Valor da ultra-sonografia na avaliação das alterações endometriais em pacientes tratadas com tamoxifeno

OBJETIVO: Avaliar as alterações endometriais por meio da ultra-sonografia transvaginal e correlacioná-las com os achados da histeroscopia e histologia, em pacientes submetidas a tratamento com tamoxifeno. MATERIAIS E MÉTODOS: No período de janeiro de 2003 a dezembro de 2005, foram incluídas pacientes com câncer de mama usuárias de tamoxifeno que apresentaram espessamento endometrial acima de 5 mm. Os achados foram correlacionados com os dados de histeroscopia e anatomopatologia. RESULTADOS: Foram selecionadas 25 pacientes com idade média de 62,6 anos. O tempo médio do diagnóstico do câncer foi de 4,3 anos e do uso de tamoxifeno, três anos. Vinte pacientes eram assintomáticas (80%) e as demais apresentaram sangramento (20%). À ultra-sonografia, 16% apresentaram espessamento endometrial entre 5 mm e 8 mm, 40% entre 9 mm e 15 mm, e 44% acima de 15 mm. Ao estudo com a histeroscopia, 40% apresentaram atrofia, 16% atrofia cística, 28% pólipos, e 16% lesão hiperplásica. O estudo anatomopatológico apresentou-se normal em 35,2% dos casos e mostrou atrofia em 5,8%, pólipo em 29,4% e hiperplasia em 11,7%. Foi observado um caso de adenocarcinoma (5,8%). CONCLUSÃO: A ultra-sonografia associada à histeroscopia apresentam-se como importantes aliados na avaliação de pacientes usuárias de tamoxifeno. A detecção de espessamento endometrial à ultra-sonografia apresenta baixa especificidade, enquanto a histeroscopia é mais acurada na detecção de pólipos, hiperplasia e alterações neoplásicas.

Information transfer between large and small two-dimensional polyacrylamide gel electrophoresis.

To determine the feasibility of data transfer, an interlaboratory comparison was conducted on colon carcinoma cell line (DLD-1) proteins resolved by two-dimensional polyacrylamide gel electrophoresis either on small (6 x 7 cm) or large (16x18 cm) gels. The gels were silver-stained and scanned by laser densitometry, and the image obtained was analyzed using Melanie software. The number of spots detected was 1337+/-161 vs. 2382+/-176 for small vs. large format gels, respectively. After gel calibration using landmarks determined using pl and Mr markers, large- and small-format gels were matched and 712+/-36 proteins were found on both types of gels. Having performed accurate gel matching it was possible to acquire additional information after accessing a 2-D PAGE reference database (http://www.expasy.ch/ cgibin/map2/def?DLD1_HUMAN). Thus, the difference in gel size is not an obstacle for data transfer. This will facilitate exchanges between laboratories or consultation concerning existing databases.

Treatment of pleural malignancies by photo-induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities.

BACKGROUND: Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. MATERIAL AND METHODS: Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. RESULTS: Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P  < 0.001). CONCLUSION: Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. © 2015 Wiley Periodicals, Inc.

Apresentação das lesões mamárias císticas à ultra-sonografia utilizando a elastografia

OBJETIVO: Demonstrar a apresentação mais freqüente das lesões mamárias císticas utilizando a elastografia e discutir a sua aplicabilidade. MATERIAIS E MÉTODOS: A casuística compôs-se de 150 pacientes encaminhadas para realização de biópsia mamária percutânea com 175 lesões. Foram excluídas as lesões com diagnóstico histológico de lesões sólidas (153 lesões) e incluídas as lesões com características císticas à histologia (22 lesões), incluindo cistos complicados, lesões papilíferas, lesões inflamatórias, hiperplasia de células colunares típica e ectasia ductal. Estas lesões foram classificadas de forma retrospectiva por meio da elastografia, conforme escores criados pelos autores, variando de 1 a 4. RESULTADOS: Das 22 lesões encaminhadas, 13 (59%) correspondiam a cistos, uma (4,6%) a ectasia ductal, duas (9,2%) a lesões inflamatórias, cinco (22,6%) a lesões papilíferas e uma (4,6%) a hiperplasia de células colunares. Foram encontrados 17 escores 2, quatro escores 3, um escore 4 e nenhum escore 1, com especificidade de 95%. CONCLUSÃO: As lesões císticas mamárias têm diferentes apresentações à elastografia, conforme o resultado histológico, sendo este um método útil para a sua diferenciação e de fácil aplicabilidade na clínica diária.

Ressonância magnética da próstata: uma visão geral para o radiologista

O adenocarcinoma prostático é o segundo tumor em incidência e mortalidade dentre as neoplasias malignas masculinas. Para adequada programação terapêutica é importante a distinção entre tumores confinados à próstata e aqueles com extensão extraprostática. Diferentes estudos têm demonstrado que a ressonância magnética da próstata com bobina endorretal auxilia no estadiamento local destes pacientes. Este artigo apresenta informações sobre a anatomia prostática, o aspecto tumoral à ressonância magnética, sinais de extensão tumoral extraprostática e invasão de vesículas seminais, sugestões de protocolo, princípios gerais e importância da espectroscopia de prótons, do estudo perfusional e da difusão, indicações da ressonância magnética na investigação de recidiva pós-operatória e pós-radioterapia, seu papel na detecção de lesões suspeitas em pacientes com suspeita clínico-laboratorial de adenocarcinoma prostático, além de apresentar os diagnósticos diferenciais e limitações do método.

Prevalence and clinical outcomes for patients with MET protein expression in patients with non-small cell lung cancer in Europe: Results from the European Thoracic Oncology Platform Lungscape Project.

Aim The reported prevalence of MET overexpression varies from 25-55% in non-small cell lung cancer (NSCLC) and clinical correlations are emerging slowly. In a well-defined NSCLC cohort of the Lungscape program, we explore the epidemiology, the natural history of IHC MET positivity and its association to OS, RFS and TTR. Methods Resected stage I-III NSCLC identified based on the quality of clinical data and FFPE tissue availability were assessed for MET expression using immunohistochemistry (IHC) on TMAs (CONFIRM anti total c-MET assay, clone SP44, Ventana BenchMark platform). All cases were analysed at participating pathology laboratories using the same protocol, after passing an external quality assurance program. MET positive status is defined as ≥ 50% of tumor cells staining with 2+ or 3+ intensity. Results A total of 2709 cases are included in the iBiobank and will be analysed. IHC MET expression is currently available for 1552 patients, with positive MET IHC staining in 380 cases [24.5%; IHC 3+ in 157 cases (41.3%) and 2+ in 223 cases (58.7%)]. The cohort of 1552 patients includes 48.2%, 44.7% and 4.4% cases of adenocarcinoma, squamous and large cell histologies, respectively. IHC MET status was independent of stage, age and smoking history. Significant differences in MET positivity were associated with gender (32% vs. 21% for female vs. male, p < 0.001), with performance status (25% vs. 18% for 0 vs. 1-3, p = 0.006), and histology (34%, 14% and 24% for adenocarcinoma, squamous and large cell carcinoma, p < 0.001). IHC MET positivity was independent of the IHC ALK status (p = 0.08). At last FU, 52% of patients were still alive, with a median FU of 4.8 yrs. No association of IHC MET was found with OS, RFS or TTR. Conclusions The preliminary results for this large multicentre European cohort describe a prevalence of MET overexpression that seems lower than previous observations in NSCLC, such as reported for the OAM4971g trial, suggesting potential biological differences between surgically resected and metastatic disease. Analysis for the full cohort is ongoing and results will be presented. Disclosure L. Bubendorf: Disclosures: Stock ownership: Roche Advisory boards: Roche, Pfizer Research support: Roche; K. Schulze: Full time employee of Roche; A. Das-Gupta: I am a full time employee of Roche. All other authors have declared no conflicts of interest.

Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Molecular profiling of non-small cell lung cancer by histologic subtype

Background: A substantial proportion of NSCLC has been shown to harbour specific molecular alterations affecting tumour proliferation and resulting in sensitivity to inhibition of the corresponding activated oncogenic pathway by targeted therapies. Comprehensive tumor profiling can diagnose such alterations and may identify new alterations opening additional treatment options for all distinct NSCLC subtypes. Methods: Over 6,700 non-small cell lung cancer cases referred to Caris Life Sciences between 2009 and 2014 were evaluated; clinical diagnoses and detailed tumor pathology were collected from referring physicians. Specific profiling was performed per physician request and included a combination of sequencing (Sanger, NGS or pyrosequencing), protein expression (IHC), gene amplification/rearrangement (CISH or FISH), and/or RNA fragment analysis within potential cancer-related genes and pathways. Results: Patients were grouped into cohorts according to histological subtype - adenocarcinoma (AD) (n=4,286), squamous cell carcinoma (SCC) (n=1,280), large cell carcinoma (LCC) (n=153) and bronchioalveolar carcinoma (BAC) (n=94). Protein overexpression of cMET (>2+ in >50% cells) was higher in AD (35.9%) compared to other subgroups (12-20%) while RRM1 and TOP2A levels were lower in AD. ALK or ROS1 were rearranged in 5.3% of patients with AD compared to 3.7% of patients with LCC and 1.2% of patients with SCC. EGFR mutations were found at low prevalence in both the LCC (0%) and SCC cohorts (2.8%) compared to 21% in AD. Similar lower rates of BRAF mutations were observed in the LCC and SCC cohorts compared to AD (0%, 1.1% and 5.1%). Pathway analysis showed activating mutations in the ERK pathway in 40% of patients with AD. Only 10-12% of patients with LCC or SCC had activating mutations in the ERK pathway. Conclusions: Despite the limitations of this retrospective series, we report comprehensive profiling of the largest cohort of NSCLC. Tumor profiling reveals that ADs may be more addicted to the ERK pathway than other histological subtypes. Drugs which target cMET may also have most utility in AD. Full analysis by histological subtype and additional correlative data on protein expression, gene copy number and mutations will be presented.

Cancerização de lóbulos: correlação de achados mamográficos e histológicos

OBJETIVO: Caracterizar os aspectos mamográficos de cancerização de lóbulos associados a carcinoma ductal in situ (CDIS), por meio de correlação entre achados de imagem e histológicos. MATERIAIS E MÉTODOS: O presente estudo retrospectivo foi baseado em uma revisão de laudos histopatológicos de 135 pacientes submetidas a biópsia de mama. O diagnóstico de cancerização de lóbulos associada a CDIS foi confirmado em 12 das pacientes. Dois casos foram excluídos porque os cortes histopatológicos não estavam disponíveis para correlação da patologia com a mamografia. Todas as imagens mamográficas foram retrospectivamente analisadas às cegas quanto aos resultados histológicos e classificados por dois experientes radiologistas especializados em mama. RESULTADOS: Nove casos (90%) apresentavam microcalcificações redondas agrupadas e um (10%) apresentava calcificações lineares. A distribuição das calcificações foi definida como lobular em todos os casos. A análise histopatológica demonstrou quatro casos de CDIS cribriforme, dois casos de comedocarcinoma, um caso de CDIS sólido, um caso de CDIS cribriforme associado com sólido e um caso de CDIS cribriforme associado com sólido e comedocarcinoma. No caso em que havia calcificações redondas e lineares, o subtipo histológico era de CDIS cribriforme. Com relação ao número de microcalcificações, nove casos apresentavam mais do que 20 e apenas um caso apresentava menos do que 10 microcalcificações. CONCLUSÃO: Na presente coorte, a avaliação mamográfica de pacientes com CDIS apresentando cancerização de lóbulos demonstrou agrupamentos de microcalcificações redondas com distribuição lobular. Embora agrupamentos de calcificações redondas sejam normalmente associados a um processo benigno, a cancerização de lóbulos por CDIS pode produzir um padrão similar, mimetizando, assim, uma condição benigna.

Nouveautés et perspectives dans la prise en charge des cancers colorectaux et gastriques avancés [News and perspectives in the treatment of advanced gastric and colorectal cancers].

Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.

Papel da ranitidina como meio de aprimorar a qualidade do exame de colangiopancreatografia por ressonância magnética

OBJETIVO: Avaliar o impacto da ranitidina por via oral na qualidade do exame de colangiopancreatografia por ressonância magnética (CPRM). MATERIAIS E MÉTODOS: Trinta e dois pacientes realizaram CPRM com aquisições 3D e 2D, com três estratégias de supressão do sinal líquido gastrintestinal: a) apenas em jejum; b) 12 horas após ingerir 300 mg de ranitidina; c) após a ingestão de solução de gadolínio. Três observadores avaliaram os estudos, atentos para o grau de visualização da árvore biliopancreática. Foi medida a concordância interobservador com o teste kappa. A diferença entre técnicas e formas de aquisição foi avaliada pela média da soma dos escores de graduação. RESULTADOS: As três estratégias de supressão do sinal líquido gastrintestinal apresentaram elevada reprodutibilidade. A supressão do sinal líquido gastrintestinal com a ranitidina foi semelhante ao jejum e ambas foram piores do que a solução de gadolínio. As aquisições 3D superaram a 2D apenas na visualização do ducto cístico e da vesícula biliar, sendo inferior ou equivalente nos demais segmentos ductais biliopancreáticos. CONCLUSÃO: O uso da ranitidina não parece justificado para aprimorar a avaliação da árvore biliopancreática em exames de CPRM. A CPRM 2D apenas em jejum permite a visualização ductal com elevada qualidade e reprodutibilidade na maioria dos casos.

Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas

Objective To correlate the results of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed with a specific protocol for assessment of breasts with histological/immunohistochemical findings in breast carcinoma patients. Materials and Methods Cross-sectional study with prospective data collection, where patients with biopsy-confirmed breast carcinomas were studied. The patients underwent PET/CT examination in prone position, with a specific protocol for assessment of breasts. PET/CT findings were compared with histological and immunohistochemical data. Results The authors identified 59 malignant breast lesions in 50 patients. The maximum diameter of the lesions ranged from 6 to 80 mm (mean: 32.2 mm). Invasive ductal carcinoma was the most common histological type (n = 47; 79.7%). At PET/CT, 53 (89.8%) of the lesions demonstrated anomalous concentrations of 18F-FDG, with maximum SUV ranging from 0.8 to 23.1 (mean: 5.5). A statistically significant association was observed between higher values of maximum SUV and histological type, histological grade, molecular subtype, tumor diameter, mitotic index and Ki-67 expression. Conclusion PET/CT performed with specific protocol for assessment of breasts has demonstrated good sensitivity and was associated with relevant histological/immunohistochemical factors related to aggressiveness and prognosis of breast carcinomas.

Complete internal audit of a mammography service in a reference institution for breast imaging

Objective Undertaking of a complete audit of the service of mammography, as recommended by BI-RADS®, in a private reference institution for breast cancer diagnosis in the city of São Paulo, SP, Brazil, and comparison of results with those recommended by the literature. Materials and Methods Retrospective, analytical and cross-sectional study including 8,000 patients submitted to mammography in the period between April 2010 and March 2011, whose results were subjected to an internal audit. The patients were followed-up until December 2012. Results The radiological classification of 7,249 screening mammograms, according to BI-RADS, was the following: category 0 (1.43%), 1 (7.82%), 2 (80.76%), 3 (8.35%), 4 (1.46%), 5 (0.15%) and 6 (0.03%). The breast cancer detection ratio was 4.8 cases per 1,000 mammograms. Ductal carcinoma in situ was found in 22.8% of cases. Positive predictive values for categories 3, 4 and 5 were 1.3%, 41.3% and 100%, respectively. In the present study, the sensitivity of the method was 97.1% and specificity, 97.4%. Conclusion The complete internal audit of a service of mammography is essential to evaluate the quality of such service, which reflects on an early breast cancer detection and reduction of mortality rates.

Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

AbstractObjective:In the present study, the authors investigated the in vitrobehavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy.Materials and Methods:The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed.Results:Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation.Conclusion:Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations

Abstract We present a case of immunoglobulin G4 (IgG4)-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease.