Long-Term Oncological and Functional Outcomes After Robot-Assisted Partial Nephrectomy for Clinically Localized Renal Cell Carcinoma.

BACKGROUND: To evaluate long-term oncological and renal function outcomes in patients treated with robot-assisted partial nephrectomy (RAPN) for renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients undergoing RAPN for clinically localized RCC between January 2014 and December 2019 at a tertiary robotic reference center were evaluated. Clinical course, pathologic characteristics, and long-term outcomes were obtained from our institutional review board-approved RCC database. RESULTS: A total of 234 patients were available for analysis. Median follow-up was 46 months (10.8-97.8 months), with 77 patients (32.9%) having at least 5-years of follow-up. Pathology revealed clear-cell RCC in 67.5% (n = 158). Among unfavorable factors, nuclear grades 3 or 4 were found in 67 (29.4%), lymphovascular invasion in 10 (4.3%), positive surgical margins in 22 (9.4%), necrosis in 21 (9%), and sarcomatoid pattern in 2 patients (0.9%). At 12 months, mean serum creatinine was 1.04 mg/dL and 12.9% of patients experienced upstaging in chronic kidney disease. Overall recurrence-free survival at 5-years was 97.8%. There were five local (2.1%) and two distant (0.9%) recurrences, none of them resulting in cancer-specific death. Median time to recurrence was 20 months (11-64 months). Warm ischemia time [hazard ratio (HR) = 1.14, p = 0.034] and sarcomatoid pattern (HR = 124.57, p = 0.001) were the only variables associated with local relapse. CONCLUSIONS: Data from this large cohort demonstrate that patients undergoing RAPN have a low incidence of local and distant relapse, resulting in excellent long-term survival while preserving stable renal function in most patients.

Densidad de APE en pacientes PI-RADS 3: un parámetro clínico útil para su manejo / PSA density as a new approach for PIRADS 3 patient's management

Resumen: Objetivo: Analizar las biopsias realizadas en paciente categorizados PIRADS 3 en nuestra institución desde el segundo semestre del año 2016 al primer semestre del año 2018 y describir la correlación de la densidad de PSA con la incidencia de cáncer de próstata. Evaluar el rol de la densidad de PSA en la indicación de estudio histológico en pacientes PIRADS 3. Método: Trabajo autorizado por el comité de ética de nuestra institución. Se realizó búsqueda en el PACs, de todos los informes de RM multiparamétricas de próstata que incluyeran la categoría ¨PIRADS 3¨ en el periodo señalado. De ellos se calculó la densidad de PSA, con el último valor de PSA registrado en la ficha clínica previo a RM y volumen prostático en RM. Se procedió a buscar los pacientes con estudio histológico. Se correlacionó los resultados de biopsias con el valor de densidad de PSA. Realizamos análisis uni y multivariados, análisis estadísticos con sensibilidad, especificidad y uso de curva ROC. Resultados: De las 2416 RMmp de próstata realizadas en nuestra institución en las fechas ya descritas, se encontraron 424 informes catalogados con score PIRADS 3, y 267 de esos pacientes tenían estudio y seguimiento institucional, de los cuales 134 contaban con biopsia. La muestra tenía un promedio de edad de 60 años, y una mediana de densidad de PSA de 0,10 (RIC 0,07-0,14). Se encontraron 36 biopsias con cáncer clínicamente significativo (Gleason > 6), lo que corresponde a 26,8% de la muestra, valor similar al encontrado en la literuatua. En estos pacientes se obtuvo un punto de corte óptimo de densidad de PSA de 0,11, con una sensibilidad y especificidad de 67% y un AUC de 0,68. Una densidad de PSA de 0,11 presenta un OR de 4,1, con una probabilidad de 4 veces más de encontrar un cáncer de próstata por sobre este valor (IC 95% 1,3-9,8), lo cuál es estadísticamente significativo con un p igual a 0,01. Conclusión: La DAPE sobre 0,11 ng/ml/cc puede considerarse como una herramienta adicional para indicar biopsia en pacientes con RMmp PI-RADS 3, aumentando la precisión para la detección de cáncer de próstata clínicamente significativos ayudando a disminuir estudios histológicos innecesarios.

Abstract: Objective: To analyze the biopsies performed in patients categorized PIRADS 3 in our institution from the second half of 2016 to the first half of 2018 and describe the correlation of PSA density with the incidence of prostate cancer. To evaluate the role of PSA density in the indication of histological study in PIRADS 3 patients. Method: Work authorized by the ethics committee of our institution. The PACs were searched for all multiparameter prostate MRI reports that included the category "PIRADS 3" in the period indicated. The PSA density was calculated, with the last PSA value recorded in the clinical record before MRI and prostate volume in MRI. We proceeded to look for patients with the histological study. The biopsy results were correlated with the PSA density value. We perform uni and multivariate analyzes, statistical analyzes with sensitivity, specificity and use of the ROC curve. Results: Of the 2416 RMmp of the prostate performed in our institution on the dates already described, 424 reports catalogued with PIRADS 3 score were found, and 267 of those patients had study and institutional follow-up, of which 134 had a biopsy. The sample had an average age of 60 years and a median PSA density of 0.10 (RIC 0.075-0.146). We found 36 biopsies with clinically significant cancer (Gleason> 6), which corresponds to 26.8% of the sample, a value similar to that found in the literature. In these patients, an optimal cut-off point of PSA density of 0.11 was obtained, with a sensitivity and specificity of 67% and an AUC of 0.68. A PSA density of 0.11 has an OR of 4.1, with a 4-fold probability of finding prostate cancer above this value (95% CI 1.3-9.8), which It is statistically significant with a p equal to 0.01. Conclusion: DAPE over 0.11 ng/ml/cc can be considered as an additional tool to indicate biopsy in patients with RMmp PI-RADS 3, increasing the accuracy for the detection of clinically significant prostate cancer helping to reduce unnecessary histological studies.

La edad es un factor predictor independiente para recurrencia tumoral en el cáncer de vejiga no músculo invasor: resultados de una serie local / Age is an independent predictor for tumoral recurrence in non muscle-invasive bladder cancer: results of a local series

Introducción: El cáncer de vejiga es en su mayoría una enfermedad de pacientes de edad avanzada. El objetivo del estudio fue evaluar la edad como factor pronóstico en una cohorte de pacientes chilenos con cáncer de vejiga no músculo invasor. Material y métodos: Se revisaron retrospectivamente los registros clínicos de 107 pacientes tratados por un cáncer no-músculo invasor de vejiga confirmado histológicamente. Se determinaron asociaciones de la edad con parámetros clínicos e histopatológicos, así como con recurrencia y progresión tumoral. Finalmente se realizó un análisis multivariado para identificar factores predictores de los desenlaces mencionados. Resultados: La mediana de edad fue 65 años (rango 29-94). Se observó una significativa asociación de unos pacientes jóvenes con el tabaquismo activo. Por otro lado, los pacientes mayores a 65 años mostraron una asociación significativa con la presencia de recurrencia y progresión tumoral en el análisis univariado. Finalmente, una edad por sobre los 65 años fue el predictor independiente más importante para la recurrencia en el análisis multivariado, por sobre el estadío pT. Conclusiones: Existen varios factores clínicos y psicosociales que contribuyen al significativo poder predictor de una edad > 65 años en el pronóstico de un paciente con un cáncer de vejiga no músculo invasor. Por lo mismo, cada paciente debe ser evaluado en forma integral, tomando en cuenta las distintas dimensiones involucradas. En un escenario de progresivo envejecimiento de la población, el urólogo debe estar preparado para resolver adecuadamente esta situación.

Introduction: Bladder cancer is most frequently a disease of the elderly. The aim of the study was to evaluate the impact of age on prognosis in a cohort of Chilean patients with non muscle-invasive bladder cancer. Methods: The medical records of 107 patients treated for non muscle-invasive bladder cancer at our institution were retrospectively reviewed. Associations of age with clinical and histopathological parameters were assessed, as well as with tumoral recurrence and progression. Finally, a multivariate analysis was performed in order to identify predictive factors for the mentioned outcomes. Results: The median age was 65 years (range 29-94). Younger patients showed a significant association with an active smoking status. On the other hand, a significant association of age > 65 years with tumoral recurrence and progression was observed on univariate analysis. Age was also the most important predictive factor for recurrence on the multivariate analysis, even more than the pT stage. Conclusions: There are several clinical and psychosocial factors related to the significant predictive power of a higher age on the prognosis of patients with non muscle-invasive bladder cancer. Therefore, every patient should be assessed integrally, taking into account all the different dimensions involved. In an era of an aging population, the urologist must be prepared to handle with this situation.

[Porphyria cutanea tarda, hemosiderosis and hepatocellular carcinoma: report of one case]. / Hepatocarcinoma, porfiria y hemosiderosis. Una asociación no reportada en nuestro país: Caso clínico.

Porphyria cutanea tarda (PCT) is a hereditary or acquired disease. It can be unleashed by iron overload, alcohol, estrogens and other conditions. In these patients, hepatic involvement can be associated to cirrhosis, iron overload or C and B viral infections, that are predisposing factors for hepatocellular carcinoma. We report a 69-year-old man with PTC, hemosiderosis and hepatocarcinoma. The tumor was diagnosed during a routine ultrasound examination for early detection of malignant lesions. The patient was subjected to a right hepatic excision. The pathological examination of the surgical piece confirmed the diagnosis and disclosed free surgical margins. After 18 months of follow up, the patient had a relapse and a liver transplantation was performed.

Hepatocarcinoma, porfiria y hemosiderosis. Una asociación no reportada en nuestro país: caso clínico / Porphyria cutanea tarda, hemosiderosis and hepatocellular carcinoma: report of one case

Porphyria cutanea tarda (PCT) is a hereditary or acquired disease. It can be unleashed by iron overload, alcohol, estrogens and other conditions. In these patients, hepatic involvement can be associated to cirrhosis, iron overload or C and B viral infections, that are predisposing factors for hepatocellular carcinoma. We report a 69-year-old man with PTC, hemosiderosis and hepatocarcinoma. The tumor was diagnosed during a routine ultrasound examination for early detection of malignant lesions. The patient was subjected to a right hepatic excision. The pathological examination of the surgical piece confrmed the diagnosis and disclosed free surgical margins. After 18 months of follow up, the patient had a relapse and a liver transplantation was performed.

Evidence-based sex-related outcomes after radical nephroureterectomy for upper tract urothelial carcinoma: results of large multicenter study.

OBJECTIVES: To assess the sex differences in the clinical and pathologic characteristics of upper tract urothelial carcinoma (UTUC) and to determine the effect on prognosis after radical nephroureterectomy (RNU) in a large multicenter series. METHODS: The records of 1363 patients who had undergone RNU were reviewed from the UTUC Collaboration database. The median follow-up was 47 months (range 0-250). The pathologic slides were re-evaluated by genitourinary pathologists unaware of the original findings from the slides and the clinical outcomes. The endpoints were freedom from tumor recurrence and disease-specific survival. RESULTS: The male-to-female ratio was 2.1:1. The women were older than the men at diagnosis (70 +/- 11 vs 68 +/- 11 years; P < .001). No significant sex-related differences were found in the presence of symptoms at presentation (P = .70), pathologic stage (P = .98), tumor grade (P = .28), tumor architecture (P = .27), presence of lymphovascular invasion (P = .42), presence of concomitant carcinoma in situ (P = .08), or the presence of lymph node metastases (P = .24). Recurrence developed in 379 patients (28%), and 313 patients (23%) died of their disease. Sex was not associated with disease recurrence (P = .07) or disease-specific survival (P = .13). An adjustment for the effects of the pathologic features did not change the lack of association of sex with the clinical outcomes. CONCLUSIONS: To our knowledge, this is the largest series analyzing the effect of sex on the outcomes after RNU. No difference was found in the clinicopathologic features or prognosis between women and men treated with RNU for UTUC. The results of this large, international series show that RNU provides durable local control and disease-specific survival for both men and women with UTUC.

[Use of Sirolimus in five pediatric patients undergoing solid organ transplantation]. / Sirolimus en trasplante de órgano sólido pediátrico: Experiencia en 5 casos.

BACKGROUND: Sirolimus (SRL) is an immunosuppressive drug increasingly used in children undergoing solid organ transplantation. SRL does not cause glucose intolerance, hypertension, nephrotoxicity or neurotoxicity offering significant potential advantages over calceneurin inhibitors (CM). AIM: To report five children treated with SRL. MATERIAL AND METHODS: A retrospective review of four children undergoing orthotopic liver transplantation (OLT) and one undergoing renal transplantation with recurrent acute rejection (RAR), chronic rejection (CR) or toxicity due to CM, treated with SRL between June 2001 and November 2006. RESULTS: As primary immunosuppressive therapy, all patients received 3 drugs: CM (Tacrolimus (FK) or Cyclosporine), mycophenolate mofetil and steroids. Mean age at treatment with SRL was 98 months. Children undergoing OLT had a late introduction of SRL (mean time after OLT: 37 months), and mean follow-up was 24 months. In this group rescue indications of SRL were RAR in one, CR in one, thrombotic thrombocytopenic purpura (TTP) in one, food allergy in one and other CM toxicity in three. Only one did not experience adverse events due to SRL, but no one required discontinuation of SRL. There were remissions of RAR, CR, TTP and food allergy. The patient with RT was switched from FK to SRL at day 18th after RT, but he had severe neutropenia that led to discontinuation of SRL. CONCLUSIONS: SRL may be useful in pediatric solid organ transplant recipients suffering from RAR, CR, TTP, food allergy and CM toxicity. Careful attention should be directed to detect side effects and avoid severe complications.

Sirolimus en trasplante de órgano sólido pediátrico: Experiencia en 5 casos / Use of Sirolimus in five pediatric patients undergoing solid organ transplantation

Sirolimus (SRL) is an immunosuppressive drug increasingly used in children undergoing solid organ transplantation. SRL does not cause glucose intolerance, hypertension, nephrotoxicity or neurotoxicity offering significant potential advantages over calceneurin inhibitors (CM). Aim: To report five children treated with SRL. Material and methods: A retrospective review of four children undergoing orthotopic liver transplantation (OLT) and one undergoing renal transplantation with recurrent acute rejection (RAR), chronic rejection (CR) or toxicity due to CM, treated with SRL between June 2001 and November 2006. Results: As primary immunosuppressive therapy, all patients received 3 drugs: CM (Tacrolimus (FK) or Cyclosporine), mycophenolate mofetil and steroids. Mean age at treatment with SRL was 98 months. Children undergoing OLT had a ¡ate introduction of SRL (mean time after OLT: 37 months), and mean follow-up was 24 months. In this group rescue indications of SRL were RAR in one, CR in one, thrombotic thrombocytopenic purpura (TTP) in one, food allergy in one and other CM toxicity in three. Only one did not experience adverse events due to SRL, but no one required discontinuation of SRL. There were remissions of RAR, CR, TTP and food allergy. The patient with RT was switched from FK to SRL at day 18th after RT, but he had severe neutropenia that led to discontinuation of SRL. Conclusions: SRL may be useful in pediatric solid organ transplant recipients suffering from RAR, CR, TTP, food allergy and CM toxicity. Careful attention should be directed to detect side effects and avoid severe complications.

Colitis microscópica: valor predictivo de la sospecha clínico-endoscópica en nuestro medio / Microscopic colitis: predictive value of clinical/endoscopical approach

Introducción. El estudio y tratamiento de la diarrea crónica es complejo y de múltiples etapas. En pacientes portadores de diarrea crónica acuosa no sanguinolenta, con estudio normal, se debe considerar la posibilidad de una lesión histológica, aún con aspecto macroscópico normal a la colonoscopía: la Colitis Microscópica (CM). Esta entidad clínico-patológica involucra dos conceptos, la colitis linfocítica (CL), que compromete a la mucosa/submucosa de revestimiento del colon con infiltrado de linfocitos CD8 citotóxicos, o bien la colitis colágena (CC) ,que compromete la membrana basal. Ante la sospecha de CM, obtener biopsias secuenciales en colon derecho e izquierdo para su correcto diagnóstico de acuerdo a patrones histológicos. Objetivos. Conocer la frecuencia de esta entidad clínica en pacientes con diarrea crónica acuosa no sanguinolenta, con colonoscopía y biopsias, y evaluar la relación entre la sospecha clínica y la confirmación histológica. Pacientes y métodos. Se incluyen pacientes estudiados por diarrea crónica acuosa no sanguinolenta en el período enero 2003-febrero 2005, que fueron referidos a colonoscopía. Requisito era estudio completo normal de acuerdo a protocolo de diarrea crónica (leucocitos fecales, estudio malabsorción, intolerancia al glúten, función tiroidea, tolerancia a la lactosa, serología VIH, parasitosis, coprocultivo y cultivos especiales, Toxina A de C. difficile, evaluación psiquiátrica, uso de fármacos, etc). En las íleocolonoscopias se efectuaron biopsias secuenciales colon derecho, izquierdo y recto. El estudio histológico se realizó con Hematoxilina y Eosina, rojo congo, Masón y tricrómico para colágeno. Se excluyeron los pacientes con causa conocida de diarrea crónica o hallazgos de lesión a la colonoscopía. Resultados: De 1.145 colonoscopías, cumplen con los criterios de inclusión 16 pacientes, los que son el objetivo del estudio (1,3 por ciento). Corresponden a 8 varones y 8 mujeres, edad promedio de 60,7 años (47-87). En 10 casos las muestras fueron informadas como Colitis leve (62,5 por ciento); un paciente como colitis moderada (6,25 por ciento) y 4 con alteraciones leves e inespecíficas. Sólo 1 paciente (6,25 por ciento) cumplía con los criterios histológicos exigidos para colitis linfocítica. Conclusiones. La frecuencia en esta serie es inferior a lo referido en la literatura, con un solo caso que cumple con los criterios histológicos de 16 pacientes sospechados.

Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence.

Germ cell tumor (GCT) is the most common genitourinary malignancy of men between the ages of 18 and 35 years. Therapy is ultimately successful in over 90% of patients, however significant morbidity and mortality can be associated with adjuvant treatment and relapse. Molecular markers that predict treatment response and/or poor outcome would have immediate clinical benefit since adjuvant treatment could be selectively reserved for patients at higher risk for relapse and those patients most likely to respond to treatment. In order to identify potential prognostic molecular markers, we evaluated 118 GCT for microsatellite instability (MSI), loss of heterozygosity (LOH) and MSH2 immunostaining to identify tumors associated with relapse and/or poor outcome following initial surgical, medical and/or radiation therapy. MSI in 3 or more markers and/or low MSH2 staining were associated with relapse while LOH in the absence of MSI and/or high MSH2 staining were not. Twenty-five percent of GCT exhibited genetic instability in 3 or more microsatellite markers (MSI+ tumors), 15% exhibited LOH in the absence of MSI (LOH only tumors) and 44% exhibited decreased or absent MSH2 immunostaining (low MSH2 staining tumors). Thirty-six patients (30%) relapsed and 27 of these patients (75%) had MSI+ and/or low MSH2 staining tumors. Only one patient (3%) with an LOH only tumor and no patients with high MSH2 staining and LOH only tumors relapsed. Therefore distinct GCT subpopulations identified by detection of MSI, LOH and MMR expression are associated with different clinical outcomes. MMR deficient testicular GCT with increased frequency of MSI had an increased association with tumor recurrence compared to GCT with an intact MMR system and LOH in the absence of MSI.

Mismatch repair gene expression and genetic instability in testicular germ cell tumor.

Human mismatch repair (MMR) genes encode highly conserved interacting proteins that correct replication errors predisposing to hereditary gastrointestinal and genitourinary malignancies. A subset of sporadic genitourinary tumors also exhibits MMR deficiency and can be identified by measuring the frequency of microsatellite instability (MSI) in cancer cell DNA. We investigated expression of the two most commonly mutated MMR genes, MSH2 and MLH1, in sporadic testicular germ cell tumor (GCT) in order to: (1) determine the expression pattern of MSH2 and MLH1 proteins in normal seminiferous tubules and histologically distinct GCT subtypes, (2) correlate MMR gene expression with genetic instability in GCT and (3) develop a panel of molecular markers that can identify genetically distinct subsets of GCT for prognostic assessment. MSH2 and MLH1 had differential staining patterns in normal seminiferous tubules and malignant tissues. MSH2 was expressed in all stages of spermatogenesis up to but excluding mature sperm whereas MLH1 was predominantly expressed in premeiotic germ cells. All histological GCT subtypes showed differential immunostaining for MSH2 and MLH1 however pure seminoma had statistically significant fewer low MSH2 staining tumors than other subtypes (p = 0.046). Twenty-five percent of GCT exhibited increased frequency of MSI (MSI+ tumors) with 73, 70 and 43% of MSI+ tumors exhibiting low MSH2, low MLH1 or low MSH2 and low MLH1 staining respectively. Fifteen percent of testicular GCT exhibited loss of heterozygosity (LOH) but no MSI (LOH only tumors). Only 28, 17 or 6% of LOH only tumors exhibited low MSH2, low MLH1 or low MSH2 and low MLH1 staining respectively.

Microsatellite analysis of synchronous and metachronous tumors: a tool for double primary tumor and metastasis assessment.

Despite well-established histopathological features and the development of immunostaining of human neoplasms, there are a number of cases in which surgical pathologists cannot assure the origin of synchronous and metachronous tumors. In many cases, the classification of these lesions as either two separate primary tumors or as a single primary tumor with a metastasis has significant implications with respect to patient prognosis and recommendations for therapy. To establish the origin of tumors, we assessed tumor cell clonality using PCR-based microsatellite analysis on microdissected archival tissues for loss of heterozygosity (LOH) and microsatellite instability (MSI) in a series of 19 paired synchronous and metachronous tumors from several organs. As a control group, 15 autopsy cases with an unequivocally recognizable primary tumor and associated metastases were also examined. Based on LOH and MSI findings, and using a panel of 4 to 12 (median 7) microsatellite markers, we were able to establish the clonal pattern of microsatellite changes in 17 out of 19 (89%) biopsy cases and thus determine if they were either double primary tumors (41%) or metastases (59%). Of interest, identical or similar pattern of microsatellite abnormalities were detected in 15 primary tumors and corresponding metastasis from autopsies. Our results indicate that microsatellite analysis for LOH and MSI, as an expression of clonality, provides a useful tool to distinguish double primary neoplasms and metastases in synchronous and metachronous tumors.