Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients.

Increased genetic risk for melanoma can occur in the context of germline pathogenic variants in high-penetrance genes, such as and , risk variants in low- to moderate-penetrance genes ( and ), and possibly due to variants in emerging genes, such as , and . We aimed to identify germline variants in high- and low- to moderate-penetrance melanoma risk genes in Brazilian patients with clinical criteria for familial melanoma syndrome. We selected patients with three or more melanomas or melanoma patients from families with three tumors (melanoma and pancreatic cancer) in first- or second-degree relatives.

Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families.

Genetic predisposition accounts for nearly 10% of all melanoma cases and has been associated with a dozen moderate- to high-penetrance genes, including CDKN2A, CDK4, POT1 and BAP1. However, in most melanoma-prone families, the genetic etiology of cancer predisposition remains undetermined. The goal of this study was to identify rare genomic variants associated with cutaneous melanoma susceptibility in melanoma-prone families.

Informed consent and a risk-based approach to oncologic surgery in a cancer center during the COVID-19 pandemic.

Background: Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC).

Early postoperative outcomes among patients with delayed surgeries after preoperative positive test for SARS-CoV-2: A case-control study from a single institution.

Background: There are limited data on surgical complications for patients that have delayed surgery after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to analyze the surgical outcomes of patients submitted to surgery after recovery from SARS-CoV-2 infection.

Methods: Asymptomatic patients that had surgery delayed after preoperative reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 were matched in a 1:2 ratio for age, type of surgery and American Society of Anesthesiologists to patients with negative RT-PCR for SARS-CoV-2.

BAP1 tumor predisposition syndrome case report: pathological and clinical aspects of BAP1-inactivated melanocytic tumors (BIMTs), including dermoscopy and confocal microscopy.

Background: BRCA1 associated-protein 1 (BAP1) tumor predisposition syndrome is associated with an increased risk for malignant mesotheliomas, uveal and cutaneous melanomas, renal cell carcinomas, and singular cutaneous lesions. The latter are referred to as BAP1-inactivated melanocytic tumors (BIMTs). When multiple BIMTs manifest, they are considered potential markers of germline BAP1 mutations.

Hereditary melanoma: a five-year study of Brazilian patients in a cancer referral center - phenotypic characteristics of probands and pathological features of primary tumors.

Background: Approximately five to 10% of all melanomas occur in families with hereditary predisposition and the main high-risk melanoma susceptibility gene is the CDKN2A.

Objectives: To describe, after a five-years study, the clinical data of patients (probands) from familial melanoma kindreds, and the pathological characteristics of their melanoma.

Methods: The inclusion criteria were melanoma patients with a family history of melanoma or pancreatic cancer (first- or second-degree relatives) or patients with multiple primary melanomas (MPM).

Agreement between Perometry and Sequential Arm Circumference Measurements in Objective Determination of Arm Volume.

Background:  Limb circumference measurements (CM) and perometry are the preferred methods for objectively measuring arm volume in lymphedema surgery research. Understanding the measurement bias involved in these measuring systems is important to properly interpret and compare studies and their results.

Methods:  Arm volumes from 91 patients were measured using sequential girths and the truncated cone formula (CM) and with the use of an automated perometer (perometry).

Reflectance confocal microscopy features of BRAF V600E mutated thin melanomas detected by immunohistochemistry.

The classification of melanoma into four histological subtypes has been questioned regarding its clinical validity in providing relevant information for treatment for metastatic tumors. Specific genetic alterations are associated with particular clinical and histopathological features, suggesting that these could be helpful in refining existing melanoma classification schemes. We analyzed BRAF V600E mutated melanomas to explore the Reflectance confocal microscopy (RCM) utility as a screening aid in the evaluation of the most appropriate patients for genetic testing.

Role of rare germline copy number variation in melanoma-prone patients.

Aim: This work evaluates a possible causative role for germline copy number variants (CNVs) in melanoma predisposition.

Patients & Methods: A total of 41 melanoma-prone Brazilian patients were investigated for CNVs using 850K single nucleotide polymorphism arrays.

Results: Ten rare CNVs were identified in nine patients, comprising 54 known genes, mostly related to cancer.

LINE-1 hypomethylation and mutational status in cutaneous melanomas.

Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation.

Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group.

Aims: The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis.

Materials And Methods: This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression.

DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients.

In melanoma development, oncogenic process is mediated by genetic and epigenetic mutations, and few studies have so far explored the role of DNA methylation either as predisposition factor or biomarker. We tested patient samples for germline CDKN2A methylation status and found no evidence of inactivation by promoter hypermethylation. We have also investigated the association of clinical characteristics of samples with the DNA methylation pattern of twelve genes relevant for melanomagenesis.

LINE-1 hypermethylation in peripheral blood of cutaneous melanoma patients is associated with metastasis.

Aberrant DNA methylation pattern is a well-known epigenetic marker of cancer cells. Recently, aberrant methylation was also reported in the peripheral blood of cancer patients and it could potentially serve as a biomarker for cancer risk. We investigated the methylation pattern of LINE-1 and other repetitive DNA elements in peripheral blood of cutaneous melanoma patients in order to search for an association with clinical characteristics.

Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations.

Melanoma is a highly aggressive cancer, accounting for up to 75% of skin cancer deaths. A small proportion of melanoma cases can be ascribed to the presence of highly penetrant germline mutations, and approximately 40% of hereditary melanoma cases are caused by CDKN2A mutations. The current study sought to investigate whether the presence of germline CDKN2A mutations or the occurrence of cutaneous melanoma would result in constitutive genome-wide DNA methylation changes.

Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma.

Approximately 10 % of all cutaneous melanoma cases occur in a familial context. The major susceptibility gene for familial melanoma is CDKN2A. In Latin America, genetic studies investigating melanoma predisposition are scarce.

Gene network analyses point to the importance of human tissue kallikreins in melanoma progression.

Background: A wide variety of high-throughput microarray platforms have been used to identify molecular targets associated with biological and clinical tumor phenotypes by comparing samples representing distinct pathological states.

Methods: The gene expression profiles of human cutaneous melanomas were determined by cDNA microarray analysis. Next, a robust analysis to determine functional classifications and make predictions based on data-oriented hypotheses was performed.

A review of the epidemiology and treatment of Merkel cell carcinoma.

Merkel cell carcinoma is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Articles in English, French, Italian, Portuguese, and Spanish from the last 20 years were identified in MEDLINE and reviewed.

Vulvar melanoma: report on eleven cases and review of the literature.

Context And Objective: Vulvar melanoma is a rare disease. We describe the experience of a single institution and review the literature.

Design And Setting: Retrospective study at the Department of Gynecology, Hospital do Cancer A.

Twelve-month safety and visual acuity results from a feasibility study of intraocular, epiretinal radiation therapy for the treatment of subfoveal CNV secondary to AMD.

Purpose: The purpose of this study was to evaluate the short-term safety and feasibility of intraocular, epiretinal delivery of beta radiation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration for 12 months. A 3-year follow-up period is planned to assess the long-term safety of the procedure.

Methods: In this nonrandomized, multicenter feasibility study, 34 treatment-naïve patients with predominantly classic, minimally classic, or occult lesions due to subfoveal choroidal neovascularization secondary to age-related macular degeneration received a single treatment with either 15 Gray (Gy) (8 patients) or 24 Gy (26 patients) beta radiation (strontium-90) using a novel intraocular delivery device.

Morphologic and clinical effects of subretinal injection of indocyanine green and infracyanine green in rabbits.

Purpose: The aim of this study was to determine the effects of subretinal injection of indocyanine green (ICG), infracyanine (IfCG), and balanced salt solution (BSS) in rabbits.

Methods: Ten (10) animals were subjected to a subretinal injection of 0.05% ICG (279 mOsm), 0.

Sentinel lymph node biopsy in cutaneous melanoma: analysis of 240 consecutive cases.

Background: The objective of this study was to evaluate practical rules for sentinel lymph node biopsy for melanoma and discuss the indications and outcomes of 240 patients.

Methods: A prospective, nonrandomized analysis was performed on 240 patients in a referral cancer center. The median patient age was 51 years, and the median Breslow thickness was 1.

[Laboratory study of the mycotic infectious eye diseases and factors associated with keratitis].

Purpose: To analyze the frequency and the etiology of mycotic infectious eye diseases diagnosed by culture at the Ocular Diseases Laboratory of the Federal University of São Paulo (LOFT-UNIFESP), São Paulo, SP, Brazil, and the factors associated with fungal keratitis.

Methods: We retrospectively analyzed the 14,391 laboratory requests regarding infectious eye diseases between 1975 and May 2003. For the fungal culture proven examinations we observed the morphologic type of the isolated fungus, the gender and age of the patient, the site of ocular involvement, the year of identification, and the factors associated with keratitis cases, according to the identified etiologic agent.