Value of Prostate-Specific Antigen Kinetics in Patients with Low-Risk Prostate Cancer under Active Surveillance.

INTRODUCTION: This study analyzes the value of PSA kinetics, PSA speed (vPSA), and PSA doubling time (PSAdt), in patients with low-risk prostate cancer who are in an active surveillance (AS) program. METHODS: An observational, retrospective, and longitudinal study of a sample of 86 patients included in AS program between January 2014 and October 2021 was conducted. A review of their medical records was performed, and PSA kinetics were calculated, analyzing the causes of discontinuation of the AS program and its relationship with PSA kinetics. RESULTS: The mean age was 63.39 years, and the median follow-up was 62.55 months. The mean PSA at diagnosis was 8.27 ng/mL. A median of PSAdt of 62.55 months and 1.3 ng/mL/year for vPSA was obtained. 35 patients left the program, with a higher percentage of patients leaving with a PSAdt less than 36 months (73.7 vs. 31.1%) and a vPSA greater than 2 ng/mL/year (68.2 vs. 31.3%). The probability of permanence and the time of permanence in AS were statistically significantly higher for those patients with favorable kinetic parameters. CONCLUSION: PSA kinetics is a parameter to take into account when making decisions to keep patients in an AS program.

[Biomarkers in renal cancer.] / Biomarcadores en cáncer renal.

The natural history of renal cell canceris unpredictable and despite the increased knowledgeof this disease, the incidence has been increasing in recent years. Renal cancer represents a tumor withsignificant mortality and efforts to understand its behaviorhavenot yet translated into a decrease in mortality.In the study of renal cell cancer, the knowledge ofmolecular pathways is very important, since they arethe basis for the development of new therapies. Thisknowledge has made it possible to reclassify these tumorsand the current challenge is the search for biomarkersthat allow to establish an adequate diagnosisand prognosis and predict the response to a certaintype of treatment.In the present manuscript we carry out a review ofthe main markers studied and their potential value inrenal cell cancer.

La historia natural del cáncer renal esimpredecible y a pesar del aumento del conocimientode esta enfermedad, la incidencia ha ido en aumentoen los últimos años. Representa un tumor con unamortalidad importante y los esfuerzos por conocer sucomportamiento todavía no se traducen en una disminuciónde su mortalidad.Dentro del estudio del cáncer renal es cada vezmás importante el conocimiento de su funcionamientomolecular, que por otra parte ha sido fundamentalpara la aparición de las nuevas terapias. Dicho conocimientoha permitido reclasificar estos tumores, siendoel desafío actual la búsqueda de biomarcadores quenos permitan establecer un adecuado diagnóstico ypronóstico y predecir la respuesta a un determinadotipo de tratamiento.En el presente trabajo realizamos una revisión delos principales marcadores estudiados y su potencialvalor en el cáncer renal.

[Urology clinics referral Patterns after initiation of a Primary Care BPH-LUTS protocol.] / Evolución de las derivaciones desde atención primaria a la consulta de urología tras la aplicación de un protocolo de pacientes con síntomas del tracto urinario inferior por hiperplasia benigna de próstata.

OBJECTIVE: In the Spanish health system, General Practitioners (GPs) play a key role in regulating the flow of patients to hospital care. Most of patients with BPH can be managed through out the evolution of the disease exclusively by the GPs.  METHODS: A pre-experimental study was carried outin two periods, before (pre-test) and after (post-test) of the dissemination of a management protocol for patients with BPH. The protocol was trialled in the health area of Villarrobledo and included all referrals to the urology clinic for BPH from Primary Care. We analyzed the appropriate referrals according with the criteria set for thin the protocol and compared the complementary tests through statistical study (descriptive, a bivariate, multivariate analysis and rate calculation) using version 21of the SPSS. RESULTS: Referral rate decreased after the application of the protocol but did not increase the rate of appropriated referrals. Patients referred after setting forth protocol by GPs that assisted to the education program were younger. There were referred less patients with elevated PSA and more patients with clinical progression. These GPs used less test to achieve diagnosis. The GPs whodid not attend were significantly younger, mainly women, with no previous specific training in BPH and without a full time GP position. CONCLUSIONS: The implementation of a protocol has reduced the referral rate, but it has not improved the appropriate referrals. More research is required to understand the determinants of inequalities in referral from primary care.

OBJETIVO: Los médicos de Atención Primaria (MAP) son fundamentales en la regulación del flujo de pacientes desde Atención Primaria (AP), por tanto,es esencial buscar métodos de adecuada gestión de la demanda asistencial y así optimizar recursos. En la hipertrofia benigna de próstata (HBP) se estima que 2/3 de los pacientes pueden ser manejados íntegramentedesd e AP a lo largo de todo el proceso de la HBP.MATERIAL Y MÉTODOS: Hemos realizado un estudio pre experimental en dos períodos, antes (pre-test) y después (post-test) de la creación de un protocolo de manejo y derivación de pacientes con HBP. Analizamos la adecuación a los criterios de derivación y el uso de los estudios complementarios para llevar a cabo el diagnóstico, realizando un análisis estadístico (descriptivo, bivariante, multivariante y cálculo de tasas) utilizando SPSS (versión 21). RESULTADOS: La tasa de derivación disminuyó tras la aplicación del protocolo, pero no logró mejorar la adecuación. Los pacientes derivados por los MAP que asistieron al programa educativo fueron más jóvenes. Se remitieron menos pacientes con PSA elevado y más pacientes con progresión clínica. Se utilizaron menos estudios complementarios. Los MAP que no acudieron a la formación eran más jóvenes, principalmente mujeres, sin formación especifica en HBP y con contrato temporal. CONCLUSIONES: A pesar de reducir la tasa de derivación no se consiguió mejorar la adecuación de la derivación de los pacientes. Consideramos necesario analizar la problemática de los MAP y valorar otras intervenciones que podrían mejorar la calidad en la transferencia de responsabilidades.

HIF1α Suppresses Tumor Cell Proliferation through Inhibition of Aspartate Biosynthesis.

Cellular aspartate drives cancer cell proliferation, but signaling pathways that rewire aspartate biosynthesis to control cell growth remain largely unknown. Hypoxia-inducible factor-1α (HIF1α) can suppress tumor cell proliferation. Here, we discovered that HIF1α acts as a direct repressor of aspartate biosynthesis involving the suppression of several key aspartate-producing proteins, including cytosolic glutamic-oxaloacetic transaminase-1 (GOT1) and mitochondrial GOT2. Accordingly, HIF1α suppresses aspartate production from both glutamine oxidation as well as the glutamine reductive pathway. Strikingly, the addition of aspartate to the culture medium is sufficient to relieve HIF1α-dependent repression of tumor cell proliferation. Furthermore, these key aspartate-producing players are specifically repressed in VHL-deficient human renal carcinomas, a paradigmatic tumor type in which HIF1α acts as a tumor suppressor, highlighting the in vivo relevance of these findings. In conclusion, we show that HIF1α inhibits cytosolic and mitochondrial aspartate biosynthesis and that this mechanism is the molecular basis for HIF1α tumor suppressor activity.

ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma.

Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.

HIF2α acts as an mTORC1 activator through the amino acid carrier SLC7A5.

The mammalian target of rapamycin (mTOR) pathway, which is essential for cell proliferation, is repressed in certain cell types in hypoxia. However, hypoxia-inducible factor 2α (HIF2α) can act as a proliferation-promoting factor in some biological settings. This paradoxical situation led us to study whether HIF2α has a specific effect on mTORC1 regulation. Here we show that activation of the HIF2α pathway increases mTORC1 activity by upregulating expression of the amino acid carrier SLC7A5. At the molecular level we also show that HIF2α binds to the Slc7a5 proximal promoter. Our findings identify a link between the oxygen-sensing HIF2α pathway and mTORC1 regulation, revealing the molecular basis of the tumor-promoting properties of HIF2α in von Hippel-Lindau-deficient cells. We also describe relevant physiological scenarios, including those that occur in liver and lung tissue, wherein HIF2α or low-oxygen tension drive mTORC1 activity and SLC7A5 expression.

Supernumerary testicle: case report and bibliographic review.

OBJECTIVE: We report a case of supernumerary testis, a rare anomaly with only around 100 cases reported in the literature. METHODS: We describe the case of a 26-year-old man who consulted for a left paratesticular tumor. Physical examination and ultrasound showed a 2-cm nodular lesion over the left epididymis. The lesion was confirmed as supernumerary testis by surgical examination and biopsy and was subsequently excised, given the malignancy potential. RESULTS: The supernumerary testis was evaluated using two standard classifications, one assessing function and embryological development, and the other assessing topography, anatomy, and reproductive potential. CONCLUSIONS: The differential diagnosis for an intrascrotal mass should include the possibility of a supernumerary testis; hence, surgical examination and biopsy are necessary. Supernumerary testes should be excised in the case of pain, dysplasia, or in situ carcinoma, or whenever the biopsy is inconclusive.

Neuroendocrine carcinoma of the urinary bladder. 15-year retrospective analysis.

OBJECTIVES: Neuroendocrine tumors (NET) are cancers found in the bronchopulmonary tract, where they were first described in 1926. The tumors are associated with poor prognosis due to their high metastatic potency even after radical treatments associated with other neo- or adjuvant therapies. NET of the urinary bladder is a rare tumor and accounts for 0.5% of bladder tumors. METHODS: The study was designed as an observational, descriptive and retrospective study of 13 patients diagnosed, treated, and followed for NET of the urinary bladder at the Hospital and University Complex of Albacete, Albacete, Spain between 1995 and 2010. RESULTS: The sample was composed of 11 men and 2 women. Mean patient age at the time of diagnosis was 71 (range, 57-88; SD, 6.98) years. T4 (6 patients) was the most common T tumor stage, followed by T2 (5 patients) and T3 (2 patients). In the case of N tumor stage, the most common was N2. In the remaining 3 patients, the degree of lymph node involvement could not be assessed. Six presented distant metastasis at the time of diagnosis. Eleven patients presented small-cell NET on histology. Seven underwent radical surgery (radical cystectomy). All other patients were treated by deep transurethral resection of bladder tumor, except for 1 patient treated by partial cystectomy. Adjuvant chemo-therapy (usually an association of carboplatin/cisplatin and etoposide) was administered to 4 patients. Of these 4 patients, 2 were also treated by pelvic radiotherapy. Two patients survived more than 5 years following diagnosis. In fact, at the time the study data was collected only 4 patients had survived and 2 presented tumor recurrence. Of the 9 deaths, 8 occurred within 6 months of diagnosis and 1 at 24 months. All of them were the result of the disease itself. CONCLUSIONS: Neuroendocrine tumor of the urinary bladder is a rare, aggressive tumor with high metastatic potential that should be considered in the differential diagnosis of urinary bladder neoplasms. Despite various multimodality treatments have been used prognosis is poor.

[Spermatic cord sarcomas: current status and report of four cases]. / Sarcomas de cordón espermático: estado actual y presentación de cuatro casos clínicos.

OBJECTIVE: To study and review spermatic cord sarcomas, including symptoms, diagnosis, and treatment. METHODS/RESULTS: We review the Spanish and international literature and report 4 new cases: 2 patients with well-differentiated spermatic cord liposarcomas (1 treated by simple tumorectomy), 1 patient with liposarcomatous degeneration of a previously excised atypical lipoma, and 1 patient operated for a malignant retroperitoneal fibrous histiocytoma with subsequent local recurrence in the paratesticular region. CONCLUSIONS: Spermatic cord sarcomas are rare entities that usually appear as painless paratesticular mass. They are diagnosed by imaging studies (ultrasound, computed tomography, magnetic resonance) and confirmed by histological examination. Spermatic cord sarcomas are treated surgically; the efficacy of adjuvant treatments such as chemotherapy or radiation therapy is still under debate.

[Impact of surgical treatment of female stress urinary incontinence on the quality of life of patients]. / Impacto de la cirugía de la incontinencia urinaria de esfuerzo en la calidad de vida de las pacientes.

OBJECTIVES: To evaluate the quality of life of patients with stress urinary incontinence (SUI) operated in the Department of Urology at the Complejo Hospitalario Universitario in Albacete (CHUA). METHODS: Between November 2001 and December 2005, 126 patients with SUI have completed a questionnaire in our centre, before and after undergoing surgery with sling techniques. The questionnaire was the King's Health Questionnaire (KHQ), which is a specific instrument for the measurement of quality of life in patients with urinary incontinence. RESULTS: Mean patient's age was 57.09 years (DE: 9.57). Twelve women (9.5%) had history of previous urinary incontinence surgery. Mean urinary incontinence evolution time was 114.48 months, with a median of 96 months. 38 patients (30.2%) did not present cystocele, 61 (48.4%) presented grade III cystocele, 25 (19.8%) grade II, and 2 (1.6%) grade I. Before surgery, the scale with best score was Personal relationships, with a mean score of 26.8, whereas the scale with worst scores was Impact of urinary incontinence, with a mean score of 82.96. All operations performed consisted in various techniques of transvaginal slings, except one case (0.8%) in which the Kelly technique was performed. Impact of urinary incontinence was the scale with a greater number of patients improving after surgery; 82.9% of the patients (101 cases) gave a better score. The scales showing greater differences of the mean value comparing before/after surgery were impact of urinary incontinence, limitation on the daily life activity, and limitation on social activity. Personal relationships and General health were the two with the smallest improvements. CONCLUSIONS: Surgery demonstrated to improve the symptoms secondary to this disease, therefore, it results in an improvement of the quality of life that is evident in all scales of the questionnaire, mainly in the impact of urinary incontinence, limitations on physical activity, limitations on daily life, and limitation on social activity scales.

[Bellini duct carcinoma: report of two cases]. / Carcinoma de los ductos de Bellini: aportación de dos nuevos casos.

OBJECTIVE: We report two cases of collecting duct carcinoma that were diagnosed in our hospital in a six-month period. METHODS/RESULTS: The first case was a 75years-old woman showing in CT scan a mass in the left kidney which infiltrated perinephric fat. The second case was a 72-years-old that showed in a CT scan a right renal pelvis lesion, involving inferior vena cava and renal vein. After surgical resection by radical nephrectomy in both cases, we confirmed the histological diagnosis of collecting duct carcinoma. CONCLUSIONS: Collecting duct carcinoma is a rare variant of renal cell carcinoma which originates from the epithelium of the collecting tubule. It is characterized by both its aggressiveness and peculiar histological and immunohistochemical diagnosis, that separates it from the rest of renal tumors.

[Voiding symptoms changes after vaginal sling surgery for female stress urinary incontinence]. / Cambios en la sintomatología miccional de la incontinencia urinaria de esfuerzo tras la cirugía con técnicas de cabestrillo transvaginal.

OBJECTIVES: To evaluate the changes in voiding symptoms in female patients with stress urinary incontinence (SUI) undergoing transvaginal sling techniques over a five-year period in the Department of Urology at the University Hospital of Albacete. METHODS: Between November 2001 and December 2005 126 patients with SUI (mean age 57.09 years; 36-78) underwent transvaginal sling techniques (Sling in Fast, TVK TOT). All patients were evaluated clinically and urodynamically. RESULTS: Average body mass index (BMI) was 28.14 kg/m2 (SD 4.66; 95% CI: 27.32-28.96). 92 patients (73%) presented between 2-4 previous pregnancies. 99 patients (80.9%) have had birth labour between 2 and 4 times. All of them were vaginal birth labours except 12 cases (9.5%) in which caesarean section had been performed. Daytime voiding frequency after surgery was over 120 minutes in 112 patients (88.9%). Night-time voiding frequency was equal or less than twice in 110 patients (87.3%). 104 patients (82.5%) presented at least two leaking episodes per day, and 105 patients (83.3%) needed to wear one pad per day or less during the last week before follow-up visit. The number of urinary leak episodes per day diminished in 114 patients (90.5%) with a mean decrease of 9.65 episodes (95% CI: 8.56-10.79) (p < 0.0001). Ninety-four patients (76.4%) were completely dry. CONCLUSIONS: Development of new surgical techniques for the treatment of SUI have improved results and diminished the number of complications, an expression of which is the favourable evolution of voiding changes after surgery.

[Late lymph node metastasis in renal cell carcinoma. Case report]. / Metástasis ganglionar tardía de carcinoma de células renales. Aportación de un caso.

OBJECTIVE: To report one case of late metastasis of a clear cell carcinoma treated by radical surgery. METHODS/RESULTS: Patient with history of radical nephrectomy and lymphadenectomy six years before presenting with regional lymph node metastasis in a followup diagnostic test. After treatment with immunotherapy, stopped because of intolerance, surgery of the metastatic lymph node mass was decided. CONCLUSIONS: Renal cancer is an unpredictable tumor in terms of oncological behaviour, so that it may metastasize any time in its evolution, even after radical surgery and several years free of disease. Surgery for the metastases of renal cancer is a good therapeutic option, with good long-term results, when they are isolated and accessible to surgery.

[Prognostic-factor-related survival in a series of patients with renal cell carcinoma]. / Supervivencia en relación a los factores pronósticos en una serie de pacientes con carcinoma de células renales.

OBJECTIVES: To analyze the survival rate in a series of patients with the diagnosis of renal cell carcinoma over a 19 year period based on prognostic factors usually employed in clinical practice. METHODS: Retrospective study of 259 consecutive patients with the diagnosis of renal cell carcinoma undergoing surgery in our department between 1988 and 2006. From clinical, pathological, and follow-up data we performed a survival study comparing the impact of usual prognostic factors: stage, tumor size, nuclear grade, etc. RESULTS: 264 surgical procedures were performed in 259 patients, with a mean age of 6 1.91 yr. The most frequent way of diagnosis was incidental finding (52.12% of the cases); radical nephrectomy was performed in 72.97% of the cases in comparison with 26.25% partial nephrectomies. Clear cell carcinoma was the most frequent histological diagnosis (69.88%). Patients with clear cell carcinoma, symptomatic tumors, bigger size, and greater Fuhrman nuclear grade presented worse survivals, mainly in tumors with stage >pT3a. The presence of involved lymph nodes or distant metastases is associated with a much lower cancer-specific survival. Global five-year cancer-specific survival was over 80%. CONCLUSIONS: The classical prognostic factors used to predict survival in renal cancer are still useful, mainly pathological stage pT. We observed a better survival in comparison with older series, but this kind of tumors continue generating important morbidity-mortality.

[Bladder endometriosis. Report of two cases and bibliographic review, with special focus on Spanish articles]. / Endometriosis vesical. Revisión de la literatura, con especial referencia a la española y aportacion de dos nuevos casos.

OBJECTIVES: To study and review the etiopathogenic hypothesis for endometriosis and the clinical features, diagnosis and treatment of bladder endometriosis. METHODS/RESULTS: We report two cases and review the international bibliography, collecting the cases published by Spanish authors. CONCLUSIONS: Bladder endometriosis is a rare pathological entity, but its diagnosis should be considered in fertile women with urinary tract symptoms during menstruation. Diagnosis is obtained by various imaging tests (ultrasound, CT scan, MRI), and is confirmed with cystoscopy and biopsy. The treatment may be surgical (TUR, partial cystectomy) and/or medical (hormonal).

Determination of vhl gene mutations in sporadic renal cell carcinoma.

OBJECTIVE: Characterization of the molecular status of the vhl gene and its relationship to the usual prognostic factors could help establish new diagnostic and therapeutic strategies. This study determines the presence of vhl gene mutations in tumor tissue from patients with sporadic renal cell carcinoma, the relationship between the mutations and classic prognostic factors, and the possible impact on protein function. MATERIALS AND METHOD: Cross-sectional analytical study investigating vhl gene mutations in tumor tissue by PCR testing of the gene exons and automatic sequencing in 96 patients with sporadic renal cell carcinoma. The characteristics of the mutations detected, as well as their relationship with various clinical and pathological parameters and the possible impact on protein function, were analyzed. RESULTS: Twenty-two mutations were found in 21 patients (21.9%); 68.2% were point mutations. The mutations were associated only with tumor histotype and were located in protein functional domains. Three mutations were detected in the intron position; 73.7% were considered relevant to protein function. CONCLUSION: The percentage of vhl gene mutations in sporadic renal cell carcinoma was relatively low, mutations were seen more often in clear cell carcinoma and were not related to the classic clinical prognostic factors. Mutations of the vhl gene produce important changes in the protein, causing it to lose its tumor suppressor function.

[Malignant melanoma of the penis. Report on one case]. / Melanoma mauligno de pene. Aportación de un caso clínico.

OBJECTIVES: Due to the fact that melanoma of the penis is rare, we perform a bibliographic review about the subject and analyze the diagnostic criteria, clinical stages and therapeutic options. METHODS: We report one case that was diagnosed and treated in our department. RESULTS: 85-year-old male who presented with hematuria and a red brownish irregular elevated lesion in the glans penis. Partial penectomy was performed. CONCLUSIONS: Melanoma of the penis is a rare tumoral entity. It accounts for about 1% of all penile malignant pathologies. It has bad prognosis due to fast metastosic dissemination (regional lymph nodes and other organs) and delayed diagnosis. First choice treatment is partial penectomy with or without bilateral inguinal lymphadenectomy (depending upon degree of tumor invasiveness). In cases with metastasis treatment is palliative with chemotherapy and immunotherapy

Paraganglioma of the bladder: controversy regarding treatment.

Paragangliomas or extra-adrenal pheochromocytomas account for approximately 15% of all pheochromocytomas. They are usually found in an intradiaphragmatic location. Paragangliomas of the urinary bladder are infrequent and represent 6% of the paragangliomas and 0.06% of all bladder tumors. We describe 2 cases of urinary bladder paragangliomas attended to our center and review the literature with special attention to treatment, since there is some controversy around the management of these tumors. Surgical options include partial or total cystectomy and transurethral resection, but there is no consensus regarding these treatment modalities. The 2 patients presented underwent transurethral resection with a good outcome and no recurrence or residual disease.

[Mutational analysis of the vhl gene in the sporadic renal cell carcinoma]. / Análisis mutacional del gen vhl en el carcinoma de células renales de aparición esporádica.

OBJECTIVES: To assess and characterize mutations in the vhl gene in tumor tissue samples from 30 patients undergoing surgery for renal cell carcinoma in our department. METHODS: Descriptive, observational and analytical study of 30 patients undergoing surgery for RCC, analyzing the vhl gene sequence in tumor tissue, and using healthy renal tissue from the same patients as controls. Tissues were processed by DNA extraction, PCR amplification of the three exons that conform the gene, and ulterior automatic sequence analysis of the amplified exons between intronic primers previously designed. The sequence is compared with the corresponding exons included in the GeneBank. Alterations were checked by backwards sequence analysis. RESULTS: 9 mutations (30%) were found in the tumoral samples analyzed. 7 of them were punctual (one of them intronic); the other two were deletions. Mutations were distributed among the three exons: 3 in exon 1, 4 in exon 2, 1 in exon 3 and 1 intronic. One of the samples showed 2 mutations. Control tissue was free of mutations. CONCLUSIONS: Sporadic RCC shows mutations in the vhl gene which mainly appear in the clear cell subtype. Such alterations result in severe disturbances in the protein, disturbing its tumor suppressing function.