Search

Descripción de casos clínicos: Se presentan tres pacientes con urostomía y catéter doble J permanente que presentaron hematuria franca, aguda y anemizante. Los tres habían recibido radioterapia por patología oncológica pélvica con realización posterior de cistectomía y urostomía por cistopatía rádica severa. En ningún paciente el TAC realizado por estudio de hematuria fue diagnóstico, precisando realizar una arteriografía urgente y evidenciando la presencia de una fístula uretero-ilíaca (FUI) a nivel de la arteria ilíaca común izquierda, ilíaca común derecha e ilíaca externa derecha, respectivamente. Tras la colocación de una prótesis ilíaca endovascular cubierta se consiguió la resolución instantánea del cuadro clínico. Relevancia: La FUI es una condición excepcional que requiere para su diagnóstico la experiencia del urólogo y el radiólogo vascular. Esta situación puede ser potencialmente letal al presentar un cuadro de hematuria franca aguda y anemizante. Implicaciones clínicas: Ante la sospecha de una FUI se debe realizar la manipulación del catéter ureteral en una sala de hemodinamia, donde el control arterial inmediato con técnicas vasculares percutáneas está fácilmente disponible. La realización de una arteriografía debe ser inmediata, obviando la realización de un TAC por su baja sensibilidad. Conclusión: El tratamiento endovascular con prótesis cubierta es un tratamiento seguro y efectivo para las FUI.

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.

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.

Elevated mRNA expression of human telomerase reverse transcriptase (hTERT mRNA) is common in many types of tumors, participating in tumor growth and progression. Such expression has not been sufficiently examined in renal cancer. The goal of the present study was to quantify it and analyze its possible clinical value in the management of this pathology.The study included 111 patients who underwent surgery for renal cell carcinoma (RCC) between 2015 and 2017. Tumor samples were taken from all patients and, in 94 of them, healthy renal tissue adjacent to the tumor was also sampled. The 2 types of tissue were histologically confirmed, after which mRNA was extracted. Using real-time quantitative PCR, the expression of hTERT and glyceraldehyde-3-phosphate dehydrogenase (as endogenous control) were indirectly quantified using the crossing point (CP), which is inversely correlated with the number of sample replicates yielding positive results. These values were correlated with patient socio-demographic variables and clinical-pathological factors of the RCC.The majority of patients were males, with an average age of 60.5 years (SD: 14.02). Most tumors (69.4%) were clear cell carcinomas. The most frequent stages were pT2 or lower (73%), while 5% were pN1 and 12% pM1. The majority of tumors (58%) were Fuhrman grades 1 or 2 (low grade). All samples of tumor and nontumor tissue expressed glyceraldehyde-3-phosphate dehydrogenase mRNA, with the CP in the tumor sample significantly lower than in the nontumor tissue (P0.001). The expression of hTERT mRNA was detected in 68% of tumor tissues and significantly correlated with histopathology: 100% in sarcomatoid RCC and 77.9% in clear cell carcinomas (P0.0001). The CP was lower in pN1 (P = 0.018), pM1 (P = 0.046), and TNM IV stages (P = 0,041). A greater number of hTERT mRNA replicas were detected in M1 patients (P = 0.0005) and TNM IV stage (P = 0.017). There was no correlation of hTERT mRNA expression with Fuhrman grade.The quantitation of hTERT mRNA expression in RCC might be useful as a complementary diagnostic tool as well as for assessing aggressiveness of the tumor.

Introduction The immune system plays an essential role in the organism's response to cancer. Several hematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumors. Material and methods Retrospective cohort study on 164 patients with germ cell tumors. 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 analyzed. Results 17.7% had NLR >4 and 14.6% ANC >8000/μL. These patients presented higher percentages of residual disease and stage II–III tumors. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet >400,000/μL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumors. 28.4% showed platelet–lymphocyte values >150. This data was associated to higher percentages of residual disease, progression, stage II and III tumors and seminomatous tumors. 83.3% had a lymphocyte–monocyte >3. These patients presented: higher tumor markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumors. The mean survival time was shorter in patients with NLR >4 and absolute neutrophil >8000/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 analyzed hematological 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 tumors.

To determine the predictive role of the neutrophil/lymphocyte ratio (NLR) in the prognosis and survival of patients with squamous cell carcinoma of the penis.A retrospective cohort study of 96 patients with squamous cell carcinoma of the penis (SCCP). Clinical and histological data, bloodwork and disease evolution information were collected. We determined neutrophil/lymphocyte ratios and analyzed their relationship to prognosis and survival.The mean age of patients was 72,1 years. The average follow-up time for the sample was 3,8 years (CI 95%: 3,0-4,6). Compared to patients with NLR3, those with NLR3 presented a higher proportion of cancers in stages cN1 (29.7% vs 6.8%;The utilization of NLR in clinical practice can be considered an additional tool to aid in the diagnosis and prognosis of patients with squamous cell carcinoma of the penis.

We report a case of congenital adrenal hyperplasia in a 29 year old patient, who presented with testicular pain, bilateral testicular masses, and oligospermia. Ultrasonography confirmed, in both testis, the presence of heterogeneous and hypoechoic lesions with irregular borders and internal and peripheral vascularization. Seric tumor markers were negative. The patient was scheduled for perioperative testicular biopsy and bilateral orchiectomy. Perioperative biopsy was suggestive of testicular adrenal rest tumor and not additional procedure was performed. Treatment was initiated with high doses of glucocorticoids, decreasing the size of testicular masses and testicular pain was alleviated.

Objectives: Recurrent urinary tract infections (R-UTIs) are very common amongst women, and alternatives to antibacterial prophylaxis are necessary. This study evaluates the effectiveness of a sublingual bacterial vaccine for the prophylaxis of R-UTIs. Methods: We conducted a quasi-experimental pretest-posttest study of 166 women diagnosed with R-UTIs. Both before and after the start of treatment with the vaccine, we analysed the total number of R-UTI episodes, the urine culture results, and the type and number of antibiotic packages consumed. Symptoms and urine cultures were evaluated 3, 6, 9, 12, 18, and 24 months after initiating treatment with the vaccine. Results: The mean time of follow-up after vaccination was 1.7 years. After vaccination, there was a 54.6% reduction in episodes of UTI, and a 56.2% reduction in positive urine cultures. At 3 months, 74.4% of the patients had no R-UTI, the rate falling to 68.1% at 6 months, 52.4% at 12 months, and 44.5% at 24 months. The cumulative probability of maintaining negative urine cultures was 76% at 3 months, 37% at 12 months, and 18% at 2 years. Conclusions: The use of a sublingual bacterial vaccine for the prophylaxis of R-UTIs in women is an effective treatment that contributes to a reduction in the number of UTI episodes.

To evaluate the performance of quantitative computed tomography (CT) texture analysis using different machine learning (ML) classifiers for discriminating low and high nuclear grade clear cell renal cell carcinomas (cc-RCCs).This retrospective study included 53 patients with pathologically proven 54 cc-RCCs (31 low-grade [grade 1 or 2]; 23 high-grade [grade 3 or 4]). In one patient, two synchronous cc-RCCs were included in the analysis. Mean age was 57.5 years. Thirty-four (64.1%) patients were male and 19 were female (35.9%). Mean tumour size based on the maximum diameter was 57.4 mm (range, 16-145 mm). Forty patients underwent radical nephrectomy and 13 underwent partial nephrectomy. Following pre-processing steps, two-dimensional CT texture features were extracted using portal-phase contrast-enhanced CT. Reproducibility of texture features was assessed with the intra-class correlation coefficient (ICC). Nested cross-validation with a wrapper-based algorithm was used in feature selection and model optimisation. The ML classifiers were support vector machine (SVM), multilayer perceptron (MLP, a sort of neural network), naïve Bayes, k-nearest neighbours, and random forest. The performance of the classifiers was compared by certain metrics.Among 279 texture features, 241 features with an ICC equal to or higher than 0.80 (excellent reproducibility) were included in the further feature selection process. The best model was created using SVM. The selected subset of features for SVM included five co-occurrence matrix (ICC range, 0.885-0.998), three run-length matrix (ICC range, 0.889-0.992), one gradient (ICC = 0.998), and four Haar wavelet features (ICC range, 0.941-0.997). The overall accuracy, sensitivity (for detecting high-grade cc-RCCs), specificity (for detecting high-grade cc-RCCs), and overall area under the curve of the best model were 85.1%, 91.3%, 80.6%, and 0.860, respectively.The ML-based CT texture analysis can be a useful and promising non-invasive method for prediction of low and high Fuhrman nuclear grade cc-RCCs.• Based on the percutaneous biopsy literature, ML-based CT texture analysis has a comparable predictive performance with percutaneous biopsy. • Highest predictive performance was obtained with use of the SVM. • SVM correctly classified 85.1% of cc-RCCs in terms of nuclear grade, with an AUC of 0.860.

Increasingly effective therapies targeting the androgen receptor have paradoxically promoted the incidence of neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), for which there is no effective therapy. Here we report that protein kinase C (PKC)λ/ι is downregulated in de novo and during therapy-induced NEPC, which results in the upregulation of serine biosynthesis through an mTORC1/ATF4-driven pathway. This metabolic reprogramming supports cell proliferation and increases intracellular S-adenosyl methionine (SAM) levels to feed epigenetic changes that favor the development of NEPC characteristics. Altogether, we have uncovered a metabolic vulnerability triggered by PKCλ/ι deficiency in NEPC, which offers potentially actionable targets to prevent therapy resistance in PCa.

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., Cell Reports, 26 (9), ISSN:2666-3864, ISSN:2211-1247

Highlights • Plasma levels of GAPDH cfDNA might be useful as complementary methods for diagnosis and prognosis of renal cell carcinoma. • Pre and postoperative levels of GAPDH cfDNA were independently associated with OS in renal cell carcinoma. • hTERT cfRNA was not a marker useful for diagnosis nor prognosis of renal cell cancer., Introduction The current challenge on renal cell carcinoma (RCC) is to finding a non-invasive biomarker for improving their diagnostic and therapeutic management. In the present study, we analyzed the clinical value of plasma levels of cell-free DNA (cfDNA) and RNA (cfRNA) of two genes: glyceraldehyde 3-phosphate-dehydrogenase (GAPDH) and human telomerase reverse transcriptase (hTERT). Materials and methods We recruited 82 patients with RCC, and 20 healthy subjects. Using RT-PCR techniques, plasma levels of cfDNA and cfRNA from hTERT and GAPDH genes were quantified pre- and post-operatively, and one year after surgery. Relationships between such plasma levels and clinicopathological features and evolution of disease were analyzed. Results Levels of GAPDH cfDNA and cfRNA were significantly higher in patients than in healthy subjects. hTERT cfDNA was detected in plasma from 35% of RCC patients and in none healthy subject. At diagnosis, plasma levels of GAPDH cfDNA were higher in advanced pT and TNM stages, and hTERT cfDNA in patients with 3–4 Fuhrman grade and affected lymph nodes. Levels of cfNAs were not related to the presence of metastasis. Following nephrectomy, GAPDH cfDNA levels dropped, and patients with higher levels before and after nephrectomy, showed lower overall survival (OS). However, Cox's multivariate model did not prove any association of the cfNA levels with progression. Conclusion Plasma levels of cfDNA from GADPH and hTERT genes were correlated to tumor diagnosis and progression and, thus, such analyses might help to diagnosis and prognosis of RCC patients.

La utilización en la Celestina de términos desaparecidos o con valor semántico cambiante a través de los siglos, como «auctor», «autor» («auctore» y «autore» en Italia), «imprimir», «imprimidor» o «impresor» y «corrector de la impresión», ha opuesto grandes dificultades al conocimiento de la gestación de la obra, de las fechas de sus primeras ediciones y de algunas nociones sobre la autoría. Mediante un concienzudo análisis de estos conceptos y de sus implicaciones, este artículo confirma la validez de algunas de las investigaciones más recientes sobre las cuestiones mencionadas.

Background The prognostic value of molecular markers in renal cell carcinoma has been investigated in several studies. Although their value is still not confirmed, various proteins are important. We describe the effect on long-term survival of the status of the von Hippel-Lindau (VHL) hypoxia-inducible factor 1-α (HIF1-α) signaling pathway as well as associated mitogen-activated protein kinase (extracellular signal-regulated kinase [ERK]1/2 and ERK5). Patients and Methods A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression. Overall survival (OS), disease-specific survival (DSS), and progression- or recurrence-free survival (PFS) were analyzed using the Kaplan–Meier method. Mantel–Haenszel was used for comparisons, and Cox proportional risk models were also constructed. Results Follow-up was 66.9 months. There were 23 (46.0%) deaths, of which 17 (73.9%) were caused by the tumor. Mean periods were 85.6 months for OS and 94.3 months for DSS. A total of 22 (44.0%) patients showed progression (PFS, 78.1 months). VHL expression (P = .045) and > 10% of HIF1-α expression (P = .034) were associated with greater OS. DSS was greater in patients without VHL methylation (P = .012), with > 10% HIF1-α expression (P = .037), or with ERK5 protein underexpression. Greater PFS was associated with absence of VHL methylation (P = .045), presence of VHL expression (P 10% (P = .04), and ERK5 protein underexpression (P = .011). The presence of VHL mutation and/or methylation and VEGF expression had no prognostic value. Fuhrman nuclear grade and Tumor, Node, Metastases (TNM) stage were the only variables that remained in the Cox model. Conclusion The HIF1-α and ERK5 pathway has prognostic value. Patients with no VHL or HIF1-α expression and ERK5 overexpression had a worse course of disease. VHL or VEGF status had no prognostic value. Only TNM stage and Fuhrman nuclear grade remained in the Cox model and, therefore, are still essential in prognostic biomarker panels.

Vascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation. However, its expression in renal carcinomas inversely correlates with tumor malignancy. Our experiments in clear cell renal cell carcinoma (ccRCC) cell lines demonstrated that von Hippel Lindau (VHL) loss, hypoxia, or PHD (for prolyl hydroxylase domain–containing proteins) inactivation decreased VCAM-1 levels through a transcriptional mechanism that was independent of the hypoxia-inducible factor and dependent on the nuclear factor κB signaling pathway. Conversely, VHL expression leads to high VCAM-1 levels in ccRCC, which in turn leads to better outcomes, possibly by favoring antitumor immunity through VCAM-1 interaction with the α4β1 integrin expressed in immune cells. Remarkably, in ccRCC human samples with VHL nonmissense mutations, we observed a negative correlation between VCAM-1 levels and ccRCC stage, microvascular invasion, and symptom presentation, pointing out the clinical value of VCAM-1 levels as a marker of ccRCC progression., This work was supported by grants from the Instituto de Salud Carlos III (co-funded by the European Union and Fondo Europeo de Desarrollo Regional; grants PI16/02166 and PIE13/00041), a grant from Red Cardiovascular (RD12/0042/0065 to M.J. Calzada), and a grant from Ministerio de Economía y competitividad (SAF2015-64215R to R. Sánchez-Prieto).

Purpose To estimate the prevalence and importance of GSTT1, GSTM1, and CYP1B1 genotypes in renal cell carcinoma (RCC), and to identify their value as a prognostic factor. Materials and methods Cross-sectional study of a group of patients diagnosed with RCC (n = 133) and a control group (n = 208) with benign conditions and no history of tumor. Controls were selected by cumulative samples and mixed pairing. All subjects pertained to the catchment area for our hospital. Sociodemographic variables, anatomical pathology features, and presence of GSTT1, GSTM1, and CYP1B1 polymorphisms by multiplex PCR and sequencing techniques. Results There were no differences in the genotype distribution of the GSTT1 and GSTM1 genes between cases and controls. In the case of CYP1B1, the GG genotype (Ala119) was more prevalent in patients with RCC (OR = 2.08; 95% CI: 1.32–2.28) and may be implicated in 34.3% (95% CI: 16.3–52.2) of RCCs. In patients with GSTT1 deletion, TNM stages III to IV were more common (39.1%); whereas in Val432 homozygous patients in CYP1B1, Fuhrman grades 3 to 4 (54.6%) were more common. Because this was a cross-sectional study, longitudinal studies are needed in the future to confirm these data. Conclusions No relationship between GSTT1 and GSTM1 genotypes and RCC risk was observed. Homozygous subjects with Ala119 in CYP1B1 had twice the risk of RCC as homozygous for Ser119 or heterozygotes. Patients with GSTT1 deletion had tumors of more advanced stages, and those with Val432 polymorphism in CYP1B1 had tumors of higher Fuhrman grade.

Resumen Contexto Ultimamente, basandose en la implicacion del gen supresor vhl en los casos de carcinoma de celulas renales (CCR), se ha evaluado la implicacion de la ruta de senalizacion entre pVHL y el factor inducible por hipoxia 1 alfa (HIF-1α), ante la necesidad de encontrar nuevos marcadores diagnosticos, pronosticos y de respuesta a farmacos. Sintesis de evidencia La sobreexpresion de HIF-1α confiere mejor pronostico en pacientes afectos de CCR de tipo celulas claras (ccRCC). Ademas HIF-1α regula otros genes, concretamente el de la anhidrasa carbonica IX (CA-IX), cuya sobreexpresion es practicamente exclusiva de los ccRCC y su determinacion util para el diagnostico de este subtipo. Sin embargo, no se ha demostrado la implicacion de CA-IX ni en el pronostico ni en la respuesta a inmunomoduladores o antiangiogenicos. Ello hace necesario la evaluacion global de toda esta ruta: pVHL → HIF-1α → CA-IX, e incluso el analisis de otras proteinas y vias de senalizacion que tambien controlan la actividad de HIF-1α. En este ultimo caso, las MAPK, son criticas en la activacion de HIF-1α, existiendo evidencias a nivel experimental del control sobre su actividad, aunque no se ha establecido su papel clinico como biomarcador. Si bien esta demostrado el papel de las MAPK en los fenomenos de resistencia a quimio y radioterapia convencional, no lo esta en la respuesta a sorafenib, dato llamativo si tenemos en cuenta que es inhibidor de varias protein quinasas. Recientemente se ha observado que las MAPK pueden estar implicadas en la respuesta a distintas terapias, incluidas las basadas en inhibidores de tirosin quinasa. Conclusiones La confirmacion de estos datos supondra una explicacion a la variacion observada entre pacientes, que con una misma alteracion funcional del gen vhl presentan un distinto comportamiento biologico y clinico, y a una mejor seleccion de terapias no quirurgicas.

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 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 one 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 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.

CYP1B1 activates procarcinogens in some human tissues, including the urinary tract. Changes related to genetic polymorphisms are a known risk factor for cancer. We analyzed the association between CYP1B1 sequence variations and bladder cancer.Sequence variations in the coding region (exons 2 and 3) and the neighboring introns of CYP1B1 were analyzed by direct polymerase chain reaction and DNA sequencing in 208 unrelated patients with bladder cancer and 208 healthy controls.We identified 6 known single nucleotide polymorphisms organized into 2 linkage disequilibrium blocks. The Ala/Ala and Leu/Val genotypes of the Ala119Ser and Leu432Val polymorphisms were significantly more common in patients than in controls (55.3% vs 42.8% and 54.8% vs 42.3%, respectively). The strongest individual single nucleotide polymorphism risk was found under an over dominant model for Leu432Val (OR 1.65, CI 95% 1.12-2.44). The 2 susceptibility single nucleotide polymorphisms were predicted to be structured into 4 haplotypes and more than 10 diplotypes. No individual haplotype was associated with bladder cancer but the diplotype Ala-Leu/Ala-Val was significantly overrepresented in cases compared to controls (31.73% vs 17.31%, OR 2.22, 95% CI 1.36-3.62, p = 0.001). The OR was approximately 1.6 for the individual genotypes Ala/Ala and Leu/Val, which increased to 2.2 for the Ala-Leu/Ala-Val diplotype. A risk occupation had a modifying effect, increasing the crude OR of the combined genotype Ala/Ala + Leu/Val from 2.2 to 8.3.This study provides strong evidence for the role of common CYP1B1 variants as risk factors for bladder cancer, which increases with occupational exposure.

What’s known on the subject? and What does the study add? Bladder cancer susceptibility may be determined by genetic differences in the activity of glutathione S-transferases, enzymes that regulate the conversion of exogenous carcinogens to excretable hydrophilic metabolites by glutathione conjugation. The discrepancy of results regarding the association of common genetic polymorphisms and complex diseases such as cancer has raised scepticism in this area of research. Although the evidence generally supports the implication of GSTM1 and GSTT1 polymorphisms in bladder cancer, there is still some debate, with some studies in favour and some against. This study shows a greater risk of bladder cancer in individuals with GSTM1 null genotype, particularly women. This relationship is less evident with GSTT1 null genotypes. Null genotypes in both genes appear to be synergistic, particularly among smokers, and to increase the predisposition to more aggressive tumours. Nevertheless, the role of GSTM1 and GSTT1 polymorphisms in predisposition to bladder cancer should be viewed with caution, due to the multifactorial genetic origin of this condition and the need for long-term longitudinal studies to confirm these results. OBJECTIVE • To estimate the prevalence and importance of GSTT1 and GSTM1 genotypes (implicated in glutathione S-transferase activity) in bladder cancer, to determine whether smoking and occupational factors influence this relationship, and to identify the value of GSTT1 and GSTM1 genotypes as prognostic factors. PATIENTS AND METHODS • A cross-sectional study was conducted with a group of patients with bladder carcinoma and a control group with benign conditions and no history of tumours. The controls were selected and paired as subjects were recruited. • Sociodemographic variables, smoking, professional occupation, histological features and the presence of GSTT1 and GSTM1 polymorphisms by multiplex PCR techniques were assessed. RESULTS • GSTM1 genotypes were investigated in 201 patients and 193 controls and GSTT1 genotypes in 190 patients and 163 controls. • In the patients group, GSTT1 null genotype was observed in 22.1% (not significant) and GSTM1 null genotype in 54.2% (P= 0.008) (odds ratio, OR, 1.7); when considered together, 15.5% (P < 0.05; OR, 3.5) of patients had both null genotypes. In the multivariate analysis, the presence of GSTM1 null genotype remained in the model (OR, 2.1) in addition to smoking and age. • Subjects with bladder tumour and GSTM1 null genotype were younger than patients without gene deletion (P= 0.049). • Women with GSTM1 null genotype presented a higher OR than men (P= 0.024). When stratified by smoking habit, smokers with both null genotypes showed an OR of 4.7. • The percentage of patients with G3 tumours was higher in patients with GSTT1 null genotype (P= 0.013) and in patients with both null genotypes (P= 0.002). • A higher percentage of infiltrating tumours was also observed in patients with both null genotypes (P= 0.035). CONCLUSIONS • The data obtained in the present study suggest a higher risk of bladder cancer in individuals with the GSTM1 null genotype. • This risk is twofold higher when GSTM1 and GSTT1 null genotypes are both present and is also higher in smokers. • A greater predisposition for more aggressive tumours appears to exist, particularly when both null genotypes are combined. • Longer-term longitudinal studies are needed to confirm these results.

Objective To determine the prognostic value of p53 gene mutations and P53 overexpression for predicting the incidence of recurrence, progression and long-term survival of patients with transitional cell carcinoma (TCC) of the bladder. Methods Prospective cohort study with 94 consecutive patients diagnosed and treated for TCC. DNA was obtained from tumor tissue to perform PCR-SSCP of p53 exons 5–9, with automatic sequencing of any mutated samples. Immunohistochemistry using anti-human P53 monoclonal antibody was also performed. Survival was analyzed and the survival curves compared (Mantel-Haenszel). Lastly, a Cox proportional hazards model was constructed. Results Mutations were found in 46.8% of samples, with 61.8% in infiltrating tumors. Exon 8 was involved in 42.3%. P53 overexpression (cutoff ≥20%) was found in 52.1%. Mean follow-up was 44.1 months; 43.6% had died by the end of this period. Mean survival was lower in patients with exon 8 mutations (38.4 months), compared with patients without this exon mutated ( P = 0.016). There were no differences in patient survival based on positive or negative immunohistochemistry (cutoff ≥20%), although survival was lower in patients with a percentage higher than 50% of antibody-stained cells ( P = 0.02). In the Cox analysis, tumor stage, pM stage, and interaction between stage ≥pT2 and mutated p53 gene were independent risk factors, with a 6.13-fold risk of death in these patients ( P = 0.019). The number of tumors, nuclear grade, pTa stage, and the interaction between GI degree and nonmutated p53 gene remained in the Cox model for superficial tumors, such that these patients had a lower risk of recurrence or progression ( P = 0.008). Conclusions Alterations in the p53 gene may be indicative of poorer prognosis and greater recurrence in patients with urothelial bladder tumor, in particular, the presence of mutations in exon 8 and a greater percentage of stained cells in the immunohistochemistry. Nevertheless, the classic prognostic factors (primarily, pTNM stage) should still be considered the most useful factors for follow-up of these patients.

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.

Bladder endometriosis is rare, although the bladder is the urinary tract structure most often affected by this condition. The common clinical manifestations of bladder endometriosis include menouria and urethral and pelvic pain syndrome occurring cyclically. Imaging methods are not conclusive for the definitive diagnosis. Cystoscopy is the most useful diagnostic test with confirmation by histologic study. Treatment must be individualized according to the patient's age, desire for future pregnancies, the severity of the symptoms, the site affected, and whether other organs are involved. Two types of treatment are currently used as follows: medical-hormonal and surgical.

Objective: To analyze the correlation between the genotypic and phenotypic patterns of p53 in patients with transitional cell carcinoma (TCC) of the urinary bladder. Materials and Methods: Cross-sectional study of 73 patients diagnosed with TCC. DNA was obtained from the tumor tissue to perform polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) of exons 5–9 of the p53 gene, with automatic sequencing done on any mutated samples. Immunohistochemistry (IHC) was also performed using anti-human P53 monoclonal antibody, and the diagnostic performance of this test was analyzed by a ROC curve, using the presence of p53 mutations found by PCR-SSCP as ‘gold standard’. Results: The cutoff point for defining immunopositivity was 20%. IHC had a specificity of 62.9%, and a sensitivity of 65.8%. The highest sensitivity values appeared in G3 tumors (75%) and infiltrating tumors (71.4%), and the highest specificity values were observed in G1 (77.7%) and G2 tumors (90%) and superficial tumors (66.6%). Mutations in exon 8 gave a positive result most frequently (73.7%) and were considered most relevant in terms of altering P53 function (60.9%). False negatives were documented in 28.5% of infiltrating tumors, and false positives in 33.4% of superficial tumors. Conclusions: There is a moderate correlation between p53 mutations and P53 protein overexpression, with this stronger in high-grade, infiltrating tumors, in exon 8 mutations, and when the mutation induces relevant changes in the protein structure. Although IHC is useful in routine clinical practice, the classic prognostic factors should still be considered the most important in the follow-up of these patients.

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.

Ureteral herniation is a rare entity. We report the first case of extraperitoneal ureteral herniation in a pediatric en bloc renal graft causing obstructive uropathy. A 70-year-old, obese patient with an en bloc renal transplant was found to have ureterohydronephrosis in the right renal graft on magnetic resonance imaging. Nephrostomy with insertion of a double-J catheter confirmed the presence of a ureteral loop within the inguinal tract. Surgery confirmed herniation of the ureter through the internal inguinal ring, crossing over the spermatic cord. We performed release, resection, ureteral reimplantation and hernioplasty. Four months later, renal function was normal and urinary tract dilation had diminished. This case illustrates an unusual cause of obstructive uropathy in a transplanted kidney. Apart from obesity, two other factors may have contributed to its development: presence of a redundant ureter, and the fact that the ureter had been placed over, rather than under, the spermatic cord.

Purpose: Alterations in the p53 gene related to neoplastic progression were studied in tumor tissue samples from patients with transitional cell carcinoma and correlated with classic staging parameters. On this basis, biological characterization of the tumor was performed to establish subgroups of patients at high risk and those with a more favorable prognosis.Materials and Methods: This observational, analytical and cross-sectional study included 115 patients divided into 4 homogeneous groups of 1—control, 2—primary superficial transitional cell carcinoma, 3—recurrent superficial transitional cell carcinoma, and 4—infiltrative transitional cell carcinoma. DNA was obtained from tumor tissue samples and polymerase chain reaction-single strand conformational polymorphism analysis was performed on exons 5 to 9 of the p53 gene. Samples showing mutations were submitted to automatic sequencing. Statistics included bivariate analysis and logistic regression.Results: Of the tumors the 63.8% were superfici...

Objectives To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. Material and methods Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables. A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable. Results The study identified 13 (26%) VHL mutations related to nuclear grade (P = 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P = 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P

Objectives: To assess the quality of life (QoL) of patients on the waiting list for benign prostatic hypertrophy (BPH) surgery and the relationship between prostate symptoms and QoL. Materials and Methods: Our study included 189 BPH patients on the waiting list for surgery, during the period from January to December 1999. A survey was conducted to obtain information on sociodemographic characteristics, associated illnesses, prostate symptoms based on the International Prostate Symptoms Score (I-PSS), and QoL based on the 36-item Short Form Health Survey (SF-36). Moreover, the case history, prostate volume measured by ultrasound, and uroflowmetry results were considered. Descriptive, bivariate and multivariate analyses were conducted based on the scores recorded on the SF-36 scales and the other variables. Results: The mean age was 68.8 ± 6.9 SD. A total of 70.4% of the subjects had other chronic illnesses, 54.1% had severe symptoms (I-PSS > 19), and 69.8% reported that they were extremely dissatisfied with their symptoms. A total of 29.6% of the patients had urethral catheters. The SF-36 scale with the highest scores was social functioning (79.9, 95% CI: 76.5–83.4), whereas the lowest scores referred to role-physical (58.2, 95% CI: 52.3–64.1). Patients with more severe symptoms assigned lower scores to the physical functioning, vitality, social functioning, mental health, role-emotional and mental component summary (MCS) scales. Irritative symptoms were associated with lower vitality, social functioning, mental health and MCS. Patients with urethral catheters recorded lower scores on the physical functioning and role-physical scales. Conclusions: The QoL of BPH patients on the waiting list for surgery is poorer than that of the general population of the same age. The increased severity of prostate symptoms, particularly the irritative symptoms, leads to a poorer QoL in terms of nearly all aspects of QoL. However, this correlation was not observed for prostate volume nor uroflowmetry data.

Fundamento y objetivo: La metilacion de los islotes CpG (secuencias del genoma ricas en guanina y citosina) presentes en las regiones promotoras constituye la forma de inactivacion epigenetica mas comun y es una alteracion en el mecanismo de regulacion de los genes que no requiere cambios en la secuencia del ADN. Se ha descrito hipermetilacion del promotor del gen hMLH1 en algunas lineas celulares procedentes de carcinoma de celulas renales (CCR). Nuestro objetivo ha sido determinar la existencia de hipermetilacion en el promotor del gen hMLH1 en muestras de ADN tumoral de pacientes con CCR esporadico. Material y metodo: Se recogieron consecutivamente 65 muestras de tejido tumoral procedente de pacientes diagnosticados de CCR. Tras la obtencion y purificacion del ADN se procedio a su digestion con las enzimas de restriccion HpaII y MspI, seguido de amplificacion mediante reaccion en cadena de la polimerasa de 3 regiones del promotor del gen hMLH1, electroforesis en gel de agarosa y analisis densitometrico de las bandas amplificadas. Resultados: La edad media de los pacientes fue de 63,7 anos. El tipo celular mas frecuente fue el carcinoma de celulas claras (67,7%). Un 73,9% de los tumores se diagnosticaron en estadios inferiores a pT2, un 9,3% tenian afectacion ganglionar y un 20%, metastasis a distancia. No se detecto hipermetilacion somatica en la region promotora del gen hMLH1 en ninguno de los pacientes estudiados. Conclusiones: La hipermetilacion del promotor del gen hMLH1 no parece intervenir en la patogenia del CCR esporadico, y es necesario analizar la existencia de otro tipo de mutaciones, inestabilidad de microsatelites y/o perdida de heterocigosis para determinar el posible papel de este gen en la patogenia del CCR esporadico.

We report a case of supernumerary testis, a rare anomaly with only around 100 cases reported in the literature.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.The supernumerary testis was evaluated using two standard classifications, one assessing function and embryological development, and the other assessing topography, anatomy, and reproductive potential.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.

This study aimed to evaluate the usefulness of carbonic anhydrase IX (CA-IX) expression in clear cell renal cell carcinoma (CCRCC) using two different techniques to detect protein expression.An experimental, cross-sectional, analytical study was conducted to analyse proteins in renal tumour and healthy tissue specimens from 38 consecutive patients who underwent nephrectomy for renal cancer. CA-IX protein expression was measured by immunohistochemistry and Western blot analysis and quantified. Statistical analysis was performed with the positive and negative specific agreements and kappa coefficient. The sensitivity and specificity of both techniques were assessed. Statistical tests were conducted to analyse the association between CA-IX expression quantitation and normal prognosis factors (TNM stage and Fuhrman nuclear grade), only in CCRCC.The mean patient age was 65 years, 78.9% of patients were men and 57.9% of tumours were CCRCC. CA-IX protein expression was positive in 63.2% of tumours by immunohistochemistry and in 60.5% by Western blot. Both techniques detected CA-IX expression only in CCRCC and unclassifiable tumours. High concordance indices were observed for CCRCC diagnosis. Western blot and immunohistochemistry had a sensitivity of 95.5% and 100%, respectively; the specificity was 100% in both techniques. CA-IX expression quantitation did not correlate with tumour stage or Fuhrman nuclear grade.Immunochemistry and Western blot techniques can be used to detect abnormal CA-IX protein expression in CCRCC and to support morphology-based diagnostic techniques.

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.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.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.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.

Vesical nephrogenic adenoma is a rare, benign entity that appearsmost commonly in middle-aged males. Its etiology is unknown,but it has been linked to chronic irritating factors, such as infection,trauma, urological surgery, kidney stones, foreign bodies andchemical agents, such as Bacille Calmette-Guerin. We report 2new cases with a history of transurethral resection of the bladderand the prostate and a history of prolonged voiding symptoms. Inboth cases, the findings of encysted tubular structures lined withflattened cuboidal cells without atypia were consistent with thediagnosis of vesical nephrogenic adenoma.

We review the literature about secondary testicular tumors.We present the case of a patient with a metastatic mucus-secreting testicular tumor who presented in the emergency room with symptoms of acute scrotum 10 months after surgery for a mixed tumor of the cecum. This type of tumor is rare, and the treatment of choice is orchiectomy; nevertheless, the prognosis of such metastasis remains poor.Because mucinous tumors can present late dissemination, long-term follow-up with assessment of the most common sites of metastasis is necessary. Our patient died 21 months after the initial diagnosisTesticular metastases and mucus-secreting intestinal tumor metastases are rare. These tumors occur in patients older than 60 years of age and young men. As in the case of primary tumors, the treatment is orchiectomy.

Objetivos: Recordar la presencia de tumores testiculares secundarios y revisar la literatura acerca de esta patología. Métodos: Presentamos un paciente con tumor mucosecretor testicular metastásico atendido en urgencias por un cuadro de escroto agudo diez meses después de ser intervenido de un tumor combinado de ciego. La aparición de este tipo de tumores es rara, y el tratamiento de elección es la orquiectomía pero aún así el pronóstico de este tipo de metástasis es malo. Resultados: Los tumores mucinosos pueden presentar diseminación de modo tardío; por lo que es necesario un seguimiento a largo plazo evaluando los lugares más frecuente de asiento. El paciente falleció a los 21 meses del diagnóstico. Conclusiones: La metástasis testiculares y de tumor intestinal mucosecretor son raras. Generalmente afectan a mayores de 60 años, pero también aparecen en jóvenes. Como en los tumores primarios el tratamiento es la orquiectomía.

OBJETIVOS Varon de 37 anos que acude a nuestro servicio por dolor en fosa renal izquierda sin fiebre, compatible con colico nefritico que cede con tratamiento analgesico oral.

Lopez-Garrido M-P, Blanco-Marchite C, Sanchez-Sanchez F, Lopez-Sanchez E, Chaques-Alepuz V, Campos-Mollo E, Salinas-Sanchez AS, Escribano J. 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.

Objetivos: Presentar dos casos de quistes de rafe medio, uno de localización peneana y otro perineal. Método: Se diagnostican y describen dos casos de quiste de rafe medio, a uno se aplicó tratamiento quirúrgico y el segundo no precisó de tratamiento alguno. Resultados: La intervención quirúrgica del paciente operado no tuvo complicaciónes y a los dos años de la misma estaba asintomático y sin recidiva. Conclusión: Los quistes de rafe medio son poco frecuentes; es una patología benigna y su etiología no está completamente aclarada. Su tratamiento consiste en la exéresis simple.

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).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.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.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.

Background The deleterious effects of elevated intra-abdominal pressure (IAP) have been known for more than a century. The proposed objectives were to measure changes in IAP and analyze increase-related factors and complications and whether high IAP and its persistence are related to complications and mortality in a predominantly medical intensive care unit. Methods Over a 1-year period, we conducted a prospective cohort study in which IAP was measured using the bladder method. Hospitalization time, demographic variables, diagnosis on admission, APACHE II score, and clinical complications were recorded. Results A total of 130 patients were studied. Overall mean IAP was 12.3 mm Hg (standard deviation [SD], 3.79; 95% confidence interval [CI], 11.7-13), and on the first day, 12.68 mm Hg (SD, 5.32; 95% CI, 11.8-13.6); maximum IAP was 16.4 mm Hg (SD, 4.6; 95% CI, 15.6-17.2). A positive correlation was found between IAP, APACHE (Acute Physiology And Chronic Health Evaluation) II, and age. Higher IAP values were independently associated with higher age, prolonged activated partial thromboplastin time, need for dialysis, and intolerance to enteral feeding. The value showing the best sensitivity and specificity in predicting mortality was persistence of IAP 20 mm Hg or greater for 4 days or more. The number of days with IAP 20 mm Hg or greater was a factor associated with a higher risk of death (odds ratio, 2.3). Patients who died showed a tendency to increased IAP. Conclusion In this study, a threshold IAP of 20 mm Hg and its permanence over time were the best predictive factors of complications and mortality. Among other relationships, we also observed that older patients had higher IAP. High IAP was a cause of intolerance to enteral nutrition.

Background: Empathy is a skill that can be acquired by practise and should become a habit.Aims: Assess the impact of a communication skills workshop on the empathy level of medical students and medical residents.Methods: Quasi-experimental pre-test/post-test study. Empathy level was assessed in 203 subjects using the Jefferson Scale of Physician Empathy (JSPE), divided in two groups: one control group, and other experimental group that participated in an activity consisting of a 25-hour theoretical/practical workshop on communication and empathy.Results: The mean pre-workshop JSPE score was similar in both groups. Post-workshop JSPE score increased 5.24 points (95 CI 3.82–7.09) (P

To review the current diagnosis and treatment of Leydig cell testicular tumors, with special attention to conservative treatment.We report two cases of Leydig cell tumor in young adults, diagnosed two years after the appearance of bilateral gynecomastia as first clinical symptom.One year and eight months after orchyectomy, respectively, clinical symptoms completely disappear in the first case and significantly improved in the second.Around 10% of the cases, and only in adult patients, these tumors may be malignant, being radical orchyectomy the treatment of choice, although conservative surgery may be performed. Independently of the operation, follow-up must be prolonged.