A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study.

Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.

Post-Transurethral Resection of Bladder Tumor Bladder Perforation Resulting in Mitomycin C Extravasation, Pudendal Neuralgia, and Ureterohydronephrosis.

Background: Mitomycin C (MMC) extravasation after transurethral resection of bladder tumor (TURBT) is a rare and highly morbid complication. Management of these cases may require a multidisciplinary approach with strategies ranging from conservative management to surgical intervention. Case Presentation: We present a 48-year-old woman who received a TURBT for a 5 mm bladder tumor. Procedure was uneventful and no bladder perforation was noticed. A single dose of instillation of MMC was performed after surgery resulting in extravasation, consequent ipsilateral pudendal neuralgia, and ureterohydronephrosis. Treatment included a second TURBT, Double-J stent placement, and multiple pain management schemes. After 8 months the patient had complete resolution of pain and ureterohydronephrosis. Conclusion: Perioperative chemotherapy is the standard of care in low-risk bladder cancer. Extravasation of MMC, although rare, can produce severe complications, sometimes irreversible. Other treatment options, such as gemcitabine, are less frequently used despite being less irritant and having similar efficacy. Further studies are needed to compare single-dose instillation regimens.

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.

Cáncer renal. Descripción poblacional en una institución académica / Kidney cancer. Population description in an academic institution

El conocimiento en cáncer renal ha sido manifiesto en la última década, con adelantos que optimizan el abordaje diagnóstico, quirúrgico y terapéutico con agentes dirigidos contra blancos específicos. El objetivo del trabajo fue la evaluación retrospectiva de pacientes con cáncer de riñón, destacando los datos demográficos, patológicos, quirúrgicos, de recurrencia, así como las modalidades terapéuticas empleadas, y describir la evolución clínica a través de parámetros de eficacia y seguridad. Fueron incluidos 417 pacientes, analizándose los datos de 356. La edad mediana fue de 56 años y 68% eran hombres. El 14% presentó otro tumor primario no renal y 14 desarrollaron otro tumor renal. El diagnóstico fue incidental en el 28% de los casos, la histología más frecuente fue el carcinoma de células claras, el tamaño mediano fue 6.1 cm y en el 20% se observó infiltración capsular. De los 298 pacientes operados, 54% fueron a nefrectomía radical y 26% parcial. El 19% presentaba metástasis al diagnóstico. Recurrencia post-operatoria en 75 de los 298 operados. Los tratamientos más frecuentemente utilizados en primera línea fueron los inhibidores de tirosina-quinasa (55% de los casos) con remisiones del 43-50% y un tiempo a la progresión de 12.1 meses. La revisión retrospectiva de los datos en cáncer renal de una población académica que incorpora la metodología diagnóstica, quirúrgica y terapéutica en enfermedad localizada y avanzada, permite reproducir los datos que surgen de países centrales y de estudios clínicos aleatorizados (AU)

Improving knowledge in renal cancer has been successful in the last decade in terms of diagnosis, surgical and therapeutic approach with targeted agents. The objective of the study was the retrospective evaluation of patients with kidney cancer, emphasizing recurrence as well as therapeutic modalities, pathological and surgical, demographic data and to describe outcome through efficacy and safety parameters. There were included 417 patients. The median age was of 56 years and 68% were men. There was a 14% of patients with another non-renal primary tumor and 14 patients developed another kidney tumor. The diagnosis was incidental in 28% of cases. The most common histology was clear cell carcinoma, medium size was 6.1 cm and capsular infiltration was observed in 20%. Of the 298 patients operated, 54% were to radical nephrectomy and 26% partial. The 19% of the patients had metastases from diagnosis. Post-operative recurrence was developed in 75 of 298 surgical patients. The most frequent systemic first line therapy was tyrosine-kinase inhibitors (55% of cases) with remissions of 43-50% and time to progression was 12.1 months. The retrospective review in renal cancer of an academic population gives the rationale of data of the real world and to compare with those that arise from central countries and randomized clinical trials (AU)

Puesta al día: estadificación del carcinoma de células renales / Update on staging of renal cell carcinoma

El cáncer de células renales o adenocarcinoma renal es el tumor renal maligno más frecuente en adultos, con una incidencia mayor entre la cuarta y sexta décadas de la vida. Los hombres se afectan el doble que las mujeres. En Argentina, por año se calcula una incidencia de 6,1 casos por 100.000 habitantes, con una mortalidad anual de 3,4 casos por 100.000 habitantes.Para la estadificación se utiliza el sistema TNM de la American Joint Committee on Cancer (AJCC), actualizado en su séptima edición (2010). Allí se reflejan algunos cambios en el T, con subdivisión de la categoría T2 (T2a > 7 cm y < 10 cm y T2b > 10 cm). Asimismo, se considera T4 a la invasión por contigüidad de la glándula suprarrenal homolateral y T3a al compromiso de la vena renal. También se simplificó el N en N0 y N1...