Contemporary retroperitoneal lymph node dissection (RPLND) for testis cancer in the UK - a national study.

OBJECTIVES: To undertake a comprehensive prospective national study of the outcomes of retroperitoneal lymph node dissection (RPLND) for testis cancer over a 1-year period in the UK. PATIENTS AND METHODS: Data were submitted online using the British Association of Urological Surgeons Section of Oncology Data and Audit System. All new patients undergoing RPLND for testis cancer between March 2012 and February 2013 were studied prospectively. Data were analysed using Tableau software and case ascertainment compared with Hospital Episode Statistics data. RESULTS: In all, 162 men underwent RPLND by 20 surgeons in 17 centres. The mean (range) case volume per centre was 9 (2-32) and the median (range) case volume per surgeon was 6 (1-30). Indications included: residual mass after chemotherapy (73%), primary treatment (6%), relapse (14%), and salvage (7%). The median time to surgery after chemotherapy was 8-12 weeks (<4 - >12 weeks) and 91% of procedures utilised open surgery. The median operating time was 3-4 h (<1.5 - >6 h). Nerve sparing was performed in 67% of patients (19% bilateral, 48% unilateral). The dissection was template in 81% and lumpectomy in 16%; 25% required additional intraoperative procedures including 11% synchronous planned nephrectomy. In all, 157/160 (98%) of recorded RPLND operations were completed. One was terminated due to bleeding and in two the mass could not be removed. There were no deaths within 30 days of surgery. In all, 75% of the men did not require a blood transfusion, 15% required 1-2 units and 10% received >2 units. There were postoperative complications in 10% of the men (Clavien-Dindo Grade I, seven men; Grade II, seven; and Grade III, one). The mean (range) length of stay was 5.5 (1-59) days. Histology showed necrosis in 22%; teratoma differentiated in 42%; and residual cancer in 36%. CONCLUSIONS: This prospective collaborative national study describes for the first time the surgical outcomes after RPLND across the UK. The quality of RPLND in the UK appears high. The study can act as a benchmark for this type of surgery across the world.

Percutaneous cryoablation of renal tumours: outcomes from 171 tumours in 147 patients.

OBJECTIVE: To evaluate the technical and oncological efficacy of an image-guided cryoablation programme for renal tumours. PATIENTS AND METHODS: A prospective analysis of technical and radiological outcomes was undertaken after treatment of 171 consecutive tumours in 147 patients. Oncological efficacy in a subset of 125 tumours in 104 patients with >6 months' radiological follow-up and a further subset of 62 patients with solitary, biopsy-proven renal carcinoma was also analysed. Factors influencing technical success, as determined by imaging follow-up, and complication rates were statistically analysed using a statistics software package and logistic regression analyses. RESULTS: No variables were found to predict subtotal treatment, although gender (P = 0.08), tumour size of >4 cm (P = 0.09) and central location of tumour (P = 0.07) approached significance. Upper pole location was the single variable that was found to predict complications (P = 0.006). Among the 104 patients (125 tumours), radiologically assessed at ≥6 months and with a mean radiological follow-up of 20.1 months, we found a single case of unexpected late local recurrence. CONCLUSION: Percutaneous image-guided cryoablation, at a mean of 20.1 months' follow-up, appears to provide a safe and effective treatment option with a low complication rate. Anteriorly sited tumours should not be considered a contraindication for percutaneous image-guided cryoablation.

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older.

UNLABELLED: What's known on the subject ? and What does the study add? The treatment of younger men with testicular germ cell cancers is well documented with established intensive chemotherapy regimens for those with advanced disease. Although the majority of patients present in the third or fourth decade, men also present in later life. These patients are typically excluded from clinical trials and there are no contemporary published series describing their management. This series describes the management of older patients with testicular germ cell tumours at both early and advanced stages of disease. Patients with stage I seminoma can be safely managed with all recognised treatment strategies and state I non-seminomas were managed with surveillance. Cure can still be achieved in older patients with advance germ cell tumours however chemotherapy regimens developed in younger patients must be tailored to the presence of co-morbidity. OBJECTIVES: • To review the practice of a large referral centre for the management of older patients with testicular germ cell cancer (GCC). • There are few published data available on the management of testicular GCC in elderly patients, who often have medical comorbidities and have been excluded from clinical trials. PATIENTS AND METHODS: • We reviewed our prospectively collected database for patients presenting with GCC who were aged ≥60 years. • Details of presentation, management and outcome were recorded. RESULTS: • In total, 60 patients aged ≥60 years were identified from 1461 patients treated with GCC from 1979-2005, representing 4% of the total population. • Median age was 67 years, 44 had seminoma (73%) and 16 had non-seminoma histology (27%). • Stage I seminoma patients were managed with surveillance, adjuvant radiotherapy and adjuvant carboplatin. All stage I non-seminomas underwent surveillance. • In total, 15 patients received systemic chemotherapy for metastatic disease with modified bleomycin, etoposide and cisplatin; etoposide and cisplatin; carboplatin-based regimens; or other combinations. Toxicity was manageable, with no toxic deaths. • In total, four patients (6.7%) died of GCC. CONCLUSIONS: • In elderly patients, GCC should be managed with curative intent. • Conventional therapies are tolerable for most men with stage I seminoma. In metastatic disease, comorbidity may necessitate treatment modifications. • Most patients are cured with manageable toxicity.

Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines.

OBJECTIVES: To examine the effects of verapamil on the intracellular drug pharmacokinetics of epirubicin using alternative dosing schedules. The results might inform the choices for optimizing clinical chemotherapy. METHODS: Sensitive parental (MGH-U1) and multidrug resistant (MDR) (MGH-U1R and MGH-U1-MMC) bladder cancer cell lines were used. Fluorescence time-lapsed studies were performed on cells incubated with epirubicin alone or combined with verapamil. Flow cytometry was performed after the alternative dosing regimens. RESULTS: Verapamil reversed the epirubicin localization patterns in MDR cells. Time-lapse imaging showed that nuclear epirubicin accumulation in MDR cells with verapamil followed the parental curve. The maximal reversal took >60 minutes. Flow cytometry showed increased epirubicin uptake in MDR cells co-incubated with verapamil. Preincubation was not as effective as co-incubation. CONCLUSIONS: The results of our model indicate that longer exposure to MDR-class drugs, exemplified by epirubicin, increases uptake and the MDR reversing action of co-treatment with verapamil. The present results highlight the need for additional clinical trials of drug dosing and scheduling for combination intravesical chemotherapy regimens.

Management of renal tumors by image-guided radiofrequency ablation: experience in 105 tumors.

AIMS: In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. MATERIALS AND METHODS: RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. RESULTS: Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson chi(2)) Five patients had complications. There have been no local recurrences. CONCLUSION: Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors.

The nuclear membrane in multidrug resistance: microinjection of epirubicin into bladder cancer cell lines.

OBJECTIVE: To assess whether microinjecting epirubicin into cells showing multidrug resistance (MDR, common to many cancers, including bladder cancer, with resistance to, e.g. anthracyclines and mitomycin C) spares the nucleus, as when these drugs accumulate, distribution in MDR cells characteristically spares the nucleus, suggesting that the nuclear membrane is responsible for excluding cytotoxic drugs from MDR nuclei. MATERIALS AND METHODS: Nuclear exclusion of drugs is an important feature of resistance in MDR cells, as many MDR-susceptible drugs have cytotoxic actions within the nucleus. Drug accumulation in 'classical' P-glycoprotein-mediated MDR cells is greatly reduced by efflux. Microinjection of epirubicin into the cytoplasm of MDR cells bypasses the P-glycoprotein efflux pump on the plasma membrane. Nuclear sparing would directly implicate the nuclear membrane in this phenomenon. Because of their fluorescence properties, which allow study by confocal microscopy and flow cytometry, anthracyclines have also been used extensively to investigate MDR. Thus sensitive (MGH-U1 and RT112) and MDR (MGH-U1R and MGH-U1-MMC) bladder cancer cell lines were used. Adherent cells from each cell line were individually microinjected with epirubicin (0.5 mg/mL) and a 77 kDa fluorescein isothiocyanate (FITC)-dextran (0.5 mg/mL). The pattern of nuclear epirubicin uptake in injected cells was then evaluated by confocal microscopy. The 77 kDa FITC-dextran allowed easier identification of injected cells and was also excluded from their nuclei. RESULTS: Sensitive bladder cancer cell lines all showed a nuclear accumulation pattern of epirubicin, consistent with their normal uptake after exposure to epirubicin. The MDR cell lines showed the characteristic nuclear-sparing pattern of epirubicin uptake, similar to the normal uptake pattern after epirubicin exposure. The 77 kDa FITC-dextran showed clearly which cells had been microinjected, and was excluded from the nuclei of all injected cells. Cell viability was confirmed by acridine-orange staining after initial visualization of injected cells. CONCLUSION: The nuclear membrane is responsible for the nuclear exclusion of epirubicin in MDR cells. Further work is necessary to determine the mechanisms involved.