Molecular landscape and functional characterization of centrosome amplification in ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.

Litiasis urinaria en el donante cadavérico: respuestas a la penumbra urológica desde un análisis bibliométrico / Urolithiasis in the brain-dead donor: responses to the urological penumbra from a bibliometric analysis

La literatura disponible sobre las implicaciones de la urolitiasis en la donación y trasplante renal (TxR) con injertos de donante cadavérico es limitada; la información disponible tiene especial énfasis en el donante vivo. Objetivo: Exponer la producción bibliográfica y las implicaciones clínicas de la urolitiasis en el proceso de donación y TxR incluyendo la perspectiva con injertos de donante cadavérico. Métodos: Análisis bibliométrico ejecutado mediante una búsqueda sistemática de la literatura en Medline, Embase, SciELO, Cochrane Central, Google Académico y Web of Science utilizando combinaciones de los términos MesH "urolithiasis", "kidney calculi", "ureteral calculi", "tissue and organ procurement", "brain death", "living donors" y "kidney transplantation". Se limitó la búsqueda a artículos publicados entre los años 2000-2022. Resultados: Se analizaron 23 artículos. El 95.6% de ellos fueron publicados en inglés, el 26% se publicaron en revistas del cuartil 1, solo un tercio de ellos tienen relación con el donante cadavérico. La urolitiasis en el injerto renal no es una contraindicación absoluta para el trasplante, se puede ofrecer manejo quirúrgico activo ex vivo durante la cirugía de banco para cálculos > 4 mm y el trasplante con observación para injertos renales con cálculos < 4 mm. Conclusiones: La producción científica en términos de litiasis urinaria y donación/TxR es limitada. El hallazgo incidental de urolitiasis en el donante vivo o cadavérico de riñón no es una contraindic

The clinical literature about the implications of urolithiasis in the process of kidney donation/transplantation (KTx) from deceased donors is scarce. Objectives: To expose the current state of bibliographic production and the clinical implications of urolithiasis in the process of kidney donation/transplantation focus on cadaveric donor grafts. Methods: We performed a bibliometric analysis based on a systematic review of the literature in Medline, Embase, SciELO, Cochrane Central, Google Scholar and Web of Science using combinations (OR, AND) of MesH terms: "urolithiasis", "kidney calculi", "ureteral calculi", "tissue and organ procurement", "brain death", "living donors" and "kidney transplantation". The search was limited to primary articles, systematic reviews or meta-analyses performed in humans published between 2000-2022. Results: Twenty-three articles were included for analysis; 95.6% of the bibliographic production was published in English, 26% were published into quartile 1 journals. One third of the references were focused on cadaveric donors. The information obtained concludes that presence of urolithiasis in the kidney graft is not an absolute contraindication for KTx and proposes the ex vivo surgical management of urolithiasis during the bench surgery for stones > 4 mm and to proceed with KTx and then follow-up for kidney grafts with stones < 4 mm. Conclusions: The scientific production related to urolithiasis and kidney donation/transplantation is limited. The literature available concludes that incidental kidney stones in kidney grafts should not be considered an absolute contraindication for KTx. Ex vivo surgical management of urolithiasis is a feasible and safe prior to KTx

Successful laparoscopic approach to intraperitoneal bladder injury caused during gynecologic surgery. a case report

ABSTRACT Introduction: Urinary tract injuries are common in the context of pelvic surgery; however, there is little information in the medical literature on the management of these injuries using a laparoscopic approach. The following is the clinical case of a patient with intraperitoneal bladder injury secondary to gynecological pelvic surgery that was successfully treated using a laparoscopic approach. Moreover, a management algorithm is proposed based on the scientific data available. Case report. A 39-year-old female patient was admitted to the hospital with generalized abdominal pain and anuria three days after undergoing a left laparoscopic salpingectomy and resection of a migrated intrauterine device. Laboratory tests showed microhematuria, serum creatinine of 4.35mg/dL, and urea nitrogen of 35.2mg/dL. Computed tomography cystography showed a solution of continuity on the left posterolateral intraperitoneal bladder. The patient underwent successful laparoscopic treatment for the bladder injury, and two weeks later, retrograde cystography confirmed its adequate resolution. Conclusions. Based on the benefits of the laparoscopic approach and after extrapolating the outcomes of the laparoscopic management of bladder trauma, it can be concluded that the laparoscopic approach to surgical injuries of the bladder is a feasible therapeutic option.

RESUMEN Introducción. Las lesiones del tracto urinario son frecuentes en el contexto de la cirugía pélvica; sin embargo, existe poca información sobre su manejo por vía laparoscópica. Se presenta el caso de una paciente con una lesión vesical intraperitoneal secundaria a cirugía pélvica ginecológica, quien recibió manejo por abordaje laparoscópico, y se propone un algoritmo de tratamiento. Presentación del caso. Mujer de 39 años quién, luego de tres días de practicársele una salpingectomía izquierda y una resección del dispositivo intrauterino migrado mediante abordaje laparoscópico, consultó al servicio de urgencias por dolor abdominal generalizado y oligoanuria. Los exámenes de laboratorio evidenciaron microhematuria, creatinina sérica de 4.35mg/dl y nitrógeno ureico de 35,2mg/dl. En cistografía por tomografía computarizada (cisto-TC) se observó una solución de continuidad de la pared vesical posterolateral izquierda intraperitoneal. A la paciente se le trató la lesión vesical de forma exitosa por vía laparoscópica, y dos semanas después, también mediante cistografía retrógrada se confirmó una adecuada resolución de la misma. Conclusión. Dados los resultados satisfactorios del manejo laparoscópico en la paciente y los beneficios de esta técnica, se puede concluir que el abordaje laparoscópico de las lesiones quirúrgicas de la vejiga es una opción terapéutica factible.

Metanephric adenoma: differential diagnosis of upper tract urothelial carcinoma. a case report

ABSTRACT Introduction: Metanephric adenoma is a rare benign kidney tumor. Patients with these tumors are usually asymptomatic, although polycythemia occurs in up 12% of cases. These masses are often described on diagnostic imaging as solid, single, well-defined, oval-shaped, unilateral lesions, located primarily in the renal medulla and without extrarenal involvement. These neoplasms are difficult to differentiate from malignant neoplasms of the upper urinary tract, so the definitive diagnosis is achieved by histopathology. Currently, the treatment of choice is radical nephrectomy. Case presentation: A 51-year-old woman from Bogotá (Colombia) was referred to the urology service of a tertiary care hospital due to bilateral lumbar pain of non-specific characteristics. At the time of consultation, the patient was asymptomatic. Renal and urinary tract ultrasound showed hydronephrosis and right renal mass. Computed tomography urography was requested, which revealed a lesion in the right renal pelvis with parenchymal invasion highly suggestive of high-risk upper urinary tract urothelial carcinoma, as well as adenopathies in the para-aortic lymph nodes. The patient underwent a radical nephroureterectomy with bladder cuff, which allowed establishing a final diagnosis of metanephric adenoma according to the histopathological study. Conclusions: Metanephric adenoma is a rare tumor that is difficult to diagnose through imaging, so it is necessary to explore additional tools to establish an accurate pre-surgical diagnosis that allows preserving the affected renal unit. Also, given their non-specificity, these tumors should be included in the differential diagnosis of lesions suggestive of upper tract urothelial carcinoma.

RESUMEN Introducción. El adenoma metanéfrico es un tumor renal benigno poco frecuente. Los pacientes con estos tumores no suelen presentar síntomas, aunque en el 12% de los casos se presenta policitemia. En las imágenes diagnósticas, los adenomas metanéfricos se observan como lesiones sólidas, únicas y bien definidas que, por lo general, comprometen la medula renal pero no ocasionan compromiso extrarenal. Estas neoplasias son difíciles de diferenciar imagenológicamente de neoplasias malignas del tracto urinario superior, por lo que el diagnóstico definitivo se logra mediante estudios histopatológicos. El tratamiento de elección es la nefrectomía radical. Presentación del caso. Mujer de 51 años procedente de Bogotá (Colombia), quien fue remitida al servicio de urología de un hospital de tercer nivel de atención por dolor lumbar bilateral de características inespecíficas. Al momento de la consulta la paciente se encontraba asintomática. Mediante ecografía renal y de vías urinarias se evidenció hidronefrosis y una masa renal derecha. Se ordenó urografía por tomografía axial computarizada que documentó una lesión en la pelvis renal derecha con invasión al parénquima renal altamente sugestiva de carcinoma urotelial de tracto urinario superior de alto riesgo, así como adenopatías en los ganglios paraaórticos, por lo que se le realizó una nefroureterectomía radical derecha con cuña vesical que permitió establecer un diagnóstico final de adenoma metanéfrico según el estudio histopatoló-gico. La paciente tuvo una evolución satisfactoria. Conclusiones. El adenoma metanéfrico es un tumor poco frecuente y de difícil diagnóstico imagenológico, por lo que se requiere explorar herramientas adicionales para establecer un diagnóstico certero prequirúrgico que permita preservar la unidad renal afectada. Asimismo, dada su inespecificidad, estos tumores deben incluirse dentro de los diagnósticos diferenciales de las lesiones sugestivas de carcinoma urotelial de tracto urinario superior.

Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial.

BACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. METHODS: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. FINDINGS: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. INTERPRETATION: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. FUNDING: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis.

New Trends and Evidence for the Management of Renal Angiomyolipoma: A Comprehensive Narrative Review of the Literature.

Treatment of renal angiomyolipoma (AML) seeks to reduce related complications and preserve kidney function. The purpose of this article was to perform an updated literature review on the diagnosis, therapeutic options, and criteria for invasive intervention in patients with renal AML. Computerized tomography is the standard diagnostic method for renal AML, while definitive diagnosis is made by histopathology. The management of choice in most cases is active surveillance (AS), with a clinical and imaging follow-up protocol. In high-risk cases, therapeutic management should be considered, with alternatives such as selective arterial embolization (SAE), nephron-sparing surgery (NSS), and mTOR inhibitors in selected patients. Renal AML in women of childbearing age, those with growth >0.25 cm/year, intralesional aneurysms >5 mm, and clinically significant symptoms may qualify for active treatment. Despite the limitations derived from the available evidence, it is possible to consider SAE, NSS, and the use of mTOR inhibitors as management alternatives for selected patients.

Strategies to Mitigate the Impact of COVID 19 Pandemic on Organ Donation and Kidney Transplantation in Latin America.

PURPOSE OF REVIEW: COVID-19 pandemics have severely affected Latin America. It has resulted in SARS-CoV-2-associated clinical adverse outcomes, but also in social and economic deterioration. Consequently, it generated a significant negative impact on organ donation and kidney transplantation (KTx) activity in our region, leading to a negative impact on these patients' survival and quality of life. For this reason, this article aimed to describe applicable logistics, organizational and clinical strategies to mitigate the effect of the COVID-19 pandemic on kidney donation and transplantation in our region. RECENT FINDINGS: Absenteeism to hemodialysis sessions in patients with end-stage renal disease has been described in up to 54% in Latin America. Not surprisingly, there was a reduction in organ donation and transplants between 21 and 59%. Also, there is a higher incidence of COVID-19 positive tests in the waiting list population than KTx recipients (9.9%). However, there was a higher mortality rate in KTx recipients than the waiting list population (32%). Additionally, 59% of living donor kidney transplant programs suspended the evaluation of new donors due to the COVID-19 pandemic. Throughout this manuscript, we summarize some practical tips to resume organ donation and KTx during pandemics in Latin America, such as selecting healthy donors and recipients, universal SARS-CoV-2 screening, implementing COVID-19 accessible pathways, and telehealth as a standard, and postpone all non-urgent visits.

Caracterización de la infección urinaria y resistencia antimicrobiana en receptores de trasplante renal de un centro colombiano / Characterization of Urinary Tract Infection and Antimicrobial Resistance in Kidney Transplant Recipients from a Colombian Tertiary Center

La infección del tracto urinario (ITU) es una de las principales complicaciones postrasplante renal, los datos a nivel nacional en ese grupo poblacional son limitados. Objetivos caracterizar la microbiología de las ITU presentadas en receptores de trasplante renal (TxR) en un centro colombiano durante el periodo 2017­2019, los factores relacionados con la resistencia antimicrobiana y el impacto de la ITU en la función del injerto renal. Métodos estudio de corte transversal ejecutado mediante el análisis de la base de datos de ingresos hospitalarios por urgencias de pacientes receptores de TxR con sospecha clínica de ITU en una institución de cuarto nivel en Bogotá, Colombia. El análisis de datos se ejecutó en STATA 13.0. Resultados La ITU causó 12,69% de visitas a urgencias en pacientes trasplantados. Los microorganismos aislados fueron: Escherichia coli 52,22%, Klebsiella pneumoniae 16,67%, Pseudomonas aeruginosa 4,44%, Salmonella spp 4,44%, Proteus mirabilis 3,33%, Serratia marcescens 2,22%, Klebsiella oxytoca 2,22%, Citrobacter koseri 1,11%, Enterobacter cloacae 1,11%, otros 2,22%; El urocultivo fue negativo en 10% de los casos. El 28,39% (n:23) de gérmenes aislados fue multisensible mientras que el 71,60% (n:58) expresó algún tipo de patrón de resistencia distribuido así: 68,96% productor de betalactamasa de espectro extendido (BLEE), 15,52% productor de carbapenemasas, 12,06% productor de betalactamasa tipo IRT, 3,45% fue catalogado como multirresistente. 17,78% de los pacientes presentó criterios de urosepsis, no se registró ningún caso de mortalidad asociada a la ITU. La creatinina sérica tuvo un incremento promedio de 0,46 mg/dl durante el episodio de ITU (p: <0,0001) y el antecedente de diabetes mellitus se relacionó con la ITU causada por gérmenes resistentes (p: 0,008). Conclusiones La ITU es una causa frecuente de atención en urgencias para pacientes receptores de TxR; la Escherichia coli es el microorganismo causal más frecuente y cerca del 70% de los gérmenes aislados presentó algún patrón de resistencia antimicrobiana.

Urinary tract infection (UTI) is one of the most common complications after kidney transplantation (KTx). This study aims to characterize the microbiology of UTIs presented in KTx recipients in a Colombian tertiary center during the period 2017­2019, factors related with antimicrobial resistance and the impact of UTI on kidney graft function. Methods A cross-sectional retrospective single center study were made through the institutional database analysis of hospital admissions to the emergency room of KTx recipients with clinical suspicion of UTI. Data analysis was run on STATA 13.0. Results UTI caused 12.69% of visits to the emergency room in transplant patients during the study period. The isolated microorganisms were Escherichia coli 52.22%, Klebsiella pneumoniae 16.67%, Pseudomonas aeruginosa 4.44%, Salmonella spp 4.44%, Proteus mirabilis 3.33%, Serratia marcescens 2.22%, Klebsiella oxytoca 2.22%, Citrobacter koseroi 1.11%, others 2.22%; Urine culture was negative in 10% of cases. 28.39% (n: 23) of isolated germs were multisensitive while 71.60% (n: 58) expressed some type of resistance pattern distributed as follows: 68.96% extended spectrum beta-lactamase (ESBL) producers, 15.52% carbapenemases producers, 12.06% IRT-type beta-lactamase producers, 3.45% was classified as multi-resistant. 17.78% of patients presented criteria for urosepsis, there was no cases of mortality due to UTI. Serum creatinine had an average increase of 0.46 mg/dl during the UTI episode (p: <0.0001) and a history of diabetes mellitus was related with UTI caused by resistant germs (p: 0.008). Conclusion UTI is a frequent cause of emergency care for KTx recipients. E. coli is the most common causative microorganism and about 70% of isolated germs showed some pattern of antimicrobial resistance.

A phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial.

BACKGROUND: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. METHODS: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. RESULTS: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. CONCLUSIONS: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.

[Kidney transplantation into the urological training in Colombia.] / Trasplante renal en el entrenamiento urológico colombiano.

Kidney transplantation (KTx) is the best therapeutic modality for end stage renal disease. Currently in Colombia there are approximately 2800 patients waiting for KTx. Historically, urologists have beenin close contact with KTx, however in Colombia the interaction between urology and KT is scarce. OBJECTIVES: To determine the perceptions and KTx training level into colombian urology residents. MATERIAL AND METHODS: We conducted a retrospective and descriptive study through 14 items survey applied to colombian urology residents. Data are summarizedas means and Pearson Chi2 test was used to evaluate differences between qualitative variables.RESULTS: The study included 76 participants. More than half of the programs of urology residency in Colombia includes KTx training into their academic programs, 36.84% of participants have received formal training (lectures, rounds, clinical rotation, seminars) on KTx, 28.95% have participated into KTx procedure, 97.37% considered the KTx as a urological field, KTx is the urological area with least academic interest for the residents, 76.32% consider their training in KTx as insufficient. The main barrier identified to increase training in KTx during urology residency is the non-availability of a formal rotation. CONCLUSIONS: KTx is not an area of primary interest for the colombian urology residents. Although most residents identify the KTx as an area related to urology and that exposure to some phases of the KTx is acceptable, 76% of residents consider their transplant training as insufficient. The main barriers identified for the urology resident's approach to KTx are modifiable.

El trasplante renal (TxR) es el mejor tratamiento para la enfermedad renal crónica terminal. En Colombia hay más de 2800 personas en lista de espera para este proceso. Históricamente el urólogo ha estado vinculado con el TxR, sin embargo, en Colombia son pocos los urólogos que ejercen su práctica clínico-quirúrgica en este ámbito. OBJETIVOS: Determinar las percepciones y el nivel de entrenamiento que reciben los médicos residentes d e urología en Colombia con relación al TxR. MATERIALES Y MÉTODOS: Se realizó un estudio descriptivo de corte transversal. Se practicó una encuesta con 14 ítems a los médicos residentes de urología de Colombia para valorar sus percepciones sobre el entrenamiento recibido en TxR. El análisis de datos incluye estadística descriptiva y las diferencias entre variables cualitativas se analizaron con la prueba de Pearson Chi2. RESULTADOS: Se incluyeron 76 participantes. 59,21% manifestó que su programa incluye formación en TxR, 36,84% ha recibido entrenamiento formal en TxR, 28,95% ha participado en un TxR, 97,37% considera el TxR como un área concerniente a la urología, el TxR fue el área de menor interés en la formación y perspectiva laboral entre los participantes, 76,32% considera que su formación en TxR es insuficiente, la principal barrera identificada para aumentar el entrenamiento en TxR durante la residencia es la no disponibilidad de una rotación formal. CONCLUSIONES: El TxR no es un área de interés principal para el residente de urología colombiano; a pesar de que la mayoría de los residentes identifica al TxR cómo un área urológica y que la exposición a algunas fases del trasplante es aceptable, el 76% de residentes considera insuficiente su formación en TxR. Las principales barreras identificadas para la aproximación der esidente de urología al TxR son modificables.

Trasplante renal en el entrenamiento urológico colombiano / Kidney transplant in Colombian urological training

El trasplante renal (TxR) es el mejor tratamiento para la enfermedad renal crónica terminal. EnColombia hay más de 2800 personas en lista de espera para este proceso. Históricamente el urólogo haestado vinculado con el TxR, sin embargo, en Colombia son pocos los urólogos que ejercen su práctica clínico-quirúrgica en este ámbito.OBJETIVOS: Determinar las percepciones y el nivel de entrenamiento que reciben los médicos residentes de urología en Colombia con relación al TxR. MATERIALES Y MÉTODOS: Se realizó un estudio descriptivo de corte transversal. Se practicó una encuesta con 14 ítems a los médicos residentes de urología de Colombia para valorar sus percepciones sobre el entrenamiento recibido en TxR. El análisis de datos incluye estadística descriptiva y las diferencias entre variables cualitativas se analizaron con la prueba de Pearson Chi2. RESULTADOS: Se incluyeron 76 participantes. 59,21% manifestó que su programa incluye formación en TxR, 36,84% ha recibido entrenamiento formal en TxR, 28,95% ha participado en un TxR, 97,37% considera el TxR como un área concerniente a la urología, el TxR fue el área de menor interés en la formación y perspectiva laboral entre los participantes, 76,32% considera que su formación en TxR es insuficiente, la principal barrera identificada para aumentar el entrenamiento en TxR durante la residencia es la no disponibilidad de una rotación formal. CONCLUSIONES: El TxR no es un área de interés principal para el residente de urología colombiano; a pesar de que la mayoría de los residentes identifica al TxR cómo un área urológica y que la exposición a algunas fases del trasplante es aceptable, el 76% de residentes considera insuficiente su formación en TxR. Las principales barreras identificadas para la aproximación del residente de urología al TxR son modificables.(AU)

Kidney transplantation (KTx) is the best therapeutic modality for end stage renal disease. Currently in Colombia there are approximately 2800 patients waiting for KTx. Historically, urologists have been in close contact with KTx, however in Colombia the interaction between urology and KT is scarce.OBJECTIVES: To determine the perceptions and KTx training level into colombian urology residents. MATERIAL AND METHODS: We conducted a retrospective and descriptive study through 14 items surveyapplied to colombian urology residents. Data are summarized as means and Pearson Chi2 test was used toevaluate differences between qualitative variables. RESULTS: The study included 76 participants. More than half of the programs of urology residency in Colombia includes KTx training into their academic programs, 36.84% of participants have received formal training (lectures, rounds, clinical rotation, seminars) on KTx, 28.95% have participated into KTx procedure, 97.37% considered the KTx as a urological field, KTx is the urological area with least academic interest for the residents, 76.32% consider their training in KTx as insufficient. The main barrier identified to increase training in KTx during urology residency is the non-availability of a formal rotation. CONCLUSIONS: KTx is not an area of primary interest for the colombian urology residents. Although most residents identify the KTx as an area related to urology and that exposure to some phases of the KTx is acceptable, 76% of residents consider their transplant training as insufficient. The main barriers identified for the urology resident’s approach to KTx are modifiable.(AU)

Is it Possible to Use Kidneys with Small Renal Masses for Transplant? A New Strategy to Face Kidney Graft Shortage for Transplantation in Ibero-America / ¿Es posible utilizar riñones con masas renales pequeñas para trasplante? Una nueva estrategia para afrontar la escasez de injertos renales para trasplante en Iberoamérica

Kidney transplantation (KTx) is the best treatment alternative for patients with end-stage renal disease (ESRD)[1]; however, there are many barriers to obtaining a KTx worldwide. One of the main barriers is the scarcity of kidney grafts from cadaveric donors.[2] Furthermore, in many Latin American countries, organ donation rates (from brain death donors) have stabilized during the last decade and do not meet the social needs for KTx.[3] Specifically, in Colombia, organ donation rates have not grown despite some recent legislative initiatives (implementation of opt-out organ donation system)[4] and there are still no protocols and regulations for donation after cardiac death. Currently, it is estimated that approximately 3000 people on the waiting list for KTx.

El trasplante renal (TxR) es la mejor alternativa de tratamiento para los pacientes con enfermedad renal terminal (ERT)[1]; sin embargo, existen muchas barreras para obtener un TxR en todo el mundo. Una de las principales barreras es la escasez de injertos renales de donantes cadavéricos[2]; además, en muchos países latinoamericanos, las tasas de donación de órganos (de donantes con muerte encefálica) se han estabilizado durante la última década y no satisfacen las necesidades sociales de KTx[3]. Específicamente, en Colombia, las tasas de donación de órganos no han crecido a pesar de algunas iniciativas legislativas recientes (implementación del sistema de donación opt-out)[4] y aún no existen protocolos y regulaciones para la donación después de muerte cardiaca. Actualmente, se estima que hay aproximadamente 3000 personas en lista de espera para KTx.

Using a repositioning splint to determine reproducibility in the color registers of a dental spectrophotometer.

OBJECTIVES: The purpose of this study was to assess if the use of intraoral positioning guides could increase the reproducibility of color measurements with a dental spectrophotometer. METHODS: Twenty-three subjects were selected, and positioning guides for the maxillary arch of each participant were fabricated with clear 4 mm thermo-sheets. One orifice was made in the center of the clinical crown of the upper-right central incisor and another in the canine, with an external 6 mm diameter trephine. Color measurements were performed with a Vita EasyShade Compact IV dental spectrophotometer by the same operator in the same conditions. Forty measurements were taken per patient, 20 for each tooth, 10 with a positioning guide, and 10 without one. Before each measurement, the spectrophotometer was calibrated following the manufacturer's instructions. RESULTS: Using the Wilcoxon test to evaluate nonparametric variables, there are statistically significant differences (P < .05) between the use or not of positioner for color recording with spectrophotometer. Greater repeatability of the measurements is obtained using repositioning split. CONCLUSIONS: Within the limitations of this study, the use of positioning guides provides greater reproducibility in spectrophotometer measurements for all parameters of tooth 11 and for some parameters of tooth 13. CLINICAL SIGNIFICANCE: The use of a positioning guide for color measurement with a dental spectrophotometer allows a greater reproducibility of the measurements to be obtained. Achieving repeatable measurements is essential for studying the same area of the tooth, for example, in bleaching treatments and in color checks for prosthetic treatments.

Donación y trasplante de órganos en medio de la pandemia COVID-19: Consecuencias y retos para un país emergente / Organ Donation and Transplantation in the Midst of the COVID-19 Pandemic: Consequences and Challenges for an Emerging Country

La pandemia del SARS-CoV 2 es uno de los eventos en salud pública más relevantes de los últimos años, sus efectos se han traducido en millones de casos de contagios, en más de 430.000 fallecimientos y en un aumento en la necesidad de camas de cuidados intensivos alrededor del mundo. En ese contexto, se ha presentado una reducción significativa de la actividad de donación y trasplantes en varios países, y Colombia no ha sido ajena a ese fenómeno. El presente artículo, pretende dar al lector una perspectiva del estado actual de la donación y trasplantes en el mundo y en Colombia, así como plantear algunos retos que genera la pandemia del SARS-CoV 2 para la ejecución segura del proceso de donación y trasplantes en países con recursos humanos, financieros y de infraestructura limitados.

The SARS-CoV 2 outbreak is one of the most important events of public health around the world; this disease has affected millions of people, has killed over 430.000 people and has increased the needed of intensive care unit beds around the world. During the pandemic the world has seen a decline in the organ donation and transplantation activities, Colombian transplant model has been affected too. This paper wants to show the current situation of organ donation and transplantation during SARS-CoV 2 pandemic and explore some dilemmas around organ donation and transplantation for emerging countries.

Phase 2 study of anastrozole in recurrent estrogen (ER)/progesterone (PR) positive endometrial cancer: The PARAGON trial - ANZGOG 0903.

BACKGROUND: The clinical benefit rate with aromatase inhibitors and the impact of treatment on quality of life (QOL) in endometrial cancer is unclear. We report the results of a phase 2 trial of anastrozole in endometrial cancer. METHODS: Investigator initiated single-arm, open label trial of anastrozole, 1 mg/d in patients with ER and/or PR positive hormonal therapy naive metastatic endometrial cancer. Patients were treated until progressive disease (PD) or unacceptable toxicity. The primary end-point was clinical benefit (response + stable disease) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life (QOL) and toxicity. RESULTS: Clinical benefit rate in 82 evaluable patients at 3 months was 44% (95% CI: 34-55%) with a best response by RECIST of partial response in 6 pts. (7%; 95% CI: 3-15%). The median PFS was 3.2 months (95% CI: 2.8-5.4). Median duration of clinical benefit was 5.6 months (95% CI: 3.0-13.7). Treatment was well tolerated. Patients who had clinical benefit at 3 months reported clinically significant improvements in several QOL domains compared to those with PD; this was evident by 2 months including improvements in: emotional functioning (39 vs 6%: p = 0.002), cognitive functioning (45 vs 19%: p = 0.021), fatigue (47 vs 19%: p = 0.015) and global health status (42 vs 9%: p = 0.003). CONCLUSION: Although the objective response rate to anastrozole was relatively low, clinical benefit was observed in 44% of patients with ER/PR positive metastatic endometrial cancer and associated with an improvement in QOL.

Gynecological Cancers Translational, Research Implementation, and Harmonization: Gynecologic Cancer InterGroup Consensus and Still Open Questions.

In the era of personalized medicine, the introduction of translational studies in clinical trials has substantially increased their costs, but provides the possibility of improving the productivity of trials with a better selection of recruited patients. With the overall goal of creating a roadmap to improve translational design for future gynecological cancer trials and of defining translational goals, a main discussion was held during a brainstorming day of the Gynecologic Cancer InterGroup (GCIG) Translational Research Committee and overall conclusions are here reported. A particular emphasis was dedicated to the new frontier of the immunoprofiling of gynecological cancers. The discussion pointed out that to maximize patients' benefit, translational studies should be integral to clinical trial design with standardization and optimization of procedures including a harmonization program of Standard Operating Procedures. Pathology-reviewed sample collection should be mandatory and ensured by dedicated funding. Biomarker validation and development should be made public and transparent to ensure rapid progresses with positive outcomes for patients. Guidelines/templates for patients' informed consent are needed. Importantly for the public, recognized goals are to increase the involvement of advocates and to improve the reporting of translational data in a forum accessible to patients.

Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN).

The discovery, structure-activity relationships, and optimization of a novel class of fatty acid synthase (FASN) inhibitors is reported. High throughput screening identified a series of substituted piperazines with structural features that enable interactions with many of the potency-driving regions of the FASN KR domain binding site. Derived from this series was FT113, a compound with potent biochemical and cellular activity, which translated into excellent activity in in vivo models.

Increased risk of HPV-associated genital cancers in men and women as a consequence of pre-invasive disease.

To assess the excess risk of HPV-associated cancer (HPVaC) in two at-risk groups-women with a previous diagnosis of high grade cervical intraepithelial neoplasia (CIN3) and both men and women treated for non-cervical pre-invasive anogenital disease. All CIN3 cases diagnosed in 1989-2015 in Scotland were extracted from the Scottish cancer registry (SMR06). All cases of pre-invasive penile, anal, vulval, and vaginal disease diagnosed in 1990-2015 were identified within the NHS pathology databases in the two largest NHS health boards in Scotland. Both were linked to SMR06 to extract subsequent incidence of HPVaC following the diagnosis of CIN3 or pre-invasive disease. Standardised incidence ratios were calculated for the risk of acquiring HPVaC for the two at-risk groups compared to the general Scottish population. Among 69,714 females in Scotland diagnosed with CIN3 (890,360.9 person-years), 179 developed non-cervical HPVaC. CIN3 cases were at 3.2-fold (95% CI: 2.7 to 3.7) increased risk of developing non-cervical HPVaC, compared to the general female population. Among 1,235 patients diagnosed with non-cervical pre-invasive disease (9,667.4 person-years), 47 developed HPVaC. Individuals with non-cervical pre-invasive disease had a substantially increased risk of developing HPVaC - 15.5-fold (95% CI: 11.1 to 21.1) increased risk for females and 28-fold (11.3 to 57.7) increased risk for males. We report a significant additional risk of HPV-associated cancer in those have been diagnosed with pre-invasive HPV-associated lesions including but not confined to the cervix. Uncovering the natural history of pre-invasive disease has potential for determining screening, prevention and treatment.

Clinical Correlation Between Computerized Tomography Findings and Pathologic Diagnosis in Patients Surgically Treated for Complex Renal Cysts in a Colombian Tertiary Center.

Introduction Recent data have reexamined the historical rates of malignancy observed in Bosniak IIF and III cystic lesions, and this has led to an endorsement of the use of active surveillance as the standard of care for Bosniak III renal cysts by affirming that overtreatment rates for this subgroup are close to 50%. In light of this, the present study describes the correlation between imaging studies and pathologic diagnosis in patients surgically treated for complex renal cysts in Colombia. Materials and methods This is a retrospective, descriptive, and observational study. We analyzed the medical histories of patients who had been surgically treated for complex renal cysts between 2010 and 2018 in the urology department of a tertiary center in Bogota, Colombia. The exclusion criteria were incomplete clinical histories and absent diagnostic images or their official interpretation. Results Out of the 235 urological procedures performed, nine were excluded. And 6.19% (n = 14) were cases of surgically treated complex renal cysts; 38.46% were compatible with Bosniak IIF, 46.15% were Bosniak III, and 15.38% were Bosniak IV. The percentage of renal cancer as revealed by the histopathological study was 60, 66.7 and 100 for renal cysts Bosniak IIF, III, and IV, respectively; 77.7% of these confirmed oncological cases had received a diagnosis of clear cell renal carcinoma. Conclusions In our study, the percentage of malignancy in patients with renal cysts Bosniak IIF and III was found to be greater compared to the findings in the recent medical literature. We believe that the management offered to the population with complex renal cysts in Colombia should be tailored to the individual risk characteristics of each patient.

Tamización poblacional para la detección temprana del cáncer de próstata: ¿Qué hemos aprendido en los últimos 10 años? / Population Screening for Early Detection of Prostate Cancer: ¿What have we Learned in the Last Decade?

Introducción Desde el inicio de la aplicación del cribado para cáncer de próstata basado en el antígeno prostático específico (PSA) hace aproximadamente dos décadas, la controversia sobre los beneficios y desventajas de su uso rutinario ha sido constante. La literatura médica cuenta con múltiples estudios que en ocasiones han revelado resultados contradictorios sobre los posibles beneficios de la tamización con PSA; la tasa de detección de cáncer de próstata indolente detectado parece ser alta y los estudios no demuestran de forma constante los beneficios en términos de reducción de la mortalidad cáncer específica o general. El propósito del presente artículo, es definir a la luz de la literatura médica reciente, la utilidad a nivel poblacional del cribado para cáncer de próstata basado en el antígeno prostático específico. Materiales y métodos Se realizó una revisión en los buscadores Pubmed, Embase y Lilacs utilizando los términos MesH "Prostatic neoplasms," "early detection of cancer," "mass screening," "prostate specific antigen," "digital rectal examination," "Outcome assesment (Health care)." Se filtró la búsqueda hacia estudios ejecutados en humanos, y/o metanálisis y revisiones sistemáticas publicados durante los últimos 10 años. Los abstracts fueron valorados por el grupo de autores e incluidos para análisis según su aporte al objetivo principal del estudio. Algunas referencias adicionales fueron añadidas dada su importancia clínica e histórica. Resultados Se identificaron 23 referencias con la estrategia de búsqueda, se excluyeron del análisis 9 referencias por no aportar datos relevantes para el presente artículo. Se incluyeron para revisión un total de 14 artículos. Discusión La tamización para cáncer de próstata con base en el antígeno específico de próstata sérico es una estrategia que permite aumentar la tasa de detección temprana de cáncer, sin embargo, se asocia a una importante tasa de detección de cáncer de próstata indolente y de sobretratamiento. Los resultados de la literatura evaluada son contradictorios con respecto al efecto que tiene la tamización sobre la mortalidad específica por cáncer, algunos estudios han revelado una disminución de ese ítem en los pacientes sometidos a tamización para cáncer de próstata. Los datos también son contundentes en demostrar que las estrategias de tamización no han impactado la supervivencia general en los grupos estudiados. Se esperan resultados de estudios que incluyan el armamento de estrategias disponibles para estimar el riesgo de cáncer de próstata (imágenes y/o nuevos marcadores tumorales) con el fin de mejorar la relación riesgo/beneficio de la estrategia de cribado para cáncer de próstata. Conclusiones La tamización para cáncer de próstata debe ser una estrategia para la detección temprana del cáncer que se usa de forma consensuada con cada paciente y que debe adaptarse al riesgo individual; el paciente a quien se le aplica el cribado debe entender los potenciales riesgos y beneficios de esta estrategia ya que los datos disponibles no permiten demostrar con alto nivel de evidencia, un beneficio clínico traducido en términos de reducción en la mortalidad del cáncer específica o general.

Introduction In the last decade, the prostate-specific antigen based screening for prostate cancer have evoque a lot of controversies on the basis of his risk ­ benefit ratio; there are controversial data about the impact of this strategy in the male cancer specific and general mortality. The aim of this article is to show the most recent findings and to define the utility of the population screening for early detection of prostate cancer. Material and Methods A literature review was performed in PubMed, Embase and Lilacs using the MeSH terms: "Prostatic neoplasms," "early detection of cancer," "mass screening," "prostate specific antigen," "digital rectal examination" and "Outcome assesment (Health care)" which was limited to scientific articles published in the past 10 years. The abstracts were evaluated and excluded if they were not related to primary aim of this article. Some references were included given their clinical relevance. Results 23 articles were retrieved, and after reviewing the abstracts, 9 articles were excluded as they were not related to our primary aim. The analysis was performed in 14 articles. Discussion The prostate-specific antigen based population screening has been associated with an early diagnosis of prostate cancer even, in a non significative clinical stage, and consequent overtreatment. The literature which was evaluated have controvesial outcomes on the cancer-specific mortality, however none of the articles evaluated shown a significant impact in male general mortality. In the overcoming years, we expect the results of some investigations which includes additional tools for the screening of prostate cancer (multiparametric prostate resonance imaging, new tumoral markers), to improve the risk-benefit of this strategy. Conclusions The population prostate cancer screening should be made in well-informed patients and shared based decision process. The urologist and patient should to know the potential benefits and risks of this strategy, because there is not high grade level of evidence which supports a significant effect of this strategy in male general and cancer-specific mortality.