Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Utilidad de la quimioterapia neoadyuvante en el carcinoma vesical músculo invasivo no metastásico / Usefulness of neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancer

Objetivo: Analizamos el perfil de pacientes candidatos a quimioterapia neoadyuvante (QTn) en estadio pT2-4aN0M0, la tolerabilidad y adherencia de nuestro protocolo basado en cisplatino y los resultados oncológicos.Material y métodosEstudio observacional de cohortes retrospectivo que incluye a pacientes con diagnóstico de carcinoma vesical músculo infiltrante tratados con QTn. Se analizaron las características clínicas, histopatológicas, terapéuticas y evolutivas de los pacientes. El uso de la QTn se evaluó mediante la respuesta completa en la pieza quirúrgica (pT0). Este y otros factores anatomopatológicos se relacionaron con la supervivencia global y el tiempo libre de progresión.ResultadosIncluimos a 90 pacientes con carcinoma vesical músculo invasivo (estadio clínico T2a-T4aN0M0) que recibieron algún esquema de QTn basado en cisplatino, entre enero de 2011 y diciembre de 2018, antes del tratamiento quirúrgico radical. El 40% de los pacientes presentaron alguna reacción adversa al tratamiento, con un cumplimiento del protocolo de QTn del 92,2%. No se presentaron muertes relacionadas con el tratamiento sistémico y ninguna reacción adversa al tratamiento imposibilitó la realización de la cistectomía radical. Tras la cistectomía radical, se objetivó la presencia de respuesta completa (pT0) en 20 pacientes (21%), un estadio inferior en pieza quirúrgica ( p = 0,012), en enfermos con afectación ganglionar respecto a pN0 (65,4 vs. 28,2 meses; p=0,014) y en aquellos con bordes quirúrgicos afectos respecto a los que presentaban márgenes libres de tumor (63,5 vs. 8,5 meses; p=0,021).ConclusiónLa selección adecuada de los pacientes con carcinoma vesical músculo infiltrante ha mostrado una buena tolerancia a la QTn, con una alta tasa de cumplimiento previo a la CR. La mejoría en la tasa de respuesta completa implica una mayor supervivencia en este grupo de pacientes. La afectación ganglionar y los bordes quirúrgicos positivos son factores pronósticos importantes. (AU)

Objective: We analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes.Material and methodsRetrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival.ResultsWe included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made radical cystectomy impracticable. After performing radical cystectomy, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen ( P=0.012), in patients with lymph node involvement compared to pN0 (65.4 vs. 28, 2 months, P=0.014) and in those with positive surgical margins compared to those with tumor-free margins (63.5 vs. 8.5 months, P=0.021).ConclusionThe adequate selection of patients with muscle-invasive bladder carcinoma has shown a good tolerance to NACT, with a high compliance rate prior to RC. The improvement in the complete response rate implies a greater survival in this group of patients, with lymph node involvement and positive surgical margins being important prognostic factors. (AU)

Usefulness of neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancer. / Utilidad de la quimioterapia neoadyuvante en el carcinoma vesical músculo invasivo no metastásico.

OBJECTIVE: We analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes. MATERIAL AND METHODS: Retrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival. RESULTS: We included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made radical cystectomy impracticable. After performing radical cystectomy, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen (

Inflammatory markers as prognostic factors in metastatic castration-resistant prostate cancer. / Marcadores inflamatorios como factor pronóstico en el cáncer de próstata resistente a la castración metastásico.

INTRODUCTION: Inflammatory markers have prognostic value in various tumors due to the role of inflammatory phenomena at different stages of tumor development. The aim of this study is to demonstrate the prognostic value of these markers, as well as other clinical and analytical variables in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIAL AND METHODS: Prospective cohort study carried out on 80 patients diagnosed with mCRPC. Clinical and analytical data were collected, and the following inflammatory markers were estimated: Absolute Neutrophil Count (ANC), Neutrophil-Lymphocyte Ratio (NLR), Total Platelet Count (TPC), Platelet-Lymphocyte Ratio (PLR), Lymphocyte-Monocyte Ratio (LMR) and Systemic Inflammation Index (SII). The values of albumin, hemoglobin (Hb), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were also determined. RESULTS: Patients with ANC>7500, NLR>3, PLR>150, LMR>3 and/or SII>535,000, presented significantly lower median survival time than the remaining patients, and TPC was the only marker which did not show a significant association. Moreover, NLR, PLR and SII were inversely correlated with survival time. Patients with hypoalbuminemia, anemia, and elevated LDH values had significantly lower median survival time. Albumin and hemoglobin were directly correlated to overall survival time. The need for analgesia was also associated with shorter survival. CONCLUSION: The values of certain inflammatory markers are associated with shorter survival time in patients with mCRPC, and their use in clinical practice can be considered to evaluate the prognosis and estimate survival.

Leukocyte and platelet counts as prognostic values of testicular germ cell tumours. / Valor pronóstico del recuento de leucocitos y plaquetas, en tumores testiculares de células germinales.

INTRODUCTION: The immune system plays an essential role in the organism's response to cancer. Several haematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumours. MATERIAL AND METHODS: Retrospective cohort study on 164 patients with germ cell tumours. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analysed. RESULTS: 17.7% had NLR>4 and 14.6% ANC>8000/µL. These patients presented higher percentages of residual disease and stage II-III tumours. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet >400000/µL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumours. 28.4% showed platelet-lymphocyte values>150. This data was associated to higher percentages of residual disease, progression, stage II and III tumours and seminomatous tumours. 83.3% had an lymphocyte-monocyte >3. These patients presented: higher tumour markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumours. The mean survival time was shorter in patients with NLR>4 and absolute neutrophil >8,000/µL. The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte >3, and prediction of survival and values NLR>4. CONCLUSION: Our results indicate that the analysed haematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumours.

Scrotal tumors. / Tumores escrotales.

OBJECTIVE: Basal cell carcinoma and leiomyoma of the scrotum are rare. We describe three cases of scrotal tumors and provide information regarding this disease. METHODS: Between 2000 and 2014, 3 patients with scrotal tumors were diagnosed and treated at our institution. A review was performed using the clinical records of these patients. RESULTS: We describe two cases of basal cell carcinoma of the scrotum in men 72 and 71 year old, who presented with a left scrotal lesion that was excised and the pathological diagnosis was basal cell carcinoma. In one patient, surgical margin was affected and a recurrent basal cell carcinoma appeared. It was excised with enlargement of surgical margin. We also describe a case of scrotal leiomyoma in a 48 year old man with an elastic, firm and nontender lesion in the right scrotum. During follow-up the patients remain clinically asymptomatic. CONCLUSIONS: Scrotal lesions in the elderly should be excised and submitted for pathological examination. The basal cell carcinoma of the scrotum appears as a plaque, nodule or ulcer. Long-term surveillance is recommended for these patients. Leiomyoma of the scrotum is presented as a non-ulcerative nodule and his treatment is complete surgical excision.

Collateral urethral duplication in an adult.

OBJECTIVE: Congenital anomalies or malformations of the urethra that involve number are extremely rare and only 7 cases of trifurcation of the urethra and under 500 cases of urethral duplication have been described. METHODS: In the case we present, urethral duplication was diagnosed in adulthood, even though glans malformation with 2 urethral orifices was clearly evident and only 1 was functional. RESULTS: The condition is usually diagnosed in childhood due to the presence of 2 urethral meatus or from double stream if both are functional; at other times, the condition is diagnosed from complications that trigger infections or obstruction or if it is associated with more extensive malformations. CONCLUSIONS: Urethral duplication is an extremely rare birth defect, and diagnosis in adulthood is even more uncommon. No single embryologic argument explains all the anatomic variants of urethral duplication. The treatment of the urethral duplication should be individualized according to the type of duplication and the clinical symtoms.

Papel de las proteínas quinasas activadas por mitógenos (MAPK) en el carcinoma de células renales esporádico / Role of Mitogen-Activated Protein Kinase (MAPK) in the Sporadic Renal Cell Carcinoma

Contexto: Últimamente, basándose en la implicación del gen supresor vhl en los casos de carcinoma de células renales (CCR), se ha evaluado la implicación de la ruta de señalización entre pVHL y el factor inducible por hipoxia 1 alfa (HIF-1α), ante la necesidad de encontrar nuevos marcadores diagnósticos, pronósticos y de respuesta a fármacos. Síntesis de evidencia: La sobreexpresión de HIF-1α confiere mejor pronóstico en pacientes afectos de CCR de tipo células claras (ccRCC). Además HIF-1α regula otros genes, concretamente el de la anhidrasa carbónica IX (CA-IX), cuya sobreexpresión es prácticamente exclusiva de los ccRCC y su determinación útil para el diagnóstico de este subtipo. Sin embargo, no se ha demostrado la implicación de CA-IX ni en el pronóstico ni en la respuesta a inmunomoduladores o antiangiogénicos. Ello hace necesario la evaluación global de toda esta ruta: pVHL → HIF-1α → CA-IX, e incluso el análisis de otras proteínas y vías de señalización que también controlan la actividad de HIF-1α. En este último caso, las MAPK, son críticas en la activación de HIF-1α, existiendo evidencias a nivel experimental del control sobre su actividad, aunque no se ha establecido su papel clínico como biomarcador. Si bien está demostrado el papel de las MAPK en los fenómenos de resistencia a quimio y radioterapia convencional, no lo está en la respuesta a sorafenib, dato llamativo si tenemos en cuenta que es inhibidor de varias proteín quinasas. Recientemente se ha observado que las MAPK pueden estar implicadas en la respuesta a distintas terapias, incluidas las basadas en inhibidores de tirosín quinasa. Conclusiones: La confirmación de estos datos supondrá una explicación a la variación observada entre pacientes, que con una misma alteración funcional del gen vhl presentan un distinto comportamiento biológico y clínico, y a una mejor selección de terapias no quirúrgicas (AU)

Context: Only on the basis of the involvement of the vhl suppressor gene in the cases of renal cell carcinomas (RCC), the involvement of the signaling pathway between the pVHL and the Hypoxia inducible factor 1, alpha (HIF-1α) has been evaluated because of the need to find new diagnostic and prognostic and response to drugs markers. Evidence synthesis: The overexpression of HIF-1α confers better prognosis in clear cell type RCC (ccRCC). Furthermore, HIF-1α regulates other genes, specifically that of the carbon anhydrase IX (CA-IX), whose overexpression is practically only of the ccRCC and its determination is useful for this subtype. However, the involvement of the CA-IX has not been demonstrated in the prognosis or in the response to immunomodulators or antiangiogenics. Therefore, it is necessary to make a global evaluation of all this pathway: pVHL → HIF-1α → CA-IX, and even the analysis of other proteins and signaling pathways that also control the HIF-1α activity. In the latter case, the MAPK are critical in the HIF-1α activation, there being evidence on the experimental level of the control on its activity. although its clinical role as a biomarkers has not been established. Although the role of the MAPK in the phenomena of resistance to conventional chemotherapy and radiotherapy has been demonstrated, it has not been demonstrated in response to sorafenib, an important piece of information if we consider that it is an inhibitor of several protein kinases. Recently, it has been observed that the MAPK may be involved in the responses to different therapies, included those based on tyrosine kinase inhibitors. Conclusions: The confirmation of these data would suppose an explanation of the variation observed between patients who, with the same functional alteration of the vhl gene, have a different biological, clinical behavior and better selection of non-surgical therapies (AU)

[Role of mitogen-activated protein kinase (MAPK) in the sporadic renal cell carcinoma]. / Papel de las proteínas quinasas activadas por mitógenos (MAPK) en el carcinoma de células renales esporádico.

CONTEXT: Only on the basis of the involvement of the vhl suppressor gene in the cases of renal cell carcinomas (RCC), the involvement of the signaling pathway between the pVHL and the Hypoxia inducible factor 1, alpha (HIF-1α) has been evaluated because of the need to find new diagnostic and prognostic and response to drugs markers. EVIDENCE SYNTHESIS: The overexpression of HIF-1α confers better prognosis in clear cell type RCC (ccRCC). Furthermore, HIF-1α regulates other genes, specifically that of the carbon anhydrase IX (CA-IX), whose overexpression is practically only of the ccRCC and its determination is useful for this subtype. However, the involvement of the CA-IX has not been demonstrated in the prognosis or in the response to immunomodulators or antiangiogenics. Therefore, it is necessary to make a global evaluation of all this pathway: pVHL → HIF-1α → CA-IX, and even the analysis of other proteins and signaling pathways that also control the HIF-1α activity. In the latter case, the MAPK are critical in the HIF-1α activation, there being evidence on the experimental level of the control on its activity. although its clinical role as a biomarkers has not been established. Although the role of the MAPK in the phenomena of resistance to conventional chemotherapy and radiotherapy has been demonstrated, it has not been demonstrated in response to sorafenib, an important piece of information if we consider that it is an inhibitor of several protein kinases. Recently, it has been observed that the MAPK may be involved in the responses to different therapies, included those based on tyrosine kinase inhibitors. CONCLUSIONS: The confirmation of these data would suppose an explanation of the variation observed between patients who, with the same functional alteration of the vhl gene, have a different biological, clinical behavior and better selection of non-surgical therapies.

Functional analysis of CYP1B1 mutations and association of heterozygous hypomorphic alleles with primary open-angle glaucoma.

Glaucoma is an inherited complex and heterogeneous disease, and one of the most prevalent causes of definitive blindness in the world. Recent reports have indicated that heterozygous mutations of the CYTOCHOROME P4501B1 (CYP1B1) gene are present in 4-10% of patients with primary open-angle glaucoma (POAG). To further evaluate the role of CYP1B1 mutations in POAG we extended our previous association study and carried out a functional analysis of the mutations identified by polymerase chain reaction (PCR) DNA sequencing of the three exons of the gene in a total of 245 unrelated Spanish patients and 326 control subjects. Eight of nine different mutations identified in these patients were cloned and functionally assessed by measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected HEK-293T cells. All these mutants showed reduced catalytic activity, ranging from 20% to 60% of wild-type and/or decreased protein stability and, therefore, they were classified as hypomorphic alleles. No null alleles were identified in these patients. We found heterozygous hypomorphic CYP1B1 mutations in 17 (6.7%) patients and in seven controls (2.1%) showing that these mutations are associated with an increased risk of POAG (p = 0.005; odds ratio = 3.2; 95% confidence interval = 1.30-9.19). Our data suggest that hypomorphic CYP1B1 mutations are, to date, the main known genetic risk factor in POAG.

VHL protein alterations in sporadic renal cell carcinoma.

AIMS: The vhl gene is a tumour suppressor gene implicated in renal tumorigenesis in both familial and sporadic renal cell carcinoma (RCC). Alterations in the gene may modify its suppressor function and allow the formation of renal tumours. The purpose of this study was to determine the existence of vhl gene mutations in renal tumour tissue among patients with sporadic RCC and to assess the effects on the structure of the VHL protein. MATERIALS AND METHODS: This was an observational, analytical and descriptive study of 96 patients who had undergone surgery for sporadic RCC. In surgical specimens of tumour tissue, the three exons of the vhl gene were amplified by polymerase chain reaction and subjected to automatic sequencing. The consequences of the mutations detected on the VHL protein were analysed, taking into account the physical and chemical properties of the amino acids changed by the mutations, the location of the alterations in the protein sequence, the degree of conservation throughout evolution, and prediction of the secondary structure of the protein. RESULTS: In total, 22 vhl gene mutations were detected in 21 (21.9%) patients; in particular, 13 exonic point mutations consisting of 11 sense mutations, one silent mutation and one missense mutation, plus five exon deletions and one insertion. The remaining three were intronic mutations. All changes occurred in protein functional domains and in regions that have been well conserved throughout evolution. Two-thirds of the intronic mutations were considered relevant for protein function. Among the mutations detected, 72.7% were considered capable of compromising the VHL protein suppressor function. CONCLUSIONS: Mutations in the vhl gene result in amino acid changes in the protein that usually occur at important functional sites that have been conserved throughout evolution and where the binding domains for other proteins are located and exert their suppressor function.

Late recurrence of ovarian granulosa cell tumor at the retroperitoneal and renal hilum level in a single-kidney patient--case report.

BACKGROUND: Ovarian granulosa cell tumors are rare tumors characterized by a long natural history and a tendency to late recurrence. Surgical resection, radiotherapy, chemotherapy and hormone therapy are possible options to treat recurrent disease. The choice will depend on the patient's condition and the site of recurrence. CASE: We describe the case of a 72-year-old patient with a single left kidney who presented retroperitoneal recurrence of ovarian granulosa cell tumor at the left renal hilum ten years after primary treatment. CONCLUSION: This case illustrates an example of very late recurrence and emphasizes the importance of extended follow-up for these patients.

[Hemoperitoneum and death due to hepatoesplenic metastasis rupture in a testicular tumor]. / Hemoperitoneo y muerte por rotura de metástasis hepatoesplénicas de tumor testicular.

We present a case of a mix germinal testicular tumor, in III-C (AJCC-UICC) stage, at a terminal phase due to massive methastasis rupture at hepatic and splenic methastasis locations.

[Vesical schistosomiasis, case report and Spanish literature review]. / Esquistosomiasis vesical, aportación de un caso y revisión de la literatura española.

Urinary schistosomiasis is an infection caused by parasite, Schistosoma haematobium. Squistosomiasis is an endemic disease in Africa and Middle East. We are presenting a case of a young immigrant male from Mali that came to our clinic with hematuria and miccional irritative syndrome during a year. Parasitological study reported Schimosoma's eggs and ecography showed a possible vesical newformation. After RTU, anatomopatological study confirms the presence of a vesical esquistosomiasis. Now pacient is asyntomatic after he was treated with Praziquantel.

[Growing incidence in renal cell carcinoma]. / Incidencia creciente en el carcinoma de células renales.

OBJECTIVES: To analyze the change in the behavior of renal cell carcinoma for its presentation, treatment, histology and mortality during a 17 year period. MATERIAL AND METHOD: Retrospective study on 212 patients diagnosed with renal cell carcinoma in our Department from the year 1988 up to 2004, analyzing the clinical and demographic data and comparing them to each other according to two periods: 1988-1996 and 1997-2004. RESULTS: An increase has been appreciated in the incidence of renal tumors in the second period and in a same way an increase in the incidental diagnosis and in the practice of nephron sparing surgery. Clear cell type was the most frequent in both periods and tumoral size was higher in the first period than in second. TNM stage I was the most frequent, although in first period it was higher percentage of stage IV. Cause-specific mortality has increased in the last years. CONCLUSION: An increase is appreciated in the incidence of renal cell tumors. Although the diagnosis is in earlier stages, a descent in the mortality has not been found.

[Urachal pathology: an overview review and report of three clinical cases]. / Patología del uraco: revisión de conjunto y presentación de tres casos.

With the use of these two clinical cases (cyst and urachal adenocarcinoma) we did an overview of the urachal pathology. The urachus cyst is usually asyntomathic, it's detected randomly when we do other diagnostic tests or when we have any complications. The urachal adenocarcinoma is a rare pathology, it usually exhibit hematuria and we need to follow the same diagnostic tools as we use in vesical tumors (cystoscopy and transurethral vesical resection). Adenocarcinoma of the dome of the bladder is the main differential diagnosis. Partial cystectomy is the first choice treatment. Quimiotheraphy and radiotheraphy offer poor results.