Manejo da mucosite oral induzida por quimioterapia e radioterapia com laser de baixa potência: resultados iniciais do Hospital A.C. Camargo

Background. Oral mucositis is a common complication of some malignancies treatment, causing therapeutic modifications due to patient's debilitation, which often interferes with the prognosis of the disease. Many attempts have been made to find an optimal treatment or preventive method to minimize the severity of oral mucositis. Several studies have shown good results with the use of low-energy laser, with the aim of accelerating the process of wound healing and promoting pain relief. Methods. Patients (n=18) who developed oral mucositis during chemotherapy and/or radiotherapy were submitted to low-energy laser applications until cessation of symptoms. Mucositis severity was scored by an oral mucositis scale based on clinical features and by an oral toxicity scale from the National Cancer Institute based on the ability to swallow; pain severity was scored by subjects on a visual analogue scale before and after the applications. Results. Immediate pain relief was achieved in 66.6% of the patients after the first application. Based on the functional scale, mucositis grade III (not capable to eat solids) was reduced in 42.85% of the cases. According to the scale based on the clinical features, mucositis grade IV (ulcerative lesions) was reduced in 75% of the patients that presented this grade of mucositis at the beginning of laser therapy. Conclusions. Low-energy laser was well-tolerated and showed beneficial effects on the management of oral mucositis, improving the quality of life during the oncologic treatment.Mucosite é a complicação oral mais comum do tratamento de algumas doenças malignas, podendo causar a necessidade de modificações terapêuticas, o que pode interferir com o prognóstico da doença. Muitas tentativas têm sido feitas com o intuito de desenvolver um tratamento ou método preventivo para minimizar a severidade da mucosite oral. Vários estudos têm mostrado bons resultados com o uso do laser de baixa potência, devido à aceleração do processo de cicatrização das lesões e da promoção do alívio da dor. Métodos: Os pacientes que desenvolveram mucosite oral durante tratamento quimioterápico e/ou radioterápico (n=18), foram submetidos a aplicações de laser de baixa potência até que fosse atingida a cessação dos sintomas. A severidade da mucosite foi avaliada através de uma escala baseada em características clínicas e de uma escala para avaliação de toxicidade oral desenvolvida pelo Instituto Nacional do Cancer, baseada na habilidade de deglutição; a dor foi avaliada através de uma escala visual, antes e depois de cada aplicação. Resultados: Alívio imediato da dor após a primeira aplicação foi referido por 66.6% dos pacientes. Com base na escala funcional, mucosite grau III (incapacidade de ingerir alimentos sólidos) foi reduzida em 42.85% dos casos. De acordo com a escala baseada em aspectos clínicos, mucosite grau IV (presença de úlceras) foi reduzida em 75% dos pacientes que apresentavam essa condição no início da terapia com laser. Conclusões: O laser de baixa potência foi bem tolerado pelos pacientes, e mostrou efeitos benéficos durante o manejo da mucosite oral, melhorando a qualidade de vida dos pacientes durante o tratamento oncológico

Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report

Malignant mixed müllerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease’s molecular features and possible therapeutic approaches

Primrose syndrome: Characterization of the phenotype in 42 patients

Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo) submitted versio

Avaliação do efeito da radiação laser de baixa potência sobre a proliferação de linfócitos humanos tratados com cisplatina

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, 2007.A radiação laser de baixa potência tem sido utilizada com sucesso na prevenção e no tratamento de ulcerações orais causadas por terapias citotóxicas (radioterapia e quimioterapia), empregadas no tratamento oncológico. Sabe-se que o efeito curativo da radiação laser decorre, principalmente, da indução da proliferação de células que participam do processo de cicatrização tecidual. No entanto, ainda pouco se sabe sobre o seu efeito preventivo, devido às limitações investigacionais inerentes aos estudos clínicos envolvendo pacientes em tratamento oncológico. Sendo assim, faz-se necessário o desenvolvimento de um modelo de estudo in vitro que possibilite investigações mais aprofundadas sem que haja o comprometimento do bem estar dos pacientes. Tendo isso em vista, o objetivo da presente investigação foi desenvolver um modelo de estudo in vitro capaz de reproduzir fenômenos observados na prática clínica, tais como indução de citotoxicidade devido ao uso de drogas quimioterápicas, neste caso a cisplatina, observação de variações de resposta entre diferentes indivíduos, estimulação da proliferação celular e indução de citoproteção a partir da irradiação com laser de baixa potência. O modelo de estudo desenvolvido teve como indicador dos fenômenos investigados a proliferação linfocitária, e mostrou-se adequado para o cumprimento de todos os objetivos apresentados. A radiação laser induziu aumento da proliferação linfocitária e reduziu a citotoxicidade causada pela cisplatina. Não foi possível observar relação de dose-resposta, pois houve grande variabilidade de resposta entre os indivíduos investigados. Essa variação de resposta interindividual ocorreu também em relação à ação tóxica da cisplatina. Esses dados corroboram com uma nova tendência da área médica: a necessidade de individualização dos tratamentos com o auxílio de técnicas laboratoriais que possam predizer padrões de resposta, orientando assim ajustes de doses e conseqüente otimização dos esquemas terapêuticos. O presente modelo de estudo pode ser utilizado em pesquisas futuras com esse propósito. ___________________________________________________________________________________ ABSTRACTLow energy laser radiation has been successfully used for the prevention and treatment of oral ulcerations induced by cytotoxic therapies (radiotherapy and chemotherapy), during oncologic treatment. The healing effect of laser radiation is a consequence of its potential to induce cell proliferation, including the cells that participate in tissue repair. In spite of its wide use, its role in the prevention of oral ulcerations is not completely understood, owing to investigational limitations. These limitations exist due to special aspects associated to the oncologic patient, including myelosupression and higher risk of infection. The development of an in vitro model that is capable of reproducing in vivo situations is mandatory to evaluate the effects caused by laser irradiation and to elucidate its mechanisms of action. With this purpose, we developed a model that was able to reproduce cytotoxicity caused by chemotherapeutic agents, cisplatin in this case, as well as interindividual response variations, stimulatory effect on cell proliferation and cytoprotection induced by low energy laser radiation. In the present model, lymphocyte proliferation was the biological marker used to study the aforementioned circumstances. Laser radiation increased the lymphocyte proliferative response and promoted cytoprotection when the cells were exposed to cisplatin. It was not possible to show any relation between energy density of laser radiation and the obtained proliferative responses because of interindividual variations. These variations were also noted in the cytotoxicity assay induced by cisplatin

Porous surface of extraoral implants: report of two cases rehabilitated with a new Brazilian extraoral implant

Maxillofacial defects caused by cancer treatment are a huge problem, affecting the quality of life of patients. Some of these deformities are minimized using facial epistheses, which needs some additional retenion devices, like glasses or skin adhesives. The use of extraoral fixtures as bone anchorage was introduced many years ago and since then many patients were rehabilitated with better results. Nevertheless, in many cases due to poor bone conditions (i.e. irradiated bone) the success rate of implants are not so good, causing difficulties to rehabilitate the cases. One possible cause of fixture failure could be the poor primary stability achieved in some cases, due to the small dimensions of the fixtures causing a few bone contact with the surface of the implant. Nowadays many researches are being done related to the surface of the fixture, searching for a better primary stability and for a increase of bone contact. Ordinary extraoral implants usually possess a machined surface, until now there is no published report about surface modifications in this kind of implant. This paper presents a new porous surfaced Brazilian extraoral implant (MasterExtraâ, Conexão, Sistema de Próteses, São Paulo, Brazil) that can provide optimal facial rehabilitation due to enhanced bone-to-implant contact and greater long-term stability. Two case reports are described to elucidate its use

Síndrome de hipoventilação central congênita associada à doença de Hirschsprung : relato de caso e revisão de literatura

Objetivo: relatar caso de neonato com episódios de apneias recorrentes, diagnosticado com síndrome de hipoventilação central congênita (SHCC) associada à doença de Hirschsprung (DH), o que configurou síndrome de Haddad. Descrição do caso: terceiro filho de casal não consanguíneo, nascido a termo, parto normal sem intercorrências, peso e comprimento adequados para idade gestacional. Logo após o nascimento apresentou bradipneia, bradicardia e cianose, foi submetido à intubação orotraqueal e iniciada antibioticoterapia empírica devido à suspeita de sepse neonatal precoce. Durante internação em UTI neonatal evoluiu com dificuldade de extubação devido a episódios de dessaturação durante sono e vigília. Apresentou quadros recorrentes de hipoglicemia, hiperglicemia, acidose metabólica, distensão abdominal, leucocitose, aumento de proteína C reativa, com hemoculturas negativas e suspeita de erro inato do metabolismo. Aos dois meses foi diagnosticada doença de Hirschsprung de segmento longo, foi submetido à ressecção do segmento e colostomia à Hartmann. Feita pesquisa genética por reação em cadeia da polimerase para pesquisa de SHCC, que evidenciou alelo mutado do gene PHOX2B e confirmou o diagnóstico. Comentários: trata-se de doença genética rara, de herança autossômica dominante, causada por mutação no gene PHOX2B, localizado na banda cromossômica 4p12, que resulta em disfunção do sistema nervoso autônomo. A SHCC também pode cursar com doença de Hirschsprung e tumores derivados da crista neural. Há correlação entre fenótipo e genótipo, além de grande variabilidade fenotípica intrafamiliar. No período neonatal pode simular quadros de sepse e erros inatos do metabolismo.Objective: to report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Case description: third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. Comments: this is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism

Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review

Abstract Objective: To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Case description: Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. Comments: This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism

Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis.

Brazil is the largest country in South America and the most genetically heterogeneous. The aim of the present study was to determine the prevalence of germline pathogenic variants (PVs) in Brazilian patients with breast cancer (BC) who underwent genetic counseling and genetic testing at a tertiary Oncology Center. We performed a retrospective analysis of the medical records of Brazilian patients with BC referred to genetic counseling and genetic testing between August 2017 and August 2019. A total of 224 unrelated patients were included in this study. Premenopausal women represented 68.7% of the cohort. The median age at BC diagnosis was 45 years. Multigene panel testing was performed in 219 patients, five patients performed single gene analysis or family variant testing. Forty-eight germline PVs distributed among 13 genes were detected in 20.5% of the patients (46/224). Eighty-five percent of the patients (91/224) fulfilled NCCN hereditary BC testing criteria. Among these patients, 23.5% harbored PVs (45/191). In the group of patients that did not meet NCCN criteria, PV detection rate was 3% (1/33). A total of 61% of the patients (28/46) harbored a PV in a high-penetrance BC gene: 19 (8.5%) BRCA1/2, 8 (3.5%) TP53, 1 (0.5%) PALB2. Moderate penetrance genes (ATM, CHEK2) represented 15.2% (7/46) of the positive results. PVs detection was statistically associated (p<0.05) with BC diagnosis before age 45, high-grade tumors, bilateral BC, history of multiple primary cancers, and family history of pancreatic cancer. According to the current hereditary cancer guidelines, 17.4% (39/224) of the patients had actionable variants. Nine percent of the patients (20/224) had actionable variants in non-BRCA genes, it represented 43.5% of the positive results and 51.2% of the actionable variants. Considering the observed prevalence of PVs in actionable genes beyond BRCA1/2 (9%, 20/224), multigene panel testing may offer an effective first-tier diagnostic approach in this population