Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model.

Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

Corrigendum to "Modified urethrovesical anastomosis during robot-assisted simple prostatectomy: Technique and results" [Prostate Int 4 (2016) 61-64].

[This corrects the article DOI: 10.1016/j.prnil.2016.04.001.].

American Confederation of Urology (CAU) experience in minimally invasive partial nephrectomy.

PURPOSE: To describe the perioperative and oncology outcomes in a series of laparoscopic or robotic partial nephrectomies (PN) for renal tumors treated in diverse institutions of Hispanic America from the beginning of their minimally invasive (MI) PN experience through December 2014. METHODS: Seventeen institutions participated in the CAU generated a MI PN database. We estimated proportions, medians, 95 % confidence intervals, Kaplan-Meier curves, multivariate logistic and Cox regression analyses. Clavien-Dindo classification was used. RESULTS: We evaluated 1501 laparoscopic (98 %) or robotic (2 %) PNs. Median age: 58 years. Median surgical time, warm ischemia and intraoperative bleeding were 150, 20 min and 200 cc. 81 % of the lesions were malignant, with clear cell histology being 65 % of the total. Median maximum tumor diameter is 2.7 cm, positive margin is 8.2 %, and median hospitalization is 3 days. One or more postoperative complication was recorded in 19.8 % of the patients: Clavien 1: 5.6 %; Clavien 2: 8.4 %; Clavien 3A: 1.5 %; Clavien 3B: 3.2 %; Clavien 4A: 1 %; Clavien 4B: 0.1 %; Clavien 5: 0 %. Bleeding was the main cause of a reoperation (5.5 %), conversion to radical nephrectomy (3 %) or open partial nephrectomy (6 %). Transfusion rate is 10 %. In multivariate analysis, RENAL nephrometry score was the only variable associated with complications (OR 1.1; 95 % CI 1.02-1.2; p = 0.02). Nineteen patients presented disease progression or died of disease in a median follow-up of 1.37 years. The 5-year progression or kidney cancer mortality-free rate was 94 % (95 % CI 90, 97). Positive margins (HR 4.98; 95 % CI 1.3-19; p = 0.02) and females (HR 5.6; 95 % CI 1.7-19; p = 0.005) were associated with disease progression or kidney cancer mortality after adjusting for maximum tumor diameter. CONCLUSION: Laparoscopic PN in these centers of Hispanic America seem to have acceptable perioperative complications and short-term oncologic outcomes.

Linfadenectomía aorto -iliaca robótica en cáncer de próstata / Aorto-iliac robotic lymphadenectomy in prostate cancer

Introducción. El beneficio de la linfadenectomía en el cáncer de próstata sigue siendo controversial. Es el único procedimiento que permite un estadiaje anatomopatológico más preciso. Antiguamente se indicaba en pacientes de riesgo intermedio o mayor. Actualmente utilizamos el Score de CAPRA sobre 2 para indicar el procedimiento con el fin de seleccionar de mejor manera los pacientes que se beneficiarían de este procedimiento. Objetivo. Analizar la utilidad de CAPRA-Score para indicar la linfadenectomía. Pacientes y Métodos. Estudio prospectivo de carácter descriptivo. De un universo de 155 Pacientes sometidos a prostatectomía radical laparoscópica entre 2003-2013 por un único cirujano, se analizaron 34 pacientes a los que se le realizó linfadenectomía . Los datos se recopilaron en el momento de la cirugía y controles postoperatorios. Se agruparon datos: edad, PSA, Estadio Clínico, Gleason y porcentaje de cilindros (+) en biopsia TR. Se agruparon según indicación por Riesgo o CAPRA-S y se compararon los resultados obtenidos en la histología de los ganglios extraídos (linfadenectomías +). Los datos se analizaron considerando p<0,05 estadísticamente significativo según prueba de T de Student. Resultados. Se incluyeron en total 34 pacientes. Hasta el año 2010 un total de 23 linfadenectomía indicadas a grupo de riesgo intermedio-alto, el 78 por ciento (18) indicado por Gleason. Se sacó en promedio 12 ganglios por paciente, 72 por ciento linfadenectomía ampliadas. Ningún paciente tuvo ganglios (+). Desde el año 2011 un total de 11 linfadenectomía por CAPRA-Score >2, sacándose promedio 15 ganglios, 9 fueron linfadenectomías ampliadas. Se obtuvo 18 ciento linfadenectomías (+) para compromiso metastásico. Conclusiones. De los pacientes previo a CAPRA-Score, un 17por ciento pacientes estarían sobreindicados según éste y coincide con la negatividad del resultado histológico. Hubo diferencia estadísticamente significativa en la aparición de ganglios (+) en pacientes que se aplicó CAPRA-Score. (P<0.05). Según la serie de pacientes presentados, CAPRA-Score seleccionaría mejor los pacientes que se beneficiarían con una linfadenectomía, sin embargo se requieren estudios de mayor cantidad de pacientes.AU

INTRODUCTION Despite the good oncological results of radical prostatectomy (PR) in the treatment of prostate cancer (PCa), more than 35 pertcent of patients will present with biochemical recurrence (RB) after surgery. In these patients, pelvic and / or distal nodes may represent the site of recurrence of the disease. Our objective is to present our surgical technique of aortoiliac robotic lymphadenectomy (LAO) in prostate cancer.AU

Modified urethrovesical anastomosis during robot-assisted simple prostatectomy: Technique and results.

BACKGROUND: Despite significant developments in transurethral surgery for benign prostatic hyperplasia, simple prostatectomy remains an excellent option for patients with severely enlarged glands. The objective is to describe our results of robot-assisted simple prostatectomy (RASP) with a modified urethrovesical anastomosis (UVA). METHODS: From May 2011 to February 2014, RASP with UVA was performed in 34 patients by a single surgeon (O.C.) using the da Vinci S-HD surgical system. The UVA was performed between the bladder neck and urethral margin using the Van Velthoven technique. Demographic, perioperative, and outcome data were recorded. Complications were recorded with the Clavien-Dindo system. RESULTS: The mean (standard deviation) age was 68 years (62-74 years). The median preoperative prostate volume (interquartile range) was 117 cc (99-146 cc). Operative time was 96 minutes (78-126 minutes), estimate blood loss was 200 mL (100-300 mL), and two (5.8%) patients required a blood transfusion. No conversion to open surgery was needed. The median specimen weight on pathological examination was 76 g (58-100 g). The average hospital stay was 2.2 days (1-4 days) and average Foley catheter time was 4.6 days (4-6 days). No intraoperative complications were recorded. There were seven (20.5%) postoperative complications, most of them Clavien less than or equal to Grade II. CONCLUSION: The results of our study show that RASP with UVA is a feasible, secure, and reproducible procedure with low morbidity. Additional series with larger patient cohorts are needed to validate this approach.

First Report: Robot-Assisted Total Pelvic Exenteration for Locally Advanced Prostate Cancer.

Pelvic exenteration is used in the treatment of several pelvic cancers, including those of the rectum, uterus, and bladder. We report the first case of robotic pelvic exenteration for the treatment of symptomatic prostate cancer involving the rectum and bladder. A six-port transperitoneal robotic approach was used. Bilateral extended lymphadenectomy up to the inferior mesenteric artery was performed. The rectum and bladder were removed en bloc, and a double-barrel anastomosis was then performed with both ureters being connected to the lower opening of the colostomy. Operative time was 249 minutes, and estimated blood loss was 600 mL. No intraoperative or postoperative complications were recorded. Biopsy of the rectum and bladder showed prostatic adenocarcinoma with a Gleason score of 9 (5+4), and 1 of 17 nodes was positive for cancer. Postoperative prostate-specific antigen level was 1.24 ng/mL. The patient is already 19 months after surgery with optimal quality of life. Thus pelvic exenteration is a feasible alternative for highly symptomatic prostate cancer involving adjacent pelvic organs.

[Testosterone replacement therapy and prostate cancer: the downfall of a paradigm?]. / Terapia de reemplazo con testosterona y cáncer de próstata: ¿la caída de un paradigma?

For six decades, it has been a part of the conventional medical wisdom that higher levels of testosterone increase the risk of prostate cancer. This belief is mostly derived from the well-documented regression of prostate cancer after surgical or pharmacological castration. However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer. Moreover, men with hypogonadism have substantial rates of prostate cancer in prostatic biopsies, suggesting that low testosterone has no protective effect against the development of prostate cancer. Moreover, prostate cancer rate is higher in elderly patients when hormonal levels are low. These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

Por casi seis décadas ha sido parte de la cultura médica en general, que los niveles altos de testosterona incrementan el riesgo de padecer o agravar un cáncer de próstata. Esta creencia se ha derivado fundamentalmente de la bien documentada regresión del cáncer de próstata luego de la castración médica o quirúrgica. Sin embargo, no existe evidencia científica que apoye la idea de que niveles altos de testosterona están asociados con un incremento del riesgo de cáncer de próstata. Más aún, los hombres con hipogonadismo tienen una tasa substancialmente alta de cáncer de próstata detectado por biopsia, lo que sugiere que los niveles bajos de testosterona no tienen un efecto protector en el desarrollo de cáncer de próstata y, además, la tasa de cáncer de próstata es más alta en los pacientes de edades avanzadas cuando sus niveles hormonales son más bajos. Estos argumentos tienden a demostrar que no existiría un incremento del riesgo de padecer un cáncer de próstata asociado a la terapia de reemplazo con testosterona.

Laparoscopic management of renal tumors with macroscopic level 1 renal vein involvement.

OBJECTIVE: To describe our surgical experience and clinical outcome in laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) with level 1 renal vein tumor thrombus. PATIENTS AND METHODS: 11 patients with RCC level 1 renal vein tumor thrombus were treated by LRN plus thrombectomy. The mean age was 66.8 years (SD ±11.313); the mean body mass index was 24.76 (SD ±5.091). In all cases, the surgical technique was defined by tumor characteristics and the surgeon's preferences. RESULTS: Surgery was technically successful in all 11 patients. A hand-assisted approach was performed in 3 patients, while pure laparoscopy was used in 8. The mean surgical time was 108.3 min (SD ±28.284); the mean estimated blood loss was 108.33 ml (SD ±106.066); the average hospital stay was 2.8 days (SD ±0.707). There was 1 intraoperative complication (splenic laceration) that was managed laparoscopically. Pathologic examination confirmed RCC in all cases. There were no positive surgical margins. With a mean follow-up of 29 months (27-39), 2 patients had a recurrence. CONCLUSION: This report provides further evidence of the technical feasibility, safety and oncologic adequacy of the laparoscopic approach in RCC with level 1 renal vein involvement. A longer follow-up and multi-institutional studies are needed to adequately evaluate its potential oncologic benefit.

Basaloid carcinoma of the prostate: an extremely rare tumor.

OBJECTIVE: The basaloid carcinoma of the prostate (BC) is a rare malignant neoplasm arising from the basal cells of prostatic ducts and acini. We report a case and review the literature. METHODS: A 76-year-old man presented with symptoms of lower obstructive uropathy, the IPSS score was 29 and prostate specific antigen (PSA)of 0,924 ng /ml. Transurethral resection of prostate (TURP) was performed in September 2008, histopathological diagnosis was BC. In February 2009 laparoscopic radical prostatectomy was performed. RESULTS: Histopathological examination revealed a BC with adenoid cystic growth pattern, perineural infiltration and focal involvement of the left seminal vesicle. Immunohistochemically, the cells were negative for PSA, stained and were strongly positive for specific monoclonal antibodies anti-cytokeratin 34ßE12, p63 and BCL-2. The patient has 23 months of follow-up, with complete continence and no evidence of tumor recurrence. CONCLUSIONS: The BC is an extremely rare subtype of malignant tumors of the prostate, where immunohistochemistry plays a fundamental role in diagnosis.

Laparoscopic vesicovaginal fistula repair.

OBJECTIVES: Vesicovaginal fistulas are uncommon and remain a surgical challenge. Abdominal hysterectomy remains their main cause. We present our experience in laparoscopic repair of vesicovaginal fistula. METHODS: Between January 2006 and January 2008, 8 laparoscopic transvesical procedures for VVF repair were performed at our institution (O'Connor technique). For each case we analyzed demographic and surgical variables as well as the outcome. Surgical technique is also described. RESULTS: Average patient age was 45 years. All patients had past history of hysterectomy and subsequent history of urine leak through vagina, with a mean evolution time of 22 months. The average operative time was 150 minutes and the mean hospital stay 4.7 days. All patients evolved without complications except one who had urinary tract infection (Pseudomonas aeruginosa) that was treated with antibiotics. After a mean follow up of 32 months, there were no recurrences. CONCLUSION: In experienced hands, transvesical transabdominal laparoscopic vesicovaginal fistula repair is a feasible and safe procedure, preserving all the advantages of minimally invasive surgery.

Ureteral inverted papilloma: laparoscopic distal ureterectomy and boari flap.

OBJECTIVE: To report a case of ureteral inverted papilloma (IP) with laparoscopic resolution. METHODS: We report the case of a 30-year-old male patient who consulted for asymptomatic hematuria with the radiological finding of a filling defect at the distal right ureter. Ureteroscopy biopsy was not diagnostic, so laparoscopic ureterectomy with a Boari flap technique was performed. The pathology report showed a ureteral inverted papilloma. CONCLUSION: Laparoscopic ureteral replacement by Boari flap is a safe surgical alternative for defects in the distal ureter with the advantages of a minimally invasive procedure.

Discontinuous intrabdominal splenogonadal fusion with germ cell tumor. Excision with robotic assistence. Adult case report.

OBJECTIVE: Present the case of a patient with a discontinuous intrabdominal splenogonadal fusion with an associated germ cell tumor. METHODS: A case of a man of 29 years with bilateral cryptorchidism and left intra-abdominal discontinuous splenogonadal fusion associated with seminoma as an accidental finding in the context of a robotic pyeloplasty due to ipsilateral ureteropelvic junction stenosis. RESULTS: The total operative time was 80 minutes (atrophic gonad removal and pyeloplasty by the Anderson-Hynes technique) with an estimated blood loss less than 100 cc. The hospitalization time was less than 36 hrs. The pathology and immunohistochemical report was compatible with intratubular germ cell neoplasia (seminoma). CONCLUSION: The splenogonadal fusion is an uncommon pathology. While a high clinical suspicion may avoid unnecessary orchiectomy in young patients, its association with disorders such as cryptorchidism should make us suspect the possible presence of a concomitant germ cell neoplasia.

Robot assisted partial nephrectomy (Da Vinci) in an angiomyolipoma associated to Wünderlich Syndrome.

OBJECTIVE: To describe a case of renal angiomyolipoma treated by robotic assisted surgery. METHOD AND RESULTS: We report the case of a 26 year old females patient, in the context of third month pregnancy, who was diagnosed of spontaneous self-limited retroperitoneal hemorrhage due to renal angiomyolipoma. The patient was treated conservatively until normal delivery. At the 3rd month postpartum a robot-assisted (Da Vinci S) nephron sparing surgery (partial nephrectomy) was performed. CONCLUSION: Despite being a benign tumor, there are cases in which the renal angiomyolipoma requires surgical treatment. To our knowledge, after a thorough review of the literature, this would be the first reported case of angiomyolipoma treated with conservative surgery with robotic assistance (Da Vinci S-HD).

Mixed epithelial and stromal tumor of the kidney (MEST).

OBJECTIVE: To report an unusual case of renal tumor and review the literature. METHODS: We present a 20 years old female with a history of acute right pyelonephritis. The ultrasound study revealed a tumor-like image in the lower pole of the right kidney . The CT-scan showed a mixed solid and cystic mass of 7 cm. in the lower pole of the right kidney. RESULTS: A right laparoscopic partial nephrectomy was performed. The total operative time was 90 minutes, with 24 minutes of warm ischemia. The estimated blood loss was 50 ml. and the length of stay (LOS) 36 hours. The pathology findings confirm a mixed epithelial and stromal tumor (MEST) of the kidney. CONCLUSION: Mixed epithelial and stromal tumor (MEST) of the kidney is a benign and rare condition that doesn't show a clear difference with other renal tumors in image studies. Nephron-sparing surgery with margin study is the standard treatment when is feasible.

Bladder hemangioma: case report.

OBJECTIVE: Bladder hemangioma is a benign rare lesion. There are no pathognomonic clinical signs and management is controversial due to the bleeding risk. We report a bladder cavernous hemangioma resolved using bipolar transurethral resection. METHODS: We review the case of a female patient who presented with asymptomatic hematuria. On cystoscopy we discovered a reddish sessile lesion compatible with bladder hemangioma. We describe the diagnostic work up, surgical management and review other therapeutic alternatives for these lesions. RESULTS: Fifty five year old healthy female patient consulting for total painless hematuria. Cystoscopic evaluation revealed a 1 cm diameter sessile reddish elevated lesion near the bladder neck. We performed a transurethral endoscopic resection using the Gyrus Bipolar resectoscope®. Pathologic report concluded cavernous angioma. CONCLUSION: Bladder hemangiomas are benign and rare lesions. Clinical presentation has no pathognomonic signs although gross painless hematuria is the most frequent complain. Management is controversial due to the bleeding risk of this highly vascularized lesion. However, it appears that small lesions could be treated using transurethral resection. Although they have a benign course, follow up is mandatory to detect recurrence or residual disease.

Histological changes due to intravesical instillation of mitomycin C.

OBJECTIVE: Transurethral resection (TUR) is highly effective in the local control of superficial bladder cancer. However, the recurrence rate can reach 80% of the cases. Adjuvant intravesical chemotherapy may decrease significantly tumor recurrence. We describe a bladder adverse reaction to mitomycin C as adjuvant therapy for non-invasive bladder cancer METHODS: Three patients with diagnosis of pTa G1 urothelial carcinoma were treated by TUR plus an instillation of 40 mg. of mitomicin C. A month later, the patients were attended for dysuria and hematuria. Cystoscopy and bladder biopsy were performed in all cases. RESULTS: Multiple sessile lesions suspicious of tumor recurrence were found on cystoscopy. The histopathological diagnosis disclosed the existence of severe atypia of the urothelium and stromal changes similar to those observed after radiotherapy CONCLUSIONS: Adjuvant intravesical chemotherapy with mitomycin C may cause local reactions with macroscopic patterns similar to tumoral recurrences.

Laparoscoscopic synchronous bilateral adrenalectomy.

OBJECTIVES: To report our experience in a series of bilateral synchronous laparoscopic adrenalectomies detailing technique and results. METHODS: A total of 242 laparoscopic adrenalectomies were performed in an 8 year period at our institution. Twenty four out of these were bilateral. Of the 24 patients, 22 (92%) were bilateral and synchronous. Mean patient age was 41.4 years (range 17 to 72 years) and male to female ratio was 1:2.1. RESULTS: Mean adrenal size was 5.5 cm (range 2 to 11 cm). In order of frequency, pathological finding was: pheochromocytoma, cushing`s disease, metastatic lesions, hyperaldosteronism, congenital adrenal hyperplasia, myelolipoma and adrenal adenoma. Complete adrenalectomy was performed in 36 cases (82%) while in 8 cases (18%) partial adrenalectomy was preferred. Mean operative time was 78.6 minutes (range 25 to 210 min) being 79.5 min and 77 min for right and left adrenalectomies respectively. Mean operative bleeding was 63 ml (range 0 to 500 ml). Only one patient received blood transfusion. Intraoperative complications occurred in only one patient (2%), a small tear in the renal vein that was successfully controlled by intracorporeal suturing. Mean hospital stay was 3.2 days (range 2 to 5 days). CONCLUSION: We believe that laparoscopic synchronous bilateral adrenalectomy is a feasible, safe and reproducible technique that should be considered of choice for the management of benign bilateral adrenal pathology.

Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells.

BACKGROUND: We have previously shown a differential expression of a family of mitochondrial ncRNAs in normal and cancer cells. Normal proliferating cells and cancer cells express the sense mitochondrial ncRNA (SncmtRNA). In addition, while normal proliferating cells express two antisense mitochondrial ncRNAs (ASncmtRNAs-1 and -2), these transcripts seem to be universally down-regulated in cancer cells. In situ hybridization (ISH) of some normal and cancer tissues reveals nuclear localization of these transcripts suggesting that they are exported from mitochondria. METHODS: FISH and confocal microscopy, in situ digestion with RNase previous to ISH and electron microscopy ISH was employed to confirm the extra-mitochondrial localization of the SncmtRNA and the ASncmtRNAs in normal proliferating and cancer cells of human and mouse. RESULTS: In normal human kidney and mouse testis the SncmtRNA and the ASncmtRNAs were found outside the organelle and especially localized in the nucleus associated to heterochromatin. In cancer cells, only the SncmtRNA was expressed and was found associated to heterochromatin and nucleoli. CONCLUSION: The ubiquitous localization of these mitochondrial transcripts in the nucleus suggests that they are new players in the mitochondrial-nuclear communication pathway or retrograde signaling. Down regulation of the ASncmtRNAs seems to be an important step on neoplastic transformation and cancer progression.