Carcinoma urotelial: presentación de un caso / Urothelial carcinoma: a case report

RESUMEN Fundamento: los tumores del urotelio se originan a partir del epitelio de revestimiento mucoso de tipo transicional y constituyen la casi totalidad de los tumores de las vías excretoras, altos. El adenocarcinoma primario de las vías urinarias, son extremadamente infrecuentes y suelen tener un comportamiento agresivo, con un pronóstico sombrío. Objetivo: exponer la forma de presentación de un paciente con carcinoma urotelial mostrando algunas características de los mismos. Presentación de caso: paciente masculino de 70 años de edad, jubilado, fumador inveterado y con antecedentes de ingerir café en grandes cantidades, acudió a consulta por hematuria macroscópica, dolor lumbar, a veces fijo, otras veces en forma de cólicos ureterales y fiebre de 39 grados. El estudio analítico solo mostró velocidad de deshidrogenasa láctica alterada. El estudio imagenológico con ecografía mostró hidronefrosis e ilio derecho agrandado con imagen heterogénea de 2 cm en el riñón, a nivel de la unión uretero pélvica, lo cual fue corroborado por la tomografía axial computarizada. El resto de los exámenes como endoscopia, colonoscopía, cistoscopia y de diferentes regiones fueron todos negativos. Se practicó nefroureterectomía derecha, encontrándose el paciente asintomático. Conclusiones: los tumores del urotelio superior son neoplasias infrecuentes, en las vías urinarias se debe descartar un origen extraurológicos. El diagnóstico diferencial debe de realizarse con el tumor de células renales o el de vejiga.

ABSTRACT Background: the urothelial carcinomas originate from the epithelium of mucous revetment of transitional type and constitute almost totality of the tumors of the excretory, high routes. The primary adenocarcinoma of the urinary tract, are extremely infrequent and they usually have an aggressive behavior, with a shaded prognosis. Objective: to express the way of presenting a patient with urothelial carcinoma showing some aspects from the sicknesses. Case report: a 70-years-old male patient, retired, inveterate smoker and with a history of ingesting coffee in large quantities, attended consultation for gross hematuria, lumbar pain, sometimes fixed, other times in the form of ureteral colic and fever of 39 degrees. The analytical study only showed altered lactic dehydrogenase rate. The imaging study with ultrasound showed hydronephrosis and enlarged right ilium with heterogeneous image of 2 cm in the kidney, at the level of the pelvic ureter junction, which was corroborated by computerized axial tomography. The rest of the examinations such as endoscopy, colonoscopy, and cystoscopy of different regions were all negative. Right nephroureterectomy was performed, and the patient is still asymptomatic. Conclusions: the tumors of the upper urothelium are infrequent neoplasias, in the urinary tract an extraurological origin must be ruled out. The differential diagnosis must be made with the renal cell tumor or the bladder tumor.

Factores pronósticos de recurrencia y mortalidad en pacientes con tumor de urotelio superior tratados con cirugía / Prognostic Factors of Recurrence and Mortality in Patients with Upper Urothelial Tumor Treated with Surgery

Objetivos: Identificación de factores pronósticos de recurrencia y mortalidad cáncer-específica en pacientes con tumor de urotelio superior tratados con cirugía. Materiales y métodos: Análisis retrospectivo de pacientes con tumor de urotelio superior operados entre 1999 y 2011 en nuestro centro (139 pacientes). Se recogieron variables demográficas, clínicas, diagnósticas y patológicas, así como el tratamiento realizado, complicaciones y evolución. Análisis descriptivo mediante la prueba de chi cuadrado (X2 ) para variables categóricas y el test ANOVA (Analysis of Variance) para variables continuas. Análisis univariante y multivariante mediante modelo de riesgos proporcionales de Cox. La significación estadística se consideró con un valor de p<0,05. Todos los cálculos fueron realizados con el paquete estadístico IBM® SPSS® Statistics v-21. Resultados: En el análisis multivariante se identificaron como factores predictores independientes de recurrencia el crecimiento sólido tumoral (cociente de riesgo [hazard ratio, HR]=4,02; p<0,001) y el alto grado citológico (G3) (HR=3,42; p=0,01). La presencia de tumor vesical previo o concomitante (HR=1,84; p=0,07) presentó una tendencia a la significación. Se identificaron como factores predictores independientes de mortalidad cáncer-específica la presencia de tumor vesical previo o concomitante (HR=2,23; p=0,02), el crecimiento sólido tumoral (HR=2,73; p=0,008), la presencia de hidronefrosis (HR=2,46; p=0,02) y el estadío patológico avanzado pT3-pT4 (HR=2,74; p=0,01). Conclusiones: En nuestra serie, la existencia de tumor vesical previo o sincrónico, el crecimiento tumoral sólido y el alto grado citológico se comportaron como factores pronósticos de recurrencia. La hidronefrosis, el tumor vesical previo o sincrónico, el estadío pT3-4 y el crecimiento tumoral sólido se comportaron como factores pronósticos de mortalidad cáncer-específica. (AU)

Objectives: Identification of prognostic factors for recurrence and cancer-specific mortality in patients with upper urothelial tumor treated with surgery. Materials and methods: Retrospective analysis of patients with upper urothelial tumor operated between 1999 and 2011 in our center (139 patients). Demographic, clinical, diagnostic and pathological variables were collected, as well as the treatment performed, complications and evolution. Descriptive analysis using the chi-square test (X2 ) for categorical variables and the ANOVA (Analysis of Variance) test for continuous variables. Univariate and multivariate analysis using the Cox proportional hazards model. Statistical significance was considered with a value of p<0.05. All calculations were made with the statistical package IBM® SPSS® Statistics v-21. Results: In the multivariate analysis, solid tumor growth (hazard ratio, HR=4.02, p<0.001) and high cytological grade (G3) (HR=3, were identified as independent predictors of recurrence. 42, p=0.01). The presence of a previous or concomitant bladder tumor (HR=1.84, p= 0.07) presented a tendency towards significance. The presence of a previous or concomitant bladder tumor (HR=2.23, p=0.02), the solid tumor growth (HR=2.73, p=0.008), the presence of hydronephrosis (HR =2.46, p=0.02) and the advanced pathological stage pT3-pT4 (HR=2.74, p=0.01). Conclusions: In our series, the existence of previous or synchronic bladder tumor, solid tumor growth and high cytological grade behaved as prognostic factors of recurrence. Hydronephrosis, previous or synchronous bladder tumor, stage pT3-4 and solid tumor growth behaved as prognostic factors for cancer-specific mortality.(AU)

Alterações fisiopatológicas em bexiga urinária de camundongos obesos resistentes à insulina / Physiopathological alterations in urinary bladder from insulin resistant obese mice

Obesidade/síndrome metabólica são fatores de risco para o desenvolvimento dos sintomas do trato urinário inferior (LUTS), incluindo hiperatividade de bexiga. Em nosso estudo visamos investigar a relação entre resistência à insulina e hiperatividade de bexiga em modelo de obesidade induzida por dieta hiperlipídica (10 semanas) em camundongos C57BL6/J. Curvas concentração-resposta a diferentes agentes contráteis e à insulina foram realizadas em bexigas isoladas de camundongos e humanos. Estudo cistométrico foi conduzido em camundongos anestesiados. Expressão protéica de PKC, canais de Ca2+ do tipo L, eNOS (Ser1177) e AKT (Ser473) fosforiladas, bem como de marcadores da resposta a proteínas mal dobradas (UPR), TRIB3, CHOP e ATF4, foi determinada por western blot. Camundongos obesos exibiram aumento do peso corpóreo, gordura epididimal, glicemia de jejum e resistência à insulina. As respostas contráteis aos diferentes agentes foram maiores nos animais obesos, o que foi normalizado pela pré-incubação com o bloqueador dos canais de Ca2+ do tipo L, amlodipino. Animais do grupo obeso apresentaram hiperatividade de bexiga, como demonstrado por estudo cistométrico. As curvas concentração-resposta ao agonista muscarínico, carbacol, foram dependentes da ativação da PKC. A resposta contrátil ao ativador da PKC, PDBu, foi abolida pela incubação com amlodipino. O tratamento com metformina melhorou a sensibilidade à insulina assim como normalizou a hipercontratilidade in vitro, a hiperatividade de bexiga e os níveis de PKC e pAKT em camundongos obesos. A insulina (1-100 nM) produziu relaxamento concentração-dependente em bexigas de camundongos e humanos, o que foi reduzido pela remoção da camada urotelial ou inibição da via de sinalização da PI3K/AKT/eNOS. Em condições fisiológicas, o estímulo com insulina resultou em um aumento de aproximadamente 3 vezes nos níveis de GMPc; porém, o relaxamento e os níveis de GMPc foram menores em bexigas de animais obesos...

Obesity/metabolic syndrome are common risk factors for lower urinary tract symptoms, including overactive bladder. This study aimed to investigate whether insulin resistance affects bladder function in a model of obesity induced by high-fat diet (10 weeks) in C57BL6/J mice. Concentration-response curves to contractile agents and insulin were performed in human and mouse bladders. Cystometric study was performed in terminally anaesthetized mice. Western blot was performed in bladders to detect PKC, Cav1.2, phosphorylated eNOS (Ser1177) and AKT (Ser473), as well as the unfolded protein response (UPR) markers TRIB3, CHOP and ATF4. Obese mice exhibited higher body weight, epididymal fat mass, fasting glucose and insulin resistance. All the contractile agents produced greater bladder contractions in obese mice, which were fully reversed by the Cav1.2 blocker amlodipine. Cystometry evidenced overactive bladder in obese group that were also prevented by amlodipine. Carbachol induced contractions was dependent on the PKC activation, and PKC expression was increased in obese mice. Metformin treatment improved the insulin sensitivity, normalized the in vitro bladder hypercontractility, cystometric dysfunction and restored PKC and pAKT expression in the obese bladders. Insulin (1-100 nM) produced concentration-dependent mouse and human bladder relaxations that were markedly reduced by mucosal removal or inhibition of the PI3K/AKT/eNOS pathway. In mouse bladders, insulin produced a 3.0-fold increase in cGMP levels (P<0.05), that was prevented by PI3K/AKT/eNOS pathway inhibition. PI3K inhibition abolished insulin-induced phosphorylation of AKT and eNOS in bladder mucosa. Obese mice showed greater voiding frequency and non-voiding contractions, indicating overactive bladder...

Ureterectomía radical distal por cáncer urotelial y reconstrucción ureteral asistida por robot / Radical distal ureterectomy secondary to an urotelial cancer and ureteral reconstruction robot-assisted: case report

Objective: To report a case of distal ureterectomy with robotic-assisted laparoscopic reimplantation using a Boari flap technique. Material and Methods: We report a 55 year old man with a diagnosis of distal ureteral urothelial carcinoma without multifocality. Results: A radical distal ureterectomy and robotic-assisted laparoscopic vesicoureteral reimplantation using a Boari flap technique was performed with the da Vinci S-HD surgical system. The operative time was 210 minutes, the estimated blood loss was 200 mL. The hospital stay was 48 hours, without perioperative complications. The histopathological study showed a high grade non-muscle invasive urothelial carcinoma of the distal ureter (pT1NxMx) with negative margins. Conclusions: The distal radical ureterectomy with Boari replacement is feasible and more precise with robotic assistance. Its oncological role must be demostrated with a larger number of cases.

Objetivo: Comunicar un caso de tumor ureteral distal tratado con ureterectomía radical y neoimplante vesicoureteral con técnica de Flap Boari asistida por robot. Material y Métodos: Paciente hombre de 55 años, con diagnóstico de carcinoma urotelial de uréter distal sin compromiso multifocal. Resultados: Se realizó ureterectomía distal radical y neoimplante vesicoureteral con Flap Boari asistido por Robot da Vinci S-HD. El tiempo operatorio fue de 210 minutos, con un sangrado estimado de 200 ml. La estadía hospitalaria fue de 48 horas, sin complicaciones perioperatorias. El estudio histológico mostró un carcinoma urotelial de alto grado con infiltración de la lámina propia (pT1NxMx) y márgenes quirúrgicos negativos. Conclusiones: La ureterectomía radical distal con reconstrucción tipo Boari es técnicamente factible y más precisa con la asistencia robótica. Su rol oncológico requiere de validación con mayor número de casos.

Análise da composição do matriz extracelular das camadas urotelial e muscular da bexiga de mulheres em diferentes idades / Analysis of the extracellular matriz of urothelial and muscle layers of the bladder in women at different ages

Acomplacência da bexiga depende de músculos lisos, fibras colágenas, fibras elásticas e suas relações. O objetivo deste trabalho é determinar a composição da matriz extracelular em amostras de bexigas normais através de análise bioquímica de colágeno e glicosaminoglicanos em amostras obtidas de mulheres em diferentes grupos de idade, analisando separadamente as camadas urotelial e muscular. Avaliamos 17 amostras de bexiga divididas em três grupos: infância (N=5), menacme (N=6) e pós-menopausa (N=6). As bexigas foram analisadas para concentração de GAG total e colágeno e para análise qualitativa de GAG por eletroforese em gel de agarose. Na camada muscular, não houve diferença entre os grupos tanto para GAG quanto para colágeno. Na camada urotelial, a análise da concentração de colágeno não mostrou diferença entre os grupos, mas a concentração de GAG no grupo da pós-menopausa (0.21 +- 0.12 ug de ácido hexurônico/mg de tecido seco) apresentou diferença em relação aos grupos do menacme (1.78 +- 1.62 ug de ácido hexurônico/mg de tecido seco) e da infância (2.29 +- 1.32 ug de ácido hexurônico/mg de tecido seco). Nosso trabalho concluiu que a concentração de GAG está substancialmente diminuída na cadama urotelial da bexiga de mulheres na pós-menopausa.

Bladder compliance is dependent on smooth muscle, collagen fibers, elastic fiber and their ratios. The luminal surface of the urothelium is covered by an adhering glycosaminoglycan (GAG) layer. The aim of this study was to determine the composition of the extracellular matrix (ECM) in normal samples of women bladders through biochemistry analysis of collagen and GAG on samples obtained from individuals from different age groups, analyzing separately the urothelial and muscular layers. We studied samples taken from bladders of 17 patients divided in three different groups: childhood (N=5), menacme (N=6) and menopause (N=6). Bladders were analyzed for total GAG and collagen concentration per mg dry tissue and for the contents of GAG species, as determined by agarose electrophoresis and reported as the percent of total sulfated GAG. In muscular layer, collagen and GAG concentration showed no difference between groups. In urothelial layer, collagen concentration showed no difference between groups but GAG concentration in menopause (0.21 +- 0.12 ug hexuronic acid/mg dry tissue) was different from menacme (1.78 +- 1.62 ug hexuronic acid/mg dry tissue) and childhood (2.29 +- 1.32 ug hexuronic acid/mg dry tissue). There was no difference between sulfated GAG in three groups. In conclusion, GAG concentration in urothelial layer was substantially lower in menopause women.

Urotelio versus mucosa intestinal en ampliación vesical con sigmoide desmucosado: resultados de histopatología de largo plazo / Comparison between intestinal mucosa and urothelium in the setting of bladder augmentation: long term results

La ampliación vesical (AV) con sigmoide desmucosado ha mostrado grandes beneficio como reducción del mucus urinario y sus complicaciones. El objetivo de este estudio es determinar los cambios histológicos que acompañan a esta observación clínica, evaluando las transformaciones del epitelio de revestimiento del parche implantado; en distintos periodos post ampliación. Métodos: En 35 pacientes operados de AV (1998-2005), se realizaron aleatoriamente 24 exámenes endoscópicos con sus respectivas biopsias. La biopsia se tomó en tres puntos distintos del parche de ampliación desmucosado (9-12 y 3hrs). En aquellos niños con cierre de cuello, se utilizó un trocar trans-vesical. Los resultados histopatológicos (HP) se compararon entre diferentes períodos, con mucosa intestinal normal y con 2 biopsias realizadas sin parche desmucosado (>10 años). Resultados: La edad promedio al momento de la biopsia fue de 12 años (rango 4 a 15). El periodo de toma de biopsia tiene una mediana de 39 meses (rango 12-84 meses) post ampliación. La descripción macroscópica mostró dos grupos; en el periodo menor a 3 años el intestino se ve recubierto con urotelio con algunas zonas de mucosa intestinal (“estrellado”), y en muestras mayores a 3 años el parche estaba completamente cubierto con mucosa intestinal pero más pálido. La HP de las biopsias efectuadas precozmente (< 36 meses) demostraron que el implante presenta mayoritariamente urotelio con pequeñas “estrellas” de mucosa sigmoidea normal con algunas glándulas atróficas. En la totalidad de las muestras > 36 meses se informó parche recubierto mayoritariamente con mucosa sigmoidea con glándulas rodeadas por tejido fibroso, mayoritariamente atróficas y ausencia de urotelio. En los 2 pacientes con ampliación vesical sin parche desmucosado las glándulas intestinales mostraron estructura normal. Conclusión: Podría plantearse la existencia de un fenómeno de regeneración y expansión de mucosa histológicamente...

Bladder augmentation (BA) using demucosalized sigmoid has showed excellent benefices as mucus reduction and its complications. The aim of this study is to determinate the histological changes of this clinical observation, evaluating the coating epithelium of the patch in different periods postaugmentation. Methods: There were 24 random endoscopies exams and biopsies performed in 35 cases who underwent a BA between 1998 and 2005. Biopsy was done in 3 different points of the augmentedpatch (9-12-3 o’clock). In those children with bladder neck surgery a trans-vesical trocar was used. Histopathology (HP) results were compared among different post augmented periods, with normal intestinal mucosa and with biopsies done in 2 cases of BA where sigmoid without demucosalized was used (>10 years). Results: The mean age at biopsy was 12 years (range 4-15 y) and the period of biopsy has a median post BA of 39 months (range 12-84 m). Macroscopic description showed 2 groups; one (< 3 years) where the intestine was covered by urothelium with some small areas of intestinal mucosa (“stars”), and the other over 3 years where the patch was covered completely with intestinal mucosa. HP results in the early biopsies (< 36 months) showed that the patch was mostly covered with urothelium with some small “stars” of sigmoid mucosa, but with atrophic glands. In the group > 36 months the patch was mostly covered with intestinal mucosa with atrophic glands surrounded by fibrotic tissue and no signs of urothelium. In the 2 cases of BA with sigmoid without demucosalized the intestinal glands were completely normal. Conclusion: It could be affirmed that there is a regenerative and expansive process of mucosa histologically similar to a normal sigmoid mucosa (< 3 years), which could begin from intestinal mucosa remnants (“stars”). While the glandular structure would be atrophic in the patch, it was normal in those cases augmented with sigmoid without...