Impact of COVID-19 pandemic on prostate cancer outcomes at an uro-oncology referral center

ABSTRACT Introduction To evaluate the possible effects of the coronavirus disease 2019 (COVID-19) pandemic on the oncologic results of patients with prostate cancer regarding clinical staging, presence of adverse pathological outcomes, and perioperative complications. Materials and methods This retrospective study included patients who underwent radical prostatectomy. The time between biopsy and surgery, staging tests, final histopathological evaluation after surgery, lymphadenectomy rate, postoperative complications, and prostatic specific antigen (PSA) levels (initial and 30 days after surgery) were analyzed and compared in a group of patients before and during the pandemic period. Results We included 226 patients: 88 in the pre-pandemic period and 138 during the pandemic period. There was no statistically significant difference in mean age, body mass index, ASA, pathological locally advanced disease, the proportion of patients who underwent lymphadenectomy, and ISUP grade in the biopsy between the groups. Positive surgical margins, prostatic extracapsular extension, and PSA levels at 30 days were also similar between the groups. The mean time between medical consultation and surgery was longer in the pandemic period than in the pre-pandemic (124 vs. 107 days, p<0.001), and the mean time between biopsy and medical consultation (69.5 days vs. 114 days, p<0.001) and between biopsy and surgery (198.5 days vs. 228 days, p=0.013) was shorter during the pandemic. The incidence of severe early and late perioperative complications was similar between the periods. Conclusions There was no delay between diagnosis and treatment at our institution during the COVID-19 pandemic period. No worsening of the prostate cancer features was observed.

Implication of FSHB rs10835638 variant in endometriosis in Brazilian women

ABSTRACT Objective The follicle-stimulating hormone subunit beta gene rs10835638 variant (c.-211G>T) may have detrimental effects on fertility and protective effects against endometriosis. A case-control analysis was performed, aiming to investigate the possible relationship between this variant and the development and/or progression of endometriosis. Methods This study included 326 women with endometriosis and 482 controls without endometriosis, both confirmed by inspection of the pelvic cavity during surgery. Genotyping was performed using a TaqMan real-time polymerase chain reaction assay. Genotype and allele frequencies and genetic models were compared between the groups. Results The genotype and allele frequencies of the rs10835638 variant did not differ between women with and those without endometriosis. Subdividing the endometriosis group into fertile and infertile groups did not result in a significant difference in these frequencies. However, the subgroup with minimal/mild endometriosis had a higher frequency of the GT genotype than the Control Group, regardless of fertility. The T allele was significantly more common in women with minimal/mild endometriosis than in the Control Group in the recessive model. Conclusion The T allele is associated with the development of minimal/mild endometriosis in Brazilian women.

FMR1 alleles in women with idiopathic infertility / Alelos do gene FMR1 em mulheres com infertilidade idiopática

INTRODUCTION: The frequency of the premutation alleles of the FMR1 gene varies from 1:100 to 1:260 Israeli, Canadian, Finnish and American women, but it is unknown in Brazil. Premutation carriers may have reduced reproductive age and are at risk of transmitting the expanded allele to their offspring, and consequently fragile X syndrome. OBJECTIVE: To observe the distribution range of the FMR1 gene alleles in a population of women with idiopathic infertility, without symptoms of premature ovarian insufficiency. METHODS: The presence of premutation in FMR1 was assessed by conventional PCR, agarose, and acrylamide gel and analysis of fragments in capillary electrophoresis. Lymphocyte DNA obtained from 283 women undergoing infertility treatment was analyzed. RESULTS: 169 patients had the normal heterozygous allele (59.7%), 114 had the normal homozygous allele (40.6%) and no patient had the premutation. Premature ovarian insufficiency is seen in 20 to 30% of women with the permutated allele. Thus, the condition can be asymptomatic in a large part of the premutation carriers. Brazil has a diverse population and, therefore, the allele frequencies of many gene variants are unknown. Previous Brazilian studies have shown a low frequency of the premutation allele in different patient cohorts. Corroborating these articles, the results demonstrated that the frequency of the premutation allele is low in the infertile women population studied. CONCLUSION: Tracking the size of the FMR1 gene alleles allows the expansion of knowledge about the frequency of risk alleles associated with genetic diseases in the Brazilian population.

INTRODUÇÃO: A frequência dos alelos pré-mutados do gene FMR1 varia de 1:100 e 1:260 mulheres israelenses, canadenses, finlandesas e americanas, mas é desconhecida no Brasil. Portadoras da pré-mutação podem apresentar redução da idade reprodutiva e possuem risco de transmissão do alelo expandido para a prole, e consequentemente a Síndrome do X frágil. OBJETIVO: Observar a faixa de distribuição dos alelos do gene FMR1 em uma população de mulheres com infertilidade idiopática, sem sintomas de insuficiência ovariana prematura. MÉTODOS: A presença da pré-mutação em FMR1 foi avaliada por PCR convencional, gel de agarose e acrilamida e análise de fragmentos em eletroforese capilar. Analisou-se DNA de linfócitos obtidos de 283 mulheres em tratamento de infertilidade. RESULTADOS: Foi observado que 169 pacientes apresentam o alelo heterozigoto normal (59,7%), 114 apresentam o alelo homozigoto normal (40,6%) e nenhuma paciente apresentou a pré-mutação. A insuficiência ovariana prematura é observada em 20 a 30% das mulheres portadoras do alelo pré-mutado. Assim, a presença de um alelo pré-mutado pode ser assintomática em grande parte dos casos. O Brasil possui uma população diversificada e, portanto, as frequências alélicas de muitas variantes gênicas são desconhecidas. Estudos brasileiros anteriores mostraram uma baixa frequência do alelo pré-mutado em diferentes coortes de pacientes. Corroborando estes autores, os resultados demonstram que frequência do alelo pré-mutado é baixa na população de mulheres inférteis estudada. CONCLUSÃO: O rastreamento do tamanho dos alelos do gene FMR1 permite ampliar o conhecimento sobre a frequência dos alelos de risco para doenças genética na população brasileira.

Analysis of adrenalectomy for the treatment of adrenal diseases performed by the Public Health Service in São Paulo between 2008 and 2019 / Análise da adrenalectomia para tratamento de doenças adrenais realizadas pelo Serviço Público de Saúde de São Paulo entre 2008 e 2019

ABSTRACT Introduction: treating benign (hormonally active or nonfunctional) and malignant adrenal cancer includes adrenalectomy. The expertise of surgeons and surgery performed by high-volume surgeons were associated with fewer complications and lower cost. We aimed to describe and compare the number of surgeries, mortality rate, and length of hospital stay for adrenalectomies performed between 2008 and 2019 in the public health system of São Paulo. Methods: this was an ecological study. The data were collected using the TabNet Platform of the Unified Health System Department of Informatics. Outcomes analyzed included the number of surgeries performed, mortality rate during hospital stay, and length of hospital stay. Public hospitals in Sao Paulo were divided into three subgroups according to the surgical volume of adrenalectomies performed as well as hospitals with and without a residency program in Urology, and the results were compared among them. Results: a total of 943 adrenalectomies were performed in Sao Paulo between 2008 and 2019. Mortality rates during hospital stay according to hospital surgical volume were no reported deaths in low-volume, 0.015% in intermediate-volume, and 0.004% in high-volume hospitals. The average length of the ICU stay was 1.03 days in low-volume, 2.8 in intermediate-volume, and 1.12 in high-volume hospitals (analysis between intermediate and high volume centers with statistical significance, p=0.016). Conclusions: despite no statistically significant differences among the groups analyzed, mortality rates were very low in all groups. ICU stay was shorter in high-volume centers than in intermediate-volume centers.

RESUMO Introdução: o tratamento do câncer de adrenal benigno (hormonalmente ativo ou não funcional) e maligno inclui a adrenalectomia. A experiência dos cirurgiões e a cirurgia realizada por cirurgiões de alto volume foram associadas a menos complicações e menor custo. O objetivo do estudo foi descrever e comparar o número de cirurgias, a taxa de mortalidade e o tempo de internação para adrenalectomias realizadas entre 2008 e 2019 na rede pública de saúde de São Paulo. Métodos: trata-se de um estudo ecológico. Os dados foram coletados da Plataforma TabNet do Departamento de Informática do Sistema Único de Saúde. Os hospitais foram divididos em três subgrupos de acordo com o volume cirúrgico e hospitais com e sem programa de residência médica em Urologia. Os resultados foram comparados entre os grupos. Resultados: no período estudado, 943 adrenalectomias foram realizadas em São Paulo. As taxas de mortalidade durante a internação de acordo com o volume cirúrgico hospitalar foram: não foram relatados óbitos em hospitais de baixo volume; 0,015% em hospitais de volume intermediário e 0,004% em alto volume. O tempo médio de permanência na UTI foi de 1,03 dias nos hospitais de baixo volume; 2,8 nos de médio volume e 1,12 nos de alto volume (análise entre centros de médio e alto volume com significância estatística, p=0,016). Conclusão: as taxas de mortalidade foram muito baixas em todos os grupos. A permanência na UTI foi menor em centros de alto volume do que em centros de volume intermediário.

Benign prostatic hyperplasia surgical treatment trends in the Public Health System in São Paulo, Brazil

ABSTRACT Objective To describe and compare the number of surgeries, mortality rate, length of hospital stay, and costs of transurethral resection of the prostate and open prostatectomy for the treatment of benign prostatic hyperplasia, between 2008 and 2018, in the Public Health System in São Paulo, Brazil. Methods Ecological and retrospective study using data from the informatics department of the Brazilian Public Health System database. Procedure codes were "open prostatectomy" and "transurethral resection of the prostate." The outcomes analyzed were compared between transurethral resection of the prostate and open prostatectomy according to the hospital surgical volume and presence or absence of a residency program. Results A total of 18,874 surgeries were analyzed (77% transurethral resection of the prostate) and overall mortality was not statistically different between procedures. Intermediate and high-volume centers had shorter length of hospital stay than low-volume centers for transurethral resection of the prostate (3.28, 3.02, and 6.58 days, respectively, p=0.01 and p=0.004). Length of hospital stay was also shorter for open prostatectomy in high-volume compared to low-volume centers (4.86 versus 10.76 days, p=0.036). Intrahospital mortality was inversely associated with surgical volume for transurethral resection of the prostate. Centers with residency program had shorter length of hospital stay considering open prostatectomy and less mortality regarding transurethral resection of the prostate. Open prostatectomy was 64% more expensive than transurethral resection of the prostate. Conclusion The findings suggest the importance of investing in specialized centers, which could be potential referral centers for surgical cases.

Radical prostatectomies for treatment of prostate cancer: trends in a ten-year period in public health services in the city of São Paulo, Brazil

ABSTRACT Objective To analyze the characteristics of public health services related to radical prostatectomy, according to hospital volume of surgeries and stratified as academic and non-academic centers. Methods An ecological study was conducted using a database available in TabNet platform of the Unified Health System Department of Informatics. Number of surgeries, length of hospital stay, length of stay in intensive care unit, in-hospital mortality rate, and cost of hospitalization were evaluated. The hospitals were divided into three subgroups according to surgery volume (tercile), and results were compared. The same comparisons were made among academic and non-academic centers. We considered academic centers those providing Urology residency program. Results A total of 11,259 radical prostatectomies were performed in the city of São Paulo between 2008 and 2018. We observed a significant trend of increase in radical prostatectomies for treating prostate cancer over the years (p=0.007). The length of stay in intensive care unit, and number of deaths were not statistically different among centers with diverse surgery volume, nor between academic and non-academic centers. However, length of hospital stay was significantly shorter in academic centers (p=0.043), while cost of hospitalization was significantly higher in high-volume center compared to low- (p<0.001) and intermediate-volume centers (p<0.001). Conclusion Length of hospital stay for radical prostatectomies performed in public services in the city of São Paulo was shorter in academic centers, whereas hospitals with a high volume of surgeries showed greater cost of hospitalization.

Accuracy of 68Ga-PSMA PET-CT and PET-MRI in lymph node staging for localized prostate cancer

ABSTRACT Objective To evaluate the predictive value of positron emission computed tomography or magnetic resonance (PET-CT and PET-MRI) using gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA) in lymph node involvement in prostate cancer. Methods A retrospective study comprising 91 patients diagnosed with prostate cancer between 2016 to 2020, who underwent 68Ga-PSMA PET-CT or PET-MRI for staging before prostatectomy. The patients were divided into Group 1, with 65 patients with satisfactory pathological lymph node analysis, and Group 2, with 91 patients representing the sum of patients with pathological lymph node analysis and those with postoperative prostate-specific antigen within 60 days after surgery. Receiver Operating Characteristic curves were used to assess accuracy of predictive capacity of imaging exams for lymph node involvement. Results Regarding local clinical staging, the groups showed similar results, and 50% were classified as staging T2a. The accuracy of 68Ga-PSMA PET-CT for prostate cancer lymph node staging was 86.5% (95%CI 0.74-0.94; p=0.06), with a sensitivity of 58.3% and specificity of 95%. The accuracy of 68Ga-PSMA PET-MRI was 84.6% (95%CI 0.69-0.94; p=0.09), with a sensitivity of 40% and specificity of 100%. Considering both 68Ga-PSMA PET-CT and PET-MRI, the accuracy was 85.7% (95%CI 0.76-0.92; p=0.015), with sensitivity of 50% and specificity of 97%. Conclusion The imaging tests 68Ga-PSMA PET-CT and PET-MRI were highly accurate to detect preoperative lymph node involvement, and could be useful tools to indicate the need for extended lymph node dissection during radical prostatectomy.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study

ABSTRACT Objective: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. Methods: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. Results: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. Conclusion: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

Genetic analysis of products of conception. Should we abandon classic karyotyping methodology? / Análise genética dos produtos de concepção. Devemos abandonar a metodologia de cariotipagem clássica?

ABSTRACT Objective: To compare the results obtained by the classic and molecular methodology in the analysis of products of conception, the advantages and disadvantages of each method. Methods: Retrospective non-randomized analysis of results obtained from product of conception samples submitted to genetic evaluation, from 2012 to 2017. The evaluations were performed using cytogenetics and/or chromosomal microarray analysis or arrays. Results: Forty samples were analyzed using classic cytogenetics, of which 10% showed no cell growth, 50% had normal results and 40% had abnormalities. Of the 41 cases sent for array analysis it was not possible to obtain results in 7.3%, 39.5% were normal and 60.5% had abnormalities. There was no statistical difference among the results (p=0.89). Most abnormal results were seen till 9 weeks' gestation. The later abnormal miscarriage was seen at 28 weeks' gestation, with karyotype 46,XX,del(15)(q26.2-qter). The results are corroborated by the international literature. Conclusion: Classic cytogenetics and array techniques showed comparable results on the type of alteration observed. Array analysis is preferable to cell culture in delayed abortions, while cytogenetics is more able to show polyploidies. Both have the same growth failure rates when product of conception tissue is not properly collected.

RESUMO Objetivo: Comparar os resultados obtidos pela metodologia clássica e molecular na análise de produtos de concepção, além das vantagens e desvantagens de cada método. Métodos: Análise retrospectiva não randomizada dos resultados obtidos a partir de amostras de produto de concepção submetidas à avaliação genética, de 2012 a 2017. As análises foram realizadas por citogenética clássica e/ou análise cromossômica de microarray ou arrays. Resultados: Quarenta amostras foram analisadas por citogenética, das quais 10% não apresentaram crescimento celular, 50% apresentaram resultados normais, e 40% apresentaram anormalidades. Dos 41 casos encaminhados para análise por array, não foi possível obter resultados em 7,3%, 39,5% eram normais, e 60,5% apresentavam alterações. Não houve diferença estatística entre os resultados (p=0,89). A maioria dos resultados anormais foi observada até a nona semana de gestação. Uma perda fetal mais tardia foi observada na 28ª semana de gestação, com cariótipo 46,XX,del(15)(q26.2-qter). Os números observados corroboraram a literatura mundial. Conclusão: As técnicas de citogenética clássica e análise por array mostraram resultados comparáveis no tipo de alteração observada. O array é preferível à cultura de células em abortos tardios, enquanto a citogenética é mais capaz de mostrar poliploidias. Ambos têm as mesmas taxas de falha de crescimento quando o tecido do produto de concepção não é coletado adequadamente.

Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study / Preservação da fertilidade com progestágeno oral em pacientes com câncer de mama: é uma opção? Estudo-piloto

ABSTRACT Objective To compare the effectiveness of oral progestins and injectable gonadotropin-releasing hormone antagonist medication in cancer fertility preservation in patients with breast cancer. Methods A cross-sectional study with 40 breast cancer patients submitted to cancer fertility preservation, who were divided into two groups according to histochemical analysis of progesterone receptors to define luteinizing hormone block: if positive, use of gonadotropin-releasing hormone antagonist, if negative, use of oral progestins. The mean age, medication days, antral follicle count, number of oocytes in metaphase II and the occurrence of ovarian hyperstimulation syndrome were compared. Results A total of 20 patients both in the group using gonadotropin-releasing hormone antagonist, and in the group with oral progestins, respectively, had a mean age of 33.9 (32-35.8) and 33.8 (32-35.6) years; days of medications of 11 (9.7-12.3) and 12.8 (11.6-13.9), p=0.037; antral follicle count of 9 (7.11-12) and 8.5 (6-11.9), p=0.370; metaphase II oocyte number of 4 (2.1-9.8) and 7.5 (3.1-10), p=0.348; and ovarian hyperstimulation syndrome of 2 (10%) and 5 (25%) cases, p=0.212. Conclusion The use of oral progestins, in spite of requiring longer treatment time, is effective in relation to the protocol with gonadotropin-releasing hormone antagonist, and offers greater comfort at a lower cost in breast cancer patients with negative progesterone receptors, submitted to cancer fertility preservation.

RESUMO Objetivo Comparar a efetividade dos progestágenos orais em relação à medicação injetável antagonista de hormônio liberador de gonadotrofina na preservação da fertilidade oncológica de pacientes com câncer de mama. Métodos Estudo transversal com 40 pacientes com câncer de mama submetidas à preservação da fertilidade oncológica, que foram divididas em dois grupos, conforme análise histoquímica dos receptores de progesterona, para definir o bloqueio de hormônio luteinizante: se positivos, uso de antagonista de hormônio liberador de gonadotrofina; se negativos, uso de progestágenos orais. Comparou-se média de idade, dias de medicações, contagem de folículos antrais, número de oócitos em metáfase II e ocorrência de síndrome do hiperestímulo ovariano. Resultados Vinte pacientes, tanto no grupo com uso de antagonista de hormônio liberador de gonadotrofina, quanto no grupo com progestágenos orais, respectivamente, apresentaram média de idade de 33,9 (32-35,8) e 33,8 (32-35,6) anos; 11 (9,7-12,3) e 12,8 (11,6-13,9) de dias de medicações com p=0,037; contagem de folículos antrais de 9 (7,11-12) e 8,5 (6-11,9), com p=0,370; número de oócitos metáfase II de 4 (2,1-9,8) e 7,5 (3,1-10), com p=0,348, e síndrome do hiperestímulo ovariano de 2 casos (10%) e 5 casos (25%), com p=0,212. Conclusão O uso de progestágenos orais, apesar de necessitar de maior tempo de tratamento, é efetivo em relação ao protocolo com antagonista de hormônio liberador de gonadotrofina e oferece maior conforto com menor custo em pacientes com câncer de mama com receptores de progesterona negativos, submetidas à preservação da fertilidade oncológica.

The effect of testosterone replacement on intramedullary, inguinal and visceral fat in ovariectomized rats / Efeito da reposição de testosterona na gordura intramedular, inguinal e visceral em ratas ovariectomizadas

Abstract Objective The present article aims to evaluate the impact of testosterone treatment on the expansion of visceral, subcutaneous and intramedullary adipose tissue of ovariectomized rats and the visceral and subcutaneous fat expression of peroxisome proliferator-activated receptors (PPARs) gamma. Methods In total 48 female Wistar rats were castrated and randomly divided into 6 treatment groups: group E2 was submitted to estradiol 5 μg/day; group T, to testosterone 5 μg/day; group E2+ T, to estradiol 5 μg/day + testosterone 5 μg/day; group TT, to testosterone 30 μg/day; group E2+ TT, to estradiol 5 μg/day+ testosterone 30 μg/day; and placebo was administered to group P. After 5 weeks, the rats were euthanized, the inguinal and visceral adipose tissues were harvested, weighted, and had their PPAR gamma expression evaluated by reverse transcription quantitative polymerase chain reaction (RTqPCR). The right femurs were harvested and histologically prepared to performthe number count of the intramedullary adipocytes. Results The expansion of visceral fat tissue was much higher in the TT group when compared with other treated groups (p < 0.001). The TT group also showed a higher expansion of inguinal fat (p < 0.01), and groups E2 +T and E2+ TT presented lower growth compared to the P group (p < 0.01). The number of femur intramedullary adipocytes only showed significant differences between groups TT and E2 + TT (p < 0.05). The expression of PPAR gamma showed no differences among the groups. Conclusion The use of testosterone in high doses leads to an important expansion in both visceral and inguinal adipose tissues. Association with estradiol exerts an expansion-repressive effect on the visceral and inguinal adipose tissues.

Resumo Objetivo Este artigo tem como objetivo avaliar o impacto do tratamento com testosterona na expansão dos tecidos adiposos visceral, subcutâneo e intramedular de ratas ovariectomizadas e a expressão de receptores ativados por proliferadores de peroxissoma (RAPPs) gama nas gorduras visceral e subcutânea. Métodos No total, 48 ratas Wistar foram castradas e divididas aleatoriamente em 6 grupos de tratamento: o grupo E2 recebeu estradiol 5 μg/dia; o grupo T, testosterona 5 μg/dia; o grupo E2 + T, estradiol 5 μg/dia + testosterona 5 μg/dia; o grupo TT, testosterona 30 μg/dia; o grupo E2 + TT, estradiol 5 μg/dia + testosterona 30 μg/dia; e o grupo P recebeu placebo. Após 5 semanas, as ratas foram submetidas a eutanásia, o tecido adiposo inguinal e visceral foi coletado, pesado, e se avaliou a expressão dos RAPP gama por reação em cadeia da polimerase via transcriptase reversa quantitativa (RCP-TRq). Os ossos do fêmur direito foram colhidos e processados histologicamente para contagem de números de adipócitos intramedulares. Resultados A expansão do tecido adiposo visceral foi muito maior no grupo TT quando comparado a outros grupos tratados (p < 0,001). O grupo TT também apresentou maior expansão da gordura inguinal (p < 0,01), e os grupos E2 +T e E2 + TT apresentaram menor crescimento em relação ao grupo P (p < 0,01). O número de adipócitos intramedulares no fêmur mostrou apenas diferenças significativas entre os grupos TT e E2 + TT (p < 0,05). A expressão de RAPP gama não mostrou diferenças entre os grupos. Conclusão O uso de testosterona emaltas doses leva a uma importante expansão nos tecidos adiposos visceral e inguinal. A associação com o estradiol exerce um efeito repressivo de expansão nos tecidos adiposos visceral e inguinal.

New WHO odontogenic tumor classification: impact on prevalence in a population

Abstract Objectives: This study approaches the history of reclassifications and redefinitions around the odontogenic keratocyst (OK), as proposed by the World Health Organization (WHO), and aims to understand the impact of those changes on the prevalence and epidemiology of odontogenic tumors (OTs). Methodology: Cases of OTs diagnosed in an Oral Pathology service between January 1996 and December 2016 were reviewed. Demographic data of patients such as age, gender and site of lesions were retrieved from their respective records. Results: Within the studied period, 7,805 microscopic reports were elaborated and 200 (2.56%) of these were diagnosed as OTs. Out of these 200, between 1996 and 2005, prior to the 2005 WHO classification, there were 41 (20.5%) OTs cases, being odontoma the most frequent (23; 56.09%), followed by ameloblastoma (8; 19.51%) and myxoma (03; 7.31%). Between 2006 and 2016, after the previous 2005 WHO classification there were 159 (79.5%) OTs, being odontogenic keratocystic tumor (KCOT) the most frequent (68; 42.76%), followed by odontoma (39; 24.52%) and ameloblastoma (21; 13.20%). Conclusions: As of today, the most recent WHO classification to be followed brings KCOT back to the cyst category, which will impact on the prevalence and epidemiology of OTs; thus, this study was able to identify a considerable increase (287.80%) in the prevalence of OTs when the 2005 WHO classification was utilized. Despite being an important academic exercise, classifying odontogenic lesions and determining whether to place the odontogenic keratocyst in a cyst or tumor category is crucial to establish the correct diagnosis and treatment to follow, whether by oral medicine or oral surgery specialist, or by the general practitioner.

Reproductive alternatives for patients with dystrophic epidermolysis bullosa / Opções reprodutivas para pacientes com epidermólise bolhosa distrófica

ABSTRACT Epidermolysis bullosa describes a group of skin conditions caused by mutations in genes encoding proteins related to dermal-epidermal adhesion. In the United States, 50 cases of epidermolysis bullosa per 1 million live births are estimated, 92% of which classified as simplex, 5% dystrophic, 1% junctional and 2% non-classified. Dystrophic epidermolysis bullosa is associated with autosomal, dominant and recessive inheritance. Epidermolysis bullosa causes severe psychological, economic and social impacts, and there is currently no curative therapy, only symptom control. Embryonic selection is available for epidermolysis bullosa patients in order to prevent perpetuation of the condition in their offspring.

RESUMO O termo "epidermólise bolhosa" descreve um grupo de afecções cutâneas causadas por mutações em genes que codificam proteínas relacionadas à aderência dermoepidérmica. Nos Estados Unidos, estima-se a ocorrência de 50 casos de epidermólise bolhosa por 1 milhão de nascidos vivos, sendo 92% deles da forma simples, 5% da forma distrófica, 1% da forma juncional e 2% não classificados. A epidermólise bolhosa do tipo distrófica foi associada a padrões autossômicos, dominante e recessivo. A epidermólise bolhosa causa sérios impactos psicológicos, econômicos e sociais, e não há tratamento curativo atualmente − apenas controle dos sintomas. A seleção embrionária é disponível para portadores de epidermólise bolhosa, a fim de evitar a perpetuação da condição em seus descendentes.

Evolução do Programa de Triagem Neonatal em hospital de referência no Ceará: 11 anos de observação / Evolution of Neonatal Screening Program in a reference hospital in Ceará: 11 years of observation

INTRODUÇÃO: O Programa Nacional de Triagem Neonatal (PNTN) tem como objetivo a detecção de doenças congênitas em fase pré-sintomática. Esse teste é realizado em todos os Estados do Brasil, porém com diferentes realidades quanto à incidência das doenças diagnosticadas devido à diversa origem étnica observada nacionalmente. O registro dos casos permite a elaboração de políticas públicas de prevenção e tratamento. OBJETIVO: Analisar a eficácia de um programa de triagem neonatal em um hospital de referência do Estado do Ceará ao longo dos últimos 11 anos. MÉTODOS: Estudo transversal realizado a partir de prontuários de crianças nascidas entre os anos de 2002 e 2012 no referido hospital. RESULTADOS: Dos 5.000 testes realizados, 2.893 prontuários completos foram incluídos no estudo (57,8%). Desses casos, dois apresentaram fenilcetonúria e três, hipotireoidismo. Uma vez que quase a metade dos resultados dos testes não estava devidamente registrada no prontuário clínico dos pacientes, tornou-se inviável o cálculo de frequência da doença na população. CONCLUSÃO: A falha no registro dos dados do teste de triagem pode fazer com que falte aos gestores municipais e hospitalares o conhecimento sobre o número de casos da região, acarretando, consequentemente, falha nas estratégias de tratamento. Verifica-se a necessidade de organização de um banco de dados informatizado e de capacitação dos profissionais de saúde para o preenchimento dos dados do teste, para viabilizar o diagnóstico e o tratamento precoces, bem como permitir o delineamento do cenário real sobre a incidência das doenças diagnosticadas pelo "Teste do Pezinho" no Brasil.

INTRODUCTION: The National Neonatal Screening Program (PNTN) aims to detect pre-symptomatic congenital diseases. This test is performed across all States of Brazil with different realities concerning the incidence of diagnosed diseases due to the diverse national ethnicity observed. Accurate knowledge about diseases' incidence allows the elaboration of public policies for prevention and treatment. OBJECTIVE: To evaluate the efficacy of neonatal screening program from a reference hospital in the State of Ceará for 11 years. METHODS: Cross-sectional study based on medical records of children born between 2002 and 2012 in the referred hospital. RESULTS: Of the 5,000 exams performed, 2,893 complete medical records (57.8%) were included in the sample. Of these, two cases of phenylketonuria and three cases of hypothyroidism were observed. As almost half of the results had not been properly registered in patients' clinical records, the calculation of diseases frequency in this population was not reliable. CONCLUSION: Failure to register data of the screening test may impair knowledge acquisition of municipal and hospital managers when it comes to the number of cases in each region, consequently leading to a failure in treatment strategies. It is necessary to organize a digital database and to train health professionals to fill test result forms in order to enable early diagnosis and treatment, as well as to properly delineate a credible scenario of diseases' prevalence in Brazil.

Vascular endothelial growth factor gene variations as a risk predictor in disc degeneration / Variação do gene fator de crescimento endotelial vascular como preditor de risco para a degeneração discal

ABSTRACT Objective: To evaluate the frequency of polymorphisms in the vascular endothelial growth factor (VEGF) gene, as well as to identify a potential risk haplotype among the polymorphic regions in this gene in patients with disc degeneration and in the Control Group. Methods: This study analyzed a total of 217 individuals distributed into the Disc Degeneration and Control Groups. Peripheral blood was collected from all patients to detect VEGF gene polymorphisms identified by qPCR (rs699947, rs1570360, rs2010963, rs833061 and rs3025039). All patients presenting disc degeneration had the confirmation by nuclear magnetic resonance test and were rated according to disc degeneration level. Results: All polymorphisms were in Hardy- Weinberg equilibrium (p>0.05) in the studied population. The genotypic frequency for Disc Degeneration and Control Group were rs699947 p = 0.475, rs1570360 p = 0.862, rs2010963 p = 0.823, rs833061 p=0.596 and rs3025039 p=0.230. In haplotype analysis, the compositions CAGGC (p=0.094) and CCGGC (p=0.054) stood out. Conclusion: The correlation between VEGF gene polymorphism as a risk predictor for disc degeneration was negative in the studied population. However, the VEGF gene has a large polymorphic region, and it is activated by various catabolic and metabolic factors in the disc degeneration process, which has not been fully elucidated.

RESUMO Objetivo: Avaliar a frequência dos polimorfismos no gene fator de crescimento endotelial vascular (VEGF), bem como identificar potencial haplótipo de risco entre as regiões polimórficas deste gene em pacientes com degeneração discal e em Grupo Controle. Métodos: Este estudo analisou 217 pacientes distribuídos nos Grupos Degeneração Discal e Grupo Controle. Foi coletado sangue periférico de todos os pacientes para a detecção dos polimorfismos do gene VEGF identificados por qPCR (rs699947, rs1570360, rs2010963, rs833061 e rs3025039). Todos os pacientes que apresentaram degeneração discal tiveram a confirmação por meio de ressonância magnética nuclear e avaliação do nível de degeneração do disco. Resultados: Todos os polimorfismos foram encontrados no equilíbrio de Hardy-Weinberg (p>0,05) na população estudada. A frequência genotípica para o Grupo Degeneração de Disco e do Grupo Controle foi rs699947 p=0,475, rs1570360 p=0,862, rs2010963 p=0,823, rs833061 p=0,596 e rs3025039 p=0,230. Para a análise do haplótipo, destacaram-se as composições CAGGC (p=0,094) e CCGGC (p=0,054). Conclusão: A correlação entre os polimorfismos do gene VEGF como preditor de risco para degeneração discal foi negativa na população estudada. No entanto, o VEGF possui grande região polimórfica, ativada por vários fatores catabólicos e metabólicos no processo de degeneração discal, que não está completamente elucidado.

Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy / Diagnóstico genético pré-implantacional associado à distrofia muscular de Duchenne

ABSTRACT Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy.

RESUMO A distrofia muscular de Duchenne é a doença muscular mais comum observadas em crianças do sexo masculino. Atualmente, não há terapia eficaz disponível para distrofia muscular de Duchenne, portanto, é essencial o diagnóstico pré-natal e o aconselhamento genético para reduzir o nascimento desses meninos. Relatamos um caso de diagnóstico genético pré-implantação associado à distrofia muscular de Duchenne. O casal E.P.R., 38 anos, heterozigota, sintomática para uma mutação de deleção dos éxons 2 a 47 no gene DMD e G.T.S., 39 anos, buscaram aconselhamento genético sobre o processo de diagnóstico genético pré-implantação. O casal relatou que tiveram um filho de 6 anos que morreu devido a complicações da distrofia muscular de Duchenne. Os pacientes realizaram quatro ciclos de injeção intracitoplásmica de espermatozoides (ICSI) e oito biópsias de embriões foram analisadas por reação em cadeia da polimerase (PCR) para análise de mutação específica, seguida hibridação genômica comparativa baseada em microarranjos ( array CGH) para a pesquisa de aneuploidias. O diagnóstico genético pré-implantação revelou que dois embriões haviam herdado a mutação materna no gene DMD , um embrião tinha uma alteração cromossômica e cinco embriões eram normais. Um blastocisto foi transferido e resultou em gravidez bem sucedida. Os outros embriões permanecem vitrificados. Concluímos que a análise de embriões utilizando técnicas associadas de PCR e CGH array mostrou-se segura para a seleção de embriões em casos de doenças ligadas ao X, como a distrofia muscular de Duchenne.

How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency / Como os marcadores polimórficos contribuem para as doenças genéticas em diferentes populações? O estudo da inibina A para insuficiência ovariana prematura

ABSTRACT Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

RESUMO Objetivo Verificar a incidência da mutação G679A no éxon 2 do gene da inibina alfa (INHA) em mulheres com amenorreia secundária e diagnóstico de insuficiência ovariana prematura e em controles. Métodos Uma amostra de 5mL de sangue periférico foi coletada de todos os participantes do estudo em tubo de EDTA e utilizada para a extração de DNA. Para o grupo de pacientes, foram coletados também 5mL de sangue em tubo contendo heparina para realização de cariótipo, e 5mL um tubo seco para dosagem de hormônio folículo-estimulante. As amostras de pacientes e controles foram inicialmente submetidas à análise da variante G679A no éxon 2 do gene INHA pela técnica de PCR-RFLP. As amostras de pacientes com insuficiência ovariana prematura após PCR-RFLP foram submetidas ao sequenciamento de Sanger dos éxons codantes 2 e 3. O sequenciamento foi realizado em equipamento ABI 3500 GeneticAnalyzer, e os resultados foram avaliados pelos programas SeqA and Variant Reporter. Resultados Foram avaliadas amostras de 70 mulheres com insuficiência ovariana prematura e de 97 controles férteis. A variante G769A foi encontrada em apenas uma paciente do Grupo Insuficiência Ovariana Prematura e em nenhum controle, e parece ser rara nas pacientes brasileiras com insuficiência ovariana prematura. Este polimorfismo foi previamente associado à insuficiência ovariana prematura em diversas populações no mundo. Conclusão O estudo evidenciou que há heterogeneidade genética quanto ao INHA em diferentes populações e entre as causas de insuficiência ovariana prematura.

Progesterone level on the day of hCG administration in relation to the pregnancy rates of patients undergoing assisted reproduction techniques / Valor da progesterona no dia do hCG em relação à taxa de gravidez de pacientes submetidas às técnicas de reprodução assistida

ABSTRACT Objective To evaluate the predictive capacity for pregnancy of the progesterone level on the day of administering human chorionic gonadotropin, in women submitted to assisted reproductive techniques. Methods An observational study with 914 women submitted to assisted reproductive techniques from August 2014 to June 2016. Results Total pregnancy rate was 34.58%; in that, the pregnancy rate in women <35 years, between 35 and 38, and >38 years was, respectively, 42.3%, 38.7% and 16.1% (p<0.001). For embryo transfer in the same cycle, and progesterone of 1.3ng/dL, sensitivity was 4.78%, specificity, 84.18%, accuracy, 56.72%, positive likelihood ratio of 0.3019, and negative likelihood ratio of 1.1312, with receiver operating characteristic curve of 0.46 (95%CI: 0.42-0.49). Conclusion The progesterone level on the day of administering human chorionic gonadotropin of 1.3ng/dL differs from that empirically adopted at the study site (1.7ng/dL), and has a better predictive capacity for pregnancy in the patients studied. However, the low sensitivity of this examination raises questions about its real importance.

RESUMO Objetivo Avaliar a capacidade preditiva para gravidez do valor de progesterona no dia da administração da gonadotrofina coriônica humana em mulheres submetidas às técnicas de reprodução assistida. Métodos Estudo observacional com 914 mulheres submetidas a reprodução assistida de agosto de 2014 até junho de 2016. Resultados Engravidaram 34,58% das mulheres, sendo a taxa de gravidez naquelas >35 anos, entre 35 e 38 anos e >38 anos, respectivamente, de 42,3%, 38,7% e 16,1% (p<0,001). Para o valor de progesterona até 1,3ng/dL visando à transferência embrionária no mesmo ciclo, encontraram-se sensibilidade de 4,78%, especificidade de 84,18%, acurácia de 56,72%, razão de verossimilhança positiva de 0,3019 e razão de verossimilhança negativa de 1,1312, com área sob a curva característica de operação do receptor de 0,46 (IC95%: 0,42-0,49). Conclusão O valor de progesterona no dia da administração de gonadotrofina coriônica humana até 1,3ng/dL difere daquele empiricamente adotado no local do estudo (1,7ng/dL) e apresenta melhor capacidade preditiva para gravidez nas pacientes estudadas. No entanto, a baixa sensibilidade deste exame abre questionamentos sobre sua real importância.

Association of the protein tyrosine phosphatase non-receptor 22 polymorphism (PTPN22) with endometriosis: a meta-analysis / Associação do polimorfismo da proteína tirosina fosfatase não receptora 22 (PTPN22) com endometriose: uma metanálise

ABSTRACT Objective To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis. Methods A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk (odds ratio and 95% confidence intervals) of endometriosis associations with the C1858T polymorphism. Results A significant increased risk in all genetic models of the variant T allele with endometriosis (odds ratio: 3.14-5.55; p<0.00001-0.002) was found. The analysis without the study whose controls deviated from the Hardy-Weinberg equilibrium exacerbated these effects in the homozygous and recessive models (odds ratio: 7.19-9.45; p<0.00001-0.0002). In the Italian subgroup, a significant risk association was found in the homozygous and recessive models (odds ratio: 8.72-11.12; p=0.002). Conclusion The associations observed between PTPN22 (C1858T) and the risk of endometriosis suggest this polymorphism might be a useful susceptibility marker for this disease.

RESUMO Objetivo Avaliar o polimorfismo PTPN22 C1858T e o risco de endometriose. Métodos Foi realizada uma metanálise de 10 estudos caso-controle publicados (a partir de quatro artigos), com uma amostra total de 971 casos e 1.181 controles. O risco da associação da endometriose com o polimorfismo C1858T foi estimado em razão de chance e intervalo de confiança de 95%. Resultados Observou-se um aumento de risco significativo em todos os modelos genéticos com o alelo variante T e a endometriose (razão de chance: 3,14-5,55; p<0,00001-0,002). A análise sem incluir o estudo, em que os controles não estavam em equilíbrio de Hardy-Weinberg, mostrou aumento significativo nos modelos homozigotos e recessivos (razão de chance: 7,19-9,45; p<0,00001-0,0002). No subgrupo italiano, uma associação significativa foi encontrada considerando os modelos homozigoto e recessivo (razão de chance: 8,72-11,12; p=0,002). Conclusão As associações observadas entre PTPN22 (C1858T) e o risco de endometriose sugerem que este polimorfismo pode ser um marcador de suscetibilidade para a endometriose.

Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study / Incidência de microdeleções do cromossomo Y em filhos de pais que passaram por reversão de vasectomia ou fertilização in vitro com aspiração do epidídimo: um estudo caso-controle

ABSTRACT Objective To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). Methods A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. Results The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. Conclusion We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions.

RESUMO Objetivo Avaliar a incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados submetidos à reversão de vasectomia ou fertilização in vitro com recuperação de espermatozoides por aspiração do epidídimo (aspiração percutânea de espermatozoides do epidídimo). Métodos Estudo caso-controle que compreende crianças do sexo masculino de casais em que o homem havia sido previamente vasectomizado e escolheu reversão da vasectomia (n=31) ou fertilização in vitro com recuperação espermática por aspiração percutânea de espermatozoides do epidídimo (n=30) para obtenção de novos filhos, e um Grupo Controle de crianças do sexo masculino de homens férteis com vasectomia programada (n=60). A pesquisa de microdeleções do cromossomo Y foi realizada por reação em cadeia da polimerase nos pais e filhos, avaliando 20 regiões do cromossomo. Resultados O resultado não revelou microdeleções do cromossomo Y em qualquer indivíduo estudado. A incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados que sofreram reversão de vasectomia ou fertilização in vitro com espermatozoides recuperados pela aspiração percutânea de espermatozoides do epidídimo não diferiu entre os grupos, e não houve nenhuma diferença entre indivíduos controle nascidos de gestações naturais ou incidência populacional em homens férteis. Conclusão Não foi encontrada nenhuma associação considerando microdeleções da região do fator de azoospermia no cromossomo Y e reprodução assistida. Não houve correlação entre microdeleções do cromossomo Y e vasectomia, o que sugere que as técnicas de reprodução assistida não aumentam a incidência de microdeleções do cromossomo Y.