César Cabello dos Santos

Evaluation of Residual Glandular Tissue After Skin-Sparing Mastectomies

BackgroundThe oncological safety of skin-sparing mastectomy (SSM) has been the object of several studies.MethodsFrom June 2003 to January 2004, 42 breast cancer patients, stage 0 to IIIA, underwent SSM. Before surgery, two lines were drawn on the breast skin, representing SSM and conventional mastectomy incisions. After surgery, the skin flap that would remain after SSM was removed, and immediate breast reconstruction was begun. The presence and amount of remaining glandular breast tissues were histologically evaluated in the skin flap. Terminal ductal lobular units (TDLUs) and residual disease were identified. These data were correlated with other clinical and pathologic parameters by using Fisher’s exact test (P value) and receiver operating characteristic curves.ResultsThe prevalence of residual breast tissue in the sample was 59.5%, and the presence of TDLUs was significantly associated with skin flaps thicker than 5 mm. Residual disease was found in 9.5% of the women and was associated with skin flaps >5 mm thick and the presence of TDLUs. There was no significant association between the presence of TDLUs and residual disease with age, body mass index, menopausal status, clinical and pathologic staging, breast volume, mammographic density, neoadjuvant chemotherapy, type of surgery, and presence of an extensive in situ component. The receiver operating characteristic curve showed that as skin flaps decrease in thickness, TDLUs also decrease.ConclusionsA high prevalence of glandular breast tissue and residual disease in the skin flap was associated with a skin flap thickness >5 mm.

Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history

CONTEXT AND OBJECTIVE BRCA1 and BRCA2 are the two principal hereditary breast cancer susceptibility genes, and the prevalence of their mutations among Brazilian women is unknown. The objective was to detect BRCA1 and BRCA2 mutations in Brazilian patients with breast cancer, so as to establish genetic profiles. DESIGN AND SETTING Cross-sectional study, in Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Brazil, and Institute of Pathology and Molecular Immunology, University of Porto, Portugal. METHODS Thirty-one breast cancer patients with positive family history (criteria from the Breast Cancer Linkage Consortium) were studied, and genomic DNA was extracted from peripheral blood. Single-strand conformation polymorphism was used for the analysis of exons 2, 3, 5, and 20 of BRCA1. Cases showing PCR products with abnormal bands were sequenced. Exon 11 of BRCA1 and exons 10 and 11 of BRCA2 were directly sequenced in both directions. RESULTS Four mutations were detected: one in BRCA1 and three in BRCA2. The BRCA1 mutation is a frameshift located at codon 1756 of exon 20: 5382 ins C. Two BRCA2 mutations were nonsense mutations located at exon 11: S2219X and the other was an unclassified variant located at exon 11: C1 290Y. CONCLUSION The BRCA1 or BRCA2 mutation prevalence found among women with breast cancer and such family history was 13% (4/31). Larger studies are needed to establish the significance of BRCA mutations among Brazilian women and the prevalence of specific mutations.

Breast density in women with premature ovarian failure using hormone therapy.

Background. Women with premature ovarian failure (POF) are treated with estrogen–progestin therapy; however, doubts remain regarding the effect of this therapy on the breasts of women with POF. Objective. To evaluate the breast density of women with POF using estrogen–progestin therapy compared with normally menstruating women. Methods. A cross-sectional study was performed in 31 women with POF using conjugated equine estrogens and medroxyprogesterone acetate and a control group of 31 normally menstruating women, paired by age. All underwent mammography, analyzed by digitization and Wolfes classification, the latter defined as non-dense (N1 and P1) or dense (P2 and Dy). Parity, breastfeeding and body mass index were evaluated, as well as duration of hormone use and ovarian failure in the POF group. Results. Digitization revealed no difference in mean breast density between the groups: 24.1±14.6% and 21.8±11.3% for POF and control groups, respectively. The Wolfe classification also failed to detect any significant difference between the groups, dense breasts being detected in 51.6% and 35.5% of cases in the POF and control groups, respectively. Conclusion. Periods of hypoestrogenism followed by hormone therapy resulted in no changes in breast density in women with POF, compared with normally menstruating women of the same age.

Lesões induzidas por papilomavírus humano em parceiros de mulheres com neoplasia intra-epitelial do trato genital inferior

RESUMO Objetivos: pesquisar a presenca de lesoes induzidas por papilomavirus (HPV) e os fatores associados em parceiros de mulheres com neoplasia intra-epitelial genital. Metodos: foram avaliados 337 homens por meio de citologia uretral, peniscopia e biopsia, quando necessario. Analisou-se a presenca de lesao induzida por HPV correlacionando-a com a idade, escolaridade, tabagismo, estabilidade conjugal, inicio da atividade sexual, numero de parceiras, antecedente de doenca sexualmente transmissivel (DST), postectomia, imagens peniscopicas e grau das lesoes nas mulheres. Resultados: a peniscopia foi positiva em 144 homens (42,7%) e 105 (31,2%) apresentaram lesoes induzidas por HPV. Somente o tabagismo, a estabilidade conjugal menor ou igual a seis meses e o antecedente de mais de uma parceira sexual estiveram associados com a presenca de lesao induzida por HPV (p<0,05). A citologia uretral foi suspeita para HPV em 4,2% dos casos, sendo este achado significativamente associado com tabagismo, peniscopia ou biopsias positivas e com parceiros de mulheres com lesao de alto grau. Das 229 biopsias realizadas, 72,1% foram positivas para HPV, independentemente da imagem peniscopica e do grau de lesao na mulher. Conclusoes: as lesoes induzidas por HPV foram diagnosticadas em 31,2% dos casos e estiveram associadas com o tabagismo, tempo de uniao conjugal menor ou igual a seis meses e mais de uma parceira sexual. O grau de lesao na mulher, escolaridade, antecedente de DST, postectomia e imagem peniscopica nao se mostraram correlacionados com a presenca de lesao induzida por HPV.

Radioguided surgery using intravenous 99mTc sestamibi associated with breast magnetic resonance imaging for guidance of breast cancer resection.

Abstract:  The purpose of this study was to evaluate the feasibility of surgery radioguided with intravenous 99mTc sestamibi associated with magnetic resonance imaging (MRI) of the breast to detect tumor extent and guide complete tumor resection. A descriptive experimental study was developed with 10 breast cancer patients (stage IIA–IIB) who underwent mastectomy. From 2 to 10 days before surgery, the patients underwent breast MRI with 0.1 mmol/kg of gadolinium and scintimammography with a 740 MBq of 99mTc sestamibi. A region of interest was drawn around the tumor image and an uptake curve as a function of time was plotted to calculate the optimal time to perform radioguided surgery. In the perioperative period, the same dose of 99mTc sestamibi was intravenously injected into the patients. Tumor resection was performed under the guidance of a gamma probe. MRI was used to evaluate the skin and deep fascia involvement and to detect occult tumor foci which were also excised. Subsequently a modified radical mastectomy was performed. Tumor and residual breast were histopathologically examined. In a series of 10 women, all demonstrated 99mTc sestamibi uptake in tumor cells. Eight patients showed no disease in the residual breast, one presented with one foci of invasive ductal carcinoma measuring 0.5 cm in diameter located 5 cm from the tumor bed, and one presented with one foci of ductal carcinoma in situ measuring 0.8 cm at the resection margin. The mean tumor size in the histopathologic assessment was 3.3 cm and in MRI was 5.0 cm. Radioguided surgery using 99mTc sestamibi associated with MRI is a feasible technique that can be employed in tumor resection.

Preservação do Nervo Intercostobraquial na Linfadenectomia Axilar por Carcinoma de Mama

Purpose: to evaluate the relationdhip between preservation of the intercostobrachial nerve and pain sensitivity of the arm, total time of the surgery, and number of dissected nodes in patients submitted to axillary lymphadenectomy due to breast cancer. Methods: an intervention, prospective, randomized and double-blind study was performed on 85 patients assisted at the State University of Campinas, Brazil, from January 1999 to July 2000. The patients were divided into two groups, according to the intention of preserving or not the intercostobrachial nerve. The surgeries were performed by the same researchers, utilizing the same technique. The postoperative evaluations were performed within 2 days, 40 days and after 3 months. The pain sensitivity of the arm was evaluated through a specific questionnaire (subjective evaluation) and through a neurological physical examination (objective evaluation). Results: the surgical technique was applied to all patients and the preservation of the intercostobrachial nerve was related to a significant decrease in the alterations of pain sensitivity of the arm, both by the subjective and objective evaluations. After three months, in the subjective evaluation, 61% of the patients were asymptomatic in the intercostobrachial nerve preservation group and 28.6% in the nerve section group (p<0.01). By the objective evaluation, 53.7% of the patients presented normal neurological examination in the intercostobrachial nerve preservation group and 16.7% in the nerve section group (p<0.01). No significant difference was observed regarding total time of surgery (p=0.76) and number of dissected nodes between the two evaluated groups (p=0.59). Conclusions: these data show that the preservation of the intercostobrachial nerve is feasible and leads to a significant decrease in the alterations of pain sensitivity of the arm, without interfering in the total time of surgery and the number of dissected nodes.

Avaliação do Parceiro Sexual e Risco de Recidivas em Mulheres Tratadas por Lesões Genitais Induzidas por Papilomavírus Humano (HPV)

OBJETIVO: estudar se a avaliacao e o tratamento em parceiros de mulheres com lesoes induzidas por HPV estao relacionados com a ocorrencia de recidivas postratamento nestas mulheres. SUJEITOS E METODOS: estudo clinico de coorte reconstituido com 144 mulheres tratadas por lesoes genitais induzidas por HPV e cujos parceiros foram avaliados, comparadas com outras 288 mulheres tratadas por lesoes semelhantes e cujos parceiros nao foram examinados, controladas por data do atendimento, idade, grau das lesoes genitais e tipo de tratamento, todos atendidos e seguidos no CAISM, UNICAMP, entre julho de 1993 e marco de 2000. Foi avaliada a semelhanca entre os grupos com relacao as variaveis de controle. Depois, estudada a associacao entre a avaliacao do parceiro ou a presenca ou nao de lesoes por HPV nos mesmos, com relacao a ocorrencia de recidivas nas mulheres, do grau destas lesoes recidivadas e do tempo livre de doenca, atraves de analise estatistica uni e multivariada com regressao logistica, utilizando os testes exato de Fisher, t de student e, para analise de sobrevivencia, o teste de Wilcoxon. RESULTADOS: a ocorrencia de recidivas nas mulheres foi de 9,0% quando seus parceiros foram avaliados contra 5,9% para aquelas cujos parceiros nao foram examinados, sendo esta diferenca nao significante. Os grupos estudados foram semelhantes com relacao as variaveis de controle, ou seja, a idade, a idade na menarca, no inicio sexual e primeiro parto, o tempo de atividade sexual, o numero de parceiros sexuais, de gestacoes, partos e abortos, o habito de fumar, o grau da lesao genital e o tipo de tratamento realizado. Nenhuma destas variaveis apresentou associacao com a ocorrencia de recidivas na analise uni e multivariada com regressao logistica. Entre as mulheres cujos parceiros foram avaliados e estes apresentaram lesoes por HPV, observou-se 1,5 vezes mais recidivas (12,5% contra 7,3%) que aquelas cujos parceiros foram negativos, mas esta diferenca nao foi significativa. Um tempo de estabilidade conjugal menor ou igual que 12 meses relatado pelo homem esteve associado a duas vezes mais recidivas (14,9% contra 6,2%) nas suas parceiras em comparacao com aquelas cujos parceiros relataram um tempo maior. O grau da lesao recidivada e o tempo livre de doenca nao estiveram associados a presenca ou nao de lesoes nos homens. CONCLUSOES: a avaliacao do homem neste estudo nao trouxe beneficios a mulher em relacao ao risco de recidivas de lesoes genitais induzidas por HPV. A presenca de lesoes por HPV nos parceiros nao se correlacionou com a ocorrencia de recidivas, com o grau das lesoes recidivadas e com o tempo livre de doenca nas mulheres. Estas observacoes nao suportam a hipotese de que os homens nao avaliados seriam uma importante causa de recidivas nas parceiras. Abstract

Localization of metastasis within the sentinel lymph node biopsies: a predictor of additional axillary spread of breast cancer?

PURPOSE To explore the relationship between morphological characteristics and histologic localization of metastasis within sentinel lymph nodes (SLN) and axillary spread in women with breast cancer. METHODS We selected 119 patients with positive SLN submitted to complete axillary lymph node dissection from July 2002 to March 2007. We retrieved the age of patients and the primary tumor size. In the primary tumor, we evaluated histologic and nuclear grade, and peritumoral vascular invasion (PVI). In SLNs we evaluated the size of metastasis, their localization in the lymph node, number of foci, number of involved lymph nodes, and extranodal extension. RESULTS Fifty-one (42.8%) patients had confirmed additional metastasis in non-sentinel lymph nodes (NLSN). High histologic grade, PVI, intraparenchymatous metastasis, extranodal neoplastic extension and size of metastasis were associated with positive NLSN. SLN metastasis affecting the capsule were associated to low risk incidence of additional metastasis. After multivariate analysis, PVI and metastasis size in the SLN remained as the most important risk factors for additional metastasis. CONCLUSIONS The risk of additional involvement of NSLN is higher in patients with PVI and it increases progressively according the histologic localization in the lymph node, from capsule, where the afferent lymphatic channel arrives, to the opposite side of capsule promoting the extranodal extension. Size of metastasis greater than 6.0 mm presents higher risk of additional lymph node metastasis.

Long term effects of manual lymphatic drainage and active exercises on physical morbidities, lymphoscintigraphy parameters and lymphedema formation in patients operated due to breast cancer: A clinical trial.

Purpose evaluate whether manual lymphatic drainage (MLD) or active exercise (AE) is associated with shoulder range of motion (ROM), wound complication and changes in the lymphatic parameters after breast cancer (BC) surgery and whether these parameters have an association with lymphedema formation in the long run. Methods Clinical trial with 106 women undergoing radical BC surgery, in the Women’s Integrated Healthcare Center—University of Campinas. Women were matched for staging, age and body mass index and were allocated to performed AE or MLD, 2 weekly sessions during one month after surgery. The wound was evaluated 2 months after surgery. ROM, upper limb circumference measurement and upper limb lymphoscintigraphy were performed before surgery, and 2 and 30 months after surgery. Results The incidence of seroma, dehiscence and infection did not differ between groups. Both groups showed ROM deficit of flexion and abduction in the second month postoperative and partial recovery after 30 months. Cumulative incidence of lymphedema was 23.8% and did not differ between groups (p = 0.29). Concerning the lymphoscintigraphy parameters, there was a significant convergent trend between baseline degree uptake (p = 0.003) and velocity visualization of axillary lymph nodes (p = 0.001) with lymphedema formation. A reduced marker uptake before or after surgery predicted lymphedema formation in the long run (>2 years). None of the lymphoscintigraphy parameters were shown to be associated with the study group. Age ≤39 years was the factor with the greatest association with lymphedema (p = 0.009). In women with age ≤39 years, BMI >24Kg/m2 was significantly associated with lymphedema (p = 0.017). In women over 39 years old, women treated with MLD were at a significantly higher risk of developing lymphedema (p = 0.011). Conclusion Lymphatic abnormalities precede lymphedema formation in BC patients. In younger women, obesity seems to be the major player in lymphedema development and, in older women, improving muscle strength through AE can prevent lymphedema. In essence, MLD is as safe and effective as AE in rehabilitation after breast cancer surgery.

Variação da densidade mamográfica em usuárias e não-usuárias de terapia de reposição hormonal

Objetivo: comparar, caso a caso, as mudancas de densidades mamograficas segundo a digitalizacao de imagens, em tres avaliacoes consecutivas, em usuarias ou nao de terapia de reposicao hormonal (TRH). Metodos: avaliamos 59 mulheres na pos-menopausa, sendo 43 usuarias de terapia de reposicao hormonal (estro-progestino ciclico ou continuo) e 16 nao-usuarias. Os criterios de inclusao foram: amenorreia de pelo menos 12 meses e exame mamografico normal, em duas incidencias (medio-lateral e craniocaudal), no inicio da TRH ou do seguimento clinico para as pacientes sem TRH. Para a avaliacao do comportamento da densidade mamaria, foram usadas as seguintes variaveis: mudanca inicial - diferenca entre a primeira mamografia realizada em 12 ± 3 meses apos inicio da TRH e a mamografia pre-TRH e mudanca final - diferenca entre a segunda mamografia realizada em 24 ± 3 meses apos inicio da TRH e a mamografia pre-TRH. Os testes de Wilcoxon e de c2 foram aplicados para avaliar as diferencas de mudancas de densidades mamograficas. Resultados: nas usuarias de TRH, mais da metade das mulheres (56,3%) com aumento inicial da densidade mamografica permaneceram com aumento apos a avaliacao final. Esse achado nao foi significativo (p=0,617). Nesse mesmo grupo, a ausencia de aumento da densidade na avaliacao inicial esteve associada ao nao aumento na avaliacao final de forma significativa (p=0,017). Dentre as nao-usuarias de TRH, todas as mamas, que nao eram totalmente substituidas por gordura na avaliacao inicial apresentaram diminuicao da densidade mamografica na avaliacao final. Conclusoes: a maioria das usuarias de TRH que apresentaram aumento da densidade mamografica em uma primeira avaliacao, apos aproximadamente um ano de uso, permaneceram com aumento em uma segunda avaliacao. Com o passar do tempo, as nao-usuarias de TRH apresentaram tendencia a diminuicao da densidade mamografica de forma significativa (p=0,003).