Epithelial mesenchymal transition in urothelial carcinoma: Twist in the tale.

Context: Epithelial to mesenchymal transition (EMT) is a process involving conversion of cells from an epithelial to mesenchymal phenotype. The role of candidate genes promoting EMT and favoring a promigratory phenotype has been demonstrated in epithelial cancer. Existing scientific research has not yielded a clinically relevant biomarker with predictive capacity beyond grade and stage in bladder cancer. Aim: The purpose of this study is to evaluate the immunohistochemical expression pattern of a panel of epithelial and mesenchymal markers in paraffin-embedded archival material of primary urothelial carcinoma as evidence of EMT. Materials and Methods: Immunohistochemical expression of transcription factor twist, epithelial (E-cadherin, cytokeratin) and mesenchymal (vimentin, N-cadherin) markers was analyzed on archival paraffin-embedded tissue samples from 48 patients with diagnosis of primary urothelial carcinoma of bladder. Statistical Analysis: Karl Pearson's χ2 test was used to evaluate the association between the expression of immunohistochemical markers and various clinico-pathologic variables. Non-parametric Kendall's tau-b statistics was used to determine the correlation between categorical variables. Results and Conclusion: The study demonstrated statistically significant association of cytokeratin, E-cadherin, vimentin, and twist with stage and grade of bladder cancer. Since these markers form part of the spectrum of changes associated with EMT, the study establishes proof of concept of the existence of this process in vivo. A significant negative correlation was noted between the expression of twist and E-cadherin. Exploiting its role as a transcriptional repressor of E-cadherin, twist may prove to be a useful candidate for targeted therapy in urologic oncology.

Carcinoma transicional de vejiga en adolescentes: un diagnóstico para tener en cuenta / Transitional cell carcinoma of the bladder in adolescents: a diagnosis to bear in mind

El carcinoma transicional de vejiga es una entidad de alta incidencia en adultos pero infrecuente en niños y adolescentes. La hematuria es la forma más frecuente de presentación y la ecografía vesical es el método diagnóstico de elección. El diagnóstico y tratamiento se realiza mediante cistofibroscopia y resección endoscópica. Presentamos dos pacientes: un joven de 18 años que exhibía un tumor pediculado en cara posterior de vejiga y una joven de 15 años con una formación de 1cm delongitud, también pediculada y en cara posterior; ambas lesiones fueron resecadas bajo control endoscópico. En ambos casos el diagnóstico fue carcinoma transicional superficial yestán libres de enfermedad con 3 y 5 años de seguimiento. Se realizó una revisión de la bibliografía para clarificar si estas lesiones vesicales deben ser consideradas malignas e intentar definir cómo y cuánto tiempo deben seguirse estos pacientes.

Outcome of post-TUR-BT combined chemo and immuno intravesical therapy in the management of papillary transitional cell carcinoma of the urinary bladder

To evaluate the outcome of post-TUR-BT combined chemo-and immune-intravesical therapy in papillary transitional cell carcinoma of the urinary bladder. From Sept 2001 to August 2007 in Alnoor specialist'hospital, Holly Makkah K.S,A and Urology Department, Benha Faculty of Medicine 158 patients of papillary transitional cell carcinoma Ta,T1,T2 were treated by TUR-BT plus combined intravesical chemotherapy and immunotherapy. TUR-BT was repeated and intravesical combined therapy if recurrence occurred on 3, 6 months cystoscopic follow up, percentage of the disease-free patient, recurrence, progression and survival with intact bladder were compared and analyzed. Follow up of the patients up to 5 years was done. At median follow up of about 24 months; 82 patients [53.6%] were disease free and recurrence was detected in 31 patients [20%] and progression was in 4 patients [2.6%]. The results of the follow up at the end of the 5 years revealed that the disease-free percentage was 64 patients [41.5%], recurrence was detected in 41 patients [26.8%] and progression was [14.4%] in 22 patients were shifted to cystectomy. Overall 5 year survival with intact bladder was 85.6% [131 patients], we did not follow cystectomy patients. Post TUR-BT combined intravesical chemo and immuno-therapy is an appropriate option for the management of papillary transitional cell carcinoma of the urinary bladder and could preserve the intact bladder for a long period and should be applied even in muscle invasive T2 tumor before shifting to cystectomy

Bacilo Calmette-Guérin intravesical em pacientes com carcinoma superficial de bexiga: atualizaçäo / Intravesical bacillus Calmette-Guérin in patients with superficial bladder carcinoma: up to date

O carcinoma de células transitional de bexiga superficial é uma doença multipotencial e a sua evoluçäo natural algumas vezes näo pode ser prevista precisamente. Tumor, grau e estádio da doença fornecem as mais importantes informaçöes até hoje. Há uma grande pesquisa e um enorme desafio nesta área, como os biomarcadores moleculares para indicar os fatores prognósticos nos pacientes de alto risco. As principais metas no tratamento do câncer superficial da bexiga säo: erradicaçäo da doença existente, profilaxia contra novas recorrências e prevençäo da progressäo da doença. O melhor tratamento é a imunoterapia com BCG liofilizado e uma resposta duradoura pode ser alcançada quando aplicada a manutençäo da terapia, mas há alguns tumores agressivos que devem ser tratados com cistectomia radical precoce. Os efeitos antitumorais do BCG intravesical contra o câncer urotelial parecem estar ligados com mecanismos efetores imunológicos, com aumento dos linfócitos T por infiltraçäo na lâmina própria da bexiga.

Superficial bladder cancer: natural history and management

This study included 61 patients suffering from urinary bilharziasis. Patients were divided into three groups; group I included 34 patients with Ta and Tl tumors, group II included 5 patients with primary Tis and group III included 22 patients with urothelial atypia neither concomitant nor sequential to superficial bladder cancer. Patients in groups I and II were subjected to transurethral resection of the tumor. Intravesical immunotherapy [BCG in 16 patients and KLH in 13 patients] was applied to twenty-nine patients in group I, all patients in group II and two patients with severe urothelial atypia in group III. The results were similar to western literature regarding that tumor stage, grade multiplicity and associated urothelial atypia or Tis are the four principle prognostic factors in the natural history of superficial bladder cancer whether or not associated with vesical schistosomiasis. The incidence of recurrence was 25% in the BCG treated patients and 15.4% in the KLH treated patients which is also comparable with the results from western literature. Recurrence pattern occurred as the same stage and grade as the primary tumor except for pT1 GIII tumor which developed muscle invasion and the patient was subjected to cystectomy

Inmunoterapia intravesical con BCG en el carcinoma superficial de células transicionales de la vejiga / Intravesical immunotherapy with BCG in bladder superficial transitional cell carcinoma

Se realizó un estudio prospectivo para conocer la eficacia del BCG intravesical como tratamiento en el carcinoma superficial del la vejiga de células transicionales y para prevenir la recurrencia de esta clase de tumores. Se trataron siete pacientes (seis varones y una mujer) con carcinoma superficial de vejiga de células transicionales estadio A, grado II, con promedio de edad de 61.2 años. Se utilizó la cepa danesa 1331 a dosis de 50 mg en 50 ml, equivalente a 500 y 1 000 millones de BCG. El esquema inicial consistió en la aplicación de 50 mg por semana durante seis semanas. Los pacientes con mayor riesgo de recurrencia se sometieron a esquema mensual de sostén. El seguimiento fue de 7.6 meses, a partir de la primera dosis, mediante vigilancia trimestral con cistoscopia, examen general de orina, urocultivo y citologías urinarias. La respuesta es de 100 por ciento, según lo establecido por el protocolo de los autores. Un paciente presentó recidiva después de haber recibido el ciclo inicial, y se sometió a un esquema de reinducción previa y RTU de tumor. Actualmente se encuentra libre de actividad tumoral. Este protocolo muestra prácticamente los mismos resultados de comparación con otros estudios sobre BCG sólo que con diferentes dosis y esquema de seguimiento

Tratamiento del carcinoma vesical con bacilos Calmette-Guerin / Treatment of vesical carcinoma with bacillus Calmette-Guerin

El carcinoma superficial de células transicionales, progresivo de vejiga urinaria, puede ser sometido a tratamiento conservador con electroresección y coagulación endoscópicas y medicación citolítica, química e inmunológica o una terapia radical con radiación o cistectomía. El criterio clínico apropiado permite aplicar un tratamiento eficaz, para evitar el progreso de la enfermedad y lograr su curación. La acción citolítica e inmunológica del BCG, ha sido establecida en la actualidad en el tratamiento del carcinoma in situ de la vejiga. Debido al menor número de recurrencias y de reacciones adversas obtenidascon el uso de esta droga, la hemos empleado a satisfacción como tratamiento coadyuvante o profiláctico después de la electroresección y coagulación endoscópicas de la neoplasia vesical. Actualmente la cistectomía y otros métodos radicales de tratamiento, son aplicados cuando fracasa la terapia conservadora

Carcinoma de células transicionais da pelve renal e do ureter / transitional cell carcinoma of renal pelvis and of ureter

No período de 1976 a 1990, 14 pacientes com tumor de células transicionais do trato urinário superior foram tratados no Serviço de Urologia do Hospital Oncológico Amaral Carvalho. Destes tumores, sete foram encontrados na pelve renal e sete em ureter distal. O tratamento de escolha para esses tumores foi a nefroureterectomia, com retirada de cone vesical, perimeatal. Em um caso de tumor de ureter, com baixo grau e estadiamento, foi realizada ureterectomia segmentar.

Cancer vesical superficial: uso de vacuna BCG en microdosis; estudio cooperativo filial sur urología / Surface vesical neoplasm: use of BCG vaccine in microdosage; cooperative study in south center of urology

Se presentan los resultados acumulados actuales de un trabajo cooperativo de la filial sur de urología sobre 83 pacientes operados por cancer vesical de células transicionales etapa T1 en profilaxis de recidiva con microdosis de vacuna BCG (1 mg) mediante instilaciones vesicales durante un año. Se pesquisa 19 por ciento de recidivas en un promedio de 28 meses de observación. No se presentaron recidivas en los pacientes grado 1 de Broders y no hubo diferencias en cuanto a recidivas de los grados 2 y 3. Como complicación sólo se presentó irritación vesical en 1 paciente