In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to "likely pathogenic". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.

Radical cystectomy with pelvic lymphadenectomy: pathologic, operative and morbidity outcomes in a Brazilian cohort.

INTRODUCTION AND OBJECTIVE: Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle invasive bladder cancer and the oncologic outcomes following it are directly related to disease pathology and surgical technique. Therefore, we sought to analyze these features in a cohort from a Brazilian tertiary oncologic center and try to identify those who could negatively impact on the disease control. PATIENTS AND METHODS: We identified 128 patients submitted to radical cystectomy, for bladder cancer treatment, from January 2009 to July 2012 in one oncology tertiary referral public center (Mario Penna Institute, Belo Horizonte, Brazil). We retrospectively analyzed the findings obtained from their pathologic report and assessed the complications within 30 days of surgery. RESULTS: We showed similar pathologic and surgical findings compared to other large series from the literature, however our patients presented with a slightly higher rate of pT4 disease. Positive surgical margins were found in 2/128 patients (1.5%). The médium number of lymph nodes dissected were 15. Major complications (Clavien 3 to 5) within 30 days of cystectomy occurred in 33/128 (25.7%) patients. CONCLUSIONS: In the management of invasive bladder cancer, efforts should focus on proper disease diagnosis and staging, and, thereafter, correct treatment based on pathologic findings. Furthermore, extended LND should be performed in all patients with RC indication. A critical analysis of our complications in a future study will help us to identify and modify some of the factors associated with surgical morbidity.

Radical cystectomy with pelvic lymphadenectomy: pathologic, operative and morbidity outcomes in a Brazilian cohort

ABSTRACT Introduction and Objective Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle invasive bladder cancer and the oncologic outcomes following it are directly related to disease pathology and surgical technique. Therefore, we sought to analyze these features in a cohort from a Brazilian tertiary oncologic center and try to identify those who could negatively impact on the disease control. Patients and Methods We identified 128 patients submitted to radical cystectomy, for bladder cancer treatment, from January 2009 to July 2012 in one oncology tertiary referral public center (Mario Penna Institute, Belo Horizonte, Brazil). We retrospectively analyzed the findings obtained from their pathologic report and assessed the complications within 30 days of surgery. Results We showed similar pathologic and surgical findings compared to other large series from the literature, however our patients presented with a slightly higher rate of pT4 disease. Positive surgical margins were found in 2/128 patients (1.5%). The medium number of lymph nodes dissected were 15. Major complications (Clavien 3 to 5) within 30 days of cystectomy occurred in 33/128 (25.7%) patients. Conclusions In the management of invasive bladder cancer, efforts should focus on proper disease diagnosis and staging, and, thereafter, correct treatment based on pathologic findings. Furthermore, extended LND should be performed in all patients with RC indication. A critical analysis of our complications in a future study will help us to identify and modify some of the factors associated with surgical morbidity.

A case of synchronous triple primary cancers of the kidney, colon and prostate

Synchronous cancers are defined as malignant tumors that present either simultaneously or within a six-month period of identification of the original tumor. We report an unusual case of triple primary neoplasia synchronously originating in the prostate, kidney and sigmoid colon in a 63-year-old male. Multiple primary cancers are rare, yet it is believed that the incidence of this is rising and thus making an early diagnosis and administering prompt treatment is important.