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)

Polymorphic deletions of the GSTT1 and GSTM1 genes and susceptibility to bladder cancer.

UNLABELLED: 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.

Tumor inside an inguinoscrotal bladder hernia.

OBJECTIVE: To describe two cases of urothelial tumors in inguinoscrotal bladder hernias and comment on the low incidence of this condition. METHODS: Two patients were diagnosed and treated by partial cystectomy and hernia repair. RESULTS: The clinical outcome of both patients was good at two and three years, respectively, and neither patient experienced hernia or tumor recurrence. CONCLUSIONS: Inguinal bladder hernias are relatively common. However, few reports of tumor in the herniated bladder have been published. Treatment consists of tumor removal, hernia repair and treatment of any associated urethroprostatic condition.

Tumor en hernia vesical inguinoescrotal / Tumor inside an inguinoscrotal bladder hernia

OBJETIVO: Mostramos dos casos de neoplasia urotelial en hernias vesicales inguinoescrotales y referimos su escasa incidencia.METODOS: Se describe el diagnóstico y tratamiento efectuado con cistectomía parcial y herniorrafia.RESULTADOS: Ambos pacientes al cabo de dos y tres años respectivamente han tenido buena evolución clínica, sin recidiva herniaria ni del tumor.CONCLUSIONES: Las hernias vesicales inguinales son relativamente frecuentes, pero los casos de tumor en la vejiga herniada son escasos en la literatura. El tratamiento persigue eliminar el tumor, reparar la hernia y tratar si existe la patología uretroprostática (AU)

OBJECTIVE: To describe two cases of urothelial tumors in inguinoscrotal bladder hernias and comment on the low incidence of this condition.METHODS: Two patients were diagnosed and treated by partial cystectomy and hernia repair.RESULTS: The clinical outcome of both patients was good at two and three years, respectively, and neither patient experienced hernia or tumor recurrence.CONCLUSIONS: Inguinal bladder hernias are relatively common. However, few reports of tumor in the herniated bladder have been published. Treatment consists of tumor removal, hernia repair and treatment of any associated urethroprostatic condition (AU)

Calcificación bilateral de conductos deferentes / Bilateral calcification of deferent ducts

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Cuerpos extraños en pene / Penile foreign bodies

OBJETIVO: Mostrar 8 casos de cuerpos extraños en pene.MÉTODOS/RESULTADOS: Realizamos una presentación fundamentalmente visual de variados artilugios o cuerpos extraños de ubicación peneana.CONCLUSIONES: Raramente la existencia de cuerpos extraños peneanos se debe a accidentes. Los cuerpos extraños en pene son colocados por muy diversas razones, destacando principalmente dentro de actividades eróticas o autoeróticas, pudiendo tener consecuencias desde leves, a casos en los que puede acabar en amputación peneana(AU)

OBJECTIVE: To describe 8 cases of penile foreign bodies.METHODS/RESULTS: We provide an essentially visual overview of various objects or foreign bodies affecting the penis.CONCLUSIONS: The presence of penile foreign bodies is rarely due to an accident. These objects are placed for a wide variety of reasons, but primarily for erotic or self-arousal purposes. The consequences of penile foreign bodies can be mild or very severe, resulting in penile amputation(AU)

Tumor testicular bilateral sincrónico de distancia histología / Bilateral synchronic testicular tumor of different histology

Objetivo: Presentar el caso de un tumor testicular germinal bilateral sincrónico de distinta histología. Método/ Resultado: Se trata de un paciente de 37 años que durante un estudio ecográfico, por sospecha de tumor testicular izquierdo, se apreció una tumoración testicular contralateral sincrónica. Se practicó orquiectomía inguinal bilateral y en el posterior estudio anatomopatológico se confirmó la presencia de la tumoración testicular bilateral de distinto componente histológico. Conclusión: Alrededor del 75% de los casos de tumoración testicular bilateral son metacrónicos, presentándose únicamente el 10% con diferente histología. El tipo histológico suele correlacionarse con el aspecto ecográfico, y el tratamiento de elección de un paciente con patología oncológica de este tipo es la orquiectomía inguinal bilateral (AU)

Objective: To report one case of bilateral synchronic germ cell testicular tumour of different histology. Methods/Results: 37-year-old patient with left testicular tumor under study was found to have a contralateral synchronic testicular tumor on ultrasound. Bilateral inguinal orchiectomy was performed and pathology reported the presence of bilateral testicular tumours of different histological type. Conclusions: Around 75% of the cases of bilateral testicular tumours are metachronic, with only 10% presenting different histology. Histological type often correlates with the ultrasound findings, and the treatment of choice in patients with this type of oncological pathology is bilateral inguinal orchiectomy (AU)

[Retroorbital metastasis in the initial diagnosis of prostate cancer]. / Metástasis retroorbitaria en el diagnóstico inicial del cáncer de próstata.

OBJECTIVE: To describe one case of advanced prostate cancer first presenting with binocular diplopia due to retroorbital metastasis. METHODS: We present the case of a 54-year-old patient with the diagnosis of disseminated prostate cancer treated by complete androgen blockade. RESULTS: After the start of hormonal treatment, the patient initially improved although survival was limited. CONCLUSIONS: Orbital metastasis is an infrequent site for prostate cancer dissemination which implies a limited survival oscillating between 7,5-30 months. In our case survival was 10 months from diagnosis.

Metástasis retroorbitaria en el diagnóstico inicial del cáncer de próstata / Retroorbital metastasis in the initial diagnosis of prostate cancer

Objetivo: Describir un caso de cáncer prostático avanzado que debutó como primera manifestación clínica con una diplopia binocular por metástasis retroorbitaria. Métodos: Presentamos un paciente de 54 años que es diagnosticado de cáncer prostático diseminado tratado mediante bloqueo androgénico completo. Resultados: Tras la instauración del tratamiento hormonal el paciente mejoró inicialmente si bien la supervivencia fue limitada. Conclusiones: La metástasis orbitaria es una localización infrecuente dentro de la diseminación tumoral del cáncer de próstata que implica una supervivencia limitada que oscila entre 7,5-30 meses. En nuestro caso fue de 10 meses desde el diagnóstico (AU)

Objective: To describe one case of advanced prostate cancer first presenting with binocular diplopia due to retroorbital metastasis. Methods: We present the case of a 54-year-old patient with the diagnosis of disseminated prostate cancer treated by complete androgen blockade. Results: After the start of hormonal treatment, the patient initially improved although survival was limited. Conclusions: Orbital metastasis is an infrequent site for prostate cancer dissemination which implies a limited survival oscillating between 7,5-30 months. In our case survival was 10 months from diagnosis (AU)

Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: a long-term study.

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 > or =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 > or =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 > or =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.

Sensitivity and specificity of p53 protein detection by immunohistochemistry in patients with urothelial bladder carcinoma.

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.

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

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

Isolated testicular polyarteritis nodosa.

Isolated polyarteritis nodosa is a rare condition that may be triggered by local exposure to certain agents capable of provoking local immunostimulation without a systemic immune reaction. Isolated polyarteritis nodosa in the testes presents similar histologic characteristics as those of systemic inflammation, although infarcted areas in the testis are more common in generalized polyarteritis nodosa. Definitive diagnosis requires histologic study. We present the case of a 26-year-old patient with isolated testicular polyarteritis nodosa whose symptoms consisted predominantly of intense testicular pain and slight enlargement of both testes.

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

Objetivo: Presentar un caso de metástasis tardía por carcinoma de células renales tratado con cirugía radical. Método/Resultados: Paciente intervenido de nefrectomía radical y linfadenectomía por tumor renal que 6 años después de la cirugía, en un control rutinario presentó metástasis a nivel ganglionar regional. Tras tratamiento con inmunoterapia, que se suspendió por intolerancia, se decidió cirugía de la masa adenopática metastásica. Conclusión: El cáncer renal constituye un tumor imprevisible en cuanto a su comportamiento, de manera que puede metastatizar en cualquier momento de su evolución, incluso tras cirugía radical y tras varios años libres de enfermedad. La cirugía de las metástasis del cáncer renal constituyen una opción terapéutica con buenos resultados a largo plazo, cuando éstas son únicas y accesibles a la cirugía (AU)

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

Determination of vhl gene mutations in sporadic renal cell carcinoma.

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

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

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