ANA AMELIA FIALHO DE OLIVEIRA HOFF
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
bookPart Síndromes endócrinas neoplásicas e paraneoplásicas(2022) JúNIOR, Delmar Muniz Lourenço; HOFF, Ana Amélia Fialho de Oliveira; ALMEIDA, Madson Queiroz de- Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study(2019) MACIEL, Rui M. B.; CAMACHO, Cleber P.; ASSUMPCAO, Ligia V. M.; BUFALO, Natassia E.; CARVALHO, Andre L.; CARVALHO, Gisah A. de; CASTRONEVES, Luciana A.; JR, Francisco M. de Castro; CEOLIN, Lucieli; CERUTTI, Janete M.; CORBO, Rossana; FERRAZ, Tania M. B. L.; V, Carla Ferreira; FRANCA, M. Inez C.; GALVAO, Henrique C. R.; GERMANO-NETO, Fausto; GRAF, Hans; JORGES, Alexander A. L.; KUNII, Ilda S.; LAURIA, Marcio W.; LEAL, Vera L. G.; LINDSEY, Susan C.; JR, Delmar M. Lourenco; MADER, Lea M. Z.; MAGALHAES, Patricia K. R.; MARTINS, Joao R. M.; MARTINS-COSTA, M. Cecilia; MAZETOR, Glaucia M. F. S.; IMPELLIZZERI, Anelise I.; NOGUEIRA, Celia R.; I, Edenir Palmero; PESSOA, Cencita H. C. N.; PRADA, Bibiana; SIQUEIRA, Debora R.; SOUSA, Maria Sharmila A.; TOLEDO, Rodrigo A.; VALENTE, Flavia O. F.; VAISMAN, Fernanda; WARD, Laura S.; WEBER, Shana S.; V, Rita Weiss; YANG, Ji H.; DIAS-DA-SILVA, Magnus R.; HOFF, Ana O.; TOLEDO, Sergio P. A.; MAIA, Ana L.Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazili an centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.
- Assessment of Depression, Anxiety, Quality of Life, and Coping in Long-Standing Multiple Endocrine Neoplasia Type 2 Patients(2017) RODRIGUES, Karine C.; TOLEDO, Rodrigo A.; COUTINHO, Flavia L.; NUNES, Adriana B.; MACIEL, Rui M. B.; HOFF, Ana O.; TAVARES, Marcos C.; TOLEDO, Sergio P. A.; LOURENCO JR., Delmar M.Background: Data on psychological harm in multiple endocrine neoplasia type 2 (MEN2) are scarce. Objectives: The aim of this study was to assess anxiety, depression, quality of life, and coping in long-standing MEN2 patients. Patients and Methods: Patients were 43 adults (age >= 18 years) with clinical and genetic diagnosis of MEN2 and long-term follow-up (10.6 +/- 8.2 years; range 1-33 years). This was a cross-sectional study with qualitative and quantitative psychological assessment using semi-directed interviews and HADS, EORTC QLQ C30, and MINI-MAC scales. Adopting clinical criteria from 2015 ATA Guidelines on MEN2, biochemical cure (39%; 16/41), persistence/recurrence (61%; 25/41), and stable chronic disease (22/41) of medullary thyroid carcinoma (MTC) were scored. Pheochromocytoma affected 19 (44%) patients, with previous adrenalectomy in 17 of them. Results: Overall, anxiety (42%; mean score 11 +/- 2.9; range 8-18; anxiety is defined as a score >= 8) and depression (26%; mean score 11 +/- 3.8; range 8-20; depression is defined as a score >= 8) symptoms were frequent. Patients who transmitted RET mutations to a child had higher scores for weakness-discouragement/anxious preoccupation and lower scores for cognitive, emotional, and physical functioning (p < 0.05). Feelings of guilt were present in 35% of patients with mutation-positive children. Lower mean score values for depression and anxiety and higher scores for role, cognitive, and emotional functioning were noticed in 33 patients who were well-informed about their disease (p < 0.05). Fighting spirit was more frequently found in patients with multiple surgical procedures (p = 0.019) and controlled chronic adrenal insufficiency (p = 0.024). Patients with MEN2-elated stress-inducing factors had lower scores for fighting spirit and cognitive functioning and higher scores for insomnia and dyspnea (p < 0.05). Eleven patients required sustained psychotherapeutic treatment. Mean global health status was relatively good in MEN2 cases (68.1 +/- 22.3), and the cured group had higher physical functioning (p = 0.021). Conclusions: Psychological distress is likely chronic in MEN2 patients. This study identified diverse MEN2-related factors (degree of information on disease, mutation-positive children, number of surgeries, comorbidities, stress-inducing factors, and cure) interfering positively or negatively with the results of the psychometrics scales. The active investigation of these factors and the applied psychological assessment protocol are useful to identify MEN2 patients requiring psychological assistance.
- Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study(2019) CASTINETTI, Frederic; WAGUESPACK, Steven G.; MACHENS, Andreas; UCHINO, Shinya; HASSE-LAZAR, Kornelia; SANSO, Gabriella; ELSE, Tobias; DVORAKOVA, Sarka; QI, Xiao Ping; ELISEI, Rossella; MAIA, Ana Luisa; GLOD, John; LOURENCO JR., Delmar Muniz; VALDES, Nuria; MATHIESEN, Jes; WOHLLK, Nelson; BANDGAR, Tushar R.; DRUI, Delphine; KORBONITS, Marta; DRUCE, Maralyn R.; BRAIN, Caroline; KURZAWINSKI, Tom; PATOCS, Atila; BUGALHO, Maria Joao; LACROIX, Andre; CARON, Philippe; FAINSTEIN-DAY, Patricia; CHAZOT, Francoise Borson; KLEIN, Marc; LINKS, Thera P.; LETIZIA, Claudio; FUGAZZOLA, Laura; CHABRE, Olivier; CANU, Letizia; COHEN, Regis; TABARIN, Antoine; UROIC, Anita Spehar; MAITER, Dominique; LABOUREAU, Sandrine; MIAN, Caterina; PECZKOWSKA, Mariola; SEBAG, Frederic; BRUE, Thierry; MIREBEAU-PRUNIER, Delphine; LECLERC, Laurence; BAUSCH, Birke; BERDELOU, Amandine; SUKURAI, Akihiro; VLCEK, Petr; KRAJEWSKA, Jolanta; BARONTINI, Marta; VARGAS, Carla Vaz Ferreira; VALERIO, Laura; CEOLIN, Lucieli; AKSHINTALA, Srivandana; HOFF, Ana; GODBALLE, Christian; JARZAB, Barbara; JIMENEZ, Camilo; ENG, Charis; IMAI, Tsuneo; SCHLUMBERGER, Martin; GRUBBS, Elizabeth; DRALLE, Henning; NEUMANN, Hartmut P.; BAUDIN, EricBackground Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. Methods This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. Findings 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0.2; hazard ratio 0.35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0.0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0.0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. Interpretation Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.
conferenceObject Treatment with sorafenib in progressive metastatic medullary thyroid cancer (MTC) is well tolerated and is associated with symptom and tumor control(2014) PAPADIA, C. M.; CASTRONEVES, L. A.; FREITAS, R.; LOURENCO, D. M.; CASTRO JR., G. de; TAVARES, M. R.; HOFF, A. O.bookPart Neoplasias Endócrinas Múltiplas(2016) LOURENçO JUNIOR, Delmar Muniz; HOFF, Ana Amélia Fialho de Oliveira; TOLEDO, Rodrigo de Almeida; TOLEDO, Sergio Pereira de Almeida- Complete Resolution of Hypercortisolism with Sorafenib in a Patient with Advanced Medullary Thyroid Carcinoma and Ectopic ACTH (Adrenocorticotropic Hormone) Syndrome(2014) BARROSO-SOUSA, Romualdo; LERARIO, Antonio Marcondes; EVANGELISTA, Joao; PAPADIA, Carla; LOURENCO JR., Delmar M.; LIN, Chin Shien; KULCSAR, Marco Antonio; FRAGOSO, Maria Candida; HOFF, Ana O.Background: The treatment of advanced medullary thyroid carcinoma (MTC) has evolved significantly over the past decade. The discovery of genetic abnormalities in MTC has led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and Ectopic ACTH (adrenocorticotropic hormone) Syndrome in whom treatment with sorafenib resulted in complete resolution of hypercortisolism. Summary: A 45-year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of Ectopic ACTH Syndrome. Treatment with sorafenib 400 mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question of whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion. Conclusions: This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action, or secretion.
- Quality of Life and Coping in Multiple Endocrine Neoplasia Type 2(2019) CORREA, Fernanda A.; FARIAS, Evelin C.; CASTRONEVES, Luciana A.; LOURENCO JR., Delmar M.; HOFF, Ana O.Scarce data are available on the quality of life and psychosocial distress of patients with multiple endocrine neoplasia type 2 (MEN2), a genetic cancer syndrome caused by RET germline mutations. Carriers of RET mutations can face several challenges, including fear for the future, guilt for transmission of a germline mutation to an offspring, side effects of cancer treatment, coping behaviors in the face of a chronic and frequently incurable cancer, and difficulties in access to adequate health care. We have addressed the effects of genetic testing on the quality of life of patients with MEN2 and the lifelong physical and psychosocial challenges experienced by these patients. We have also suggested strategies to minimize the burden of living with this chronic condition and the perspectives on future studies to improve the health-related quality of life of the patients.
- Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group(2017) RIECHELMANN, Rachel P.; WESCHENFELDER, Rui F.; COSTA, Frederico P.; ANDRADE, Aline Chaves; OSVALDT, Alessandro Bersch; QUIDUTE, Ana Rosa P.; SANTOS, Allan dos; HOFF, Ana Amelia O.; GUMZ, Brenda; BUCHPIGUEL, Carlos; PEREIRA, Bruno S. Vilhena; LOURENCO JUNIOR, Delmar Muniz; ROCHA FILHO, Duilio Reis da; FONSECA, Eduardo Antunes; MELLO, Eduardo Linhares Riello; MAKDISSI, Fabio Ferrari; WAECHTER, Fabio Luiz; CARNEVALE, Francisco Cesar; COURA-FILHO, George B.; PAULO, Gustavo Andrade de; GIROTTO, Gustavo Colagiovanni; BEZERRA NETO, Joao Evangelista; GLASBERG, Joao; CASALI-DA-ROCHA, Jose Claudio; REGO, Juliana Florinda M.; MEIRELLES, Luciana Rodrigues de; HAJJAR, Ludhmila; MENEZES, Marcos; BRONSTEIN, Marcello D.; SAPIENZA, Marcelo Tatit; FRAGOSO, Maria Candida Barisson Villares; PEREIRA, Maria Adelaide Albergaria; BARROS, Milton; FORONES, Nora Manoukian; AMARAL, Paulo Cezar Galvao do; MEDEIROS, Raphael Salles Scortegagna de; ARAUJO, Raphael L. C.; BEZERRA, Regis Otaviano Franca; PEIXOTO, Renata D'Alpino; AGUIAR JR., Samuel; RIBEIRO JR., Ulysses; PFIFFER, Tulio; HOFF, Paulo M.; COUTINHO, Anelisa K.Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
- New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations(2019) FAGUNDES, Gustavo F. C.; PETENUCI, Janaina; JR, Delmar M. Lourenco; TRARBACH, Ericka B.; PEREIRA, Maria Adelaide A.; D'EUR, Joya Emilie Correa; HOFF, Ana O.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose Luis; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Context: Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective: Genotype-phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design: We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results: PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-yearold boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion: VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.