Oncogene targeted therapy for metastatic primary scrotal melanoma.

Primary scrotal melanoma represents the rarest genitourinary malignancy. We describe the 25th reported case. The 79-year-old patient presented with a rapidly enlarging right cutaneous scrotal mass which after local excision demonstrated pT4b nodular malignant melanoma (BRAF V600E mutation positive). The patient underwent wide local excision of his hemiscrotum and inguinal lymph node dissection demonstrating nodes positive for melanoma (pN2b). Postoperatively, the patient developed a left sided malignant pleural effusion (M1b). Per American Joint Commission Cancer staging, BRAF mutant targeted therapy (dabrafenib) was initiated. This case documents the first instance in which metastatic scrotal melanoma will be treated with oncogene targeted therapy.

Robotic post-chemotherapy retroperitoneal lymph node dissection for testicular cancer: A multicenter collaborative study.

OBJECTIVES: To evaluate the perioperative and oncological/functional outcomes of robotic post-chemotherapy retroperitoneal lymph node dissection for testicular cancer. METHODS AND MATERIALS: In this retrospective study, we included patients who underwent robotic post-chemotherapy retroperitoneal lymph node dissection at 7 academic centers between 2011 and 2021. Patients' characteristics, perioperative findings, as well as oncological and functional outcomes are reviewed. Relationships with the main outcome (90-day complications) were analyzed using multivariable logistic regression. RESULTS: A total of 90 patients with a median (IQR) age of 30 (25-37) years were included. The main primary histologic type was non-seminomatous germ cell tumor (89%). Seven patients (8%) were electively converted to open. Median estimated blood loss, operative time, and length of hospital stay were 150 ml, 5.6 hours, and 2 days, respectively. Final pathology revealed teratoma in 49 (55%), necrosis/fibrosis in 29 (32%), and viable germ cell tumor in 12 (13%) patients. The 90-day complication rate was 16.7%, most of which were low-grade (Clavien-Dindo < III) and managed conservatively. On multivariable analysis, pure seminoma (odds ratio 17.4) and bilateral dissection template (odds ratio 4.2) were independently associated with 90-day complications. No 90-day hospital readmission was recorded. With a median (IQR) follow-up of 16 (4-32) months, 6 (6.7%) patients had disease recurrence and there was 1 cancer-related death. CONCLUSION: With appropriate patient selection at centers with expertise in testicular cancer and minimally invasive surgery, robotic post-chemotherapy retroperitoneal lymph node dissection appears safe and effective, although longer follow-up is warranted.

Cost Analysis of Flexible Ureteroscope Repairs: Evaluation of 655 Procedures in a Community-Based Practice.

INTRODUCTION: The frequency of flexible ureteroscopy has increased with the introduction of improved instrumentation. Ureteroscopes allow increased endoscopic access to the ureter and kidney. However, maintenance and repair of scopes may increase the total procedure expense. METHODS: In 3 years (8/2011-7/2014), 655 flexible ureteroscopies were performed at a single-specialty, urology, ambulatory surgery center. Procedures were performed by 26 board-certified urologists using four Olympus URF P5 flexible ureteroscopes. The instruments were handled by a single team and sterilized through the STERIS System E1. Repairs were performed by the manufacturer on an as needed basis. Patient records were reviewed to determine the preoperative diagnosis, operative time, location and size of the stone, and use of laser or ureteral sheath. The occurrence, nature of flexible ureteroscope damage, and cost of repairs were evaluated. RESULTS: Of the ureteroscopies performed, 78% was for the treatment of calculi (50.1% in the kidney). Mean stone size was 8.5 ± 0.2 mm, with larger stones (11 mm) located in the kidney. The flexible ureteroscope was advanced over a guidewire (88% of cases); a laser fiber was introduced in 70%, and a ureteral sheath was used in 13.4%. Mean procedure time was 40 minutes. The most common reasons for ureteroscope repair were cloudy lens (16 repairs) and broken optic fibers (9 repairs). There were 31 repairs during the study period (average 21 cases per repair). Flexible ureteroscopes were out of service for an average of 11 days per repair (range 3-20). The total cost of repairs was $233,150 or ∼$7521 per repair. The average repair cost per flexible ureteroscopy performed was $355. CONCLUSIONS: Expenses associated with instrument repair can significantly impact a procedure's net revenue, thus efforts should be made to minimize instrument breakage. The expense of repairing a flexible ureteroscope per procedure can be significant and needs to be considered when pricing this procedure.

Two myristoylated alanine-rich C-kinase substrate (MARCKS) paralogs are required for normal development in zebrafish.

Myristoylated alanine-rich C-kinase substrate (MARCKS) is an actin binding protein substrate of protein kinase C (PKC) and critical for mouse and Xenopus development. Herein two MARCKS paralogs, marcksa and marcksb, are identified in zebrafish and the role of these genes in zebrafish development is evaluated. Morpholino-based targeting of either MARCKS protein resulted in increased mortality and a range of gross phenotypic abnormalities. Phenotypic abnormalities were classified as mild, moderate or severe, which is characterized by a slight curve of a full-length tail, a severe curve or twist of a full-length tail and a truncated tail, respectively. All three phenotypes displayed abnormal neural architecture. Histopathology of Marcks targeted embryos revealed abnormalities in retinal layering, gill formation and skeletal muscle morphology. These results demonstrate that Marcksa and Marcksb are required for normal zebrafish development and suggest that zebrafish are a suitable model to further study MARCKS function.