Papel da tomografia torácica e abdominal no estadiamento do carcinoma mamário localmente avançado

Pós-graduação em Cirurgia Veterinária - FCAV

Cirúrugia torácica videoassistida por porta única : um caso de adenocarcinoma do pulmão

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Prognostic Value Of Dna And Mrna E6/e7 Of Human Papillomavirus In The Evolution Of Cervical Intraepithelial Neoplasia Grade 2.

This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

Up-regulation Of Dnam-1 And Nkp30, Associated With Improvement Of Nk Cells Activation After Long-term Culture Of Mononuclear Cells From Patients With Ovarian Neoplasia.

This study aimed at evaluating the functional activation and activating receptors expression on resting, short- and long-term NK and NK-like T cells from blood of ovarian neoplasia patients. Blood from patients with adnexal benign alterations (n = 10) and ovarian cancer (grade I-IV n = 14) were collected after signed consent. Effector cells activation was evaluated by the expression of the CD107a molecule. Short-term culture was conducted overnight with IL-2 and long-term culture for 21 days, by a method designed to expand CD56(+) lymphocytes. Short-term culture significantly increased NK cells activation compared to resting NK cells (p<0.05), however, the long-term procedure supported an even higher increase (p<0.001). Resting NK-like T cells showed poor activation, which was not altered by the culture procedures. The long-term culture effectively increased the expression of the activating receptors on NK and NK-like T cells, either by increasing the number of cells expressing a given receptor and/or by up-regulating their expression intensity. As a conclusion, the long-term culture system employed, resulted in a high number of functional NK cells. The culture system was particularly efficient on the up-regulation of NKp30 and DNAM-1 receptors on NK cells.

P16(ink) (4a) Expression As A Potential Marker Of Low-grade Cervical Intraepithelial Neoplasia Progression.

To evaluate p16(INK) (4a) immunoexpression in CIN1 lesions looking for differences between cases that progress to CIN2/3 maintain CIN1 diagnosis, or spontaneously regress. Seventy-four CIN1 biopsies were studied. In the follow-up, a second biopsy was performed and 28.7% showed no lesion (regression), 37.9% maintained CIN1, and 33.4% progressed to CIN2/3. Immunostaining for p16(INK) (4a) was performed in the first biopsy and it was considered positive when there was strong and diffuse staining of the basal and parabasal layers. Pearson's chi-square was used to compare the groups (p ≤ 0.05). The age of the patients was similar. There was no significant difference in p16(INK) (4a) immunoexpression in the groups, however, statistical analyses showed a significant association when only the progression and regression groups were compared (p = 0.042). Considering p16(INK) (4a) positivity and the progression to CIN2/3, the sensitivity, specificity, positive, and negative predictive values in our cohort were 45%, 75%, 47%, and 94%, respectively. We emphasize that CIN1 with p16(INK) (4a) staining was associated with lesion progression, but the sensitivity was not high. However, the negative predictive value was more reliable (94%) and p16(INK) (4a) may represent a useful biomarker that can identify CIN1 lesions that need particular attention, complementing morphology.

Desmoid tumor in patients with familial adenomatous polyposis

CONTEXT: Desmoid tumors constitute one of the most important extraintestinal manifestations of familial adenomatous polyposis. The development of desmoids is responsible for increasing morbidity and mortality rates in cases of familial adenomatous polyposis. OBJECTIVES: To evaluate the occurrence of desmoid tumors in familial adenomatous polyposis cases following prophylactic colectomy and to present patient outcome. METHODS: Between 1984 and 2008, 68 patients underwent colectomy for familial adenomatous polyposis at the School of Medical Sciences Teaching Hospital, University of Campinas, SP, Brazil. Desmoid tumors were found in nine (13.2%) of these patients, who were studied retrospectively by consulting their medical charts with respect to clinical and surgical data. RESULTS: Of nine patients, seven (77.8%) were submitted to laparotomy for tumor resection. Median age at the time of surgery was 33.9 years (range 22-51 years). Desmoid tumors were found in the abdominal wall in 3/9 cases (33.3%) and in an intra-abdominal site in the remaining six cases (66.7%). Median time elapsed between ileal pouch-anal anastomosis and diagnosis of desmoid tumor was 37.5 months (range 14-60 months), while the median time between colectomy with ileorectal anastomosis and diagnosis was 63.7 months (range 25-116 months). In 6/9 (66.7%) patients with desmoid tumors, the disease was either under control or there was no evidence of tumor recurrence at a follow-up visit made a mean of 63.1 months later (range 12-240 months). CONCLUSIONS: Desmoid tumors were found in 13.2% of cases of familial adenomatous polyposis following colectomy; therefore, familial adenomatous polyposis patients should be followed-up and surveillance should include abdominal examination to detect signs and symptoms. Treatment options include surgery and clinical management with antiestrogens, antiinflammatory drugs or chemotherapy.

Long-term follow-up of an 8-year-old boy with insulinoma as the first manifestation of a familial form of multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.

Ressecções eletiva e de urgência para tratamento de neoplasia maligna do cólon em hospital universitário: estudo de 66 casos

O câncer de cólon é uma doença de alta prevalência e mortalidade, cujo tratamento baseia-se na ressecção cirúrgica. A possibilidade de cura aumenta com o diagnóstico precoce, daí a importância dos programas de rastreamento populacional do câncer colorretal. O presente estudo analisou, retrospectivamente, 66 pacientes submetidos a ressecções do cólon por neoplasia em um período de 58 meses no Hospital Universitário da Universidade de São Paulo. Os pacientes foram divididos em dois grupos: grupo 1, submetidos a cirurgia eletiva (28 pacientes), e grupo 2, submetidos a cirurgia de urgência (38 pacientes). Os grupos foram comparados com relação às variáveis sexo, idade, apresentação clínica, aspectos da técnica cirúrgica, sítio anatômico da lesão, estádio patológico, taxas de complicações, permanência hospitalar pós-operatória e óbitos na internação. Verificou-se no presente estudo que a idade entre os grupos foi semelhante. Houve uma predominância do sexo masculino entre os pacientes operados de urgência. No grupo de cirurgia eletiva, o principal sintoma foi a hematoquezia, enquanto os operados na urgência, tinham como principal queixa dor abdominal. A grande maioria dos pacientes, no momento da cirurgia, apresentava-se sintomática há meses. Os pacientes operados na urgência apresentaram mais tumores pT4 e os operados eletivamente apresentaram mais neoplasias em estádio I. Em ambos os grupos, o caráter oncológico dos procedimentos foi preservado, bem como foi alto o índice de anastomoses primárias (81,8%). As taxas de complicações pós-operatórias, o tempo de permanência hospitalar pós-operatório e a mortalidade foram semelhantes.

Nova técnica para o fechamento dinâmico da parede abdominal

Os avanços nos cuidados com o paciente traumatizado e com infecções abdominais graves são responsáveis por um número crescente de peritoneostomias. O manejo desta entidade é complexo e várias técnicas foram descritas para seu tratamento. Recentemente foi introduzido na literatura o conceito de fechamento dinâmico da parede abdominal, com elevadas taxas de sucesso. O objetivo deste trabalho é de servir como nota prévia de uma nova abordagem para o tratamento das peritoneostomias, desenvolvida no Hospital Universitário da Universidade de São Paulo. Trata-se de um procedimento simples e de baixo custo, facilmente realizado por cirurgião geral. O procedimento também foi utilizado como reforço em fechamentos abdominais tensos, de maneira profilática. O procedimento é descrito em detalhes, assim como os resultados nos primeiros pacientes. Apesar de promissora, refinamentos técnicos e estudos complementares são necessários para a validação da técnica.

Avaliação citométrica dos adipócitos localizados no tecido subcutâneo da parede anterior do abdome após infiltração percutânea de CO2

OBJETIVO: Avaliar os efeitos da infiltração de dióxido de carbono em adipócitos presentes na parede abdominal. MÉTODOS: Quinze voluntárias foram submetidas a sessões de infusão de CO2 durante três semanas consecutivas (duas sessões por semana com intervalos de dois a três dias entre cada sessão). O volume de gás carbônico infundido por sessão, em pontos previamente demarcados, foi sempre calculado com base na superfície da área a ser tratada, com volume infundido fixo de 250 mL/100cm² de superfície tratada. Os pontos de infiltração foram demarcados respeitando-se o limite eqüidistante 2cm entre eles. Em cada ponto se injetou 10mL, por sessão, com fluxo de 80mL/min. Foram colhidos fragmentos de tecido celular subcutâneo da parede abdominal anterior antes e após o tratamento. O número e as alterações histomorfológicas dos adipócitos (diâmetro médio, perímetro, comprimento, largura e número de adipócitos por campos de observação) foram mensurados por citometria computadorizada. Os resultados foram analisados com o teste t de Student pareado, adotando-se nível de significância de 5% (p<0,05). RESULTADOS: Encontrou-se redução significativa no número de adipócitos da parede abdominal e na área, diâmetro, perímetro, comprimento e largura após o uso da hipercapnia (p=0,0001). CONCLUSÃO: A infiltração percutânea de CO2 reduz a população e modifica a morfologia dos adipócitos presentes na parede abdominal anterior.

Aversão alimentar adquirida e qualidade de vida em mulheres com neoplasia mamária

OBJETIVO: Avaliar o comportamento alimentar de mulheres com câncer de mama submetidas à quimioterapia, e sua relação com a qualidade de vida destas pacientes. MÉTODOS: A partir de um ensaio clínico do tipo antes e depois, selecionou-se 25 mulheres do Hospital AC Camargo (São Paulo, Brasil) durante o período de outubro de 2005 a abril de 2006. As pacientes inclusas no estudo apresentavam diagnóstico de câncer de mama, com estadiamento I e II e indicação de tratamento quimioterápico adjuvante. Nos momentos T0 (antes) e T1 (após o tratamento quimioterápico), o comportamento alimentar (consumo e aversão alimentar) foi avaliado por três recordatórios 24 horas e um questionário Food Action, respectivamente. A qualidade de vida foi monitorada por meio do questionário Functional Assessment of Cancer Therapy-Breast. RESULTADOS: Após o tratamento quimioterápico (T1), o consumo de macro e micronutrientes não apresentou alterações significantes, mas o consumo de frutas e sucos aumentou (p=0,03). Perfil inverso foi observado em relação à preferência por café preto (p=0,01) e pelo grupo de bebidas (p<0,001). Alimentos gordurosos (38%), laticínios (23%), café preto (15%), chá (15%), chocolate (7%) e carne vermelha (7%) foram os principais alimentos associados ao desconforto das pacientes. Análises de qualidade de vida mostraram que o tratamento quimioterápico promoveu significante redução no bem estar físico (p<0,01). Após o mesmo, algumas variáveis do comportamento alimentar foram significantemente correlacionadas com os parâmetros de qualidade de vida. CONCLUSÃO: A relação bilateral entre comportamento alimentar e qualidade de vida foi modificada negativamente pelo tratamento quimioterápico.

Primary Hyperparathyroidism as the First Clinical Manifestation of Multiple Endocrine Neoplasia Type 2A in a 5-Year-Old Child

Background: Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life. Summary: A5-year-old girl was referred for prophylactic thyroidectomy as she carried the p.C634R RET mutation. She was clinically asymptomatic, with a normally palpable thyroid and with the cervical region free of lymphadenopathy or other nodules. Preoperative tests revealed hypercalcemia associated with elevation of parathyroid hormone (PTH) (calcium = 11.2mg/dL, calcium ion = 1.48mmol/L, phosphorus = 4.0 mg/dL, alkaline phosphatase = 625U/L, parathyroid hormone (PTH) PTH = 998 pg/mL). A thyroid ultrasound was normal and parathyroid scintigraphy with (99m)Tc-Sestamibi revealed an area of radioconcentration in the upper half of the left thyroid lobe suggesting hyperfunctioning parathyroid tissue. She underwent total thyroidectomy and parathyroidectomy and developed hypocalcemia. The anatomopathological examination showed no histopathological changes in the thyroid tissue and an adenoma of the parathyroid gland, confirming the diagnosis of hyperparathyroidism. Conclusions: Primary hyperparathyroidism can be a precocious manifestation of MEN2A. This case report highlights that asymptomatic hypercalcemia should be scrutinized in children related to patients with MEN2A who carry a mutation in the RET proto-oncogene, especially mutations in the codon 634, before the currently recommended age of 8 years.

Comparison of multispectral wide-field optical imaging modalities to maximize image contrast for objective discrimination of oral neoplasia

Multispectral widefield optical imaging has the potential to improve early detection of oral cancer. The appropriate selection of illumination and collection conditions is required to maximize diagnostic ability. The goals of this study were to (i) evaluate image contrast between oral cancer/precancer and non-neoplastic mucosa for a variety of imaging modalities and illumination/collection conditions, and (ii) use classification algorithms to evaluate and compare the diagnostic utility of these modalities to discriminate cancers and precancers from normal tissue. Narrowband reflectance, autofluorescence, and polarized reflectance images were obtained from 61 patients and 11 normal volunteers. Image contrast was compared to identify modalities and conditions yielding greatest contrast. Image features were extracted and used to train and evaluate classification algorithms to discriminate tissue as non-neoplastic, dysplastic, or cancer; results were compared to histologic diagnosis. Autofluorescence imaging at 405-nm excitation provided the greatest image contrast, and the ratio of red-to-green fluorescence intensity computed from these images provided the best classification of dysplasia/cancer versus non-neoplastic tissue. A sensitivity of 100% and a specificity of 85% were achieved in the validation set. Multispectral widefield images can accurately distinguish neoplastic and non-neoplastic tissue; however, the ability to separate precancerous lesions from cancers with this technique was limited. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3516593]

Neoplasia and paracoccidioidomycosis

Published studies on the association between cancer and paracoccidioidomycosis consist either isolated cases or clinical data based on hospital cohorts of paracoccidioidomycosis. The frequency of neoplasia in series of >= 80 patients with paracoccidioidomycosis ranges from 0.16 to 14.1%, mean of 3.96%. There are only two retrospective controlled studies, one of them showing greater incidence of carcinoma in biopsy and necropsy samples of paracoccidioidomycosis (12 cases in 147 patients with the mycosis: 8.2%) than in the necropsies of the control group (320 cases in 7,302 necropsies: 4.9%). In the other, 22,409 autopsies were reviewed and 4,372 cases of cancer were found; of the 85 patients with paracoccidioidomycosis, 12 were diagnosed with cancer. No differences were observed in the frequency of malignancies between the group of patients with paracoccidioidomycosis (14.1%) and the control group (19.5%). Considering all the reported cases, carcinoma was more frequent than hematological malignancies, and was more often found at the same site or in a neighboring site affected by the mycosis, usually occurring after the diagnosis of the mycosis. Commonly, the basic cause of death was related to secondary infections or neoplasia. Lymphoma was associated with poorly organized rich in fungi granuloma. The clinical course and mortality were related to the cancer evolution or secondary infections and was worse in lymphoid series, metastatic carcinoma or in patients under cytotoxic chemotherapy. Additionally, as in several cases the clinical and histopathological data may mimick neoplasia, the correct diagnosis of both diseases is essential to guarantee an early and safe intervention.

The assessment of oral cytology utilizing ploidy analysis and virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality which is due, at least in part, to late detection. Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until they are well advanced. Over the past several years there has been renewed interest in oral cytology as an adjuvant clinical tool in the investigation of oral mucosal lesions. The purpose of the present study was to compare the usefulness of ploidy analysis after Feulgen stained cytological thin-prep specimens with traditional incisional biopsy and routine histopathological examination for the assessment of the pre-malignant potential of oral mucosal lesions. An analysis of the cytological specimens was undertaken with virtual microscopy which allowed for rapid and thorough analysis of the complete cytological specimen. 100 healthy individuals between 30 and 70 years of age, who were non-smokers, non-drinkers and not taking any medication, had cytological specimens collected from both the buccal mucosa and lateral margin of tongue to establish normal cytology parameters within a control population. Patients with a presumptive clinical diagnosis of lichen planus, leukoplakia or OSCC had lesional cytological samples taken prior to their diagnostic biopsy. Standardised thin preparations were prepared and each specimen stained by both Feuglen and Papanicolau methods. High speed scanning of the complete slide at 40X magnification was undertaken using the Aperio Scanscope TM and the green channel of the resultant image was analysed after threshold segmentation to isolate only nuclei and the integrated optical density of each nucleus taken as a gross measure of the DNA content (ploidy). Preliminary results reveal that ploidy assessment of oral cytology holds great promise as an adjunctive prognostic factor in the analysis of the malignant potential of oral mucosal lesions.