Genetic counseling in prostate cancer: How to implement it in daily clinical practice? / Asesoramiento genético en cáncer de próstata: ¿cómo implementarlo en la práctica clínica diaria?

Prostate cancer plays an undeniably prominent role in public health in our days and health systems. Its epidemiological impact is quantitatively very close to that of other tumors such as colon cancer and breast cancer, in which genetic counseling is part of their routine clinical practice, both in the initial evaluation and in the selection of therapeutic strategies. Hereditary cancer syndromes, breast/ovarian and Lynch syndrome are part of genetic counseling in these tumors. Currently, we also know that they can be associated to prostate cancer. The time has come to implement genetic counseling in prostate cancer from the earliest stages of its approach, from initial suspicion to the most advanced tumors. We present an updated review carried out by our interdisciplinary working group on scientific literature, clinical practice guidelines and consensus documents, aimed at the creation and drafting of a'Protocol for genetic counseling in prostate cancer' for the study of germline, with easy application in different healthcare settings. This protocol is currently being implemented in our routine practice and provides answers to 3 specific questions: Who should receive genetic counseling for prostate cancer? Which gene panel should be analyzed? How should counseling be done according to the results obtained? Other aspects about who should perform genetic counseling, ethical considerations and regulations are also collected.

[Are there any differences between the characteristics and the behavior of bladder cancer according to the age of presentation? Our experience]. / Existen diferencias en las caracteristicas y en el comportamiento del tumor vesical según edad de presentación? Nuestra experiencia.

INTRODUCTION: Owing to the different results from the series that evaluate the behavior of the bladder cancer according to the age at the moment of the diagnosis, our objective is based on valuing the characteristics and behaviour according to age of appearance. METHODS: A retrospective study of bladder cancer diagnosed in our area during decade 1993-2003, distributed in 3 intervals of age and some characteristics and behaviour are valued. RESULTS: Elderly patients present greater tumors, non differentiated and with greater rate of progression to infiltrated. Moreover the age, the pathological stage and the tumorlike degree appear as independent significant factors in the multivariant study. CONCLUSIONS: In our experience, the patients greater than 70 years present neoplasms of similar clinical characteristics, although pathologically more aggressive, with greater percentage of progression and worse survival.

[Steroid and xenobiotic receptor (SXR), multidrug resistance gene (MDR1) and GSTs, SULTs and CYP polymorphism expression in invasive bladder cancer, analysis of their expression and correlation with other prognostic factors]. / Expresion del receptor de esteroides y xenobioticos (SXR) y del gen de multirresistencia drogas (MDR1) y de los polimorfismos de las enzimas Gsts, SULTs y CYP en tumores vesicales profundos, analisis de su expresion y correlación con otros factores pronósticos.

INTRODUCTION: Steroid and Xenobiotic Receptor (SXR) has demonstrated its activation by numerous drugs, including cytochrome P450 potent inducers like rifampicina or cotrimazol. The role of SXR is well known, and lies regulating in a positive manner cytochrome P450 3A4 (CYP3A4) transcription and the multidrug resistance gene (MDR1), it's considered a key in the xenobiotic detoxification mechanism, being involved in all phases of the detoxification process. Enzymes involved in Policyclic Aromatic hidrocarbures (PAH) metabolism and degradation are polymorphic in humans, including glutation S-transferases (GSTs), N-acetiltransferases (NATs), sulfotransferases (SULTs)1A1 and cytochrome p450 (CYP)1B1. OBJECTIVES: The objectives we've planned are: 1. Analyze the expression of the transcription factor SXR and MDR1 in bladder by means of RT-PCR real time, both in normal bladder and in tumoral bladder. 2. Analyze the relation between clinical and pathological factors with the expression of SXR and MDR1. 3. Analyze the expression of the polymorphims CYP1B1, GSTM1 GSTT1 and SULT1A1 and their correlation with different clinic-pathological and molecular factors. MATERIAL AND METHODS: In a prospective way the size of the sample was estimated. In 67 patients from two institutions (Hospital Universitario Miguel Servet (49 HUMS) and Clinica Universitaria de Navarra (18 CUN)), diagnosed of invasive bladder cancer and treated by means of radical cystectomy, were determined the expression of both SXR and MDR1 by means of real time PCR, as well as the polymorphisms CYP1B1, GSTM1 GSTT1 y SULT1A1 by means of RFLP (Restriction fragment length polymorphism). Correlations with other prognostic factors by contingency tables were performed. RESULTS: Average follow up was 23.7 months with a median of 28.26 months. Of the 67 patients studied, 31 patients (46.3) presented disease progression, in form of local recurrence or in distant metastasis or both. With a average time to progression of 12.4 months and a median of 10 months, with a range of 1.1 month to 31.9 month. 36 patients (53.7%) did not have any evidence of disease progression during follow up. The Steroid and Xenobiotic Receptor as well as the Multidrug Resistance Gene (MDR1) are expressed in both normal bladder (0.94DeltaCt y 0.94DeltaCt) and tumoral bladder in the cystectomy specimen (1.09 DeltaCt y 0.45 DeltaCt). We've analyzed their expression in a quantitative manner and in a qualitative manner. The expression of SXR correlates with the presence of ca. in situ (p=0.024), vasculo-lymphatic invasion (p=0.05) mean while MDR1 correlates with presence of vasculo-lymphatic invasion (p=0.05) Both factors are correlate between each others (p=0.011). Polymorphisms: CYP1B1, GSTM1, GSTT1 and SULT1A1, are expressed in these patients but their expression doesn't correlates with any prognostic factor CONCLUSIONS: Both SXR and MDR1 are expressed in normal bladder as well as in tumoral bladder. And their expression correlates with different prognostic factors with influence in the survival described in the literature.

[Stage pT0 bladder tumors after radical cystectomy: a review of our series]. / Tumores de vejiga pT0 tras cistectomía radical: análisis de nuestra serie.

OBJECTIVES: To evaluate the data of progression and survival in 43 patients who underwent cystectomy with stage pT0 according to classification TNM-2002. MATERIALS AND METHODS: between 1988 and 2003 in our center had realized 420 cystectomies, 43 patients (10.2%) had not tumor in the cystectomy specimen. RESULTS: In these 43 cases the initial clinical stage (in the transuretral resection of bladder) was T1 in 10 cases (23,3 %), T2 in 31 cases (72%) and T3 in 2 cases. As far as the degree 24 patients presented G2 (55.8%) and 19 (44.2%) were G3. Median time from the transuretral resection to the cistectomy was of 44 days at a median follow-up of 89.3 months. Progression-free survival in the 43 patients was of 180,6 months, but during the follow-up it appeared progression in 7 patients, with disease free survival at 36 months (3-126), since the date of the cistectomia. During the follow up, 5 patients died. When we analyzed the cancer-specific survival according to tumor stage, for the T2 with an average cancer-specific survival is of 180 months, decreasing to 35 months considerably for T3. Similar it happens with the degree of differentiation, significantly diminishing as it advances the degree, with an average of cancer-specific survival for the G3 at 122.6 months. In the same way it happens with pathological positive lymph nodes in the radical cistectomy, with a cancer-specific survival of 188 months when it is N0 and of 54 months if the adenopathy was positive (N+). CONCLUSION: In our experiencie urothelial carcinoma pT0 present a prolonged free period of disease (medium of 180 months). The associated factors of risk to a smaller free period of disease are high degree of differentiation (G3, 116 months), the infiltration of deep layers in the transuretral resection (T3, 32 months) and the ganglionary affectation (pN+ 45 months).

A Preliminary Study of the Ability of the 4Kscore test, the Prostate Cancer Prevention Trial-Risk Calculator and the European Research Screening Prostate-Risk Calculator for Predicting High-Grade Prostate Cancer.

INTRODUCTION: To prevent the overdiagnosis and overtreatment of prostate cancer (PC), therapeutic strategies have been established such as active surveillance and focal therapy, as well as methods for clarifying the diagnosis of high-grade prostate cancer (HGPC) (defined as a Gleason score ≥7), such as multiparametric magnetic resonance imaging and new markers such as the 4Kscore test (4KsT). By means of a pilot study, we aim to test the ability of the 4KsT to identify HGPC in prostate biopsies (Bx) and compare the test with other multivariate prognostic models such as the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC 2.0) and the European Research Screening Prostate Cancer Risk Calculator 4 (ERSPC-RC 4). MATERIAL AND METHODS: Fifty-one patients underwent a prostate Bx according to standard clinical practice, with a minimum of 10 cores. The diagnosis of HGPC was agreed upon by 4 uropathologists. We compared the predictions from the various models by using the Mann-Whitney U test, area under the ROC curve (AUC) (DeLong test), probability density function (PDF), box plots and clinical utility curves. RESULTS: Forty-three percent of the patients had PC, and 23.5% had HGPC. The medians of probability for the 4KsT, PCPTRC 2.0 and ERSPC-RC 4 were significantly different between the patients with HGPC and those without HGPC (p≤.022) and were more differentiated in the case of 4KsT (51.5% for HGPC [25-75 percentile: 25-80.5%] vs. 16% [P 25-75: 8-26.5%] for non-HGPC; p=.002). All models presented AUCs above 0.7, with no significant differences between any of them and 4KsT (p≥.20). The PDF and box plots showed good discriminative ability, especially in the ERSPC-RC 4 and 4KsT models. The utility curves showed how a cutoff of 9% for 4KsT identified all cases of HGPC and provided a 22% savings in biopsies, which is similar to what occurs with the ERSPC-RC 4 models and a cutoff of 3%. CONCLUSIONS: The assessed predictive models offer good discriminative ability for HGPCs in Bx. The 4KsT is a good classification model as a whole, followed by ERSPC-RC 4 and PCPTRC 2.0. The clinical utility curves help suggest cutoff points for clinical decisions: 9% for 4KsT and 3% for ERSPC-RC 4. This preliminary study should be interpreted with caution due to its limited sample size.

[Primitive neuroectodermal tumor. Ewing's sarcoma]. / Tumor neuroectodérmico primitivo renal/sarcoma de Ewing.

Primitive neuroectodermal tumor is an extraordinarily rare primary tumor in the kidney and can be mistaken for a variety of other round cell tumors. It is important to recognize each of these entities, because each carries unique therapeutic and prognostic implications. However, accurate diagnosis of these tumors is hindered by their significant morphologic overlap and complicated by their rarity. These neplasm are highly aggressive that tend to recurence and to metastatize. Standard therapy combining surgery, chemotherapy, radiation and genetic therapy. We report a case of primitive neuroectodermal tumor of the kidney in a 50 year old female patient.

[Cancer of the prostate: current diagnostic aspects]. / Cáncer de próstata: aspectos actuales del diagnóstico.

Presentation of the initial results from a program for early diagnosis of prostate cancer, implemented a year ago at the Urology Unit of the Miguel Servet Hospital with the collaboration of the Region's specialists. All patients attending the Urology services, regardless the pathology, are evaluated when rectal examination is suspicious or the plasma PSA levels are higher than 4 ng/ml. Assessment is made through transrectal ultrasound scanning, with random or ultrasound-directed prostatic biopsy depending on the findings. A total of 83 prostatic biopsies have been analyzed n patients thus selected, presence of prostatic carcinoma becoming apparent in 52 (62.6%), 19 of which have undergone radical prostatectomy. The association suspected rectal examination/increased PSA has produced the higher percentages of diagnostic precision (80%) clearly improving those of rectal examination and PSA alone. The methods for local and nodular staging are analyzed, considering the systematic use of laparoscopic lymphadenectomy and biopsy of seminal vesicles highly useful for higher diagnostic precision in these patients. The diagnostic relevance of prognostic factors in advanced cancer is analyzed, this analysis being mandatory to evaluate the different therapeutic.

[Unusual association of transitional cell carcinoma in the upper urinary tract, with contralateral renal metastasis and renal lithiasis of long clinical course]. / Infrecuente asociación de: carcinoma de células transicionales en T.U.S., con metástasis renales contralaterales y litiasis renal de larga evolución.

Presentation of a case reporting an infrequent association of transitional cell carcinoma of the upper urinary tract (UUT) with a long-standing renal polylithiasis and multifocal metastasis in contralateral kidney. A description is made of the incidence, etiology, prognostic factors as well as diagnosis and therapeutical approach.

[Analysis of a series of radical prostatectomies]. / Análisis de una serie de prostatectomías radicales.

OBJECTIVE: Radical prostatectomy (RP) is an elective therapeutical procedure for localized prostate cancer. The paper describes the critical analysis of our 10-year series. MATERIAL AND METHODS: A total of 216 RP have been performed between June 1986 and December 1996 (60 of them in the last year); with the purpose of securing a minimum follow-up of 4 months, the 204 procedures performed up to October 1996 were studied. Mean age was 64.9 years and PSA median 10.8 ng/ml. Intraglandular clinical stage was found in 192 cases versus 12 cases extraglandular. Up to the end of 1993 Walsh's technique with erectors' preservation was being used although the poor results obtained with regard to potency as well as the existence of positive borders have compelled us to perform the standard extracapsular technique since beginning of 1994. RESULTS: Mean follow-up in our series has been 29.62 months. Post-operative complications reached 29.9%, anastomosis fistula (21 cases) among the early ones and anastomosis stenosis (16 cases) among the late ones. 82.04% patients have total continence or minimal incontinence, the percentage of obstruction being 3.58%. Total impotence is estimated at 92.77%. One patient (0.49%) died in the immediate post-operative. Understaging was observed in 36.7%. 84 patients had extracapsular disease. Our percentage of positive surgical borders is of around 43.13%. Progression has been seen in 47 of 204 patients (23.03%): 8 local relapses, 12 metastasis, 3 with both conditions and 24 biological progression. Progression has been related to pathological stage, pre-operative PSA and Gleason's sum of the specimen. Difference was statistically significant. Overall survival at 1 and 5 years is 99.2% and 95.5% respectively while tumour specific survival is 97.8% and 75.8% at 1 and 5 years. CONCLUSIONS: RP is a surgery with minimal mortality but noticeable morbidity (incontinence 14.35%; impotence 92.77%; other complications from surgical technique 29.9%). Our clinical understaging is of around 36.7%. Progression is related to the specimen's pathological stage, and pre-operative PSA and Gleason. Our overall survival at 1 and 5 years is 99.2% and 95.5% respectively while tumour specific survival is 97.8% and 75.8%.

[Early diagnosis of cancer of the prostate. 5-year analysis]. / Diagnóstico precoz del cáncer de próstata. Análisis de cinco años.

The authors present the results obtained using a program for early diagnosis in symptomatic patients, within a specific population area. The effectiveness of this diagnosis program for prostate cancer, which is expected to be used also for diagnosis of less advanced stages, is established with the analysis of results obtained in 1000 patients: 42.5% positive biopsies. Biopsy indication in case of suspicious rectal examination and/or PSA over 10 ng/ml is considered useful. There are more reservations towards this indication with PSA values between 4 and 10 ng/ml, where evaluation of other complementary options is considered necessary.

[Positive margins. Surgical techniques and progression after radical prostatectomy]. / Márgenes positivos. Técnica quirúrgica y progresión tras prostatectomía radical.

OBJECTIVE: Repercussion of positive surgical borders (SB+) after radical prostatectomy (RP) in the oncological management of this condition is not yet well defined. The article analyzes their incidence and relevance for tumoral progression. MATERIAL AND METHODS: A review of 204 RPs is made. The erectors' preservation technique has been preferentially used until 1994, while the extracapsular standard technique was used afterwards. SB+ have been correlated to pre-operative PSA, Gleason grade, pathological stage and surgical technique. Also, status of borders has been correlated to progression. RESULTS: SB+ have been detected in 88 patients (43.13%) and were significantly correlated to the pathological stage and Gleason, but not to pre-operative PSA. Although no relation has been ascribed to the surgical technique used in terms of incidence, a decrease of posterolateral borders from 51.8% to 26.2% has been noticed using the extracapular standard technique. Progression is greater in SB+ patients (27.2% vs. 19.2%) but the difference is not statistically significant. SB+ patients who have progressed had all extracapsular tumour, 66% poorly differentiated. CONCLUSIONS: There is a decrease of posterolateral SB+ when the extracapsular standard technique is used. A correlation between presence of SB+ and progression has not been established. No patients with intracapsular tumour and SB+ has progressed. Therefore, it can be inferred his factor has little influence on the evolution of these patients.

[Current validity of urethroplasty in two stages]. / Vigencia actual de la uretroplastia en dos tiempos.

Review of 18 patients with complex urethral stenosis, who underwent a two-stage urethroplasty in our Unit over the last three years. Clinical results have been favourable in all patients and, from the radiological point of view, there has been only one re-stenosis. Complications rate has been low and can be superimposed to that of any urethroplasty procedure. The paper emphasizes the enormous relevance of the care taken between both surgical stages on the procedure's final result.

[Skin metastasis of urothelial bladder tumor]. / Metástasis cutánea de tumor urotelial vesical.

We want to present a case of tranticional cell bladder carcinoma, where the first sign of disease progression was the appearance of a skin metastase. An unusual manifestation in a patient without another metastatic lesions.

[Non-radical treatment and bladder conservation in infiltrating tumor of the bladder]. / Tratamiento no radical y conservación vesical para el tumor infiltrante de vejiga.

The fate of some infiltrant tumours of the bladder locally advanced (pT2-3NxM0) which were radically resected, with or without association to other treatments, has been similar to those in which initial radical treated was used. To carry out simultaneously a radical RTU as a local action plus systemic chemotherapy (M-VAC), for microscopic metastasis, clinically undetected, seems to us the most effective combination. In our Urology Unit, the evolution (September 88-January 91) of 9 patients presenting this tumour and preservation of the bladder is being followed-up. The primary tumour was treated with radical RTU in 7 cases and partial cystectomy in 2. There are 5 tP2, 1 pT2 + "in situ" carcinoma (Ca) and 3 pT3, 4 G1, 4 G2 and 1 G3. All tumours were single, small (2-4 cm), with varied location and nearly all with medium to low differentiation. Later all patients underwent systemic chemotherapy with M-VAC (3 cycles). Following RTU and QMT every three months, the likely local and systemic progression of the disease has been evaluated through cystoscopy and multiple biopsies including from the prostatic urethra, RTU of anterior scar, two-hand palpation, urinary cytology, blood testing, CAT, abdominal ECO, chest X-ray and laparoscopic lymphadenectomy (coinciding with its development within the Unit) in the last case. Average follow-up (at the time of the review) has been 15.77 months (6-28 months).(ABSTRACT TRUNCATED AT 250 WORDS)

[Metastasis in maxillary sinus as presentation form of adenocarcinoma of the prostate]. / Metástasis en seno maxilar como presentación de un adenocarcinoma de próstata.

Presentation of one case of prostate adenocarcinoma its initial clinical manifestation being the appearance of facial tumour secondary to metastatic affectation of left maxillar sinus. After stressing its rarity, the relevance of immunohistochemical studies for the specific prostatic antigen and acid phosphatase in determining the unconnected origin of metastatic lesions is addressed.

[Value of CAT staging in renal adenocarcinoma. Correlation with anatomo-pathologic findings]. / Valor del estadiaje del TAC en el adenocarcinoma renal. Correlación con los hallazgos anatomo-patológicos.

On a total of 128 renal adenocarcinomas diagnosed in our Unit between January 1975 and August 1990, the data provided by CATs carried out in 85 of them was compared with that from surgical and anatomo-pathological findings. The precision in both the diagnosis and the tumour staging was determined, evaluating the involvement of perirenal, nodular, venous and neighbouring structures fat. The diagnosis of renal adenocarcinoma was made correctly in 96% cases. With regard to staging, maximal precision was achieved in the involvement of adjacent structures and vena cava, followed by the renal vein, perirenal fat and lymphatic nodes, in this order. We conclude that CAT provides a high diagnostic reliability, permitting with a single study the determination of the most defining parameters of renal cancer staging.

[Pelvic recurrence of urothelial tumor, after radical cysto-prostatectomy with orthotopic neo-bladder]. / Recidiva pélvica de tumor urotelial, tras cistoprostatectomía radical con neovejiga ortotópica.

We present a case of an urothelial tumor pelvic recurrence, five months after radical cystoprostatectomy. No fat infiltration was demonstrated in the pathological study of the transurethral resection pieces. The treatment was a radical cystoprostatectomy with an ileal ortothopic Hautmann type neo-bladder. The pathological study of the surgical piece demonstrated fat infiltration in some points but urethra and lymphatic nodes free.

[Metastasizing kidney cancer. Experience with interferon alfa-2a and vinblastine]. / Cáncer metastásico de riñón. Experiencia con interferón alpha-2a y vimblastina.

Management of renal cells carcinoma still remains a therapeutic challenge. Nephrectomy is the primary therapy when the disease has a definite location. In advanced or disseminated cases, the various traditional procedures, including radiotherapy, chemotherapy or hormonal regimes, have obtained poor responses. Survival shows a direct relationship with the biological aggressiveness of the tumour and histological factors. Results recorded in the literature using specific immunotherapeutic agents are encouraging although the real value of this regimes has not yet been established in large series of prospective studies. The Oncology Unit of our Urology Service has obtained optimal follow-up in a group of patients included in a combined protocol of interferon alpha-2a and vinblastine as cytotoxic agent.

[Systemic candidiasis and ureteral fungus ball. Ketoconazole and irrigating solutions in the management of urinary candidiasis]. / Candidiasis sistémica y fungus ball ureteral. Ketoconazol y soluciones irrigantes en el manejo de la candidiasis urinaria.

A case of systemic candidiasis is presented in a patient with one kidney in the post-operative period from a cysto-prostatouretrectomy with Bricker ureteroileal derivation, performed due to multifocal superficial vesical tumour non controllable by endoscopy. The clinical picture developed with anuria and temporary diuresis periods associated to a severe septic picture; a deep Candida albicans infection was demonstrated by laboratory tests and a fungus ball ureteral obstruction was demonstrated by radiology. Urinary derivation by means of percutaneous nephrostomy, associated with oral treatment with ketoconazole and local treatment with amphotericin B solution intermittently irrigated through the nephrostomy allowed the patient's resuperation and the fungus ball was spontaneously ejected after 30 days of treatment. The different forms of presentation of urinary candidiasis are discussed together with the diagnostic methods and present therapeutical options, with special reference to the imidazole derivative ketoconazole and irrigation solutions.

[Camey II type substitution ileocystoplasty. Our experience]. / Ileocistoplastia de sustitución tipo Camey II. Nuestra experiencia.

We present our experience in the performance of Camey II type substitution ileocystoplasty. The operation was performed between January 1988 and February 1989 on 11 patients who had been diagnosed as having vesical tumour by means of transurethral resection. All of them had received preoperative systemic chemotherapy. Technically, we single out the performance of ileo-obturating lymphadenectomy prior to the cystoprostatovesiculectomy in the same operation, creation of the neobladder with detubulized terminal ileum, uretero-ileal reimplantation according to Le Duc-Camey technique and use of mechanical sutures to reestablish intestinal continuity. Operative and postoperative mortality has been null. As complications, we may mention a urthro-ileal fistula as a result of the suture tension at this level, due to shortness of the mesointestine, and which yielded with conservative measures. Amongst tardive complications we may single out a urethro-ileal stenosis, which required performance of an internal urethrotomy. Daytime continence in all patients, except one. Night continence in six cases. Absence of ureteral reflux and upper urinary tract with correct function and morphology in all cases. The follow-up time ranges from 3 to 16 months. We conclude that this type of vesical substitution offers all patients a good quality of living and adequate mictional comfort.