Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful?

OBJECTIVE: To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management. METHODS: We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick's classification. RESULTS: Before TMT, thrombus level was staged I for 1 (7%), II for 10 (72%) and III (21%) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1-5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43%) patients had a measurable decrease, 6 (43%) had no change, and 2 (14%) had an increase in the thrombus. One patient (7%) had a downstage of thrombus level, 12 (85%) had stable thrombi, and 1 (7%) had an upstage. Regarding primary tumor, 7 (50%), 5 (36%) and 2 (14%) patients had a decrease, stabilization and an increase in tumor size, respectively. CONCLUSION: Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi.

Transrectal focused ultrasound combined with transurethral resection of the prostate for the treatment of localized prostate cancer: feasibility study.

PURPOSE: We studied the feasibility of combined treatment with high intensity focused ultrasound (HIFU) and transurethral resection or incision of the prostate for localized prostate cancer to decrease the risk of posttreatment prolonged urinary retention. MATERIALS AND METHODS: Included in this feasibility study were 30 patients fulfilling certain criteria, namely localized prostate cancer indicated for HIFU, age 60 years or older, prostate volume 45 cc or less, no more than 4 positive samples at sextant biopsy, baseline prostate specific antigen (PSA) 10 ng/ml or less and no evidence of cancer extension. They received the combined treatment under general anesthesia using an Ablatherm HIFU device (EDAP SA, Lyon, France). RESULTS: The enrolled patients were a mean of 72 years old and presented with a median prostate volume of 30 cc. Median Gleason score was 6, median PSA was 7 ng/ml and pretreatment sextant biopsies provided a median of 2 positive samples. Mean operative time was 2 hours 48 minutes, including resection and HIFU. An average of 616 HIFU shots were delivered. The urinary catheter was removed at day 2 after treatment. Median hospital stay was 3 days. Only a few complications were observed. In regard to the oncological aspects at a mean of 20 months of followup 86% of the patients had negative biopsies after HIFU. Median PSA was 0.9 ng/ml. At 1 year of followup the mean International Prostate Symptom Score was 8. Regarding sexual function, 73% of previously potent patients reported preserved sexual activity. CONCLUSIONS: The combination of endoscopic resection or incision of the prostate with HIFU treatment decreases urinary catheterization time and improves posttreatment urinary status without additional morbidity.

Evidence for a mitochondrial impact of trimetazidine during cold ischemia and reperfusion.

In organ transplantation, ischemia-reperfusion injury (IRI) has been implicated in delayed graft function (DGF) as well as in short- and long-term complications. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in CEL, UW and particularly HEH in combination with TMZ, particularly after 48 and 72 h. Mitochondria integrity was improved in TMZ-preserved groups. This study indicates that TMZ is efficiently protective against IRI even after prolonged preservation and in different preservation solutions.