Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.info:eu-repo/semantics/publishedVersio

Prevenir Complicações: Linfadenectomia Inguinal Modificada Vídeo-Assistida no Estadiamento do Tumor do Pénis

Modified inguinal lymphadenectomy allows for correct staging in most cases of penile cancer without palpable inguinal lymph nodes. Currently, it is possible to reproduce the classic surgical technique by video assisted surgery, with similar oncological results and smaller rate of complications. In this article, we report the case of a patient with penile cancer subjected to a total penectomy (pT3NxMx), where bilateral video assisted modified inguinal lymphadenectomy (VMIL) was conducted, being described surgical technique of right VMIL. In this article surgical steps are described (patient positioning, blunt dissection of deep Scarpa fascia, identification of anatomical boundaries, identification of femoral vessels, identification and isolation of saphenous vein until the fossa ovalis, excision of lymph nodes and closure). The great advantage of VMIL is the reduction of post-operatory complications, particularly the low rate of wound dehiscence and lower limb edema, allowing for a much quicker recovery when compared with the classical approach.A linfadenectomia inguinal modificada permite um estadiamento correto na maioria dos casos de carcinoma do pénis sem gânglios inguinais palpáveis. Atualmente, é possível reproduzir a técnica cirúrgica clássica por via vídeo-assistida, com resultados oncológicos semelhantes e menor taxa de complicações. O artigo reporta um caso de tumor do pénis, sujeito a penectomia total (pT3NxMx), sem gânglios inguinais palpáveis, onde se realizou uma linfadenectomia inguinal modificada vídeo-assistida (LIMVA) bilateral, sendo descrita a técnica cirúrgica da LIMVA direita. Neste artigo são descritos todos os passos da técnica cirúrgica (posicionamento do doente, disseção romba profundamente à faixa de Scarpa, identificação dos limites anatómicos da disseção, identificação dos vasos femorais, identificação da veia safena até a fossa ovalis, excisão dos gânglios e encerramento). A grande vantagem da LIMVA é a diminuição de complicações pós-operatórias, nomeadamente a baixa taxa de deiscência da ferida operatória e de edema dos membros inferiores