Genetic profile and immunohistochemical study of clear cell renal carcinoma: Pathological-anatomical correlation and prognosis.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for 2-3% of all tumors being the most frequent solid lesion in the kidney. OBJECTIVE: To determine what genetic alterations and immunohistochemical (IHC) of clear cell renal carcinoma (ccRCC) are associated with prognosis and tumor aggressiveness. PATIENTS AND METHODS: Experimental analytical study with 57 patients who underwent radical and partial nephrectomy between 2005 and 2011, all with diagnosis of ccRCC and minimum post-operative follow-up of 36 months. The pathological study included IHC determination of biomarkers associated (CAIX, CAM 5.2, CD10, c-erbB-2, EGFR, HIF-1a, Ki67, MDM2, PAX-2 y 8, p53, survivin and VEGFR 1 and 2). Genetic analysis was carried out using multiplex ligation-dependent probe amplification (MLPA). Clinical data were collected and summarized using an access-type database, adding genetic analysis and IHC data of each patient's tumor sample. IHC statistical analysis included Chi-square, Kruskal-Wallis and multivariate analysis. The genetic analysis was performed using multivariate logistic regression (normal/deletion-duplication). Significance level p<0.05. RESULTS: Pathologic stage was: pT1 (61.8%), pT2 (32.7%); pT3-T4 (5.4%); 16.3% were pN+ and 19.3% M1. 23.6% recurred being predominantly to distance in 83.3%. 27.3% of patients died (73.3% ccCCR). CAIX (Carbonic anhydrase IX) and tumor size were associated with worse Fuhrman grade (p = 0.035; p = 0.001 respectively). Deletion-duplication of genes increased the likelihood: of death (APC, Bcl-2 and CDKN2A by 11, 7 and 4 respectively and SMAD4 reduced the probability by 88%); tumor recurrence (CDKN2A by fifteen fold and VHL reduced the probability by 87%); pT greater than 2 (CCND2, MDM2 and WT1 multiplied by 6, 7 and 9); risk of N+ (CDK4 and EBF1 by 13); distant metastases (BRCA2 and DLEU1 by 5); Fuhrman grade ≥3 (BRCA1, BRCA2 and p53 by 40, 75 and 34 respectively, while that FHIT reduced by 96%). Deletion-duplication of CDK4 and DCC increased survival by a factor of 13 and 16, while that DLEU1 and RUNX1 decreased survival time by 80%. CONCLUSION: CAIX and tumor size are associated with increased aggressiveness. The mutations to level 5q, 9p, 11p, 12, 13q, 17, 18q and 21q are associated with more aggressive tumors and with worse survival rate.

Caracterización clínica del cáncer de próstata potencialmente insignificante en la biopsia prostática / Clinical Characterization of Prostate Cancer Potentially Insignificant in the Prostate Biopsy

Objetivo: El objetivo de este trabajo es conocer el porcentaje de pacientes que, cumpliendo criterios de adenocarcinoma insignificante de próstata en la biopsia, tiene realmente un tumor clínicamente significante en la pieza de prostatectomía, analizando si existe algún factor pronóstico para cáncer clínicamente significante. Material y método: Seleccionamos como cánceres potencialmente insignificantes aquellos con PSA menor igual 10ng/ml, estadio T1c, puntuación de Gleason en la biopsia menor igual 6, afectando un solo cilindro, con menos del 5% de tumor e intervenidos de prostatectomía radical. Analizamos las variables: edad, PSA previo, densidad de PSA, cociente PSA libre/total, volumen ecográfico prostático y la relación con la presencia de cáncer clínicamente insignificante o significante en la pieza quirúrgica. Se realizó un análisis de regresión logística múltiple para conocer si alguna de las variables podría tener valor predictivo sobre la presencia de cáncer significante. Resultados: Entre el 1 de enero de 2003 y el 31 de julio de 2009 se realizaron 2.424 biopsias, entre las cuales 77 pacientes cumplieron los criterios de inclusión. Cincuenta y uno (66,23%) presentaron cáncer clínicamente significativo en la pieza de prostatectomía radical. Mediante análisis univariante se comprobó que el volumen prostático fue significativamente mayor y la densidad de PSA significativamente menor en los cánceres clínicamente insignificantes, sin diferencias en el resto de variables estudiadas. El análisis mediante regresión logística muestra la densidad de PSA como único factor con valor predictivo, de tal forma que a mayor densidad de PSA mayor probabilidad de que el tumor sea clínicamente significativo (OR: 25067,101; IC 95%: 26,79–2,34×107; p=0,004). Conclusión: Los hallazgos del presente estudio sugieren que un porcentaje alto de pacientes con sospecha de cáncer de próstata insignificante en la biopsia tienen en realidad un tumor clínicamente significante, siendo la densidad de PSA el único factor predictivo independiente (AU)

Objective: The aim of this study was to identify the rate of clinical significant disease (Gleason score major 6 or tumor volume major 0.5 cc in the RP specimen) among patients who had an insignificant prostate cancer on biopsy, evaluating the presence of prognostic factors. Patients and methods: Patients who fulfilled the following criteria were included: PSA minor= 10ng/ml, T1c disease, biopsy Gleason Score minor= 6 affecting minor 5% of only 1 core and who had undergone a radical prostatectomy. The following variables were studied: Age, PSA, dPSA, free/total PSA ratio and prostatic volume assessed by transrectal ultrasound. Results: In a series of 2424 biopsies, 77 patients completely fulfilled the inclusion criteria, with 66.23% (n=51) of clinical significant disease in the prostatectomy specimen. No differences were observed between these patients and those with insignificant disease in age, PSA, free/total PSA ratio. However, prostatic volume was significantly greater and PSA density significantly lower in those patients with an insignificant disease. Statistical analysis using a logistical regression showed that dPSA was the only prognostic factor (OR: 25067.10, CI 95%: 26.79–2.34×107, P=0.004). Conclusions: These findings suggest that a high rate of patients who have a suspected insignificant prostate cancer on biopsy have a clinical significant disease, being dPSA the only independent prognostic factor (AU)

[Clinical characterization of prostate cancer potentially insignificant in the prostate biopsy]. / Caracterización clínica del cáncer de próstata potencialmente insignificante en la biopsia prostática.

OBJECTIVE: The aim of this study was to identify the rate of clinical significant disease (Gleason score>6 or tumor volume>0.5 cc in the RP specimen) among patients who had an insignificant prostate cancer on biopsy, evaluating the presence of prognostic factors. PATIENTS AND METHODS: Patients who fulfilled the following criteria were included: PSA ≤ 10ng/ml, T1c disease, biopsy Gleason Score ≤ 6 affecting <5% of only 1 core and who had undergone a radical prostatectomy. The following variables were studied: Age, PSA, dPSA, free/total PSA ratio and prostatic volume assessed by transrectal ultrasound. RESULTS: In a series of 2424 biopsies, 77 patients completely fulfilled the inclusion criteria, with 66.23% (n=51) of clinical significant disease in the prostatectomy specimen. No differences were observed between these patients and those with insignificant disease in age, PSA, free/total PSA ratio. However, prostatic volume was significantly greater and PSA density significantly lower in those patients with an insignificant disease. Statistical analysis using a logistical regression showed that dPSA was the only prognostic factor (OR: 25067.10, CI 95%: 26.79-2.34×10(7), P=.004). CONCLUSIONS: These findings suggest that a high rate of patients who have a suspected insignificant prostate cancer on biopsy have a clinical significant disease, being dPSA the only independent prognostic factor.

[Risk factors in the failure of surgical repair of pelvic organ prolapse]. / Factores de riesgo en el fracaso de la reparación quirúrgica del prolapso de suelo pelviano.

INTRODUCTION: Pelvic organ prolapse (POP) surgery has variable results of recurrence and complications. We have aimed to analyze our outcomes in order to know the factors associated with anatomical and functional failure in POP surgery. MATERIAL AND METHODS: A retrospective study of 69 patients who underwent POP surgery at our hospital was performed. Registered variables were: Age, BMI, number of deliveries, previous pelvic surgery, menopause, quality of life, urinary incontinence, associated frequency-urgency symptoms, high POP stage, vaginal compartments repaired, type of mesh, urethro-suspension and vaginal hysterectomy during POP surgery and its complications. Patients were evaluated at 1, 6 and 12 months post-surgery. The technique was considered as failed when relapse or mesh erosion occurred and when the patient is not satisfied or there was relapse. The sample is described, analyzing the relationship of the variables studied by univariate analysis (Chi square and Mann-Whitney U test) and a study was made of which variables may have predictive value in the failure of the repair (multiple logistic regression). RESULTS: Surgery failed in 17 patients during the follow-up at one year. BMI (29.6±2.03 vs 27.1±3.32), delivery number (3.4±0.71 vs. 2.8±1.88), menopause, frequency- urgency symptoms and number of vaginal compartments repaired were associated with treatment failure although only BMI, delivery number and frequency-urgency symptoms were defined as independent predictive variables when the logistic regression was carried out. CONCLUSIONS: Overweightness-obesity, previous delivery number and frequency-urgency symptoms before surgery are factors associated to anatomical and functional failure after POP repair.