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Millions of individuals in United States are affected by Prostate Cancer (PCa), with tens of thousands dying every year, as therapeutic options for more advanced stages are not yet curative. A lack of suitable models of human cancer and inter-patient tumor heterogeneity often hinder the drug discovery process. In fact, the lost-in-translation phenomenon is one of the major causes of failure for compounds in the transitioning process from the workbench to the clinic. These limitations implicate considerable costs for the society in terms of both financial assets and human lives. To accelerate the drug discovery process, we devised and experimentally validated OncoLoop, a data-driven framework for the identification of clinically-relevant compounds that can be validated in preclinical models that optimally match patient-specific tumor dependencies. Specifically, we generated a set of Genetically-Engineered Mouse Models (GEMMs) of prostate cancer that recapitulate a wide variety of established prostate-cancer driver mutations. Their RNA profiles were then used to reverse-engineer a murine prostate cancer regulatory network, which was used to assess the activity profile of thousands of GEMM-specific regulatory proteins using the VIPER algorithm. We then assessed the match between the GEMM repertoire and several human prostate cancer databases–including from The Cancer Genome Atlas (TCGA) and Stand-Up To Cancer (SU2C) consortia–based on GEMM vs. patient Master Regulator (MR) protein conservation. This allowed selecting an optimally matched GEMM model, for virtually every patient in these databases, to serve as an in vivo surrogate model for screening patient-relevant drugs (i.e., a patient avatar). We then leveraged large-scale perturbational databases, comprising RNASeq profiles of 2 prostate cancer cell lines treated with >400 drugs, to prioritize drugs presenting the greatest ability to reverse MR protein activity in both the patient and in its optimally-matched GEMM, using the OncoTreat algorithm (Alvarez, et al. Nat Genet 2018). This formed a closed loop between each patient, its optimally matched GEMM and the drug(s) inferred to invert the activity of MR proteins in both the patient and the GEMM. OncoLoop selection of candidate drugs was validated in vivo. Notably, four out of five drugs were validated in the GEMM, including two inducing complete abrogation of tumor growth and two inducing significant tumor size reduction. In summary, we propose that given a patient's tumor biopsy, OncoLoop can identify an optimal GEMM model for in vivo validation and dramatically reduce the combinatorial search space of candidate drugs to a handful that may be effectively tested in that model. OncoLoop can be applied to any other cancer for which clinically-relevant tumor models are available. Citation Format: Alessandro Vasciaveo, Min Zou, Juan Arriaga, Andrea Califano, Cory Abate-Shen. OncoLoop: Closing the loop between patient-centered drug discovery and preclinical testing in precision-oncology [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 822.

Since the Food and Drug Administration (FDA), USA granted its approval to use the da Vinci Robotic Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA) for gynecological practice, it has been documented that the advantages of robotics apply well to urogynecologic procedures. The two most common operative techniques in this area are Burch’s procedure for stress urinary incontinence and sacrocolpopexy for correct the pelvic organs prolapse. During both procedures, complications can arise. The most common in retropubic cystourethropexy are injuries to the urinary organs during dissection and suture fixation; vascular damage, ureteral entrapment, and obturator nerve damage can occur, furthermore others less frequent that have been reported. Regarding to sacrocolpopexy, vascular injuries to promontory and iliac vessels may occur, mesh erosion and migration is an important issue and rarely but osteomyelitis can befall. It is mandatory to understand the anatomy of the Retzius and presacral spaces to avoid the mentioned complications, as well to be prepared to control and repair of the injuries in these procedures, with patience and efficiency. Proved skills in laparoscopic and robotic suturing is mandatory for the appropriate performance of urogynecologic procedures. In this chapter, the complications reported and how to resolve them are described.

The urologist is a specialist in the diseases of the urinary tract, which includes the kidneys, ureters, bladder, and urethra, all present in both men and women. Therefore, the urologist works with both men and women. This specialist also deals with men’s genital diseases—specifically those that affect the penis, testicles, or prostate—and those related to the male sexual function.

The complete removal of the stone is the ultimate goal in management, a result that might not be attained even after several sessions of percutaneous nephrolithotomy (PCNL) and/or extracorporeal shockwave lithotripsy (SWL) and/or retrograde intrarenal surgery (ureteroscopy). The objective of this study is to assess our technique of anatrophic nephrolithotomy, with decreased renal ischemia and reduced patient morbidity.From 2007 to 2010, we performed eight anatrophic laparoscopic nephrolithotomies in adult patients with staghorn renal calculus. The mean patient age was 49 years (range 35-62 y). The mean stone size was 53 mm (range 35-70 mm). All patients had complex renal calculi, with stones occupying more than 80% of the caliceal system. In all cases, a Double-J stent was placed before surgery. After clamping the hilum, the incision was made laterally and longitudinally through full thickness of cortex using a laparoscopic scalpel. A running cortical suture was performed with Hem-o-lok reinforcement. Renal function was assessed in three patients, using renography with technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA), before and 3 months after the surgery.Procedures for all patients were completed laparoscopically. The mean operative time was 142.5 minutes, and the mean warm ischemia time was 20.8 minutes. The estimated blood loss was 315 mL. The hospital stay average was 3.5 days. Only one patient had a complication--a vascular fistula with permanent postoperative hematuria. This patient subsequently underwent successful endovascular embolization. Residual stones were identified in 37% of cases (three patients) during follow-up imaging at 15 days. There were minimal changes on serum creatinine values.Laparoscopic surgery is feasible when anatrophic nephrolithotomy is indicated. This technique minimizes the barriers of an open flank incision, while achieving excellent stone-free rates. This minimally invasive technique should be considered for complex stones that would necessitate multiple renal access tracks and secondary procedures.