Medicine and Health Sciences Commons^™

Testing For Homologous Recombination Repair Or Homologous Recombination Deficiency For Poly (Adp-Ribose) Polymerase Inhibitors: A Current Perspective, Thomas J Herzog, Ignace Vergote, Leonard G Gomella, Tsveta Milenkova, Tim French, Raffi Tonikian, Christian Poehlein, Maha Hussain

Department of Urology Faculty Papers

Poly (ADP-ribose) polymerase inhibitors (PARPis) have demonstrated clinical activity in patients with BRCA1 and/or BRCA2 mutated breast, ovarian, prostate, and pancreatic cancers. Notably, BRCA mutations are associated with defects in the homologous recombination repair (HRR) pathway. This homologous recombination deficiency (HRD) phenotype can also be observed as genomic instability in tumour cells. Accordingly, PARPi sensitivity has been observed in various tumours with HRD, independent of BRCA mutations. Currently, four PARPis are approved by regulatory agencies for the treatment of cancer across multiple tumour types. Most indications are specific to tumours with a confirmed BRCA mutation, mutations in other HRR-related genes, …

The Significance Of Functional Renal Obstruction In Predicting Pathologic Stage Of Upper Tract Urothelial Carcinoma., Michael J. Amirian, Kushan Radadia, Hadley Narins, Kelly A. Healy, Scott G. Hubosky, Demetrius H. Bagley, Edouard J. Trabulsi, Costas D. Lallas

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Assessing the severity of upper tract urothelial carcinoma (UTUC) has been difficult because of inadequate biopsy specimens. Additional predictive parameters of disease stage would be useful when deciding a treatment plan; it has been suggested that preoperative hydronephrosis can be a surrogate. We examined the relationship between preoperative ipsilateral renal obstruction identified by imaging with final pathologic stage after nephroureterectomy (NU) for UTUC. We then analyzed those patients with ipsilateral renal obstruction and examined if tumor location is associated with an advanced pathologic stage.

METHODS: Patients who underwent NU for UTUC between the years 2001 to 2013 …

Safety Of Hexaminolevulinate For Blue Light Cystoscopy In Bladder Cancer. A Combined Analysis Of The Trials Used For Registration And Postmarketing Data., J Alfred Witjes, Leonard G. Gomella, Arnulf Stenzl, Sam S. Chang, Dirk Zaak, H Barton Grossman

Department of Urology Faculty Papers

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience.

METHODS: Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed.

RESULTS: In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% …

Prevention Of Stone Migration With The Accordion During Endoscopic Ureteral Lithotripsy., Christopher J Pagnani, Magdy El Akkad, Demetrius H Bagley

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Endoscopic lithotripsy is often prolonged secondary to the retrograde migration of calculous fragments. Various balloons, baskets, and other devices have been used to prevent this migration. Our purpose is to analyze the effect of the Accordion(®) on stone migration and overall efficiency during lithotripsy.

PATIENTS AND METHODS: We prospectively evaluated 21 patients with a total of 23 distal ureteral stones. Patients underwent lithotripsy using an endoscopic impact lithotriptor. The Accordion was randomly used in 11 of these 21 patients. Data were collected regarding stone migration, stone size, stone ablation, ureteral clearing, and lengths of time for various …

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Microrna Expression Profiling Of Male Breast Cancer., Matteo Fassan, Raffaele Baffa, Juan P Palazzo, Joshua Lloyd, Marco Crosariol, Chang-Gong Liu, Stefano Volinia, Hannes Alder, Massimo Rugge, Carlo M Croce, Anne Rosenberg

Department of Urology Faculty Papers

INTRODUCTION : MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers. METHODS : Paraffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast …

The Minimally Invasive Treatment Of Ureteropelvic Junction Obstruction: A Review Of Our Experience During The Last Decade., Brent V. Yanke, Costas D. Lallas, Christopher Pagnani, David E. Mcginnis, Demetrius H. Bagley

Department of Urology Faculty Papers

PURPOSE: The minimally invasive treatment of ureteropelvic junction obstruction has evolved during the last decade from endoscopic to laparoscopic and robotic. We review our 10-year experience with ureteropelvic junction obstruction, and report on our experience and followup.

MATERIALS AND METHODS: We reviewed all patients treated during the last 10 years. There were 294 procedures performed with complete records on 273 patients including 128 retrograde endopyelotomies, 116 laparoscopic pyeloplasties and 29 robotic pyeloplasties. Technique for each procedure is reviewed. Statistical analysis was performed on all results. Variables evaluated were gender, age (younger than 41 vs 41 years or older), …

Robotic Dismembered Pyeloplasty In A Horseshoe Kidney After Failed Endopyelotomy., Mark L. Pe, Steven N. Sterious, Ji-Bin Liu, Costas D. Lallas

Department of Urology Faculty Papers

We report our experience performing a robot-assisted dismembered pyeloplasty on a patient with a ureteropelvic junction obstruction in a horseshoe kidney and a prior history of endopyelotomy. We provide 18-month follow-up demonstrating that robotic pyeloplasty is a reasonable second treatment option for patients with horseshoe kidneys with failed prior endourological management.

Collecting Duct Carcinoma Of The Kidney: An Immunohistochemical Study Of 11 Cases., Andrea Vecchione, Tommaso Prayer Galetti, Marina Gardiman, Hideshi Ishii, Enrico Giarnieri, Francesco Pagano, Leonard G Gomella, Carlo M Croce, Raffaele Baffa

Department of Urology Faculty Papers

BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27kip1, and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation …