Summary In cancer-treatment, potentially therapeutic drugs trigger their effects through apoptotic mechanisms. Generally, cell response is manifested by Bcl-2 family protein regulation, the impairment of mitochondrial functions, and ROS production. Notwithstanding, several drugs operate through proteasome inhibition, which, by inducing the accumulation and aggregation of misfolded or unfolded proteins, can lead to endoplasmic reticulum (ER) stress. Accordingly, it was shown that Amblyomin-X, a Kunitz-type inhibitor identified in the transcriptome of the Amblyomma cajennense tick by ESTs sequence analysis of a cDNA library, obtained in recombinant protein form, induces apoptosis in murine renal adenocarcinoma (RENCA) cells by: inducing imbalance between pro- and anti-apoptotic Bcl-2 family proteins, dysfunction/mitochondrial damage, production of reactive oxygen species (ROS), caspase cascade activation, and proteasome inhibition, all ER-stress inductive. Moreover, there was no manifest action on normal mouse-fibroblast cells (NHI3T3), suggesting an Amblyomin-X tumor-cell selectivity. Taken together, these evidences indicate that Amblyomin-X could be a promising candidate for cancer therapy.

Renal cell carcinoma (RCC), also called kidney cancer or renal adenocarcinoma, is highly resistant to current treatments. It has been previously reported that a Kunitz-type inhibitor domain-containing protein, isolated from the salivary glands of the Amblyomma cajennense tick, triggers apoptosis in murine renal adenocarcinoma cells (Renca) by inhibiting the proteasome and endoplasmic reticulum stress. Of note, Amblyomin-X is the corresponding recombinant protein identified in the cDNA library from A. cajennense salivary glands. Herein, using orthotopic kidney tumors in mice, we demonstrate that Amblyomin-X is able to drastically reduce the incidence of lung metastases by inducing cell cycle arrest and apoptosis. The in vitro assays show that Amblyomin-X is capable of reducing the proliferation rate of Renca cells, promoting cell cycle arrest, and down-regulating the expression of crucial proteins (cyclin D1, Ki67 and Pgp) involved in the aggressiveness and resistance of RCC. Regarding non-tumor cells (NIH3T3), Amblyomin-X produced minor effects in the cyclin D1 levels. Interestingly, observing the image assays, the fluorescence-labelled Amblyomin-X was indeed detected in the tumor stroma whereas in healthy animals it was rapidly metabolized and excreted. Taken the findings together, Amblyomin-X can be considered as a potential anti-RCC drug candidate.

LESS-PRA presented comparable functional and perioperative outcomes to LRA for small adrenal tumors. Although LESS-PRA was associated with longer operative time, it provided inferior estimated blood loss, analgesic time, and improved cosmetic satisfaction.

Introduction: Salvage Radical Prostatectomy after radiation therapy is challenging and associated with high rates of serious complications ( 1 , 2 ). The novel Retzius-Sparing RARP (RS-RARP) approach has shown excellent continence outcomes ( 3 , 4 ). Purpose: To describe step-by-step our Salvage Retzius-Sparing RARP (sRS-RARP) operative technique and report feasibility, safety and the preliminary oncological and continence outcomes in the post-radiation scenario. Materials and Methods: Twelve males presenting local prostate cancer recurrence after radiotherapy that underwent sRS-RARP were included. All patients performed preoperative multiparametric MRI and PSMA-PET. Surgical technique: 7cm peritoneum opening at Douglas pouch, Recto-prostatic space development, Seminal vesicles and vas deferens isolation and section, Extra-fascial dissection through peri-prostatic fat, Neurovascular bundle control, Bladder neck total preservation and opening, Anterior dissection at Santorini plexus plane, Apex dissection with urethra preservation and section, Prostate release, Vesicouretral modified Van Velthoveen anastomosis, Rocco Stitch, Oncological and continence outcomes reported with minimum 1-year follow-up. Results: Ten patients had previously received external beam radiation (EBR) whereas two received previous brachytherapy plus EBR. At 1, 3 and 12 months after surgery, 25%, 75% and 91.6% of the men used one safety pad or less, respectively. No major complications or blood transfusions were reported. Final pathology reported pT2b 41.6%, pT2c 33.3% and pT3a 25%, positive surgical margins 25%, positive lymph nodes were not found, biochemical recurrence 16.6%. Conclusion: Salvage Retzius-Sparing Robotic Assisted Radical Prostatectomy approach appears to be technically feasible and oncologically safe with potential to provide better continence outcomes.

PurposeThe LRP has a steep learning curve to obtain proficiency during which patient safety may be compromised. We present an adapted modular training system which purpose to optimize the learning curve and perform a safe surgery.Materials and MethodsA retrospective analysis of the LRP safe learning protocol applied during a fellowship program over eight years (2008-2015).The surgery was divided in 12 steps and 5 levels of difficulty. A maximum time interval was stipulated in 240 minutes. After an adaptation, the fellows had 120 minutes to perform all the corresponding modules to its accumulated skill. The participants gradually and safely pass through the steps and difficulty levels. Surgeries performed by fellows were analyzed as a single group and compared to a prior series performed by tutor.ResultsIn eight years, 250 LRP were performed (25 per apprentice) during fellowship program and 150 procedures after completion. The baseline characteristics were comparable. Most cases operated were of intermediate risk. Mean operative time was longer in the fellow group when compared to the tutor (150 min). Mean estimated blood loss were similar among the groups. Functional and oncological outcomes were better in the Tutor's group. No conversion to open surgery was performed.ConclusionsThe LRP safe learning protocol proved to be an effective method to optimize the learning curve and perform safe surgery. However, the tutor's functional and oncological results were better, showing that this is a procedure with a steep learning curve and proficiency demands more than 25 cases.