Outcomes and expanding indications for robotic retroperitoneal lymph node dissection for testicular cancer.

Treatment of testicular cancer has made significant progress in the past decades in terms of reduction of treatment-associated morbidity and preventing over-treatment. At the forefront of this progression is utilization of the da Vinci robot to perform retroperitoneal lymph node dissections (RPLNDs) via a minimally invasive approach. The robot offers multiple potential advantages such as smaller incisions, improved 3D visualization, more precise dissection, and faster convalescence, leading to its increased usage the past several years. In this chapter, we summarize the recent progress made in robotic surgery for testicular cancer and its potential in the future. Promising preliminary data has also renewed interest in defining the role of primary RPLND in patients with seminoma, potentially sparing patients of the harmful long-term radiation and cisplatin-based chemotherapy. SEMS and PRIMETEST trials are ongoing trials that will provide significant insight into this area and potentially expand the role of robotic RPLND.

Robotic assisted reconstruction for complications following urologic oncologic procedures.

Despite technical refinements in urologic oncologic surgery, complications are inevitable and often carry significant morbidity. Similar to oncologic surgery, reconstructive surgery has realized a paradigm shift from mainly open to an increasingly minimally invasive approach. Robotic assisted surgery has facilitated this transition as it mitigates some of the limitations of traditional laparoscopy. With continued technological advances in robotic technology along with improved training and experience, the breadth and complexity of cases expand annually. Few head to head trials exist and data is overall heterogeneous. Herein, we review and summarize the currently available literature describing robotic assisted reconstruction for complications following urologic oncologic procedures.

The metastasis efficiency modifier ribosomal RNA processing 1 homolog B (RRP1B) is a chromatin-associated factor.

There is accumulating evidence for a role of germ line variation in breast cancer metastasis. We have recently identified a novel metastasis susceptibility gene, Rrp1b (ribosomal RNA processing 1 homolog B). Overexpression of Rrp1b in a mouse mammary tumor cell line induces a gene expression signature that predicts survival in breast cancer. Here we extend the analysis of RRP1B function by demonstrating that the Rrp1b activation gene expression signature accurately predicted the outcome in three of four publicly available breast carcinoma gene expression data sets. In addition, we provide insights into the mechanism of RRP1B. Tandem affinity purification demonstrated that RRP1B physically interacts with many nucleosome binding factors, including histone H1X, poly(ADP-ribose) polymerase 1, TRIM28 (tripartite motif-containing 28), and CSDA (cold shock domain protein A). Co-immunofluorescence and co-immunoprecipitation confirmed these interactions and also interactions with heterochromatin protein-1alpha and acetyl-histone H4 lysine 5. Finally, we investigated the effects of ectopic expression of an RRP1B allelic variant previously associated with improved survival in breast cancer. Gene expression analyses demonstrate that, compared with ectopic expression of wild type RRP1B in HeLa cells, the variant RRP1B differentially modulates various transcription factors controlled by TRIM28 and CSDA. These data suggest that RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure.

Complications of Renal Surgery.

The incidence of the small renal mass continues to increase owing to the aging population and the ubiquity imaging. Most of these tumors are stage I tumors. Management strategies include surveillance, ablation, and extirpation. There is a wide body of literature favoring nephron-sparing approaches. Although nephron-sparing surgery may yield decreased long-term morbidity, it is not without its drawbacks, including a higher rate of complications. Urologists must be attuned to the complications of surgery and develop strategies to minimize risk. This article reviews expected complications of surgery on renal masses and risk stratification schema.

Uretero-Arterio-Enteric Fistula Formation and Stent Thrombosis After Endovascular Treatment of Ureteroarterial Fistula: A Case Report and Review of Literature.

Background: Ureteroarterial fistulas (UAFs) are rare life-threatening complications of indwelling ureteral stents. Endovascular repair of these fistulas is now commonly used but the long-term outcomes are unknown. Case Presentation: We present a 51-year-old African American female with history of cervical cancer status after a hysterectomy and radiation. She has bilateral ureteral strictures that were managed with chronic, indwelling ureteral stents. She subsequently developed a right UAF and was treated with an endovascular stent to the external iliac artery. After 2 years, she subsequently developed hematuria and hematochezia and was found to have a uretero-arterial-enteric fistula. We performed an exploratory laparotomy and repair of the fistula. The patient was subsequently managed with indwelling nephrostomy tubes and had no further episodes of bleeding. Conclusion: To our knowledge, this is the first reported case of uretero-arterial-enteric fistula after endovascular treatment of UAF. Our experience demonstrates the need for a high index of suspicion and close surveillance after treatment for patients with UAF.

Dartos Fascia Interposition Flap for Penetrating Cavernosal and Urethral Trauma.

We present an unusual case of a single gunshot to the genitalia in which the bullet trajectory injured the urethra, corpus cavernosum, and both testicles. All injuries were successfully repaired during initial exploration. Our report serves as a reminder to clinicians to have a high index of suspicion in this circumstance and consider immediate exploration of all the injured areas. We also demonstrate the use of a dartos fascia interposition flap to cover and separate the concomitant urethral and corporal sutures lines. Our dartos flap bolstered the urethral and cavernosal repairs and helped prevent postoperative corporourethral fistula formation.

Impact of Stone Density on Percutaneous Nephrolithotomy Outcomes with a Dual Frequency Ultrasonic Lithotripter: Computerized Tomography Based Outcomes at a Low Volume Center.

INTRODUCTION: We studied the safety and efficacy of the CyberWand™ lithotripter and how stone density affects the efficacy. METHODS: We retrospectively analyzed the outcomes of percutaneous nephrolithotomy performed using the CyberWand dual frequency ultrasonic lithotripter at our institution between November 2009 and July 2015. A total of 63 procedures were performed on 57 renal units and, thus, we may be considered a low volume center. We assessed the outcomes of each renal unit in terms of the clinically insignificant residual fragment rate, complication rate, operating room time, estimated blood loss and length of hospitalization. We evaluated the effect of HU of the stone (less than 1,000 HU considered soft and greater than 1,000 HU considered hard) on outcome. RESULTS: Our outcomes using the CyberWand lithotripter were comparable to those of other lithotripsy modalities in terms of the complication rate and clinically insignificant residual fragment rate. We achieved clinically insignificant residual fragment status (defined as less than 4 mm residual stone size) in 54% of renal units and the overall complication rate was 24%. There were no appreciable differences between soft stones and hard stones in terms of any outcome parameter including complication rate, clinically insignificant residual fragment rate and operative time. CONCLUSIONS: The CyberWand lithotripter is an acceptable, noninferior modality of percutaneous lithotripsy of renal calculi. The efficacy of the CyberWand lithotripter is not affected by stone density.

Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy.

Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitors (PIs) are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic activities through non-competitive binding to PR, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS) system, thus increasing the chances of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of fission yeast as a possible surrogate system to study the effects of HIV-1 protease on cellular functions and to explore its utility as a HTS system to search for new PIs to battle HIV-1 resistant strains.

Monitoring structural transitions in IDPs by vibrational spectroscopy of cyanylated cysteine.

The fast intrinsic time scale of infrared absorption and the sensitivity of molecular vibrational frequencies to their environments can be applied with site-specificity by introducing the artificial amino acid ß-thiocyanatoalanine, or cyanylated cysteine, into chosen sites within intrinsically disordered proteins. This amino acid can be inserted through native chemical ligation at single cysteines introduced via site-directed mutagenesis. The CN stretching band of cyanylated cysteine is sensitive to local changes in both structural content and solvent exposure. This dual sensitivity makes cyanylated cysteine an especially useful probe of binding-induced structural transitions in IDPs. The general strategy of creating single-site cysteine mutations and chemically modifying them to create the vibrational chromophore, as well as observation, processing and analysis of the CN stretching band, is presented.