Beyond the Briganti nomogram: Individualisation of lymphadenectomy using selective sentinel node biopsy during radical prostatectomy for prostate cancer. / Más allá del nomograma de Briganti: individualización de la linfadenectomía utilizando la biopsia selectiva del ganglio centinela durante la prostatectomía radical por cáncer de próstata.

OBJECTIVE: To validate the technique of selective sentinel node biopsy for diagnosing and staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. METHODS: We applied the technique to 45 patients. After an intraprostatic injection of 99mTc-nanocolloid and preoperative single-photon emission computed tomography (SPECT/CT), we extracted the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. RESULTS: SPECT/CT showed radiotracer deposits outside the eLFD territory in 73% of the patients and the laparoscopic gamma probe in 60%. The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The mean number of extracted sentinel lymph nodes was 4.3 (0-14), with 26% outside the eLFD territory. The lymph nodes were metastatic in 10 patients (22%), 6/40 (15%) when the prostatectomy was the primary treatment. In all cases with metastatic lymph nodes, there was at least one positive sentinel node. Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/10 patients (30%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%. CONCLUSION: Selective sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement and can avoid eLFD when metastatic sentinel lymph nodes are not found (85%), with the consequent functional advantages.

FIRST STEPS TOWARDS ORGAN BANKS: VITRIFICATION OF RENAL PRIMORDIAL.

BACKGROUND: Kidney transplantation from deceased or living human donors has been limited by donor availability as opposed to the increasing demand, by the risks of allograft loss rejection and immunosuppressive therapy toxicity and by limitations of organ preservation protocols, which is essential to organise staff and facilities, transport organs, and perform necessary laboratory tests. However, the cryopreservation of composite tissues poses technical challenges beyond those seen in the preservation of single tissue types or organs. OBJECTIVE: The purpose of our study was to establish a protocol for long-term storing of renal primordia, that generates new adult kidneys after transplant into a syngeneic non-immunosuppressed host. MATERIALS AND METHODS: Metanephroi from 16-days-old embryos were microdissected and vitrified following the minimum essential volume method and using Cryotop as a device and VM3 as vitrification solution. After 3 months of storage in liquid nitrogen (-196 degree C), 20 metanephroi were warmed and transplanted using minimally invasive laparoscopic surgery into retroperitoneal fat of 5-month-old immune-competent New Zealand rabbits. In the same way, 22 fresh metanephroi were transplanted. Twenty-one days after transplantation, hosts were euthanized and developed kidneys were recovered and evaluated morphologically and histologically. RESULTS: Significant growth and fully differentiated mature glomeruli and tubule were observed in all kidney graft explants recovered. In total, 5 metanephroi (25.0%) were successfully grown after vitrification. In the same way, 12 metanephroi (54.5%) were successfully grown in the fresh group. CONCLUSION: These encouraging results reported that metanephroi not only survive vitrification, but they vascularized and developed morphologically normal glomeruli after their allotransplantation. These results suggest that it's possible to create a long-term biobank of kidney precursors as an unlimited source of organs for transplantation, and open new therapeutic possibilities for the patients with chronic renal failure.

Laparoscopic transplantation of metanephroi: A first step to kidney xenotransplantation.

BACKGROUND: Embryonic kidney xenotransplantation could represent a new solution to the scarcity of kidneys for transplantation. OBJECTIVE: To determine the feasibility of allogeneic laparoscopic transplantation of metanephroi (M) in rabbits. MATERIAL AND METHOD: Microscopic dissection was conducted to obtain metanephroi from 14-day-old (24M), 15-day-old (20M) and 16-day-old (26M) embryos. Using single-port abdominal laparoscopy, a spinal needle was inserted percutaneously, through which the metanephroi were deposited (using an epidural catheter) close to a patent blood vessel in the retroperitoneal fat. Seventy metanephroi were transplanted to 18 rabbits. Three weeks later, the animals were examined through open surgery. We compared the embryonic maturity, the morphometric variables of the metanephroi and the development rate of the transplanted metanephroi. RESULTS: The lower time limit for the extraction of metanephroi from the rabbits was day 14. Three weeks after transplantation, only 3/24 14-day-old metanephroi grew at minimal expression (12.5%). In contrast, 10/20 (50%) 15-day-old and 12/26 (46.1%) 16-day-old metanephroi grew. These metanephroi had differentiated sufficiently for the glomeruli, proximal and distal tubules and collecting ducts to develop normally. We detected no relevant immunological changes in the peripheral blood. CONCLUSIONS: We have described for the first time in the literature the allogeneic laparoscopic transplantation of metanephroi from embryos as a feasible and noninvasive technique. The recipients did not require immunosuppression.

Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

OBJECTIVE: To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. MATERIALS AND METHODS: 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). RESULTS: 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. CONCLUSION: the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases.

[Baltasar Llopis Mínguez (1934-1990). A pioneer in research on bladder cancer and introduction of computing in Urology]. / Baltasar Llopis Mínguez (1934-1990). Pionero en la investigación del cáncer vesical y en la introducción de la informática en Urología.

OBJECTIVE: To recall the figure of a great Valencian urologist, to emphasize his great personality and humanity, and to draw particular attention to his significant contribution to the study of prognostic factors in urology and estimation of individual oncological risk, as well as to introduction of computing in urology. METHOD: His work, the testimony of colleagues who treated him, and data obtained from his close relatives, as well as our own personal knowledge, are reviewed. Result. Baltasar Llopis was born in Valencia, and obtained his degree and doctorate in Medicine at the Valencia University. He specialized in urology with Dr. Tramoyeres Cases, for whom he acted as assistant surgeon and with whom he shared work at La Fe Hospital, where he carried out his complete urological activity, since its inception. Dr. Llopis opted for oncological research, with a special focus on urothelial tumors. He pioneered diagnosis of these tumors using tumor markers and the study of prognostic factors to assess the individual risk of relapse and to implement a specific chemotherapeutic treatment, which he introduced in clinical practice at La Fe Hospital. He thus demonstrated the two essential components of his personality, his investigative and human sides. CONCLUSION: A multi-faceted person with great skills and intelligence, Dr. Llopis eagerly devoted himself to research aimed at understanding the biological behavior of cancer, particularly urothelial tumors. In the early 80s he pioneered worldwide the development of specific markers, estimations of individual oncological risk, and prognostic factors useful for planning treatment. He was 20 years ahead of the era of predictive nomograms and their clinical INTRODUCTION: In addition to being a forerunner of computing applications in Urology, he designed a database for registration of superficial bladder tumors, which allowed him to perform statistical and multivariate analyses using multiple regression models to predict the risk of relapse.

Cutaneous horn in glans penis: a new clinical case.

This report presents a case of a 65-year-old male suffering from a penile cutaneous horn. This lesion is usually seen in sun-exposed areas and its occurrence on the penis is rare. One-third of cases of penile horns are associated with underlying malignancies. Standard treatment is electrosurgical excision with removal of a broad base.

[Gene therapy: is possible a vaccine for prostate cancer?]. / Terapia génica en el cáncer de próstata. Es posible una vacuna?

BACKGROUND: New approaches for prostate cancer are needed due to limitations of current therapies for the treatment in advanced stages of the disease. In fact, there is no effective treatment for these patients. Development in molecular biology research on prostate cancer has improved the knowledge of common alterations encoded in DNA sequence, which may be useful as targets for prostate cancer approach. In this review we give an overview of current gene therapy concepts, the most common gene alterations in prostate cancer and the gene therapy treatment strategies.

[The treatment of prostatic cancer: present and future, realities and possibilities]. / El tratamiento del cáncer de próstata: presente y futuro, realidades y posibilidades.

The routine determination of PSA has generated an important consequence: a really favourable migration of the tumour stage at the moment of diagnosis. It implies an exponential increase in the requirement of primary treatments with curative intention. Radical prostatectomy with preservation of neuro-vascular bundles is the gold standard for the treatment of localized prostate cancer but laparoscopic and robotic surgery have arrived with force during last five years. These therapeutic approaches and the new emerging techniques (those interventions that are not routine practice in the prostate cancer) guided by images present a constant research activity. Here, we perform a review of every possibility to treat the cancer of prostate.

[Photodynamic therapy in localised prostate cancer]. / Terapia fotodinámica en el cáncer de próstata localizado.

Photodynamic therapy is based on the administration of an energy source in form of light of a specific wavelength, on a previously photosensitized tissue by a chemical compound, in the presence of oxygen, so that the great deal of free radicals and oxygen derivatives generated (hydroxyl compounds) produces necrosis of the treated tissue. Technique improvement during the last years has allowed its recent development as a therapeutic method for localised prostate cancer. At present, several clinical trials are ongoing in patients with organ-confined prostate cancer both as a first line and salvage treatment. There is no risk either of cancer dissemination in surrounding tissues or accumulative pharmaco-toxicity. Therefore, the technique can be repeated as often as needed and can be administered on a previously irradiated tissue. The literature review shows that photodynamic treatment will become a therapeutic option for patients with prostate cancer in the very near future.

[Indications, results and techniques of permanent prostate brachytherapy for localized prostate cancer]. / Braquiterapia de baja tasa en el tratamiento del cáncer de próstata localizado.

INTRODUCTION AND OBJECTIVE: Prostate brachytherapy is a first-line therapeutic approach for localized prostate cancer in selected patients. We present our experience in brachytherapy and a thorough review of the literature. MATERIALS AND METHODS: A review of the literature and evaluation of patient's selection was done. Furthermore the implantation technique, oncological results according to the different risk groups and acute and chronic complications were also analyzed. RESULTS: The biochemical relapse-free 10 year survival rate was 87-96% in low risk tumours and 63-86% in intermediate risk tumours. A total of 3-24% underwent urinary retention that required TURP in 0-8,7%. Other complications were urinary incontinence in 0-6,7%, proctitis in 0-15,5%, erectile dysfunction in 6,3-30%, rectal ulcer/fistula in 0-5,4%. CONCLUSIONS: Prostate brachytherapy is a safe and effective treatment in low and intermediate risk patients with prostate cancer.

[Cryosurgery in the management of prostate cancer]. / Criocirugía en el tratamiento del cáncer de próstata.

This article reviews the current status of the prostatic cryosurgery in the management of patients with prostate cancer. Recent advances in cryoablative technology have allowed to treat these patients successfully with decreased morbidity. Using transrectal high-resolution ultrasound imaging, prostate cryotherapy is delivered with multiple ultrathin (17-gauge) cryo-needles, via percutaneous transperineal approach. The extent of freezing can be precisely controlled and monitored with thermic devices, tissue destruction is monitored with real-time visualization of the prostate and surrounding structures, and urethral warming is used to avoid urethral sloughing. However, the results with the second and third-generation cryosurgical equipment will have to be confirmed by means of prospective and randomized trials, because up to now we only have data based on retrospective analyses, which are very heterogeneous. The ability of prostate-specific antigen (PSA) to predict long-term outcome after cryotherapy for localized prostate cancer is not well known because experience with this treatment modality is still limited; however, it seems that a PSA value of 0.5 ng/ml or less after 6 months or longer after cryotherapy would be associated with a high probability (greater than 95%) of negative post-treatment biopsy. Cryosurgery could also be an option of treatment for men with recurrent local disease who have undergone radiotherapy or radical prostatectomy. We have to keep in mind possible complications (incontinence, impotency, urethrorectal fistula or bladder outlet obstruction. The favorable side effect profile and preliminary oncologic and funtional results could suggest that cryosurgery will have a role in the minimally invasive management of selected patients with prostate cancer.

[Cell cycle and apoptosis mechanisms implicated in intravesical chemotherapy resistances in superficial bladder cancer]. / Mecanismos del ciclo celular y la apoptosis implicados en las resistencias a los fármacos de uso intravesical en el cáncer superficial de vejiga.

It is well documented the effectiveness of intravesical chemotherapy following transurethral resection to prevent recurrences of superficial bladder cancer. But it is also known that efficacy may be limited by tumour cell resistance to one or several of the drugs available for instillation. In addition to the genetically determined unicellular mechanisms classically described in the literature such as glycoprotein P-170 expression (mdr-1), overexpression of Bcl-2 or glutation S-transferase activity, it has been recently shown that multicellular mechanisms may also be involved in drug resistance. Multicellular resistance can only be demonstrated in three-dimensional cultures and fails to be shown in monolayers or cell suspensions. This is explained by the fact that cell-to-cell and cell-to-stroma adhesion limits drug penetration and by the variable susceptibility to cytotoxicity determined by oxygen and tissue proliferation gradients. A better understanding of the molecular mechanisms involved in drug resistance is necessary to increase intravesical chemotherapy effectiveness. Current research includes improving drug penetration, searching resistance reversing agents and developing in vitro chemosensitivity tests to identify drug resistance.

[Study of the angiogenesis as prognostic factor of pT1G3 bladder tumours]. / Estudio de la angiogénesis como factor pronóstico de los tumores vesicales pT1G3.

INTRODUCTION AND OBJECTIVES: Angiogenic activity has been considered like prognostic factor in several solid tumors. This activity can be analysed by two ways: immunohistochemical determination of molecules that activate/inhibit angiogenesis or quantitive measure of microvascular density (MD). Our objective is to determine the prognostic value of Vascular Endothelial Growth Factor (VEGF) and Microvascular Density (MD) in pT1G3 bladder tumours. MATERIAL AND METHODS: We have studied retrospectively 83 patients with pT1G3 tumors treated by TUR + endovesical instillations with a follow up of 3 years at least. We analysed VEGF expression monoclonal antibody No. 360P. To determine MD we have marked vessels with FVIII antibody and detected "hot spots" areas. The number of microvessels is quantited by a digital image analyser excluding those that have more than 50 micras of diameter. We established the correlation of these findings with recurrence, progression and survival by using Chi-square test and Kaplan-Meier curves (log-rank). RESULTS: Average follow up was 58 +/- 28 months. We have established like cut-off 50% of tumor cells (VEGF) and 30 microvessels/fields (MD). Chi-square test did not show correlation with survival neither recurrence but it was positive for progression p(VEGF) 0.048 and p(DM) 0.021. Kaplan Meier curves determined significative differences only for free of progression time respect to MD (p 0.038). CONCLUSIONS: We did not find statistically significant value for recurrence nor survival. Just MD reached prognostic value for progression. More studies and multivariant analysis are required to determine the clinical utility of MD, specially in order to make more aggressive therapeutic options in this kind of patients.

[Factors affecting the PSA:alpha 1 antichymotrypsin/total PSA ratio]. / Factores que influencian el cociente PSA:alpha 1 antiquimotripsina/PSA-total.

OBJECTIVES: To evaluate the influence of several factors, including age, prostate volume, total PSA (PSA-T), clinical stage and Gleason on the PSA:alpha 1ACT/PSA-T (C/T) ratio. MATERIAL AND METHODS: Using in-house assays, we measured plasma levels of PSA-T and PSA:alpha 1ACT complex in 622 patients with benign prostate hyperplasia (BPH) (455 with hystological confirmation and 167 with clinical evidence of absence of malignance) and in 255 patients with prostate cancer (CaP), and determined the correlation between different parameters. RESULTS: In BPH patients, PSA-T and PSA:alpha 1ACT significantly increased with age. There was a positive correlation between age and PSA-T (r = 0.161, p < 0.0001) and PSA:alpha 1ACT (r = 0.141, p = 0.001). In contrast, the C/T ratio remained constant and below 70% in all decades. Similar results were obtained in CaP patients. In BPH patients, there was a positive correlation between prostate volume and PSA-T and PSA:alpha 1ACT, but not with the C/T ratio. In CaP patients, however, there was a negative correlation between prostate volume and the C/T ratio. An excellent correlation was found between PSA-T and PSA:alpha 1ACT, and a good correlation between PSA-T and the C/T ratio and between PSA:alpha 1ACT and C/T ratio. A multiple regression analysis showed that, in HBP and CaP patients, PSA-T and PSA:alpha 1ACT complex were the only parameters that significantly and independently influenced the C/T ratio. CONCLUSIONS: The C/T ratio is independent of age, prostate volume, Gleason and clinical stage. Therefore, these factors need not to be considered when using the C/T ratio.

[PSA:alpha 1-antichymotrypsin ratio/total PSA in the diagnosis of prostatic cancer in the range of total PSA from 4 to 10 ng/ml]. / El cociente PSA:alpha 1 antiquimotripsina/PSA total (C/T) en el diagnóstico del cáncer de próstata en el rango de PSA total entre 4 y 10 ng/ml.

OBJECTIVE: To evaluate the usefulness of the ratio PSA:alpha-1-antichymotrypsin/total PSA (C/T) in the diagnosis of prostate cancer in the range of total PSA between 4 and 10 ng/mL. MATERIAL AND METHODS: By using home-made ELISAs we have determined plasmatic concentrations of total PSA and complex PSA:alpha-1-ACT in 300 patients with total PSA between 4-10 ng/mL. All samples were obtained before any manipulation that could interfere the PSA levels. RESULTS: By prostatic biopsy 85 patients (28.3%) were diagnosed of prostate cancer (CaP) and 215 (71.6%) of benign prostatic hyperplasia (BPH). The mean values of the complex PSA:alpha-1-ACT (4.2 ng/mL in the BPH patients vs 5.0 ng/mL in the CaP patients) and of the C/T ratio (0.70 vs 0.82, respectively) showed significant differences between both groups (p = < 0.0001). The total PSA did not show differences (6.1 ng/mL vs 6.0 ng/mL; p = 0.79). From all three parameter evaluated, the ratio C/T had the biggest area under the ROC (0.884) and statistically significant differences in comparison with total PSA (0.490; p = < 0.001) and the complex PSA:alpha-1-ACT (0.696: p = < 0.001). Therefore, by using a ratio C/T > 0.62 to decide the performance of a biopsy, 27% of the patients with BPH could have avoided this procedure with a 100% sensitivity. Increasing the ratio to 0.68 the specificity is 47% and the sensitivity is 95.2%. Rectal examination did not have influence on the cut-off, sensitivity, specificity and area under the ROC of the ratio C/T. CONCLUSIONS: Our results confirm that the ratio C/T improve the diagnostic capacity of the total PSA between 4-10 ng/ml. Moreover, the rectal examination does not influence the selection of ratio C/T cut-off suggestives of CaP neither the diagnostic efficacy.

[Primary transitional carcinoma of the prostatic ductus]. / Carcinoma transicional primario de ductus prostáticos.

Primary prostate transitional cell carcinoma is a very rare tumour originating in the transitional epithelial cells of the intraprostate periurethral ductus. Only 17 of 829 patients diagnosed with prostate carcinoma were found to have the transitional cell variety. Eight (8) of those had pure transitional cell carcinoma and 9 a mixed presentation of acinar adenocarcinoma and transitional cell ductal carcinoma. Bladder origin of the tumour was ruled out in all cases. We report a retrospective study on the clinical behaviour of prostate transitional cell carcinoma. Compared to acinar carcinomas, few differences were found when age, symptoms, physical findings and imaging diagnosis were evaluated. Clinical presentation, DRE, PSA, metastatic spread and presence of supravesical obstructive uropathy where also studied to establish a diagnosis. Radiotherapy was the most frequently used therapeutical approach. Mean survival is 26.6 months (4-60 months) and there has been 11 death up to now. Compared to acinar forms, this tumour shows a hormone-resistant, aggressive biological behaviour with poor prognosis. Early diagnosis and radical surgery are the only options available to increase life expectancy for these patients.

[Mucinous prostate adenocarcinoma initially presented as an intestinal subocclusive picture]. / Adenocarcinoma mucinoso de próstata inicialmente manifiesto como cuadro suboclusivo intestinal.

Mucinous prostate adenocarcinoma is an infrequent tumour, with no more that 50 cases described to date. This paper contributes a new case of the entity. Rather than on the rarity of the tumour, the interest in our case focuses in the unusual nature of its clinical presentation. It initially appeared as a presumable rectoanal neoplasia but the pathoanatomical examination discovered the prostatic origin of the tumoration.

[Bladder cancer: general and epidemiological aspects, histopathological diagnosis, clinico-pathological classification, diagnosis of metastasis and risk groups]. / Cáncer vesical: aspectos generales y epidemiológicos, diagnóstico histopatológico, clasificación clínico-patológica, diagnóstico de extensión y grupos de riesgo.

Carcinoma of the bladder is the sixth most frequent tumor worldwide. It is more prevalent in the male and has been associated with exogenous triggering factors such as smoking, aromatic amines, etc. Its classification into superficial or infiltrating tumor is a simplification since there are four groups by clinical behaviour that require different therapeutic approaches. The epidemiological, clinical and pathological aspects of carcinoma of the bladder reviewed.