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PubMed | Fleury Institute, Coordinator of Clinical Neurophysiology Education Programm and University of Sao Paulo
Type: Journal Article | Journal: Clinics in dermatology | Year: 2016

Leprosy neuropathy is dependent on the patients immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation.


Costa-Barbosa F.A.,Federal University of São Paulo | Tonetto-Fernandes V.F.,Federal University of São Paulo | Carvalho V.M.,Fleury Institute | Nakamura O.H.,Fleury Institute | And 5 more authors.
Clinical Endocrinology | Year: 2010

Background: Congenital adrenal hyperplasia caused by classic 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with a high prevalence of asymptomatic heterozygote carriers (HTZ) in the general population, making case detection desirable by routine methodology. HTZ for classic and nonclassic (NC) forms have basal and ACTH-stimulated values of 17-hydroxyprogesterone (17OHP) that fail to discriminate them from the general population. 21-Deoxycortisol (21DF), an 11-hydroxylated derivative of 17OHP, is an alternative approach to identify 21OHD HTZ. Objective: To determine the discriminating value of basal and ACTH-stimulated serum levels of 21DF in comparison with 17OHP in a population of HTZ for 21OHD (n = 60), as well as in NC patients (n = 16) and in genotypically normal control subjects (CS, n = 30), using fourth generation tandem mass spectrometry after HPLC separation (LC-MS/MS). Results: Basal 21DF levels were not different between HTZ and CS, but stimulated values were increased in the former and virtually nonresponsive in CS. Only 17·7% of the ACTH-stimulated 21DF levels overlapped with CS, when compared to 46·8% for 17OHP. For 100% specificity, the sensitivities achieved for ACTH-stimulated 21DF, 17OHP and the quotient [(21DF + 17OHP)/F] were 82·3%, 53·2% and 87%, using cut-offs of 40, 300 ng/dl and 46 (unitless), respectively. Similar to 17OHP, ACTH-stimulated 21DF levels did not overlap between HTZ and NC patients. A positive and highly significant correlation (r = 0·846; P < 0·001) was observed between 21DF and 17OHP pairs of values from NC and HTZ. Conclusion: This study confirms the superiority of ACTH-stimulated 21DF, when compared to 17OHP, both measured by LC-MS/MS, in identifying carriers for 21OHD. Serum 21DF is a useful tool in genetic counselling to screen carriers among relatives in families with affected subjects, giving support to molecular results. © 2010 Blackwell Publishing Ltd.


De Melo Maia B.,Camargo Cancer Center | Fontes A.M.,Camargo Cancer Center | Lavorato-Rocha A.M.,Camargo Cancer Center | Rodrigues I.S.,Camargo Cancer Center | And 5 more authors.
Human Pathology | Year: 2014

Epidermal growth factor receptor (EGFR) protein expression was assessed by immunohistochemistry (IHC) in 150 cases of invasive vulvar squamous cell carcinoma. In addition, gene copy number status by fluorescence in situ hybridization was performed in a smaller set of samples. Results were correlated with patient's clinical data and prognostic factors. EGFR overexpression (2+ and 3+) was observed on the membrane in 24.66% and 21.33% of all cases, respectively. Higher EGFR expression was associated with depth of invasion (P =.0409) and disease recurrence (P =.0401). Cytoplasm staining was found in 21.33% of the cases and was associated with absence of nodal metastasis (P =.0061) and better survival (P =.0199). Intratumor heterogeneity of EGFR IHC staining was frequently observed (55.33%) and was associated with the presence of nodal metastasis (P =.0207) and tumor invasion (P =.0161). Worse survival outcomes have been demonstrated in tumors with EGFR heterogeneity (P =.0434). EGFR gene status evaluated by fluorescence in situ hybridization did not correlate with protein expression evaluated by IHC. In conclusion, EGFR cytoplasm staining has no link with poorer outcome; still, this pattern of staining is even more related to better prognosis. EGFR heterogeneity of staining correlated with more aggressive tumors, and presented to be an important marker of poor prognosis in vulvar squamous cell carcinoma. The usage of small biopsies or even tissue microarrays for vulvar cancer evaluation should be carefully reconsidered for the assessment of EGFR as the results may be misleading. Protein overexpression may be independent on gene amplification, showing that other molecular mechanisms than copy number variation may regulate protein expression of EGFR in vulvar cancer. © 2014 Elsevier Inc. All rights reserved.


Rodrigues I.S.,Camargo Cancer Center | Lavorato-Rocha A.M.,Camargo Cancer Center | De M Maia B.,Camargo Cancer Center | Stiepcich M.M.A.,Fleury Institute | And 4 more authors.
British Journal of Cancer | Year: 2013

Background:Epithelial-to-mesenchymal transition (EMT) still remains an obscure event in vulvar squamous cell carcinoma (VSCC).Methods: Immunohistochemistry (IHC) expression of E-cadherin, β-catenin, Snail, Slug, Twist and Vimentin was analysed in 87 VSCC, controlled for human papillomavirus (HPV) positivity, considering tumour front and central tumour as different morphological categories from the same tumour.Results:Lower β-catenin and higher Vimentin expression was associated with invasive front when compared with the central tumour (P=0.013 and P≤0.001, respectively). Higher expression of E-cadherin in central tumour was significantly related to absence of vascular and perineural invasion, lower invasion depth and ≤2 lymph node involvement. Loss of β-catenin and high Slug, Snail and Twist expression was associated with HPV-negative tumours. Moreover, β-catenin lower expression associated with gain in Slug expression predicts a subgroup with worst outcome (P=0.001). Lower expression of β-catenin in both central tumour and invasive front correlated with lower overall survival (P=0.021 and P=0.011, respectively). Also, multivariate analysis showed that lower β-catenin expression was independently associated with poorer outcome (P=0.044).Conclusion:Human papillomavirus-related tumours show better prognosis and outcome; besides, they do not progress through EMT phenomenon. Immunohistochemical analysis of β-catenin in invasive tumour front is a key issue for establishing prognosis of vulva cancer. © 2013 Cancer Research UK. All rights reserved.


De Melo Maia B.,Hospital AC Camargo | Lavorato-Rocha A.M.,Hospital AC Camargo | Rodrigues L.S.,Hospital AC Camargo | Coutinho-Camillo C.M.,Hospital AC Camargo | And 6 more authors.
Cancer Prevention Research | Year: 2013

Unregulated expression of microRNAs is well known and has already been demonstrated in many tumor types. However, in vulvar carcinoma this field has been unknown territory. Our study characterizes microRNA in vulvar tumors through an expression profile of 754 miRNAs, relating this with clinical and anatomopathologic data, and presence of HPV infection. Twenty HPV-negative and 20 HPV-positive samples, genotyped for high-risk HPVs (HPV16, 18, 31, 33) and a pool of seven normal vulvar skin samples were used for the identification of differentially expressed miRNAs by TLDA Quantitative Real Time PCR (qRT-PCR). Twenty-five differentially expressed microRNAs between HPV-positive and HPV-negative groups and 79 differentially expressed on the tumor compared with normal samples were obtained. A network between microRNA expression profiles and putative target mRNAs predicted by target prediction algorithms and previously demonstrated as relevant in vulvar carcinomas, such as TP53, RB, PTEN, and EGFR was constructed. Downregulation of both miR-223-5p and miR-19-b1-5p were correlated with the presence of lymph node metastasis; downregulation of miR-100-3p and miR-19-b1-5p were correlated with presence of vascular invasion; overexpression of miR-519b and miR-133a were associated with advanced FIGO staging. In conclusion, our study demonstrates that microRNAs may be clinically important in vulvar carcinomas and our findings may help for further studies on functional implications of miRNA deregulation in this type of cancer. ©2013 AACR.


Heise C.O.,Fleury Institute | Machado F.C.N.,Fleury Institute | de Amorim S.C.,Fleury Institute | de Toledo S.M.,Fleury Institute
Arquivos de Neuro-Psiquiatria | Year: 2012

Diabetic polyneuropathy can be confirmed by nerve conduction studies. The data can be analyzed in the form of a combined index instead of individual parameters. Methods: The combined index included five parameters of nerve conduction studies commonly used for evaluation of polyneuropathies. We evaluated sensitivity in 100 diabetic patients with suspected polyneuropathy, and specificity in 200 non-diabetic patients with suspected lumbosacral radiculopathy. All results were expressed in number of standard deviations (SD). Results: The sensitivity of the combined index was 81 or 74%, and specificity was 97 or 98%, using respectively -2.0 or -2.5 SD as cutoff. The range of sensitivity of the other parameters was 57-65% or 48-56%, and specificity range was 96-98% or 98-100%, using the same criteria. Discussion: The combined index had higher sensitivity and equivalent specificity compared to isolated parameters.


De Melo Maia B.,Hospital Ac Camargo | Munhoz Cestari F.,Hospital Ac Camargo | Lavorato-Rocha A.M.,Hospital Ac Camargo | Sant'ana Rodrigues I.,Hospital Ac Camargo | And 7 more authors.
Gynecologic and Obstetric Investigation | Year: 2013

Aim: To investigate sociodemographic and clinical-epidemiological profiles of patients with vulvar carcinoma in São Paulo, the largest city of Brazil, to establish a more consistent profile of these features once the incidence of vulvar carcinoma has risen considerably. Data regarding the epidemiological aspects of this tumor are scarce. Methods: A retrospective study was performed using 300 medical records from patients diagnosed with squamous cell carcinoma of the vulva and surgically treated at A.C. Camargo Hospital in São Paulo, Brazil, from 1978 to 2009. Results: The median age of onset was 70 years, ranging from 15 to 98 years, and most women were white (88.51%). Most patients (83.54%) had little or no schooling and had the lowest survival curve. Many patients were diagnosed in the early stages of the disease (57.09% FIGO IB), 59% had complications due to surgery and 43.71% had disease recurrence, of which about 70% died. Conclusions: Our study adds 300 Brazilian cases of vulvar carcinoma to the world literature. Given the high rate of disease recurrence and mortality in Brazil, we conclude that regular gynecologic evaluation and educational policies should be reinforced in order to raise awareness for vulvar cancer. Copyright © 2012 S. Karger AG, Basel.


Garbino J.A.,Instituto Lauro Of Souza Lima | Heise C.O.,Fleury Institute | Marques W.,University of Sao Paulo
Clinics in Dermatology | Year: 2016

Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation. © 2016 Elsevier Inc.


Lavorato-Rocha A.M.,Cancer Hospital AC Camargo | De Melo Maia B.,Cancer Hospital AC Camargo | Rodrigues I.S.,Cancer Hospital AC Camargo | Stiepcich M.M.A.,Fleury Institute | And 5 more authors.
Annals of Surgical Oncology | Year: 2013

Purpose: This study was designed to determine the prognostic role of p14ARF in vulvar squamous cell carcinoma (VSCC). Methods: Immunohistochemistry for p14ARF and p53 and fluorescent in situ hybridization (FISH) for TP53 were performed in 139 cases of VSCC. Human papillomavirus (HPV) genotyping by hybridization was employed in 100 cases. qRT-PCR for p14ARF and p53 transcript assessment was performed in 16 cases. All results were correlated with clinicopathological variables. Results: Immunohistochemistry analysis showed p14ARF and p53 positivity in 16.4 % and 53 % cases respectively. Positive p14ARF expression was significantly associated with the following variables: shorter cancer-specific survival (P = 0.04) and shorter disease-free survival (P = 0.02), presence of perineural invasion (P = 0.037), vascular invasion (P = 0.047), and node metastasis (P = 0.031). Also, p14ARF-positive HPV-negative cases had the shortest cancer-specific survival (P = 0.03) and disease-free survival (P = 0.04). HPV infection was detected in 32.8 % of the cases; HPV16 was the most prevalent type. Viral infection was more common in poorly differentiated tumors (P = 0.032). qRT-PCR demonstrated that CDKN2A (p14ARF) had higher expression in tumor samples compared with paired noncancerous samples (P < 0.001). The opposite relationship was seen in TP53 expression evaluation (P < 0.001). FISH demonstrated 4 cases with deleted TP53 (6.3 %). Conclusions: p14ARF represents an important marker of poor prognosis in VSCC. p53 and HPV infection did not show any prognostic importance. Further clinical trials concerning p14ARF positivity may result in important contributions due to its relationship with poor outcome. Mainly due to the relationship of p14ARF with lymph node metastasis, the immunohistochemistry evaluation of this marker may help to identify a subset of patients more suitable to less radical procedures. © 2012 Society of Surgical Oncology.


PubMed | Fleury Institute and Camargo Cancer Center
Type: Journal Article | Journal: Human pathology | Year: 2014

Epidermal growth factor receptor (EGFR) protein expression was assessed by immunohistochemistry (IHC) in 150 cases of invasive vulvar squamous cell carcinoma. In addition, gene copy number status by fluorescence in situ hybridization was performed in a smaller set of samples. Results were correlated with patients clinical data and prognostic factors. EGFR overexpression (2+ and 3+) was observed on the membrane in 24.66% and 21.33% of all cases, respectively. Higher EGFR expression was associated with depth of invasion (P = .0409) and disease recurrence (P = .0401). Cytoplasm staining was found in 21.33% of the cases and was associated with absence of nodal metastasis (P = .0061) and better survival (P = .0199). Intratumor heterogeneity of EGFR IHC staining was frequently observed (55.33%) and was associated with the presence of nodal metastasis (P = .0207) and tumor invasion (P = .0161). Worse survival outcomes have been demonstrated in tumors with EGFR heterogeneity (P = .0434). EGFR gene status evaluated by fluorescence in situ hybridization did not correlate with protein expression evaluated by IHC. In conclusion, EGFR cytoplasm staining has no link with poorer outcome; still, this pattern of staining is even more related to better prognosis. EGFR heterogeneity of staining correlated with more aggressive tumors, and presented to be an important marker of poor prognosis in vulvar squamous cell carcinoma. The usage of small biopsies or even tissue microarrays for vulvar cancer evaluation should be carefully reconsidered for the assessment of EGFR as the results may be misleading. Protein overexpression may be independent on gene amplification, showing that other molecular mechanisms than copy number variation may regulate protein expression of EGFR in vulvar cancer.

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