methylation pattern at APC (actin beta), CDH1 (E-cadherin), GSTP1 (glutathione S-transferase pi 1), RASSF1A (Ras association domain family member 1A) and TIMP3 (TIMP metallopeptidase inhibitor 3); a sequence of ACTB without CpG was used to normalize for DNA input and to calculate the relative amount of methylated DNA (normalized index of methylation, NIM). RESULTS: RASSF1A hypermethylation was observed in most pRCC and normal samples (100 vs 94.4%), but the median NIM was significantly higher in pRCC samples (2.11 vs 0.61; P < 0.001). RASSF1A hypermethylation allowed discrimination of pRCC and normal tissue with a sensitivity of 87.5% and a specificity of 73.3% as determined via receiver operator characteristic analysis (area under curve = 0.814). Hypermethylation at APC (3.0 vs 6.7%), CDH1 (15.6 vs 0%), GSTP1 (21.9 vs 6.7%) and TIMP3 (6.3 vs 0%) was infrequent in pRCC and normal tissue. CDH1 was significantly correlated with pathological stage (P= 0.015), and patients with methylated CDH1 methylation showed a trend towards shorter recurrence-free survival (log-rank P= 0.057). The number of methylated gene sites was correlated with pathological stage (P= 0.007) and lymph node metastasis (P= 0.008). CONCLUSIONS: DNA hypermethylation at RASSF1A is common in pRCC tissue irrespective of the histological subtype, but also frequently seen at lower levels in normal adjacent tissue. Aberrant hypermethylation could be a prognostic marker for pRCC.

The growth rate of large renal masses opposes active surveillance.

OBJECTIVE: To retrospectively determine the growth rate of renal masses with a diameter of > or =4 cm at the time of surgery, as the average growth rate of untreated small (<4 cm) renal masses is assumed to be 0.1-0.7 cm/year, but little is known about the progression of large masses. PATIENTS AND METHODS: Of 256 patients who had their renal tumour surgically removed between January and December 2008, we identified nine (five men and four women; median age 65.2 years, range 29.2-74.2) with solitary large renal masses (>4 cm) who had abdominal imaging with identification of renal masses >6 months before admission. In none of the patients had the initial imaging led to admission, either by accident or because the masses were overlooked. The tumour growth rate was calculated based on images taken > or =6 months before admission and actual imaging, as well as histological results. RESULTS: All patients had surgical resection of their renal masses in 2008. The median (range) follow-up from initial diagnosis to surgery was 14.6 (6.5-58.4) months. The median observed tumour growth rate was 6.41 (2.47-8.66) cm/year. The histological diagnosis was clear cell renal cell carcinoma (RCC) in seven patients, papillary in one and clear cell RCC with portions of sarcomatoid de-differentiation in one; two patients had lymph node metastases and one had pulmonary metastases, and five had tumours of > or =T3. CONCLUSIONS: The growth rate of large tumours is much higher than of small renal masses and most patients present with advanced disease. Thus, tumours of > or =4 cm seem not to be candidates for active surveillance but require immediate therapy. Further studies are warranted to determine the clinical relevance of progressive tumour growth and the underlying mechanisms.

Liver resection for metastatic disease prolongs survival in renal cell carcinoma: 12-year results from a retrospective comparative analysis.

UNLABELLED: The value of surgical resection of renal cell carcinoma (RCC) liver metastases still remains unclear. OBJECTIVE: Of our study was to evaluate the efficacy of liver resection by comparing patients who could have undergone metastasectomy due to limited disease, but refused surgery. MATERIALS AND METHODS: Eighty-eight patients were identified with liver metastases and indication of surgery between 1995 and 2006. In 68 patients, liver resection was performed, 20 patients denied surgery and served as comparison group. Patients were followed for survival. RESULTS: Median age was 58. Median amount of liver metastases was 2 (range 1-30). Median follow-up was 26 months (range 1-187). In both groups, 79% received systemic therapy. The 5-year overall survival rate (OSR-5) after metastasectomy was 62.2% +/- 11.4% (SEM) with a median survival (MS) of 142 (95% confidence interval (CI) 115-169) months. OSR-5 in the control group was 29.3% +/- 22.0% (SEM) with a MS of 27 (95% CI 16-38) months (P = 0.003). MS was 155 (95% CI 133-175) months with metachronous metastases compared to 29 (95% CI 25-33) months in the comparison group (P = 0.001). Low-grade primary RCC had a MS of 155 (95% CI 123-187) months compared to 29 (95% CI 8-50) months without resection (P = 0.0036). High-grade RCC as well as patients with synchronous metastases did not benefit from surgery. CONCLUSIONS: Liver metastasectomy is an independent valuable tool in the treatment of metastatic RCC and significantly prolongs patient's survival, even if further systemic treatment is necessary. With the evidence given, patients may benefit from liver metastasis resection if technically feasible.

Plasma N-terminal pro-brain natriuretic peptide as prognostic marker in fatal cardial decompensation with sunitinib malate therapy.

A 74-year-old man with metastatic renal cell carcinoma and a history of cardiac failure was treated with sunitinib malate. MUGA echocardiography could not detect a relevant change in the ejection fraction although the clinical situation of the patient worsened dramatically. The only parameter to hint at the deteriorated cardiac function was plasma N-terminal pro-brain natriuretic peptide (BNP). Finally, the patient died after only one cycle of sunitinib treatment. We propose to prospectively include BNP for the early detection of cardiovascular decompensation in high-risk patients. Future studies concerning the relevance of BNP in drug-related cardiotoxicity are urgently needed.

Dual energy CT characterization of urinary calculi: initial in vitro and clinical experience.

OBJECTIVE: The purpose of this study is to assess the accuracy of dual energy CT (DECT) in the characterization of renal and ureteral stones. MATERIAL AND METHODS: Twenty-four renal calculi of known variable composition were scanned on a dual-source CT scanner (Somatom Definition; Siemens Medical Solutions, Forchheim, Germany) in dual energy (DECT) mode. Scan parameters for DECT were: tube potentials, 80 and 140 kV; tube current, 342 and 76 mA.s; collimation, 14 x 1.2 mm2. Dual energy properties of calculi were used to differentiate between uric acid (UA) and other calculi. Differentiation was based on a 3-material decomposition implemented in the dual energy software (Syngo VA 11; Siemens Medical Solutions). Color coding was used to display different types of stones and their DECT properties were characterized with density measurements at both photon energies. Subsequently, 20 consecutive patients with known or suspected uroliths were scanned using identical scan parameters. Stone size and material were assessed in DECT and compared with the chemical analyses of stones after mechanical extraction. RESULTS: With DECT characterization, differentiation of UA from other calculi was possible. Additionally, differentiation between cystine and struvite stones was shown to be feasible in vitro. In the patient cohort, DECT correctly characterized 4 UA calculi, 4 mixed, multiple calcified, and 1 cystine stone. The calculi were displayed in specific colors, ie, UA stones in red and calcified stones in blue. CONCLUSION: With dual energy CT techniques, the UA, cystine, struvite, and mixed renal calculi can be differentiated from other types of stones in vitro and in vivo. This is of clinical relevance as UA uroliths may be treated pharmacologically rather than with surgical extraction or extracorporal shockwave lithotripsy.

Renal surgery in the elderly: morbidity in patients aged >75 years in a contemporary series.

OBJECTIVES: To evaluate the surgical complications in a contemporary group of elderly patients with renal masses, as almost a quarter of patients with newly diagnosed renal mass are aged >74 years, with the potential for significant comorbidity. PATIENTS AND METHODS: From April 2004 to June 2007, of 379 surgical resections of renal tumours, we assessed 117 consecutive patients aged >or=75 years, who had either radical nephrectomy (RN) or partial nephrectomy (PN) for assumed renal cell carcinoma. Also elderly patients who had nephroureterectomy (NU) for upper urothelial cancer were followed. RESULTS: Fifty patients had RN, 57 PN and 10 had NU; the median (range) age of all patients was 78.1 (72.7-92.5) years and was similar in all groups. No patient died during surgery and only one died within 90 days. The complication rates during and after surgery RN, PN and NU were 12%, 15% and 20%, respectively; the major complications within 30 days were 4%, 7% and 10%; major complications included bleeding during surgery and one acute bleeding event after surgery in the PN group. CONCLUSIONS: Open renal surgery in elderly patients can be done safely; there was no difference in morbidity among RN, PN and NU. Renal surgery in the elderly patient is safe if done at a specialized centre. Mortality and morbidity can be very low, rendering this a feasible approach in the treatment of renal masses even if the prognosis is not determined by the oncological situation but by comorbidity.

Laparoscopic marsupialisation of pelvic lymphoceles in different anatomic locations following radical prostatectomy.

BACKGROUND: Pelvic lymphoceles (LCs) following radical prostatectomy (LC-RPs) are a well-described complication. Symptomatic LC-RPs are the most frequent, nonfunctional, postradical prostatectomy complications. OBJECTIVES: Description of the clinical presentations of LC-RPs and the detailed technique of laparoscopic pelvic LC marsupialisation (LM), including perioperative results and follow-up. DESIGN, SETTING, AND PARTICIPANTS: Data from 105 patients (age range: 57-76 yr) with symptomatic LC-RPs who underwent surgery in our institute were evaluated retrospectively. Pelvic ultrasound (US) and computed tomography scans, performed on all patients, revealed LC volumes ranging from 100 to 1200 ml. Fifty-five patients were refractory to prior percutaneous tube drainage and/or sclerotherapy. LM was performed using a three-trocar (n=60 patients) or two-trocar technique (n=45 patients). SURGICAL PROCEDURE: With the patient in Trendelenburg position, LCs were accurately identified by inspection, compressibility, and/or laparoscopic needle aspiration. A Foley catheter was inserted. Through one or two working trocars in the left lower abdomen, an adequate peritoneal window (wide ellipse) was excised. The LC cavity was inspected and septae, membranes, and haematomas were removed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative surgical outcomes, analgesic medication, and inflammation parameters were recorded. Follow-up and success rates were estimated with US for LC recurrence. RESULTS AND LIMITATIONS: Five pelvic LC locations could be identified: paravesical, lateral pelvic (encapsulated and uncapsulated), prevesical, and with retroperitoneal extension. These were relevant for clinical diagnosis and management options. Pelvic LCs were right-sided in 37 patients, left-sided in 15, and on both sides in 53. All LM were uneventful and operating time (mean) ranged from 15 to 265 (31.7) min, which became shorter with increasing experience. One conversion with postoperative blood transfusion was necessary. Patients were discharged between 2 and 4 (mean: 2.3) d postoperatively. Postoperative US revealed primary success in all cases. Three patients developed recurrence from 1 to 3 wk posthospitalisation; otherwise, none had treatment for LC during a mean follow-up of 20 mo. Limitations include the retrospective study design and the small number of patients. CONCLUSIONS: LC-RPs are common and can be classified into five different patterns of clinical/anatomic presentation. LM is simple, feasible, and safe as the first-line treatment for large, noninfected, symptomatic or refractory LC-RPs with fewer complications and an overall 97% success rate.

Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer.

OBJECTIVES: Radiotherapy (RT) is considered oncologically ineffective in metastatic renal cell cancer (mRCC). Inhibition of angiogenetic pathway may lead to radiosensitization in mRCC. The aim of this study was to evaluate the efficacy of the simultaneous combination of RT with systemic treatment of bulky (mRCC) using sunitinib. METHODS AND MATERIALS: We included 22 patients with progressive mRCC between 04/2007 and 08/2008 at the University Hospital Munich Großhadern. All patients underwent high-dose hypofractionated RT while they were simultaneously treated systemically with sunitinib 50 mg. RESULTS: Median age was 63.0 years (range 26.7-84.4). Median dose of radiation was 40 Gy (range 25-50) in a median of 8 fractions (range 5-30). Treatment sites were brain, retroperitoneal and mediastinal lymph nodes, spinal cord, bones, liver, and kidney. Median follow-up was 14.3 months. After 3 months, 2 patients had complete remission (CR), 9 patients showed partial remission (PR) as measured by response evaluation criteria in solid tumors (RECIST) criteria, 2 patients had minor response (MR), and 8 patients had stable disease (SD). Only 1 patient did not respond to therapy. Toxicity was very low with only 1 grade 4 hypertension. Skin toxicities were manageable with no grade 3 event during the combination period. CONCLUSIONS: The combination of RT with simultaneous systemic treatment using sunitinib is effective in patients with progressive mRCC. With high dose RT, complete response seems to be possible. Further evaluation should be based upon combination of RT with systemic therapy, rather than sequential RT regiments.

Outcome assessment of patients with metastatic renal cell carcinoma under systemic therapy using artificial neural networks.

BACKGROUND: The outcome of patients with advanced renal cell carcinoma (RCC) under systemic therapy shows remarkable variability, and there is a need to identify prognostic parameters that allow individual prognostic stratification and selection of optimal therapy. Artificial neural networks (ANN) are software systems that can be trained to recognize complex data patterns. In this study, we used ANNs to identify poor prognosis of patients with RCC based on common clinical parameters available at the beginning of systemic therapy. PATIENTS AND METHODS: Data from patients with RCC who started systemic therapy were collected prospectively in a single center database; 175 data sets with follow-up data (median, 36 months) were available for analysis. Age, sex, body mass index, performance status, histopathologic parameters, time interval between primary tumor and detection of metastases, type of systemic therapy, number of metastases, and metastatic sites were used as input data for the ANN. The target variable was overall survival after 36 months. Logistic regression models were constructed by using the same variables. RESULTS: Death after 36 months occurred in 26% of the patients in the tyrosine kinase inhibitors group and in 37% of the patients in the immunotherapy group (P = .22). ANN achieved 95% overall accuracy and significantly outperformed logistic regression models (78% accuracy). Pathologic T classification, invasion of vessels, and tumor grade had the highest impact on the network's decision. CONCLUSION: ANN is a promising approach for individual risk stratification of patients with advanced RCC under systemic therapy, based on clinical parameters, and can help to optimize the therapeutic strategy.

Profile of temsirolimus in the treatment of advanced renal cell carcinoma.

Temsirolimus is a potent inhibtor of the mammalian target of rapamycin (mTOR). In various clinical trials temsirolimus has shown an overall survival benefit for patients with metastatic renal cell carcinoma (mRCC). Thus it is approved for first-line therapy in high-risk mRCC patients. We discuss the indication, side effects and clinical implications of temsirolimus treatment.