Prognostic Value of the Neutrophil/Lymphocyte Ratio in Squamous Cell Carcinoma of the Penis.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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 NLR <3, those with NLR >3 presented a higher proportion of cancers in stages cN1 (29.7% vs 6.8%; p = 0,004), stages pT3 and pT4 (24,3% vs 9,5%; p = 0,05), and stages TNM III and IV (32,4% vs 10,2%; p = 0,01); additionally, there were more cases of perineural invasion in the NLR >3 patients (29,7% vs 10,2%; p = 0,03). The mean overall survival (OS) was 7,9 years (CI 95%: 6,2-9,6) and the cancer-specific survival (CSS), 1,3 years (CI 95%: 0,7-1,9). There were no differences in OS, CSS or in progression-free survival (PFS) in patients with NLR >3 compared to those with NLR <3 . However, in the Cox regression analysis, a higher NLR was independently associated (along with metastasis and need for adjuvant treatment) with lower PFS, with an HR: 1,27 (CI 95%: 1,02-1,57; p = 0,02). CONCLUSIONS: 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.

Prognostic Value of the Neutrophil/Lymphocyte Ratio in Squamous Cell Carcinoma of the Penis

Introduction: 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. Materials and Methods: 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. Results: 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 NLR <3, those with NLR >3 presented a higher proportion of cancers in stages cN1 (29.7% vs 6.8%; p = 0,004), stages pT3 and pT4 (24,3% vs 9,5%; p = 0,05), and stages TNM III and IV (32,4% vs 10,2%; p = 0,01); additionally, there were more cases of perineural invasion in the NLR >3 patients (29,7% vs 10,2%; p = 0,03). The mean overall survival (OS) was 7,9 years (CI 95%: 6,2–9,6) and the cancer-specific survival (CSS), 1,3 years (CI 95%: 0,7–1,9). There were no differences in OS, CSS or in progression-free survival (PFS) in patients with NLR >3 compared to those with NLR <3 . However, in the Cox regression analysis, a higher NLR was independently associated (along with metastasis and need for adjuvant treatment) with lower PFS, with an HR: 1,27 (CI 95%: 1,02–1,57; p = 0,02). Conclusions: 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 (AU)

[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.

Biomarcadores en cáncer renal / Biomarkers in renal cáncer

La historia natural del cáncer renal esimpredecible y a pesar del aumento del conocimientode esta enfermedad, la incidencia ha ido en aumento en los últimos años. Representa un tumor con unamortalidad importante y los esfuerzos por conocer sucomportamiento todavía no se traducen en una disminución de su mortalidad.Dentro del estudio del cáncer renal es cada vezmás importante el conocimiento de su funcionamiento molecular, que por otra parte ha sido fundamentalpara la aparición de las nuevas terapias. Dicho conocimiento ha permitido reclasificar estos tumores, siendo el 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. (AU)

The natural history of renal cell canceris unpredictable and despite the increased knowledge of this disease, the incidence has been increasing in recent years. Renal cancer represents a tumor withsignificant mortality and efforts to understand its behavior havenot 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 tumors and the current challenge is the search for biomarkers that 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. (AU)

Clinical value of perioperative levels of DNA and mRNA in plasma of patients with renal cell carcinoma.

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.

Analysis of the Efficacy of a Sublingual Bacterial Vaccine in the Prophylaxis of Recurrent Urinary Tract Infection.

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.

Diagnostic and prognostic value of the detection of hTERT mRNA in renal tumors.

INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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 (P < 0.001). 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 (P < 0.0001). 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. CONCLUSIONS: 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.

Increased Serine and One-Carbon Pathway Metabolism by PKCλ/ι Deficiency Promotes Neuroendocrine Prostate Cancer.

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.

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.

Prognostic Value of the VHL, HIF-1α, and VEGF Signaling Pathway and Associated MAPK (ERK1/2 and ERK5) Pathways in Clear-Cell Renal Cell Carcinoma. A Long-Term Study.

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 < .0001), HIF1-α expression > 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.

VHL promotes immune response against renal cell carcinoma via NF-κB-dependent regulation of VCAM-1.

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 α4ß1 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.

Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis.

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<0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P<0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P<0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P = 0.014). CONCLUSIONS: VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages.

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.

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.

Poliorquia: presentación de un caso y revisión de la literatura / Supernumerary testicle: case report and bibliographic review

OBJETIVO: Presentar un caso de teste supernumerario, rara anomalía de la que existen descritos y fundamentados aproximadamente 120 casos. MÉTODOS: Presentamos el caso de un varón de 26 años que consultó por presentar tumoración paratesticular izquierda. La exploración física y ecográfica evidenciaron una lesión nodular de aproximadamente 2 cm sobre epidídimo izquierdo que se confirmaría posteriormente durante la exploración quirúrgica y biopsia. Dada la posibilidad de malignización se decidió extirpar el teste supernumerario. RESULTADOS: Para evaluar un teste supernumerario disponemos de varias clasificaciones que evalúan la funcionalidad y el desarrollo embriológico del mismo, así como la topografía, la anatomía y su potencial reproductivo. CONCLUSIONES: Ante una masa intraescrotal debemos tener en cuenta a la hora de realizar el diagnóstico diferencial la presencia de un teste supernumerario, siendo fundamental la exploración quirúrgica y biopsia. Realizaremos exéresis del teste supernumerario siempre que sea origen de dolor, displasia, carcinoma in situ, o la biopsia arroje dudas(AU)

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(AU)

Carbonic anhydrase IX as a specific biomarker for clear cell renal cell carcinoma: comparative study of Western blot and immunohistochemistry and implications for diagnosis.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 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.

Carcinoma neuroendocrino de vejiga. Analisis retrospectivo de 15 años / Neuroendocrine carcinoma of the urinary bladder. 15-year retrospective analysis

OBJETIVO: Los tumores neuroendocrinos (TNE) son tumores propios del árbol broncopulmonar, donde fueron descritos por primera vez en 1926. Son tumores de mal pronóstico debido a su gran poder metastásico aun después de tratamientos radicales asociados a otras terapias neo o adyuvantes. El TNE de vejiga representa el 0,5% de los tumores vesicales. MÉTODOS: Estudio observacional, descriptivo y retrospectivo de 13 pacientes diagnosticados, tratados y controlados por carcinoma neuroendocrino de vejiga en el Complejo Hospitalario Universitario de Albacete por el periodo entre los años 1995 y 2010. RESULTADOS: La muestra estaba formada por 11 hombres y 2 mujeres. La edad media fue de 71 años. El estadio tumoral T más frecuente hallado fue T4. El estadio tumoral N más frecuente hallado fue N2 . Seis pacientes presentaron metástasis a distancia en el momento del diagnóstico. Once pacientes presentaron histológicamente TNE de células pequeñas. A 7 pacientes se les realizó cirugía radical (cistectomía radical). La quimioterapia adyuvante se administró a 4 pacientes basada principalmente en la asociación de carboplatino/cisplatino y etopósido. A 2 de estos 4 pacientes se les administró radioterapia pélvica complementaria. La Mediana de supervivencia hallada fue de 5,1 meses. Dos pacientes presentaron supervivencia por encima de 5 años tras el diagnóstico. De los 9 éxitus letalis acontecidos, 8 de ellos se produjeron en los primeros 6 meses después del diagnóstico. El caso restante falleció a los 24 meses. Todas estas muertes fueron debidas a la propia enfermedad. CONCLUSIONES: El carcinoma neuroendocrino de vejiga es un tumor infrecuente, agresivo y con alto potencial metastásico que debe ser tenido en cuenta a la hora de realizar el diagnóstico diferencial en las neoplasias de vejiga. A pesar de utilizar distintos tratamientos multimodales el pronóstico es infausto(AU)

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(AU)

Role of CYP1B1 gene polymorphisms in bladder cancer susceptibility.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: This study provides strong evidence for the role of common CYP1B1 variants as risk factors for bladder cancer, which increases with occupational exposure.