External validation of a predictive model of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

INTRODUCTION: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era. METHODS: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed. RESULTS: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset. CONCLUSIONS: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN.

Resection of metastasis and local recurrences of renal cell carcinoma after presurgical targeted therapy: probability of complete local control and outcome.

PURPOSE: To analyse probability of complete local control and outcome in patients with metastases and local recurrences who have a high probability of failure of local therapy and who were treated with presurgical targeted therapy with the intention to reconsider complete resection or other local therapies such as radiotherapy or ablation. METHOD: From two institutional databases, patients with metastatic or locally recurrent RCC were retrospectively identified who received targeted therapy based on a multidisciplinary tumour board decision because of high probability of failure of local control. RESULTS: From January 2007 until November 2014, 34 patients were treated and included in the analysis. Five patients underwent no local therapy due to insufficient downsizing to attempt resection. The probability of proceeding to local therapy was 85.3 %. Median overall survival of 29 patients with local therapy after pretreatment was 67 months (range 9-173, 95 % CI 90.87) with a median disease-free survival of 12 months (range 0-147 months). The probability to achieve complete local therapy and discontinue targeted therapy was 73.5 % (25 of 34 patients). Median time without systemic therapy was 12 months. CONCLUSION: In a retrospective series of patients with a high probability of failure of local therapy, neoadjuvant targeted therapy was associated with successful complete local treatment in approximately 70 % of patients with a time off targeted therapy of ≥1 year in 50 %. Only number of metastatic sites and the disease-free interval after treatment were associated with outcome.

Damage to the spermatic cord by the Lichtenstein and TAPP procedures in a pig model.

BACKGROUND: Mesh implantation is regarded as the standard treatment of inguinal hernias. Obstructive azoospermia induced by mesh implantation is a rare but serious complication. Whether different operative techniques or mesh materials used have an effect on the integrity of the testicle and spermatic cord remains unclear. MATERIALS: In 12 minipigs a bilateral inguinal hernia repair, either open or laparoscopic, was performed using a standard small-pore polypropylene (PP) or large-pore polyvinyliden fluoride (PVDF) mesh. Next to measurement of the testicular size, thermography of the groin and testicle as a parameter for perfusion was performed preoperatively and at a follow-up at 6 months. Obstructions of the vas deferens were estimated radiographically. Testicular function (Johnson score) and mesh integration (granuloma size, apoptotic cells) were analyzed histologically. RESULTS: Mean testicular size did not change significantly in follow-up compared to preoperative values. Technique and mesh material used failed to have a significant influence. Thermography of the groin following the Lichtenstein technique had significantly higher values at follow-up regardless of the mesh used. This could not been shown for laparoscopic treatment. Thermographic measurements at the testicle showed a significantly increased temperature in all groups compared to preoperative measurements. Only the Lichtenstein PP group showed significantly decreased values in testicular function. Quantity and quality of obstructions seen at vasography were most detectable in the Lichtenstein PP group. There was significantly decreased granuloma formation following PVDF mesh implantation compared to the PP mesh group regardless of the technique used. CONCLUSIONS: Both the technique and the mesh material have an impact on integrity of spermatic cord and testicular function. According to the results of this study, the laparoscopic TAPP procedure using a large-pore PVDF mesh has the least effect compared to preoperative values.