Dissertations / Theses on the topic 'Sentinel lymph node concept'

Objective: To prospectively evaluate the role of sentinel lymph node (SLN) biopsy in the management of well differentiated thyroid carcinoma (WDTC)Methods: I designed and implemented a SLN biopsy protocol and subsequently performed it on consecutive patients undergoing thyroid surgery. Thyroid nodules were injected with methylene blue dye. A central compartment neck dissection (CCND) was performed. Frozen section analysis of the SLNs was performed.Results: 157 patients are included in this study. 94 patients had WDTC. Sevently three percent (69/94) of WDTC patients were found to have detectable SLNs. Twenty percent (14/69) of patients with SLNs were found to have central compartment metastases. The sensitivity, specificity, positive predictive value and negative predictive value of our SLN biopsy technique to remove all disease from the central compartment was 92.9%, 100%, 100% and 98.8% respectively (p < 0.0001). Conclusion: This data series suggests that if a patient has SLNs deemed as negative for malignancy on frozen section, the rest of the central compartment is unlikely to have lymph node metastasis.
Contexte: Notre objectif est d'évaluer prospectivement le rôle du biopsy ganglion sentinelle dans la gestion du cancer de la thyroïde bien différencié Méthodes: Nous avons conçu et mis en place un protocole de biopsie du ganglion sentinelle et par la suite effectuées notre protocol sur des patients consécutifs subissant une thyroïdectomie. Les nodules ont été injectés avec du bleu de méthylène. Un dissection du cou central a été effectuée. Examen intra-operatoire des ganglion a été réalisée.Résultats: 157 patients sont inclus dans cette étude. 94 patients avaient un dissection central du cou. 73% (69/94) des patients ont été trouvés à avoir ganglion détectable. 20% (14/69) des patients atteints de ganglion ont été trouvés à avoir des métastases compartiment central. La sensibilité, spécificité, valeur prédictive positive et valeur prédictive négative de notre technique de biopsie du ganglion sentinelle pour enlever toutes les maladies à partir du compartiment central était de 92,9%, 100%, 100% et 98,8% respectivement (p <0,0001).Conclusion: Cette série de données volumineux suggère que si un patient a jugé comme négatif intra-operatoire de malignité sur la section gelée, un dissection central peut être preventire.

Introduction and Aims Sentinel lymph nodes are the first nodes draining a primary tumour and the most likely sites of early metastases. A minimally invasive technique of identifying sentinel nodes in oesophageal adenocarcinoma could revolutionise management by determining whether patients with submucosal disease can be treated solely by endoscopic resection and whether other patients are suitable for a less radical lymphadenectomy. We evaluated a laparoscopic technique of identifying abdominal sentinel lymph nodes in patients with oesophageal adenocarcinoma and assessed whether these nodes could predict overall lymph node status. Methods This trial recruited patients with lower-third oesophageal adenocarcinoma planned for two-stage oesophagectomy with two-field lymphadenectomy. Sentinel node identification occurred immediately before resection, following endoscopic submucosal injection of 99mTechnetium-nanocol!oid. A laparoscopic gamma probe measured radioactivity from all nodal stations at laparoscopy, from the open abdomen, from the mediastinum following thoracotomy and ex vivo following removal of the specimen. Sentinel nodes had in vivo radioactivity greater than twice and ex vivo greater than 10 times background. Specimens were examined using haematoxylin and eosin and immunohistochemistry. Results A total of 1297 lymph nodes were examined from 40 patients (median 31 nodes). The median age and BMI were 65.5years and 26.5kg/m2 re s pectively. The overall sentinel node detection rate was 85% and sensitivity 88%. The laparoscopic abdominal sentinel node detection rate was 58% (23/40). Lymph node metastases were identified in 13 of these 23 patients, in whom laparoscopic abdominal sentinel nodes were positive in 10 but negative in three (sensitivity 77%). Two of these negative patients had mediastinal sentinel node micrometastases. Eleven patients had only mediastinal sentinel nodes. Five patients had no sentinel nodes. Adhesions prevented laparoscopy in one patient. Conclusions Laparoscopic identification of abdominal sentinel lymph using 99mTechnetium in patients with oesophageal adenocarcinoma was safe and technically feasible but not sensitive enough to predict overall nodal status.

Includes bibliographical references (leaves 72-90).
Sentinel lymph node (SLN) biopsy is being used increasingly for staging early breast carcinoma in place of complete axillary lymph node dissection. The optimal method to identify the SLN and has not been clearly elucidated in the literature. A number of techniques have been proposed for identifying SLN/s. The main debate centres on whether to use a blue dye or radiopharmaceutical method either singly or in combination.

Background Axillary nodal status is the single most important prognostic factor in breast cancer diagnosis. If cancerous cells are present, the sentinel lymph node (SLN) is the axillary lymph node that is most likely to contain metastatic disease. In early stage breast cancer, the SLN is localised (then surgically removed for pathological analysis) using a radioisotope and/or a blue dye injected into the breast Super-paramagnetic iron oxide (SPIO) nanoparticles are novel agents that, when injected, could potentially both localise and characterise the SLN using MRI such that surgical SLN biopsy is no longer required. Aims To evaluate axillary SLN localisation after SPIO injection with, pre-operatively, axillary MRI and, intra-operatively, with a hand held magnetometer and to characterise SLN SPIO uptake using ex-vivo MRI. Methods From November 2009 - March 2011, 51 patients with early stage breast cancer underwent SLN biopsy following a subcutaneous injection of SPIO in addition to the standard injection of radioisotope (Tc99M) and blue dye. SPIO injection technique was refined during the trial with an initial dose of 2mls and then 4mls in 8 and then 43 women respectively. Pre-operative axillary in vivo MRI (1.5T) was carried out on 14 women and ex vivo high resolution MRI (9.4T) on 36 nodes. During surgery, an SLN was defined as either "hot", "blue", "palpable" or "SPIO detected". Axillary clearance was carried out for SLN-positive disease. Results In total, 11 of the 51 patients had positive SLNs. On pre-operative axillary MRI, SPIO uptake was noted in at least one node in all 14 patients. A total of 35 nodes were identified. Uptake of SPIO in the SLN was seen at a minimum of 12mins post injection. Involved SLNs were not differentiated from normal SLNs following morphological characterisation or based on loss of T2 signal within the individual SLN. At SLN biopsy, 134 hot, blue, palpable or SPIO-containing nodes were identified in 51 patients. The magnometer identified 92 SPIO-containing nodes in 51 (84%) patients. One node in one patient was not identified using the combined technique but was found to contain SPIO. Of the 16 hot, blue or palpable involved nodes in 11 patients, 9 contained SPIO. In summary, the SPIO SLN localisation rate and FNR in patients was 84% and 16% respectively. Ex vivo SLN MRI demonstrated SPIO uptake in all 35 SLNs preferential to the sinuses and sub-capsular spaces. Of the 3 involved nodes, areas of metastasis did not take up SPIO, whereas in normal areas of the node, SPIO was positively identified. Conclusion In our study, subcutaneous SPIO, a novel SLN-localising agent, was taken up by axillary nodes and identified on pre-operative axillary MRI. Node positive SLNs were identified on ex vivo MRI, but SPIO did not demonstrate sufficient accuracy at SLN localisation for routine clinical use.

Breast cancer is the single most prevalent form of cancer in the UK today, accounting for around 16% of all diagnoses, and around 31% of diagnoses in women. The survival rates are good, however the prognosis is heavily dependent on the stage to which the cancer has progressed at diagnosis. In order to help accurately determine this stage, the sentinel lymph node of patients undergoing tumour resection surgery is removed and examined cytologically for the presence of cancerous cells. This examination of the lymph node is currently the rate-limiting step in the operation as a whole. There is evidence in the literature to suggest that cancerous tissue has a measurably different infrared spectrum from healthy tissue owing to chemical and morphological differences in the tissue. There is further evidence to suggest that in the visible and near infrared region, the spectra of healthy lymph node tissue is different from that of cancerous tissue. This thesis details a project, performed in collaboration with a surgical team at St Mary's Hospital, Newport, Isle of Wight, to analyse spectral images taken in the visible and near infrared, of biopsied lymph node tissue. In the course of the project, an unsupervised classificaton technique, based on an extension to the well establised 'spectral angle', was developed to analyse the spectral images. Psoriasis affects 2-3% of the UK population causing itchy and/or painful plaques on the skin. One of the main treatments for psoriasis is UV phototherapy, exposure to which is a risk factor for burning and the development of cancers. This thesis details an investigation into the possibility of developing a targeted UV phototherapy system based on spectral imaging to delineate the plaques and a proposed new UV laser for treatment.

Quantum Dots (QDs) are fluorescent nanoparticles that can be used as fluorescent probes for cancer localisation and sentinel lymph node biopsy (SLNB). The current tracers for SLNB including the blue dye and radiocolloid have various drawbacks limiting their widespread use. Near Infrared (NIR) QDs can potentially replace these tracers, based on their deep tissue visibility as the biological window is transparent to NIR wavelengths. QDs can also be conjugated to specific biomolecules for targeted cancer localisation and therapy. Their main limitation is toxicity as most QDs are based on heavy metal salts. This project aims to develop a biocompatible QD for clinical application using a novel nanoparticle - Polyhedral Oligomeric Silsesquioxane (POSS) based surface coatings. Materials & Methods A novel nanocomposite polymer emulsion POSS-PCU was synthesized by integrating POSS units into poly(carbonate-urea)urethane (PCU) chains and used to encapsulate QDs based on CdTe/CdSe/ZnSe and CdTe/CdS/ZnS. Mercapto-POSS on its own was also used to coat CdTe core QDs. Characterization was performed using various techniques and in vitro toxicity was established. QDs were bioconjugated to anti-HER2 antibody and used to localise HER-2 receptors on SK-BR-3 breast cancer cells. In vivo biodistribution was determined using a tail vein injection of QDs into male Sprague-Dawley rats for 1 and 24h. Organ biodistribution was quantified by fluorescence studies and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). A live NIR imaging system was set up and NIR-QDs used to demonstrate SLN localisation in a rat model. Results POSS-PCU coated QDs showed significantly reduced toxicity and enhanced photostability on in vitro and in vivo studies. QD-anti-HER2-Antibody bioconjugate successfully localised HER-2 receptors in vitro. Biodistribution studies showed maximal uptake by the liver and spleen. NIR-QDs localised to the SLN and were visualised by the live NIR imaging system. Conclusion NIR-QDs can be used as fluorescent probes for cancer localisation and SLNB. POSS nanocomposite based surface coatings can stabilise QDs for overall reduced toxicity and enhanced photostability allowing relentless possibilities for clinical application.

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care.

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care.

This thesis consisted a series of sentinel node biopsy (SNB) studies in Chinese patients to evaluate its impact on the management of breast cancer. Pilot studies The first SNB pilot study was performed in 30 patients using the blue dye technique. Accuracy was verified by axillary lymph node dissection (ALND). The success rate was 83% and the false-negative rate was 25%. The second pilot study was performed in 50 patients using combined mapping with isotope and dye. The success rate was 94% with no false-negative. SNB is shown to be feasible and accurate in Chinese. The optimal mapping method Combined mapping was superior to the blue dye technique. This could be due to the mapping technique or improved experience. One hundred and twenty-three women were randomly assigned to either the blue dye or combined mapping. Combined mapping had a higher success rate than the blue dye technique (100% versus 86%). False-negative rates were similar (0% versus 4.5%). Combined mapping is the preferred method. Accuracy of frozen section (FS) FS was used intra-operatively to guide the need of ALND. In 260 SNB, FS was compared to serial section and immuno-histochemical staining. FS detected 53 of 86 patients with SN metastases with a false-negative rate of 38.4%. The false-negative rates for macro-, micro-metastases and isolated tumour cells (ITC) were 2.4%, 57.7% and 94.4%. FS was accurate to diagnose macro-metastases but not micro-metastases and ITC. Can we skip ALND in SN metastases? 139 patients with SNB and ALND were studied to identify predictive factors for non-SN metastases. 55 had metastatic SN but 38 (69%) had no residual metastases in non-SN. Tumours <3 cm, a single metastatic SN, micro-metastases and absence of extra-capsular spread were significant factors to predict no residual nodal disease. Non-SN metastases were found in 42%, 19% and 0% when SN contained macro-, micro-metastases and ITC. Based on risk of non-SN involvement, ALND is indicated for macro- and micro-metastases but not for ITC. Extended indication for ductal carcinoma in situ (DCIS) SNB may be useful for staging of patients with a pre-operative diagnosis of DCIS because invasive cancer is not infrequently found on pathological examination of resected specimens after surgical excision. One hundred and seven patients with DCIS on core biopsy underwent SNB. Thirty-two patients (29.9%) were upstaged to invasive cancer and 9 (28.1%) had SN metastases. Performing SNB reduced the re-operation rate from 29.9% to 1.9%. Palpable mass and radiological mass lesion were associated with upstage. Extended indication: Sentinel Node Occult Lesion Localisation (SNOLL) Radioisotope is used to localise non-palpable breast cancer and SN. Seventy-four patients with non-palpable breast cancers underwent SNOLL. Radioisotope was injected into cancer and gamma probe guided breast cancer and SN resection. Primary cancer was removed in 73 patients (99%) after the first-round excision and 82% had complete excision. Gamma probe identified SN in 82% and supplementary blue dye increased SN detection to 97%. SNB modified the practice of breast cancer surgery. It has a major impact on the diagnosis, staging and treatment of breast cancer.
published_or_final_version
Surgery
Master
Master of Surgery

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior
Introduction and objective: Sentinel Lymph Node Biopsy (SLNB) has currently replaced axillary dissection in early-stage breast cancer in clinically tumor-free patients. Technetium-99 (99Tc) is the gold standard for the identification of Breast Sentinel Lymph Node (SLN). Blue dyes are a less expensive and widely used option in Brazil. These dyes are responsible for several adverse and hypersensitivity reactions that â although rare â can put patientsâ lives at risk. There is an interest in the discovery of new equivalent substances with less side effects than those used in SLNB. This research assesses the safety and equivalence of the use of hemosiderin in SLNB in breast cancer compared to technetium-99 (99Tc). Hemosiderin is a hemoglobin derivate identified in a preclinical trial that has proven to be effective in the SLNB of female dogsâ breasts. The aim of this research is to assess the safety and potential equivalence of the use of hemosiderin in SLNB in human breast compared to the 99Tc. Method: The experiments took place in the period from September 2011 to September 2013. Patients were selected from the Mastology Service of the MEAC/HC/UFC and included 14 volunteer women with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla who were submitted to SLNB using hemosiderin, produced based on an aseptic hemolysate obtained from autologous blood, injected in the periareolar region 24h before surgery on an outpatient basis. 0.5 mCi of 99Tc was also injected in the subareolar region in the immediate preoperative period. Patients underwent breast MRI and mammary scintigraphy. In the operating room, patients â under general anesthesia â were submitted to SLNB, with incision in the axillary fold guided by Gamma-Probe and dissection by planes until the identification of the point of maximum uptake of 99Tc, identifying the marked sentinel lymph nodes (SLN) and their colors. Breast procedure was defined based on the correlation of the size and location of primary tumor and the axilla procedure was performed based on the presence or not of SLN metastasis. All surgical specimens were sent for pathological and immunohistochemical study. Results: There were no side effects, allergic reactions, surgical infection or toxicity related to the method applied. The conocordance rate between hemosiderin and 99Tc was 100%. The sensitivity and accuracy of hemosiderin was 100%. An incidental finding refers to magnetic properties of axillary lymph nodes (ALN) identified as an hypersignal in the NMR with hemosiderin in 100% of the exams. In two of four cases with positive SLN on histopathology, the image of the NMR with hemosiderin suggested neoplastic involvement of the marked lymph node. Conclusion: Hemosiderin proved to be an efficient and safe dye that is equivalent to 99Tc in breast SLNB.
IntroduÃÃo e objetivo: Atualmente, a Biopsia do Linfonodo Sentinela (BLS) substitui o esvaziamento axilar no estadiamento do cÃncer de mama inicial com axila clinicamente negativa. O tecnÃcio 99 (Tc99) à o padrÃo ouro para identificaÃÃo do Linfonodo Sentinela (LS) da mama. Os corantes azuis sÃo uma opÃÃo menos onerosa e mais difundida no Brasil. Estes corantes sÃo responsÃveis pelas reaÃÃes adversas e de hipersensibilidade que, embora raras, podem pÃr em risco à vida dos pacientes. Hà interesse na descoberta de novas substÃncias equivalentes e com menores efeitos colaterais Ãs usadas na BLS. Aqui se avaliam a seguranÃa e a equivalÃncia do uso da hemossiderina, em comparaÃÃo ao tecnÃcio 99 (Tc99) na BLS no cÃncer de mama. A hemossiderina à um derivado da hemoglobina, identificada em estudo prÃ-clÃnico, que se mostrou eficaz na BLS da mama da cadela. O objetivo desta pesquisa à avaliar a seguranÃa e a potencial equivalÃncia do uso da hemossiderina em comparaÃÃo com o Tc99 na BLS da mama humana. MÃtodo: Os experimentos ocorreram no perÃodo de setembro de 2011 a setembro de 2013. As pacientes selecionadas no ServiÃo de Mastologia da MEAC/HC/UFC, foram 14 mulheres, voluntÃrias, portadoras de cÃncer de mama, com tumores iniciais (T1/T2) e axila clinicamente negativa, que se submeteram a BLS, utilizando hemossiderina, produzida com base em um hemolisado, assÃptico, obtido de sangue autÃlogo, injetada na regiÃo subareolar, ambulatorialmente, 24h antes da cirurgia. No prÃ-operatorio imediato, injetou-se, tambÃm, na regiÃo subareolar, 0,5mci de Tc99. As pacientes foram submetidas a ressonÃncia magnÃtica das mamas, e a cintilografia mamÃria. No Centro CirÃrgico, as pacientes sob anestesia geral realizaram a BLS com incisÃo na prega axilar, guiada pelo gamma-probe, dissecÃÃo por planos atà a identificaÃÃo de ponto de captaÃÃo mÃxima do Tc99, identificando-se o Linfonodo Sentinela (LS) marcado e a sua coloraÃÃo. O procedimento da mama foi definido em correlaÃÃo com o tamanho e localizaÃÃo do tumor primÃrio e a conduta em relaÃÃo à axila em funÃÃo da presenÃa ou ausÃncia de metÃstase no LS. Toda peÃa cirÃrgica foi encaminhada à avaliaÃÃo anatomopatolÃgica e imunohistoquÃmica. Resultados: NÃo foram observados efeitos colaterais, reaÃÃes alÃrgicas, infecÃÃo cirÃrgica ou toxicidade relacionados ao mÃtodo empregado. A taxa de concordÃncia entre a hemosiderina e o Tc99 foi de 100%. A sensibilidade e acurÃcia da hemossiderina foi 100%. Um achado incidental foi o magnetismo dos linfonodos axilares (LA) identificados como hipersinal à RNM com hemossiderina em 100% dos exames. Em dois de quatro casos de LS positivos na histopatologia, a imagem da RNM com hemossiderina sugeria comprometimento neoplÃsico do linfonodo marcado. ConclusÃo: A hemossiderina se mostrou um corante eficiente, seguro e equivalente ao TecnÃcio 99 na BLS da mama

Orientador: Antônio José Maria Cataneo
Resumo: Introdução: No melanoma primário, a aplicabilidade da biópsia de linfonodo sentinela (BLS), seguida ou não de esvazimento linfonodal (EL) é conhecida. Na recidiva locorregional (RL) de melanoma, alguns serviços tendem a indicá-la, buscando estadiamento mais acurado para embasar condutas individualizadas aos pacientes, ainda que as evidências sejam insuficientes. Objetivo: Avaliar o sucesso da BLS no encontro do linfonodo sentinela (LNS) e sua positividade na RL. Comparar a sobrevida entre os pacientes com LNS positivo e negativo. Verificar diferença na sobrevida pós EL. Métodos: Revisão sistemática, através das bases MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE e CENTRAL, buscando estudos experimentais e observacionais sobre BLS na RL de melanoma. Desfechos avaliados: sucesso na BLS pelo encontro do LNS, positividade para melanoma no LNS; sobrevida no subgrupo LNS positivo comparado com o negativo; sobrevida livre de doença no subgrupo LNS positivo comparada com o negativo; sobrevida dos pacientes submetidos ao EL. Para metanálises, utilizaram-se RevMan 5.3 e StatsDirect 3.0.121. Resultados: Foram identificados 1872 estudos, destes, seis estudos observacionais foram incluídos, totalizando 449 pacientes. O LNS foi encontrado em 98% das BLS (IC 95-100%, I2=53,7% - seis estudos). LNS com 32% de positividade para melanoma (IC 19-47%, I2= 84,6% - seis estudos). A chance de sobrevida global em cinco anos foi 2,49 vezes maior no subgrupo com LNS negativo (IC 95% 1,41-4,38, I2=0% - qua... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Background: In primary melanoma, the applicability of sentinel lymph node biopsy (SLB), followed or not by complete lymph node dissection (CLND) is known. In locoregional recurrence (LR) of melanoma, some groups may indicate it for more accurate staging to support individualized management, even with scarce evidence. Objective: To evaluate success in SLB and its positivity in LR. Compare survival between patients with positive and negative sentinel lymph node (SLN). Check for survival modification after CLND. Methods: Systematic review through databases such as MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE and CENTRAL, searching for experimental and observational studies on SLB in melanoma LR. Outcomes assessed: success in SLB by finding the SLN, positivity for melanoma in the SLN; survival in the positive SLN subgroup compared to the negative one; disease-free survival in the positive versus negative SLN subgroup; survival of patients undergoing CLND. For meta-analyzes, RevMan 5.3 and StatsDirect 3.0.121 were used. Results: The total number of patients in six observational studies was 449, over 1872 studies indentified. The SNL was found in 98% of SLB (95-100% CI, I2 = 53.7%, 6 studies). SLB detected 32% positivity for melanoma on SNL (CI 19-47%, I2 = 84.6%, 6 studies). The chance of five year overall survival was 2,49 higher in the negative SNL subgroup (95% CI 1.41-4.38, I2 = 0%, 4 studies). Meta-analyzes were not performed due to lack of objective data for disease-free survi... (Complete abstract click electronic access below)
Doutor

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
Os benefÃcios da identificaÃÃo do linfonodo sentinela no tratamento do cÃncer em vÃrios ÃrgÃos e locais jà estÃo bem definidos, porÃm hà uma carÃncia de estudos em relaÃÃo ao cÃncer de canal anal, principalmente pela ausÃncia de modelos experimentais com esse fim. Neste estudo propÃs-se um modelo para pesquisa do linfonodo sentinela no canal anal em cÃes. Foram selecionados 13 cÃes mestiÃos da espÃcie Canis familiaris, fÃmeas, com peso aproximado de 10,9kg e idade variando de 12 a 24 meses, provenientes do Centro de Controle de Zoonoses do MunicÃpio de Fortaleza; distribuÃdas em dois grupos (I e II) de acordo com o local de injeÃÃo dos marcadores no canal anal. ApÃs anestesia geral, as cadelas do grupo I receberam injeÃÃo de 0,5 ml de 99mTc e 5ml de azul de metileno 1% em regiÃo anterior do canal anal, e as cadelas do grupo II receberam injeÃÃo dos marcadores na regiÃo posterior do canal anal. ApÃs 30 minutos da injeÃÃo do radiofÃrmaco, as regiÃes inguinais foram dissecadas em busca de linfonodos marcados com o corante vital ou radiofÃrmaco atravÃs da captaÃÃo de radiatividade do linfonodo pelo aparelho Gamma-Probe. Posteriormente, foi realizada laparotomia do animal em busca de linfonodos marcados em cadeias ilÃacas e pararretais. Todos os linfonodos marcados foram retirados e enviados para anÃlise histopatolÃgica. No total, foram marcados 34 linfonodos em ambos os grupos. O mÃtodo de detecÃÃo com azul de metileno 1% corou 13,6 vezes mais linfonodos no grupo I e 15,8 mais linfonodos no grupo II, com baixa concordÃncia pelo coeficiente de Kappa. A curva ROC comparando os dois mÃtodos mostrou maior especificidade do radiocolÃide. Ambos os mÃtodos encontraram mais linfonodos em cadeia ilÃaca direita tanto no grupo I como no grupo II. O grupo II mostrou maior marcaÃÃo de linfonodos unilaterais pelo mÃtodo de corante vital com significÃncia pelo teste exato de Fischer unicaudal (p=0,043), mas o tecnÃcio nÃo tendeu a mostrar diferenÃa significante entre a marcaÃÃo de linfonodos unilaterais ou bilaterais. Apenas um linfonodo, marcado apenas com azul, nÃo foi confirmado como tecido linfoide na anÃlise histopatolÃgica. Conclui-se que o mÃtodo de detecÃÃo do linfonodo sentinela de canal anal na cadela pelo azul de metileno e o tecnÃcio à factÃvel e possui um alto grau de acurÃcia.
Os benefÃcios da identificaÃÃo do linfonodo sentinela no tratamento do cÃncer em vÃrios ÃrgÃos e locais jà estÃo bem definidos, porÃm hà uma carÃncia de estudos em relaÃÃo ao cÃncer de canal anal, principalmente pela ausÃncia de modelos experimentais com esse fim. Neste estudo propÃs-se um modelo para pesquisa do linfonodo sentinela no canal anal em cÃes. Foram selecionados 13 cÃes mestiÃos da espÃcie Canis familiaris, fÃmeas, com peso aproximado de 10,9kg e idade variando de 12 a 24 meses, provenientes do Centro de Controle de Zoonoses do MunicÃpio de Fortaleza; distribuÃdas em dois grupos (I e II) de acordo com o local de injeÃÃo dos marcadores no canal anal. ApÃs anestesia geral, as cadelas do grupo I receberam injeÃÃo de 0,5 ml de 99mTc e 5ml de azul de metileno 1% em regiÃo anterior do canal anal, e as cadelas do grupo II receberam injeÃÃo dos marcadores na regiÃo posterior do canal anal. ApÃs 30 minutos da injeÃÃo do radiofÃrmaco, as regiÃes inguinais foram dissecadas em busca de linfonodos marcados com o corante vital ou radiofÃrmaco atravÃs da captaÃÃo de radiatividade do linfonodo pelo aparelho Gamma-Probe. Posteriormente, foi realizada laparotomia do animal em busca de linfonodos marcados em cadeias ilÃacas e pararretais. Todos os linfonodos marcados foram retirados e enviados para anÃlise histopatolÃgica. No total, foram marcados 34 linfonodos em ambos os grupos. O mÃtodo de detecÃÃo com azul de metileno 1% corou 13,6 vezes mais linfonodos no grupo I e 15,8 mais linfonodos no grupo II, com baixa concordÃncia pelo coeficiente de Kappa. A curva ROC comparando os dois mÃtodos mostrou maior especificidade do radiocolÃide. Ambos os mÃtodos encontraram mais linfonodos em cadeia ilÃaca direita tanto no grupo I como no grupo II. O grupo II mostrou maior marcaÃÃo de linfonodos unilaterais pelo mÃtodo de corante vital com significÃncia pelo teste exato de Fischer unicaudal (p=0,043), mas o tecnÃcio nÃo tendeu a mostrar diferenÃa significante entre a marcaÃÃo de linfonodos unilaterais ou bilaterais. Apenas um linfonodo, marcado apenas com azul, nÃo foi confirmado como tecido linfoide na anÃlise histopatolÃgica. Conclui-se que o mÃtodo de detecÃÃo do linfonodo sentinela de canal anal na cadela pelo azul de metileno e o tecnÃcio à factÃvel e possui um alto grau de acurÃcia.

Abstract Introduction Knowledge about the oncologic status of pelvic lymph nodes forms an essential and integral part in the management of women with uterine cancer. Lymph node status is part of endometrial cancer staging and plays an important role in primary treatment and adjuvant treatment planning and prognosis in women with cervical cancer. Current practice in the management of uterine cancers involves systematic full pelvic lymphadenectomy, mainly to determine the oncological status of the nodes, as there is no high-quality evidence suggesting a therapeutic effect attributable to lymphadenectomy. Imaging in the form of computed tomography (CT) scans and magnetic resonance (MRI) scan is not accurate to determine pelvic lymph node status in women with uterine cancer. Functional scans such as 18Fluoro-deoxy-glucose positron emission/computed tomography (FDG-PET/CT) scan might provide better access in this setting. Sentinel lymph node biopsy (SLNB) procedures, specifically the SLNB algorithm, have been proposed as a safe and accurate alternative procedure to full systematic lymphadenectomy in women with uterine cancers. It has also been proposed as a better alternative than complete omission of lymphadenectomy in women with presumed low risk early stage endometrial cancer. SLNB procedures might also be able to detect higher rates of lymph node metastases with the detection of micro metastases following pathological ultrastaging The presence or absence of high risk human papilloma virus (hrHPV) DNA in sentinel lymph nodes of women with cervical cancer has also been suggested to be a useful adjunct to frozen section examination (FSE) in assisting with determination of the status of the non-sentinel nodes. Some data suggest the combination of negative FSE and absence of hrHPV accurately predict the absence of metastases. South African women have high prevalence of human immunodeficiency virus infection, tuberculosis (TB) and pelvic inflammatory disease (PID). All these infections involve the lymphatic system. Data on SLNB procedures are form well-developed countries with different disease burdens and socioeconomic profiles, and there is no data from women living in low-resource settings. Aims This study aimed to determine the efficacy of and performance of FDG-PET/CT scan and SLNB and SLNB algorithm in accurately predicting the regional lymph node status of the pelvis in women with early stage cervical cancer and presumed early stage endometrial cancer. It also aimed to investigate the usefulness of HPV DNA testing of sentinel nodes in women with cervical cancer. Population and setting This was a prospective observational study performed in the Gynaecologic Oncology Unit at the Kalafong Provincial Tertiary Hospital and Steve Biko Academic Hospital. Patients aged 18 years and older, with operable stages cervical cancer and presumed early stage endometrial cancer willing and able to provide informed consent were eligible for inclusion. Materials and methods Sentinel node mapping was done using methylene blue (MB) and indocyanine green (ICG) injected into the cervix after induction of anaesthesia at the time of primary surgery. 99Technetium nanocolloid (99Tc) was administered one day pre-operatively followed by lymphoscintigram. FDG-PET/CT scans were performed prior to surgery. Following mapping and removal, FSE, HPV DNA typing, haematoxylin and eosin (H&E) examination with ultrastaging on H&E negative specimens were performed on the SLNs. All patients underwent systematic full pelvic lymphadenectomy and appropriate cancer surgery. Results One hundred patients were prospectively recruited to the study and results of 94 patients were available for analysis. SNL detection rate of the whole group was 60.6% with bilateral detection 29.2%. Twenty-four patients (25.5%) had pelvic metastases. Sixty-five percent of women with cervical cancer in this study were HIV positive, and the SLN detection rate in this group was 65% with bilateral detection rate of 30%. The detection rate was significantly higher in women without nodal metastases, those with stage IA2 – IB2 disease, with tumour less than 2 cm and women with BMI less than 25 kg/m2. HIV status, history of TB, PID and the presence of adhesions did not influence the SLN detection rate. The sentinel lymph node biopsy algorithm has a sensitivity of 100%, NPV of 100% and a false negative rate of 0% in this study. The SLNB procedure identified two women with only micro metastases (15.4%). These women would not have been identified with systematic lymphadenectomy and H&E examination. Indocyanine green and the combination of methylene blue and 99Technetium nanocolloid had significantly better sentinel node detection rates compared to methylene blue alone FDG-PET/CT scan was performed in 28 women. The sensitivity, specificity, positive and negative predictive values of FDG-PET/CT scans to accurately predict nodal status, were 66.67%, 82%, 30.77% and 95.38% respectively. The false negative rate of FDG-PET/CT scans was 33.3%. The sensitivity, specificity, PPV and NPV for FSE in this cohort was 66.67%, 100%, 100% and 96.05% respectively. The FNR for FSE was 23.1%. Thirty-two patients with cervical cancer had tumour and SLN hrHPV DNA data. The sensitivity, specificity, PPV and NPV of sentinel lymph node HPV DNA to predict metastases was 50%, 69.6%, 30 and 84.2% respectively with a false negative rate of 42.8%. Conclusions Although the SLN detection rate was lower compared to the published literature, the SLNB algorithm performed excellently in this group of patients of which the majority were HIV-infected. The SLNB procedure can be considered as a treatment option in selected cases in the management of women with early stage endometrial and cervical cancer. PET/CT should not be used as part of the primary diagnosis and staging investigations in women with uterine cancer, and is recommended only in selected cases for initial staging of locally advanced cervical cancer being considered for radical chemoradiation therapy. In this study, testing for the presence of hrHPV DNA in the sentinel lymph nodes was not useful as a predictor of pelvic lymph node status. The combination of negative FSE and negative hrHPV in the SLNs did not have a reliable negative predictive value for the absence of pelvic nodal metastases.
Thesis (PhD)--University of Pretoria, 2017.
Obstetrics and Gynaecology
PhD
Unrestricted

Objectives The diagnostic efficacy of sentinel lymph node biopsy(SLNB) in early oral squamous cell carcinoma(OSCC) still remains controversial. This meta-analysis was conducted to assess the diagnostic value of SLNB in clinically neck-negative T1-2 OSCC. Methods A systematic literature search for relevant literature published up to September 11, 2016 was conducted in PubMed, Embase, Web of Science, Cochrane Library and ClinicalTrials, and the reference lists of eligible studies were examined. Data from different studies were pooled to estimate the summary sentinel lymph node(SLN) identification rate, sensitivity, negative predictive value. Summary receiver operator characteristic curve(SROC) was plotted and area under the SROC curve (AUC) was calculated to evaluate the overall diagnostic efficacy. Threshold effect was assessed with use of the spearman correlation coefficient. Between-study heterogeneity was tested using the Q tests and the I-2 statistics. Subgroup analyses were conducted in view of the greater effect of different study characteristics on diagnostic efficacy of SLN. Deeks' funnel plot asymmetry test was performed to evaluate publication bias. Sensitivity analysis was evaluated through omitting studies one by one and comparing the pooled results of random-effects model and fixed-effects model. All analyses were performed using Review Manager (version 5.3.5), Meta-DiSc (version 1.4), Comprehensive Meta Analysis (version 2.0) and STATA (version 12). Results 66 studies comprising 3566 patients with cT1-2N0 OSCC were included in this meta-analysis. The pooled SLN identification rate was 96.3%(95% CI: 95.3%-97.0%). The pooled sensitivity was 0.87 (95% CI: 0.85-0.89), pooled negative predictive value was 0.94 (95% CI: 0.93-0.95), and AUC was 0.98 (95% CI: 0.97-0.99). Subgroup analyses indicated that SLN assessment with immunohistochemistry(IHC) achieved a significantly higher sensitivity than without IHC. Conclusions This meta-analysis suggests that SLNB has a high diagnostic accuracy in cT1-2N0 oral squamous cell carcinoma, and is an ideal alternative to elective neck dissection. Furthermore, the use of IHC can significantly improve SLNB diagnostic sensitivity for early OSCC.

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Objective: The objective of this study is to describe the reproducibility of the sentinel lymph node technique in patients with prostate cancer and verify if there is improved accuracy over modified lymphadenectomy. Material and methods: Twenty-three patients with biopsy proven prostate cancer were enrolled in this study. Lymphoscintigraphy was performed after the transrectal administration of 99mTc-Sulphur Colloid guided by ultrasound, with one injection in each prostate lobe. Images were obtained 15 and 180 minutes after injection. Sentinel lymph node was harvested during surgery using a gamma probe, followed by extended lymphadenectomy. Results: The mean age of the patients in this study was 66 years old. An average of 3.36 sentinel lymph nodes was found for each patient. Radioactive lymph nodes were identified by the gamma probe in 21 out of 23 patients. In one of the patients there was no radiopharmaceutical migration from the injection site and in another the sentinel lymph node was visualized by lymphoscintigraphy but was not found during surgery. Three patients had lymph node metastasis; in one of these patients the sentinel lymph node was the only positive node and was found outside the modified lymphadenectomy region (dissection of the lymph nodes from the obturator fossa and the external iliac). Conclusion: Sentinel lymph node biopsy in prostate cancer adds important information to the staging of patients, not always attained through the lymphadenectomy restricted to the obturator fossa and external iliac. Such information is essencial for the choice of the best treatment to be applied.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Objetivos. Desenvolver um modelo experimental para identificaÃÃo de linfonodo sentinela (LS) da mama da cadela com uso de corante azul de metileno e comparÃ-lo com o azul patente, controlados por tecnÃcio. MÃtodos. O trabalho foi realizado em 23 cadelas, tendo-se observado a marcaÃÃo dos LS do primeiro par superior de mamas ao se injetarem 0,2 ml de TecnÃcio 99m ligado ao fitato (Tc 99m) e 0,5 ml de azul patente Guerbet V 2,5 % nos espaÃos subpapilares das mamas direitas e 0,2 ml de Tc-99m e 0,5 ml do azul de metileno 1 % nos mesmos espaÃos das mamas esquerdas. Resultados. Na mama direita, as tÃcnicas de biopsia de LS quando utilizados o Tc-99m e azul patente foram concordantes. Dos 23 LS estudados, somente um nÃo corou nem foi captante. O azul patente foi eficaz em 100 % quando comparado com os dois mÃtodos associados. Na mama esquerda, dos 23 LS estudados, somente dois nÃo coraram e um nÃo foi captante, sendo esta diferenÃa estatisticamente nÃo significante. A tÃcnica de biopsia do LS utilizando-se o azul de metileno apresentou-se com eficÃcia de 91,3 % quando utilizado isoladamente e de 100 % quando associado ao Tc-99m. ConclusÃo. O uso do azul de metileno associado ao radiofÃrmaco pode ser considerado como tÃcnica potencial na pesquisa transoperatÃria do LS das mamas, sendo uma opÃÃo menos onerosa e com menores efeitos alergÃnicos do que o azul patente
Objetivos. Desenvolver um modelo experimental para identificaÃÃo de linfonodo sentinela (LS) da mama da cadela com uso de corante azul de metileno e comparÃ-lo com o azul patente, controlados por tecnÃcio. MÃtodos. O trabalho foi realizado em 23 cadelas, tendo-se observado a marcaÃÃo dos LS do primeiro par superior de mamas ao se injetarem 0,2 ml de TecnÃcio 99m ligado ao fitato (Tc 99m) e 0,5 ml de azul patente Guerbet V 2,5 % nos espaÃos subpapilares das mamas direitas e 0,2 ml de Tc-99m e 0,5 ml do azul de metileno 1 % nos mesmos espaÃos das mamas esquerdas. Resultados. Na mama direita, as tÃcnicas de biopsia de LS quando utilizados o Tc-99m e azul patente foram concordantes. Dos 23 LS estudados, somente um nÃo corou nem foi captante. O azul patente foi eficaz em 100 % quando comparado com os dois mÃtodos associados. Na mama esquerda, dos 23 LS estudados, somente dois nÃo coraram e um nÃo foi captante, sendo esta diferenÃa estatisticamente nÃo significante. A tÃcnica de biopsia do LS utilizando-se o azul de metileno apresentou-se com eficÃcia de 91,3 % quando utilizado isoladamente e de 100 % quando associado ao Tc-99m. ConclusÃo. O uso do azul de metileno associado ao radiofÃrmaco pode ser considerado como tÃcnica potencial na pesquisa transoperatÃria do LS das mamas, sendo uma opÃÃo menos onerosa e com menores efeitos alergÃnicos do que o azul patente
Objectives. To develop an experimental model for identification of sentinel lymph node (SLN) of breast bitch with the use of methylene blue and compares it with the patent blue, both associated with technetium. Methods. 23 dogs, there was the marking of the SLN of the first upper pair of breasts to inject 0.2 ml of Tc-99m phytate bound to (99m) and 0.5 ml of patent blue Guerbet V 2,5 % in subpapilar spaces right breast and 0.2 ml of 99mTc and 0.5 ml of 1% methylene blue in the same spaces left breast. Results. In the right breast biopsy techniques using 99mTc SLN and blue dye are in agreement. Of the 23 SLN studied, only one was not flushed nor uptake. The patent blue was effective in 100% when compared with the two methods together. The left breast of 23 SLN studied, only two non-stained and one was not uptake, this difference was not statistically significant. The SLN biopsy technique using methylene blue appeared with a 91.3% effectiveness when used alone and 100% when associated with 99mTc. Conclusion: The use of methylene blue associated with the radiotracer technique can be considered as potential research intraoperative SLN of breast, suggesting a less costly and less allergenic effects that blue patent.
Objectives. To develop an experimental model for identification of sentinel lymph node (SLN) of breast bitch with the use of methylene blue and compares it with the patent blue, both associated with technetium. Methods. 23 dogs, there was the marking of the SLN of the first upper pair of breasts to inject 0.2 ml of Tc-99m phytate bound to (99m) and 0.5 ml of patent blue Guerbet V 2,5 % in subpapilar spaces right breast and 0.2 ml of 99mTc and 0.5 ml of 1% methylene blue in the same spaces left breast. Results. In the right breast biopsy techniques using 99mTc SLN and blue dye are in agreement. Of the 23 SLN studied, only one was not flushed nor uptake. The patent blue was effective in 100% when compared with the two methods together. The left breast of 23 SLN studied, only two non-stained and one was not uptake, this difference was not statistically significant. The SLN biopsy technique using methylene blue appeared with a 91.3% effectiveness when used alone and 100% when associated with 99mTc. Conclusion: The use of methylene blue associated with the radiotracer technique can be considered as potential research intraoperative SLN of breast, suggesting a less costly and less allergenic effects that blue patent.

Introduction: Sentinel lymph node biopsy is an established method used to investigate the riskof lymphatic metastasis especially in breast cancer and melanoma patients. SPECT/ CT isconsidered to be an advantageous method in mapping of sentinel nodes. Aim: The aim of this systematic literature review was to investigate the clinical value ofSPECT/ CT in the detection of sentinel lymph nodes in breast cancer patients. Method: Using specific search terms the database PubMed was used to find studies of potentialrelevance for this systematic review. Criteria for inclusions and exclusion were decided todetermine article relevance. Eligibility of articles was determined according to these criteriawhich lead to the selection of the specific articles included in this study. Results: Eleven studies were included in this systematic review. Seven out of 8 studies foundhigher identification rates of sentinel lymph nodes with SPECT/ CT in comparison to planarlymphoscintigraphy. SPECT/ CT could detect additional lymph nodes in 9 out of 9 studies.SPECT/ CT detected additional extra-axillary lymph nodes in 6 out of 7 studies. SPECT/ CTdetected lymph nodes in 9 out of 9 studies where planar lymphoscintigraphy was negative.Information from additional SPECT/ CT lead to changes in surgical treatment plan in 4 out of4 studies. None of the included studies contained information about change in oncologicaltreatment plan due to findings on SPECT/ CT. Conclusion: SPECT/ CT is an imaging technique with much potential as it seems to allow amore accurate SLN mapping and more precise anatomical localization of SLN in breast cancerpatients, specifically in certain clinical situations. Despite this however, the impact of SLNmapping through SPECT/ CT on patient prognosis remains uncertain.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
To identify the lymph node positioned along the internal mammary vessels in isolated sternum of human cadaver, to distinguish the number of lymph nodes at the second, third and forth intercostals spaces and to standardize the surgical approach to those nodes, in order to establish anatomical landmarks to be used with the current techniques of mammary gland sentinel lymph node detection. Ten sternum plates removed from unclaimed cadavers were used in this study. Sternal plates were removed using bilateral incisions of the ribs at the midclavicular lines. The characterization of the internal mammary vessels and the anatomical integrity of the parietal pleura were indispensable requirements during the procedure. The study was descriptive experimental. A total of 56 lymph nodes were removed from the second, third and forth intercostals spaces, being 30 at the right side and 26 ones at the left side. The second intercostal space was the one that shows the greatest number of lymph nodes in both sides. The lymph nodes of the chain of internal mammary vessels were dissected by a safe and practical technique, different from the one practiced by the Italian surgeons, pioneers at the dissection of the lymph nodes of the internal mammary vessels. The first stage of the dissection consisted of detaching the pectorals major muscle from its attachments to the manubrium and sternal body, exposing the sternocostal joints. Upon identification and detachment of the intercostals muscles approximately five cm from the ribs, special attention is paid to the neurovascular structures located at the superior border of the intercostal space, forming a window in a format of âUâ, exposing the internal mammary vessels and the lymph nodes to them related. The approach used is a reliable surgical technique for removing lymph node from sterna plates. The model is therefore valuable for breast surgeons training in sentinel node biopsy, an important procedure for breast cancer patients
Identificar os linfonodos localizados ao longo dos vasos mamÃrios internos em esternos isolados de cadÃveres, discriminar o nÃmero de linfonodos nos 2Â, 3Â e 4Â espaÃos intercostais e padronizar a abordagem cirÃrgica desses linfonodos, registrando os pontos de reparo a serem utilizados nas tÃcnicas atuais de pesquisa do linfonodo sentinela da mama. Estudaram-se dez esternos isolados de cadÃveres humanos. Os esternos foram obtidos atravÃs de secÃÃo bilateral do gradil costal ao nÃvel das linhas hemiclaviculares. A individualizaÃÃo e a integridade anatÃmica da pleura parietal e dos vasos mamÃrios internos foram requisitos imprescindÃveis durante a dissecÃÃo das peÃas. O estudo foi experimental descritivo. Um total de 56 linfonodos foram removidos dos 2Â, 3Â e 4Â espaÃos intercostais, sendo 30 Ã direita e 26 Ã esquerda. O 2Â espaÃo intercostal foi o que apresentou maior nÃmero de linfonodos nos lados direito e esquerdo. Os linfonodos da cadeia mamÃria interna foram abordados por uma tÃcnica segura, prÃtica e diferente da praticada pelos italianos, pioneiros na dissecÃÃo de linfonodos da cadeia mamÃria interna. Ocorre a divulsÃo do mÃsculo peitoral maior da sua inserÃÃo do manÃbrio e corpo do esterno, expondo as cartilagens esternocostais. Desinsere-se um segmento do mÃsculo intercostal de aproximadamente cinco cm a partir do bordo esternal de sua inserÃÃo no bordo superior da costela inferior do espaÃo intercostal, formando uma janela em âUâ, expondo assim os vasos mamÃrios internos e os linfonodos a eles relacionados. A abordagem cirÃrgica usada neste estudo demonstrou ser uma tÃcnica adequada para a exÃrese de linfonodos esternais. Conclui-se assim que o modelo utilizado se presta ao treinamento para o procedimento de biÃpsia de linfonodo sentinela, de grande valor na abordagem das pacientes portadoras de cÃncer de mama

Orientador: Luís Otávio Zanatta Sarian
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivo: Esta tese visou avaliar os parâmetros vasculares arteriais e venosos dos vasos axilares e braquiais em mulheres submetidas a tratamento para câncer de mama. Subdividimos estas avaliações conforme os objetivos abordados em duas publicações, respectivamente: 1) Comparar aos parâmetros de circulação venosa e arterial nos vasos axilares e braquiais em função do tipo de abordagem cirúrgica da axila (BLS ou LAT) em até seis meses após a intervenção. 2) Identificar os fatores que influenciam os parâmetros vasculares da veias axilares e braquiais ipsilaterais à cirurgia para tratamento do câncer de mama. Métodos: Foram identificadas 547 pacientes consecutivas, submetidas a tratamento cirúrgico para câncer de mama entre agosto de 2012 e janeiro de 2014. Depois de seguir critérios de inclusão e exclusão, 197 mulheres foram recrutadas. O projeto foi aprovado pelo comitê de ética do hospital e todos os pacientes assinaram o termo de consentimento informado. Os critérios de inclusão foram 1) câncer da mama primário operável 2) abordagem axilar cirúrgica; 3) não ter sido submetida a reconstrução da mama. Os critérios de exclusão foram 1) câncer de mama bilateral, 2) história prévia de procedimentos cirúrgicos para um dos membros superiores ou no tórax, 3) comprometimento ortopédico ou neurológico de um dos membros superiores, 4) insuficiência renal ou cardíaca. Todas as pacientes responderam a um breve questionário sobre suas características clínicas e epidemiológicas. Foi então realizada avaliação ultrassonográfica dos vasos braquiais e axilares, bilateralmente, nos seguintes momentos: no dia anterior à cirurgia e 1, 3, 6 e 12 meses após a cirurgia. No primeiro artigo, comparamos os parâmetros arteriais e venosos, até seis meses após a cirurgia, em função da realização de dissecção linfática completa ou linfonodo sentinela; no segundo, restringimos as análises ao sistema venoso e estendemos a avaliação para até 1 ano após a cirurgia, comparando os parâmetros vasculares em função de características clínicas e epidemiológicas das pacientes e das modalidades de tratamentos utilizados. Resultados: Foram encontradas restrições de diâmetro em veias do braço ipsilateral ao câncer de mama de mulheres submetidas à dissecção axilar (LAT), efeito que não foi observado no grupo BLS. A área da secção transversal de veias braquial e axilar diminuiu progressivamente até seis meses, com a redução do fluxo sanguíneo concomitante destes vasos. Encontramos, na mulher sem linfedema, que a área de secção transversal e fluxo venoso do sangue (especialmente veia braquial) são negativamente afetados pela cirurgia e / ou quimioterapia / radioterapia. Este efeito prejudicial parece persistir até um ano. Não houve diferença significativa em nenhum dos parâmetros estudados entre os vasos ipsi e contralaterais ao câncer de mama. Conclusões: De maneira geral, nosso estudo demonstra que os tratamentos cirúrgicos, especialmente LAT, e a radio e quimioterapia, possuem efeitos deletérios sobre a circulação sanguínea dos vasos axilares e braquiais, sobretudo venosos. Esses efeitos são aparentemente permanentes e há necessidade de extensão do tempo de follow-up a fim de avaliar se o desenvolvimento subsequente de linfedema ocorrerá em associação às alterações vasculares
Abstract: Objective: The aim of this thesis was to evaluate the arterial and venous vascular parameters of the axillary and brachial vessels in women who underwent treatment for breast cancer. We subdivided these assessments according to the following objectives, in two publications: 1) To compare the venous and arterial vascular parameters in the axillary vessels and brachial depending on the type of axillary surgical approach (SLNB or ALND) within six months after the intervention. 2) To identify which factors influence the vascular parameters of axillary and brachial veins ipsilateral to surgical for treatment of breast cancer. Methods: We identified 547 consecutive patients undergoing surgical treatment for breast cancer between August 2012 and January 2014. After following inclusion and exclusion criteria, 197 women were recruited. The project was approved by the hospital's ethics committee and all patients signed an informed consent form. Inclusion criteria were 1) primary operable breast cancer 2) surgical axillary approach; 3) not having undergone breast reconstruction. Exclusion criteria were 1) bilateral breast cancer, 2) history of previous surgical procedures for one of the upper limbs or breast, 3) orthopedic or neurological impairment of one upper limb, 4) kidney or heart failure. All patients completed a brief questionnaire about their clinical and epidemiological characteristics. Then we performed Doppler ultrasonography evaluation of axillary and brachial vessels, bilaterally, at the following times: the day before surgery and 1, 3, 6 and 12 months after surgery. In the first article, we compared the arterial and venous parameters, up to six months after surgery, depending on SLNB or ALND; in the second, we restricted the analysis to the venous system and extend the evaluation for up to 1 year after surgery, comparing the vascular parameters with clinical and epidemiological characteristics of patients and treatment modalities used. Results: diameter restrictions were found in the ipsilateral veins of the arm in women with breast cancer undergoing ALND, and that effect was not observed in SLNB group. The cross sectional area of brachial and axillary veins progressively decreased up to six months, with concomitant reduction of blood flow to these vessels. In women with no lymphedema, the cross-sectional area and venous blood flow (especially brachial vein) are negatively affected by surgery and / or chemotherapy / radiotherapy. This detrimental effect seems to persist up to one year. There was no significant difference on studied parameters between ipsilateral and contralateral vessels to breast cancer. Conclusions: In essence, our study shows that surgical treatments, especially ALND, and the radiation and chemotherapy, have deleterious effects on blood circulation of the axillary and brachial vessels, especially venous. These effects are apparently permanent, prompting the extension of the follow-up evaluation in order to assess whether subsequent lymphedema formation will be associated with vascular abnormalities
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
O cÃncer de vulva corresponde a aproximadamente 1% das neoplasias malignas da mulher e de 3% a 5% de tumores genitais femininos. 90% destes sÃo carcinomas espino-celulares, curÃveis quando diagnosticado precocemente. O tratamento radical inclui o esvaziamento inguinal bilateral na maioria dos casos. Aproximadamente 30% das pacientes operÃveis tÃm disseminaÃÃo linfonodal, as 70% restantes tÃm mutilaÃÃo desnecessÃria. A possibilidade de aplicar o conceito de linfonodo sentinela, na conservaÃÃo dos linfonodos regionais da vulva, ainda nÃo à consenso. O modelo experimental na vulva da cadela à um passo importante no reconhecimento das peculiaridades da drenagem linfÃtica deste ÃrgÃo pela similaridade com a drenagem em humanos. Este trabalho experimental, em modelo canino tem como objetivo apresentar o modelo para a pesquisa do linfonodo sentinela na vulva da cadela usando o Azul Patente e Fitato de TecnÃcio; avaliar o Azul Patente como marcador do linfonodo sentinela da vulva da cadela; avaliar o Fitato de TecnÃcio como marcador do linfonodo sentinela na vulva da cadela, comparar os mÃtodos obtidos pelas duas tÃcnicas. Foram utilizados nos procedimentos 25 cadelas, adultas, sadias, com peso variando entre 10 e 12kg. InjeÃÃo de 5ÂCI de TecnÃcio na regiÃo vulvar, com espera de 30â. Rastreamento com probe das regiÃes de drenagem vulvar, injeÃÃo de 0,5mL de azul patente na regiÃo vulvar, com espera de 15â. Definidos os pontos âquentesâ com o probe, por incisÃes inguinais abordou-se o linfonodo, avaliando-se com o probe o linfonodo sentinela in-vivo e ex-vivo, anotando-se os valores; registrados os linfonodos corados e nÃo corados com azul patente; comparados os dois mÃtodos. Em 88% dos linfonodos houve presenÃa da lateralidade, tal diferenÃa foi significante ( = 28.88 e p<0,0001). NÃo houve diferenÃa significante (p>0,05) entre os lados direito e esquerdo, quanto à intercessÃo dos dois mÃtodos. Os nÃveis de radiaÃÃo detectados foram idÃnticos em ambos os lados (p>0,05), tambÃm nÃo foi verificada diferenÃa significante (p>0,05) em ambos os lados, nas contagens in vivo e ex vivo, e no nÃmero de linfonodo corado com azul patente. O modelo experimental apresentado foi capaz de definir o linfonodo sentinela utilizando o Azul Patente e TecnÃcio(99mTc). A identificaÃÃo do linfonodo sentinela à exequÃvel com Azul Patente no mapeamento da cadeia linfÃtica; o mapeamento linfÃtico com TecnÃcio(99mTc), permite identificar com detalhes o sistema de drenagem linfÃtica; nÃo houve diferenÃa significante entre os dois mÃtodos (p=1,0), Azul Patente e TecnÃcio(99mTc).

Objetivos: Avaliar a eficácia da injeção intraoperatória para identificação do linfonodo sentinela (LS) em câncer de mama com o uso do Dextran 500-99m-Tecnécio (Tc) e azul patente. Analisar se as doses do radiofármaco, o IMC (índice de massa corporal) e o volume da mama influenciam no tempo para migração ao LS. Metodologia: Estudo prospectivo, realizado entre abril de 2008 e junho de 2009, que incluiu 74 biópsias de LS em pacientes com câncer de mama em estádios T1N0 e T2N0. Injetou-se, após indução anestésica, de 0,5 a 1,5 mCi de Dextran 500-99m-Tc filtrado 0,22 μm na região subareolar num volume de 5 ml e 2 ml de azul patente. Resultados: Identificou-se o LS em 100% dos casos. Um LS (1,35%) estava marcado apenas com o azul patente. A taxa de identificação com o “probe” foi de 98% (73/74 casos). A dose média de radiofármaco aplicada foi 0,97 mCi + 0,22. O tempo médio para marcação do LS foi de 10,7 minutos (+ 5,7min). Identificamos em média 1,66 LS com o radioisótopo. A dose aplicada não apresentou relação com o tempo para captação (p=0,73). Quanto maior o volume da mama e IMC, maior o tempo para captação na região axilar (Pearson Correlation r=0,393 p<0,01; r=0,469 p<0,01 - respectivamente). Conclusão: A injeção intraoperatória do radiofármaco é eficaz para identificação do LS em câncer de mama. O tempo para marcação do LS é maior em pacientes com IMC elevado e mamas volumosas. Doses maiores de radiofármaco não diminuem o tempo de migração.
Objectives: To determine the identification of sentinel lymph node (SLN) in breast cancer after intraoperative injection of Dextran 500‐99mTechnetium (Tc) and blue dye. To analyze if the doses of the radioisotope, body mass index (BMI) and breast volume influence the migration time of the SLN. Methodology: Prospective study between april 2008 and june 2009, which included 74 biopsies of SLN in patients with breast cancer in stages T1N0 and T2N0. Intraoperative injection after induction of general anesthesia, 0.5 to 1.5 mCi of dextran 500‐99m‐Tc filtered 0.22 μm in the subareolar region in a volume of 5 ml and 2 ml of blue dye. Results: We identified the SLN in 100% of cases. In one case (1.35%) the SLN was marked only with the blue dye. The SLN identification rate with the probe was 98% (73/74 cases). The mean dose of radioisotope injected was 0.97 + 0.22 mCi. The average time to mark the SLN was 10.7 minutes (+ 5.7 min). We identified an average 1.66 SLN with the radioisotope. The dose had no effect on the time to capture (p = 0.73). The larger breast volume and BMI, the greater the capture time in the axillary region (Pearson Correlation r=0.393 p <0.01, r=0.469 p <0.01 - respectively). Conclusion: Intraoperative injection of the radioisotope is effective for the identification the SLN in breast cancer. Time to mark the SLN is higher in patients with high BMI and large breasts. Higher doses of radioisotope do not decrease the migration time.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Este trabalho aborda a influÃncia da incisÃo para-areolar no quadrante superior externo da mama, na localizaÃÃo do linfonodo sentinela em modelo canino. A BiÃpsia do linfonodo sentinela (BLS) à um mÃtodo de amostragem seletiva, minimamente invasivo, altamente sensÃvel em predizer o estado axilar, podendo evitar o esvaziamento ganglionar em pacientes sem comprometimento metastÃtico. Mulheres, com cirurgias mamÃrias previas, foram excluÃdas da realizaÃÃo da BLS por muitos cirurgiÃes por acreditar que teriam um Ãndice de falso negativo elevado, inviabilizando o mÃtodo. Outros mastologistas passaram a empregar, empiricamente, a injeÃÃo do marcador corante ou radioativo acima da borda da incisÃo prÃvia, porÃm fica a dÃvida se o gÃnglio identificado à realmente o Linfonodo Sentinela (LS). Este trabalho experimental, em modelo canino, tem como objetivo identificar a influÃncia das incisÃes para-areolares prÃvias, no quadrante superior externo (QSE) da mama na identificaÃÃo do linfonodo sentinela. à utilizado o radiocolÃide TecnÃcio99 injetado na derme sub-areolar das mamas torÃcicas craniais, para marcar o LS. Esperado o tempo de migraÃÃo do radiofÃrmaco para axila e identificado o local de marcaÃÃo com probe. Procede-se incisÃo arciforme para- areolar no QSE, entre 9 e 12h à direita e 12 e 3 h à esquerda, a 2cm do mamilo. O corante azul patente Ã, entÃo, injetado na borda superior destas incisÃes. No ponto marcado com o gama-probe à realizada a incisÃo axilar mÃnima, onde o LS à identificado com auxÃlio do probe, que capta a radiaÃÃo do gÃnglio, eou pela visualizaÃÃo direta do linfonodo impregnado com o corante. SÃo comparadas duas tÃcnicas de local de injeÃÃo e a concordÃncia entre os mÃtodos de identificaÃÃo do LS. Os experimentos da pesquisa ocorreram entre Janeiro 2008 e Maio 2009. A amostra à composta de 40 mamas torÃcicas craniais, oriundas de 23 cadelas adultas, sem raÃa definida, da espÃcie Canis familiaris. A anÃlise estatÃstica foi realizada com o auxÃlio do programa Graphpad e utilizados o Teste de McNemar e Coeficiente de ConcordÃncia de Kappa. Os resultados demonstram que em 95% das mamas estudadas (3840) obtiveram o LS identificado na axila apÃs a injeÃÃo de tecnÃcio na regiÃo subareolar e em 82% dos casos (33/40) coraram com azul patente injetado no bordo superior da incisÃo padronizada. Os resultados obtidos indicam a concordÃncia entre os mÃtodos em 82% dos casos na identificaÃÃo do LS (3340). As incisÃes para-areolares prÃvias, nos quadrantes superiores externos, das mamas torÃcicas craniais da cadela, nÃo demonstram interferir, de maneira significante, na BLS quando o corante à injetado na borda superior da incisÃo. O linfonodo encontrado a partir de injeÃÃo na borda superior da incisÃo previa, corresponde ao linfonodo sentinela da mama da cadela, em 95% dos casos (3233).
This paper discusses the influence of para-areolar incision in the upper outer quadrant of the breast for the location of the sentinel lymph node in canine model. Sentinel lymph node biopsy (SLNB)―a minimally invasive selective sampling technique highly predictive of the condition of the armpit―can spare metastasis-free patients from unnecessary axillary dissection. The high incidence of false-negative results has led many surgeons to no longer indicate SLNB to women with previous breast surgery. Some mastologists prefer to empirically inject a dye or radio-labelled marker above the border of the previous incision, though it is not always clear if the identified ganglion is in fact the sentinel lymph node. The objective of the present study was to evaluate the influence of previous para-areolar incisions in the upper outer quadrant (UOQ) of the breast upon the identification of the sentinel lymph node (SLN) in a canine model. The SLN was marked with Technetium-99m (99mTc) injected into the subareolar skin of the cranial breast. Once the marker had migrated to the axilla and the marked site had been identified with a gamma probe, an arcuate para-areolar incision was performed 2 cm from the nipple in the UOQ (between the 9 and 12 oâclock position on the right side, and between the 12 and 3 oâclock position on the left side). Patent blue dye was then injected above the upper border of the incision. At the marked site a minimal axillary incision was made and the SLN was identified by gamma probe and/or by direct visualization of the dye. The agreement between the two injection sites and the two SLN identification methods was determined. The experiments were carried out between January 2008 and May 2009 on a sample of 40 cranial breasts of 23 adult females of the species Canis familiaris. Using the statistics software Graphpad, the data were submitted to the McNemar test and the Kappa agreement coefficient was calculated. Our findings show that in 95% (38/40) of the breasts the SLN was identified by injection of 99mTc in the subareolar region, and that in 82% (33/40) of cases the SLN was identified by injection of patent blue dye above the upper border of the incision. Thus, the methods agreed in 82% (33/40) of cases. Previous para-areolar incisions in the UOQ of the cranial breasts did not interfere significantly with the biopsy when the dye was injected above the upper border of the incision. The lymph node identified by injection above the upper border of the previous incision corresponded to the SLN in 95% (32/33) of cases.

Orientadores: Luiz Roberto Lopes, Celso Dario Ramos
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução - Com os estudos de Gould et al. (1960), Cabanas (1977) e Morton et al. (1992), estabeleceu-se o conceito da pesquisa do linfonodo sentinela. Esse se baseia na teoria de que ao identificar a presença ou ausência de metástase no primeiro linfonodo que recebe a drenagem linfática a partir do tumor (sentinela), poderia representar o estado de acometimento dos outros linfonodos. Isto evitaria a realização desnecessária de linfadenectomias. Com o passar dos anos, foi consagrada para ser aplicada em casos de melanoma e câncer de mama. Nesta última década, tenta-se estender os princípios da utilização da pesquisa de linfonodo sentinela para os cânceres do aparelho digestivo. Entretanto, no caso do estômago, existem algumas dificuldades, como: presença de sistema de drenagem linfática multidirecional, ocorrência de metástases saltatórias e identificação de mais de um linfonodo sentinela por indivíduo. Objetivo - Criar e padronizar um modelo animal para o treinamento de pesquisa de linfonodos sentinelas em estômago. Método - Trinta e dois coelhos, saudáveis, foram submetidos à anestesia exclusivamente intramuscular. Por meio de laparotomia, foi injetado na subserosa da parede anterior do corpo gástrico, 0,1 ml de fitato marcado com tecnécio-99m (0,2 mCi), em seguida pelo mesmo orifício, de 0,2 ml de Azul Patente V® 2,5%. A cavidade abdominal foi avaliada, "in vivo", para pesquisa de suspeitas de linfonodos azuis (corados em azul) e com detector manual de radiação gamma aos 5, 10 e 20 minutos para detecção de suspeitas de linfonodos radioativos (radioatividade identificada superior a 10X o valor apresentado pelo fundo). Após 20 minutos, realizou-se ressecção e exérese total do estômago, baço e suspeitas de linfonodos, para posterior avaliação da radioatividade "ex vivo". A seguir, encaminharam-se as suspeitas de linfonodos para estudo histológico para identificação de tecido linfóide. Resultados - Foram identificados linfonodos em 30 coelhos (93,75%) com média de 2,2 por animal. Das 90 suspeitas de linfonodos detectadas, em 70 casos (77,77%) obteve-se confirmação histológica para tecido linfóide. Dessas, a maioria foi identificada e localizada na região entre o esôfago e o fundo gástrico durante a avaliação "in vivo" aos 5 minutos. Dois coelhos faleceram durante os experimentos (Taxa de mortalidade = 6,25%). Conclusão - O modelo experimental em coelhos para pesquisa de linfonodos sentinelas em estômago por métodos combinados foi factível, de fácil execução e baixa mortalidade, podendo ser usado para treinamento
Abstract: Introduction - The concept of sentinel lymph node was established by the studies of Gould et al. (1960), Cabanas (1977) and Morton et al. (1992). It is based on the theory that, whenever the presence or absence of metastasis is identified in the first lymph node that receives the lymphatic drainage from the tumor (sentinel) the status of involvement of other lymph nodes might be infered. This could avoid the performance of unnecessary lymphadenectomies. Over the years, its use was consecrated by its application in melanoma and breast cancer. In the last decade, attempts have been made to extend the principles of sentinel lymph node investigation to cancers of the digestive tract. In the case of stomach cancer, additional difficulties were found, such as multiple and aberrant lymphatic routes, the occurrence of skip metastasis and the possible identification of more than one sentinel lymph node in the same patient. Aim - To develop and evaluate an animal model for training sentinel lymph node navigation in the stomach. Methods - Thirtytwo healthy rabbits, were prepped and given intramuscular anesthesia. Through a formal laparotomy, they received a subserosal injection of 0.1 ml of phytate labeled with technetium-99m (0.2 mCi) in the anterior wall of the gastric corpus, followed by 0.2 ml of Blue Patent ® V 2.5%, through the same puncture site. Suspicious lymph nodes were searched in-vivo at 5, 10 and 20 minutes, both visually (Blue Patent stained lymph nodes) and with a manual gamma radiation detector (to detect suspected radioactive lymph nodes, displaying radioactivity levels over 10X the value displayed by the background). En-block resection of the stomach, spleen, visible limph nodes and local fat tissue was then performed and the specimen was assessed "ex vivo" for radioactivity. Suspected lymph nodes were sent for histological study to evaluate the presence of lymphoid tissue. Results - Radiolabeled or stained lymph nodes were identified in 30 rabbits (93.75%) with an average of 2.2 specimens per animal; of the 90 suspicious lymph nodes detected, histology confirmed lymphoid tissue in 70 cases (77.77%). Most lymph nodes were identified at the 5-minute in-vivo evaluation and their most common location was found to be in the region between the esophagus and the gastric fundus. Two rabbits died during the procedure resulting in a 6.25% mortality. Conclusion - The rabbit model proved adequate for training in sentinel node navigation in the stomach by combined methods (dye and radiocolloid) being easy to execute and associated with low mortality
Doutorado
Fisiopatologia Cirúrgica
Doutor em Ciências

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
A gastrectomia com linfadenectomia ampliada ainda à o padrÃo ouro para o tratamento curativo do cÃncer de estÃmago (CaE), embora este procedimento possa levar a alto Ãndice de morbidade ou mortalidade, principalmente nos pacientes que nÃo apresentem disseminaÃÃo linfÃtica da doenÃa. A pesquisa do linfonodo sentinela (LS), jà consagrada nos tumores iniciais de mama e nos melanomas, apresenta-se cada vez mais freqÃente no trato digestÃrio, em especial no CaE com resultados animadores. Estudos iniciados nos meados do ano 2000 retratam busca crescente e bastante prÃspera para esclarecimento desta questÃo. O objetivo deste trabalho à elaborar um modelo experimental que possa demonstrar tecnicamente, em laboratÃrio, a viabilidade da pesquisa do LS no antro gÃstrico da cadela. Foram estudadas 25 cadelas com peso aproximado de 11 Kg e idade de 01 a 02 anos, sem raÃa definida (SRD), clinicamente saudÃveis, proveniente do Centro de Controle de Zoonoses do MunicÃpio de Fortaleza (CCZ) que tinham programaÃÃo para eutanÃsia. Com escolha aleatÃria, estes animais foram estudados individualmente e semanalmente. Utilizou-se, separadamente, TecnÃcio (99mTc) com traÃador/colÃide Fitato e corante vital azul patente V Guerbert 2,5 % (AP) injetados a 01 cm do piloro, na pequena curvatura no antro gÃstrico da cadela e analisados nos tempos zero, 05, 10, 15 e 20 minutos. ApÃs este perÃodo realizou-se pesquisa âin vivoâ do local de injeÃÃo do marcador e linfonodos encontrados e âex-vivoâ destes linfonodos. Para o estudo com o 99mTc utilizou-se o aparelho Gamma Probe modelo Nuclearlab DGC-II - detector para cirurgia radioguiada e sonda captadora de irradiaÃÃo acoplada com unidade de contagem e rastreamento sonoro e para o AP, visÃo direta. Para a anÃlise estatÃstica utilizou-se o teste de McNemar e o Coeficiente de ConcordÃncia de Kappa. Foi estabelecido em 5% o nÃvel de significÃncia (p≤0,05). Com o uso do 99mTc isolado foi identificado a presenÃa do LS em 20 animais (80%). Quando se utilizou o corante AP isolado a presenÃa do LS foi identificada em 24 animais (96 %). NÃo houve significÃncia estatÃstica quanto ao uso destes marcadores para a pesquisa do LS no antro gÃstrico da cadela. Concluiu-se que (1) O estÃmago da cadela à adequado para modelo experimental de pesquisa âin vivoâ do linfonodo sentinela e (2) O tecnÃcio (99mTc) e corante vital â azul patente V Guerbert 2,5 % (AP) sÃo eficientes como marcadores de linfonodo sentinela do antro gÃstrico da cadela.
The gastrectomy with extensive lymphadenectomy still is the gold standard for the dressing treatment of the gastric cancer (GC), even so these procedures can take high index of morbidity or mortality, mainly in the patients who do not present lymphatic dissemination of the illness. The research of sentinel lymph node (SLN), already consecrated in the initial tumors of breast and the melanomas, presents each time more frequent for upper gastrointestinal cancers, specially in GC with encouraging results. Studies initiated in the middles of 2000 portray increasing and sufficiently prosperous search for clarification of this question. The objective of this work is to elaborate an experimental model that can demonstrate technically, in laboratory, the research viability of SLN in gastric antrum of the dog. 25 female dogs had been studied with approach weight of 11 kg and age of 01/02 years, without definite race (WDR), healthful clinically, proceeding from the Control Center of Zoonosis of Fortaleza City with programming for euthanasia. With random choice, these animals had been studied individually and weekly. It was used, separately, radioisotopic 99mtechnetium labeled phytate and patent blue dye (V Guerbert 2.5%) injected at 01 cm above the piloro, on the small bending in the antrum gastric of the dog and analyzed in the times zero, 05, 10, 15 and 20 minutes. After this period, the injection place of the markers and gastric lymph nodes were appraised âin vivoâ (in the animal) and the gastric lymph nodes âex vivoâ (out of the animal). For the study with the 99mtechnetium it was used the device Gamma Probe model Nuclearlab DGC-II (radioguiada surgery with sounding lead of irradiation connected to unit of counting and sonorous tracking) and for the patent blue dye, direct vision. For the analysis statistics were used the test of McNemar and the Quantify agreement with Kappa. The level of significance was established in 5% (p≤0,05). When the radioisotopic 99mtechnetium labeled phytate was used single, the LS was identified in 20 animals (80%). With the patent blue dye single, in 24 animals (96%). There is no statistic significance with the use of those markers for the LS research in the gastric antrum of the dog. The conclusions are (1) The stomach of the dog is adjusted for experimental model in alive research of the sentinel lymph node (2) The radioisotopic 99mtechnetium labeled phytate and patent blue dye (V Guerbert 2.5%) are efficients as markers of sentinel lymph node of the dogâs gastric antrum.

O câncer de mama (CA de mama), com exceção do câncer de pele do tipo não melanoma, é o tumor de maior incidência dentre as mulheres, sendo que no Brasil são encontrados principalmente nas regiões Sul e Sudeste. Seu principal tratamento é o cirúrgico. A disseminação do tumor pode ocorrer por via linfática, acometendo linfonodos regionais. A biópsia do linfonodo sentinela (BLNS) é um procedimento altamente relevante, é altamente sensível na identificação de metástases. A técnica de linfocintilografia (LINCT) pré-operatória é essencial, pois permite avaliar a cadeia linfática acometida e possibilita a visualização do linfonodo sentinela (LNS) durante a cirurgia. O objetivo é descrever os padrões de drenagem linfática e avaliar a contribuição da LCINT na localização dos LNS em pacientes com CA de mama. No período de março de 2009 a agosto de 2011 foram estudados 70 casos sequenciais da rotina clínica, submetidos ao tratamento cirúrgico do CA de mama com estudo do LNS através da técnica de LCINT. Na LCINT foram aplicadas 4 injeções intradérmicas contendo 37 MBq (1,0 mCi) do FITATO-Tecnécio99m, ao redor da aréola mamária. Após a localização do LNS foi realizado marcações na pele, nas incidências anterior, oblíqua e lateral, para auxiliar o cirurgião na abordagem cirúrgica ulterior, juntamente com a sonda gama intra-operatória e corante azul patente. Dos 70 casos submetidos ao estudo, todos são do sexo feminino (100%) com faixa etária entre 28 e 77 anos, média de 54 anos. O tamanho médio do tumor encontrado nos pacientes foi de 1,4 cm. Os tipos histológicos mais incidentes foram o carcinoma ductal invasivo com 45 (64,4%) pacientes, seguido de carcinoma ductal in situ com 16 (22,8%). No exame de LCINT, todos os pacientes apresentaram drenagem linfática do radiofármaco a partir do local da injeção. Em 43 (61.5%) pacientes, observamos drenagem para 1 LNS, em 21 (30%) para 2 LNS/LNNS (linfonodo não sentinela), em 5 (7%) para 3 LNS/LNNS e em 1 (1.5%) para 4LNS/LNNS. Dos 70 pacientes, 68 (97%) apresentaram drenagem linfática ipsilateral e 2 (3%) apresentaram drenagem linfática bilateral. Em relação aos territórios de drenagem linfática dos LNS/LNNS, em 68 (97%) pacientes apresentaram drenagem para a região axilar, 1 (1,5%) para a região mamária interna e 1 (1,5%) para as regiões axilar e mamária interna. Os LNS/LNNS presentes na cadeia mamária interna não foram retirados. No intra-operatório, os cirurgiões utilizaram o corante azul patente em 35 (50%) pacientes, destes o corante identificou os LNS/LNNS em 79% dos casos. A técnica de LCINT possibilitou a visualização de todos os LNS e em alguns casos não foi possível a visualização do LNNS, o qual foi localizado e retirado com a sonda gama. Com isso, a técnica de LCINT foi eficaz em 88,5% dos casos. Dos 69 pacientes submetidos à BLNS apenas 13 (18,8%) pacientes apresentaram LNS/LNNS metastáticos, sendo estes submetidos à linfadenectomia axilar. Conclui-se que o exame pré-operatório de LCINT foi muito eficiente para o estudo da drenagem linfática, visualizando os canais linfáticos, linfonodos funcionalmente ativos e seus respectivos territórios de drenagem. Por tanto, esta técnica auxiliou o cirurgião na abordagem cirúrgica juntamente com a sonda gama intra-operatória e corante azul patente para a realização da BLNS.
With the exception of non-melanoma skin cancer, the Breast cancer (breast CA) is the most incident cancer in women. In Brazil, the breast CA is more often found in South and Southeast regions. The main treatment of breast CA is the surgery. The main pathway for the tumor spreading is the lymphatic system, which may affect the regional lymph nodes. The sentinel node biopsy (SLNB) is of considerable importance, once it has a high sensitivity in identifying metastases. The technique of preoperative lymphoscintigraphy (LINCT) is essential because it allows evaluating the lymphatic drainage chain and enables the visualization of sentinel lymph node (SLN) during surgery. We aim here to describe the lymphatic drainage patterns and to evaluate the contribution of LCINT to the location of SLN in patients with breast CA. We evaluated 70 patients sequentially selected from the clinical routine, between march 2009 and august 2011, and that underwent the surgical treatment for breast CA, including the usage of the technique of LCINT for the SLN location. The LCINT were performed by the injection of four periareolar intradermal injections containing 37 MBq (1.0 mCi) of the radiopharmaceutical PHYTATE-99m-Technetium. Based on the LCINT images, we performed skin marks in the dermal projections of the SLN in all anterior/posterior, oblique and lateral views. Additionally, the gamma probe and blue dye were used to help surgeons in the surgical location of the SLN. All of the 70 patients of our study were female, ranging from 28 to 77 years, mean 54 years. The average tumor size was 1.4 cm. The most commonly found histological types were invasive ductal carcinoma (45 patients, 64.4%), followed by the in situ ductal carcinoma (16 patients, 22.8%). All LCINT procedures were well succeeded in demonstrating at least one SLN in our sample of patients. We observed lymphatic drainage for only one SLN in 43 patients (61.5%), for 2 SLN/SLNN in 21 (30%) (non sentinel lymph node), for 3 SLN/SLNN in 5 (7%) and for 4 SLN/SLNN in one patient (1.5%). From the 70 patients, 68 (97%) exhibited ipsilateral and 2 (3%) exhibited bilateral lymphatic drainage. Concerning the lymphatic territories, 68 patients (97%) exhibited drainage to SLN/SLNN in the axillary region, 1 patient (1.5%) in the internal mammary region and another patient (1.5%) in both axillary and internal mammary regions. The two SLN/SLNN found in the internal mammary chain were not removed. Complimentary to the LCINT, the surgeons used blue dye in 35 patients (50%), which enabled them to identify the SLN/SLNN in 79% of cases. On the other hand, LCINT allowed the visualization of all SLN (100%). In some cases, in which was not possible to visualize the SLNN, these ones were found by the use of the gamma probe. Thus, the LCINT technique was effective to localize the SLN in 88.5% of cases. From the 69 patients who underwent SLN biopsy, only 13 patients (18.8%) exhibited metastatic infiltration of the SLN/ SLNN. All these patients were submitted to the axillary dissection. We conclude that the preoperative LCINT was very effective for the study of lymphatic drainage, enabling the visualization of the lymphatic channels, functionally active nodes and their drainage areas. Therefore, this technique helped surgeons in the surgical approach with intraoperative gamma probe and patent blue dye for SLNB.

Dissertação de Mestrado Integrado em Medicina Veterinária
Os golfinhos comuns (Delphinus delphi) são animais sentinela para avaliação da integridade dos ecossistemas marinhos, protegidos ao abrigo da lei. Compreender o funcionamento do seu sistema imunitário é essencial, mas a sua captura premeditada é proibida. Através do estudo da expressão de citoquinas em amostras recolhidas na necrópsia de animais capturados acidentalmente é possível determinar os elementos do sistema imunitário em ação. Com o objetivo de criar um grupo controlo para analisar o perfil de resposta a morbilivirus dos cetáceos (CeMV), foram recolhidas amostras de linfonodo pulmonar e pulmão de 15 animais negativos ao vírus. Foi extraído o mRNA e analisada a expressão das Interleucinas (IL)-1β, 4, 6, 10, 12 e Fator de Necrose Tumoral (TNF) por PCR quantitativo. A expressão no pulmão foi heterogénea entre animais, verificando-se uma grande variação na expressão de IL-4, IL-12 e IL-1β, devido à exposição deste órgão ao meio exterior. A expressão no linfonodo foi homogénea entre animais, havendo uma expressão mais acentuada de TNF-α e IL-1β em relação às outras citoquinas, consistente com processos de inflamação aguda. Este estudo preliminar sugere a possibilidade de criar um grupo controlo a partir de animais de vida livre com amostras de linfonodo, mas não com amostras de pulmão, com aplicabilidade em estudos futuros tais como a avaliação de expressão de citoquinas em golfinhos infetados com CeMV.
ABSTRACT - Evaluating the Expression of Immune Response Mediators in Samples from Accidentally Captured Cetaceans in the Portuguese Continental Coast - Common dolphins (Delphinus delphi) are sentinel animals for assessing the integrity of marine ecosystems, protected under the law. Understanding their immune system is essential, but their deliberate capture is prohibited. Through the study of cytokine expression in samples collected at necropsy from animals caught accidentally it is possible to determine the acting elements of the immune system. In order to create a control group for the study of Cetacean Morbilivirus (CeMV) response profile, pulmonary lymph node and lung samples were collected from 15 animals negative to the vírus. mRNA was extracted and the expression of interleukins (IL)-1β, 4, 6, 10, 12 and Tumor Necrosis Factor (TNF) was analyzed by quantitative PCR. The expression in the lung was heterogeneous among animals, with a wide variation in IL-4 expression, IL-12 and IL-1β due to the organ’s exposure to the external environment. The expression in lymph nodes was homogeneous among animals, with a higher expression of TNF-α and IL-1β compared to other cytokines, consistent with acute inflammation processes. This preliminary study suggests the possibility of creating a control group from free roaming animals with lymph node samples, but not with lung samples, with applicability in future studies including the evaluation of cytokine expression in CeMV infected dolphins.

Résumé:IntroductionLa chirurgie reste le seul traitement à visée curative pour les patients porteurs d’un cancer colorectal (CCR) primitif ou métastatique. L’établissement précis de l’extension de la maladie, au niveau de la tumeur primitive, des ganglions loco-régionaux et des métastases à distance représente un élément essentiel pour la prise en charge thérapeutique. Les ganglions locorégionaux et la technique du ganglion sentinellePour les patients présentant un CCR non métastatique, l’analyse pathologique des ganglions (pN) conditionne la décision d’administrer ou non une chimiothérapie adjuvante. Les patients présentant un envahissement ganglionnaire (pN+) recevront un traitement adjuvant, celui-ci n’étant le plus souvent pas indiqué chez les patients sans envahissement ganglionnaire (pN0). Près de 20 à 30% des patients classés pN0 vont cependant développer des récidives tumorales. Parmi ces patients, il est probable qu’une partie ait été sous-classée au moment du diagnostic. La technique du ganglion sentinelle (GS) permet d’identifier les ganglions les plus susceptibles d’être envahis et de réaliser des analyses anatomopathologiques plus approfondies sur un nombre plus limité d’échantillon. Cette technique est recommandée dans le cancer du sein et dans le mélanome, mais son rôle reste discuté dans le CCR. Le premier volet de cette thèse concerne les résultats d’études cliniques que nous avons menées pour évaluer le rôle de la technique du GS au bleu patenté (BP) et de l’imagerie en fluorescence (IF) au vert d’indocyanine ou indocyanine green (ICG) dans le staging ganglionnaire des patients présentant un CCR. Les principaux objectifs de ces travaux étaient d’évaluer la faisabilité de ces techniques et leur apport dans le staging des patients présentant un CCR.Notre première étude sur la technique du GS au BP, représentant la plus grande cohorte monocentrique européenne, a permis de démontrer la faisabilité de la technique. En outre, cette approche a modifié le geste chirurgical dans 12% des cas (technique in vivo) et a permis de reclasser 10% des patients initialement classés pN0 en pN+ par la réalisation de coupes sériées spécifiquement réalisées sur les ganglions démontrés comme GS. Dans une seconde étude sur la technique du GS comparant l’IF-ICG à la technique au BP, nous avons montré que ces 2 techniques étaient complémentaires, permettant d’augmenter la sensibilité globale pour la détection des métastases ganglionnaires. De plus, l’IF-ICG apparaît comme plus sensible chez les patients présentant une surcharge pondérale. En termes de sensibilité, la recherche du GS par IF est supérieure à la technique BP, ces résultats restant cependant limités, notamment en raison d’un taux élevé de faux négatifs (FN) pour les tumeurs localement avancées (pT3-4). Les métastases ganglionnaires et la carcinose péritonéaleDans le CCR, les patients métastatiques, présentant une carcinose péritonéale (CP) et/ou un envahissement ganglionnaire, ont un pronostic sombre. La chirurgie d’exérèse de la CP associée à une chimiothérapie hyperthermique intrapéritonéale (CHIP) et la réalisation de curages ganglionnaires chez les patients porteurs d’une maladie oligométastatique permettent toutefois d’obtenir des survies prolongées et parfois des guérisons, avec des résultats similaires à ceux observés chez les patients opérés pour métastases hépatiques isolées. Pour la CP, l’étendue de la maladie et la radicalité de la résection sont les principaux facteurs pronostiques de survie. La sensibilité des examens d’imagerie conventionnelle et métabolique reste cependant faible pour déterminer l’extension de la maladie péritonéale. L’évaluation de l’étendue de la CP et son exérèse sont donc essentiellement fondées sur la palpation et l’exploration visuelle réalisée durant l’intervention chirurgicale, représentant un facteur limitant pour la radicalité de la chirurgie. De façon similaire, chez les patients présentant une maladie métastatique ganglionnaire limitée, la détection peropératoire est souvent difficile, nécessitant la réalisation de curages étendus de principe, afin de s’assurer de l’exérèse des ganglions pathologiques.L’utilisation de l’IF après injection iv intra-opératoire d’ICG a été rapportée comme une technique permettant la détection de tissu tumoral tant visible que non visible (infraclinique), pouvant potentiellement aider le chirurgien et guider les gestes de résection. Aucune étude n’avait particulièrement analysé le rôle de l’IF-ICG dans la détection de CP et de métastases ganglionnaires de CCR. Le second volet de cette thèse concerne l’évaluation de l’apport de l’IF après injection iv d’ICG pour la détection de la CP et des métastases ganglionnaires dans le CCR. L’objectif primaire était de vérifier si les métastases péritonéales (MP) et ganglionnaires visibles par le chirurgien étaient effectivement détectées par l’IF-ICG peropératoire. En parallèle, nous avons évalué si l’IF-ICG permettait de détecter une maladie infraclinique, non détectée par le chirurgien dans les conditions habituelles. La première étude de cette seconde partie a permis de montrer que les MP étaient visualisées comme hyperfluorescentes à l’IF-ICG pour autant qu’elles ne soient pas d’origine mucineuse. De plus, l’IF-ICG a permis de détecter des MP non visualisées en lumière visible, permettant d’adapter le geste chirurgical et d’augmenter la radicalité de la résection dans près de 38% des cas. Dans une seconde étude, nous avons rapporté que la technique d’IF utilisée in vivo et ex vivo après injection iv d’ICG permettait d’identifier des ganglions métastatiques, détectés ou non par les imageries conventionnelles et métaboliques préopératoires. Les résultats de cette étude constituant une preuve de concept ont été ensuite confirmés dans une étude rétrospective réalisée sur l’analyse ex vivo des ganglions de patients ayant reçu une injection iv d’ICG. Dans ce travail, nous avons montré que les ganglions envahis étaient plus fluorescents que les ganglions non envahis. Toutefois, cette preuve de concept doit encore être confirmée et évaluée plus largement dans une étude prospective. Ces 2 travaux montrent donc le bénéfice potentiel de l’utilisation de l’IF après injection iv d’ICG à 2 niveaux, pour guider la chirurgie en améliorant la détection peropératoire des sites métastatiques infracliniques et pour guider l’analyse histologique, en identifiant des ganglions fluorescents sur la pièce de résection, permettant une étude anatomopathologique plus ciblée et plus approfondie. Conclusions et perspectivesNos travaux sur la recherche du GS dans le CCR par la technique au BP et à l’IF-ICG ont montré que ces techniques étaient faisables mais que leurs sensibilités restaient limitées, en particulier chez les patients porteurs de tumeurs localement avancées. Dans la CP d’origine colorectale, nous avons montré que l’IF-ICG permettait d’améliorer la stadification de la CP des patients opérés de métastases péritonéales non mucineuses, de révéler des lésions non visibles dans les conditions standards et d’améliorer la radicalité de la chirurgie. Pour la détection de ganglions métastatiques, nous avons montré que l’IF-ICG permettait, in vivo, de détecter des ganglions infracliniques durant l’intervention et ex vivo, de guider l’analyse anatomopathologique de la pièce de résection. Enfin, nous pensons que ces observations pourraient nous permettre d’élaborer un nouveau concept de GS systémique par opposition au GS classique correspondant aux ganglions de drainage anatomique de la tumeur. Nous proposons que les capacités particulières de rétention de l’ICG dans les tissus cancéreux après injection par voie systémique pourraient permettre d’identifier des sites ganglionnaires métastatiques en dehors des sites de drainage révélés par les injections de marqueurs au sein ou en périphérie de la tumeur elle-même. Pour vérifier cette hypothèse, nous avons élaboré un nouveau protocole d’une étude clinique prospective dans laquelle la détection du GS systémique après injection iv d’ICG sera comparée aux résultats obtenus suite à l’injection péritumorale de BP. Les ganglions révélés par ces 2 techniques seront recherchés ex vivo sur la pièce de résection et analysés en anatomopathologie. Outre la démonstration de métastases ganglionnaires extra-anatomiques, nous pensons que cette approche systémique pourrait permettre de réduire le taux de FN observé suite à une injection péritumorale, notamment pour les tumeurs localement avancées, celles-ci pouvant perturber le drainage lymphatique selon les voies anatomiques. Summary:This thesis reports several clinical research works on the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of colorectal tumoral tissue. We first evaluate and compare the role of ICG-FI in the detection of sentinel lymph node (SLN) in colorectal cancer (CRC) in view to upstage patients. We have reported that both techniques (blue dye and ICG-FI) are similar in term of sensitivity with a high rate of false negative results. Therefore, we think that new approaches for SLN detection should be developped in CRC. Secondarily, we evaluate the role of ICG-FI after IV ICG injection for the detection of peritoneal carcinomatosis (PC) from CRC origin. We have reported that ICG-FI is able to detect non-mucinous PM with a sensitivity of 86%. Moreover, ICG-FI was able to guide surgery modifying the surgical procedure in 38% of patients. Thirdly, we investigate the role of ICG-FI for the detection lymph node (LN) metastases. We have reported that ICG-FI performed after IV ICG injection is able to detect LN metastases both in vivo and ex vivo. These findings have been confirmed in a retrospective study. Fiinally, we propose a new protocol to evaluate a new approach for SLN detection. In comparison with the standard technique using peritumoral injection, we propose a new approach using systemic (intravenous) ICG injection. We have called this approach the 'systemic' SLN detetion. This approach will be compared with the standard one using peritumoral blue dye injection. Sensitivity, specificity of both technique will be compared. In conclusion, the results of these preliminary clinical studies using ICG-FI for tumoral staging and treatment are encouraging and further larger studies should be performed.
Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished

Orientador: Luiz Carlos Zeferino
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Objetivos: Avaliar a detecção do linfonodo sentinela em pacientes com câncer do colo do útero utilizando a combinação de azul patente com tecnécio99m e complicações associadas ao uso do azul patente. Sujeitos e métodos: Este foi um estudo de uma série de casos, para o qual foram selecionadas 56 mulheres com diagnóstico de câncer do colo do útero estádios Ia2,Ib1,Ib2 e IIa da FIGO, que se submeteram ao procedimento de identificação do linfonodo sentinela. O período de realização do estudo foi de maio de 2006 a dezembro de 2007. O estudo é apresentado em dois artigos: o primeiro consiste na detecção do linfonodo sentinela no câncer do colo do útero pela combinação do azul patente com tecnécio 99m e avalia a concordância entre a linfocintigrafia pré-operatória e o mapeamento linfático intra-operatório com o gama probe; o segundo consiste na avaliação das alterações da oximetria de pulso das pacientes submetidas à cirurgia após a injeção do azul patente. Resultados: No primeiro artigo identificou-se pelo menos um linfonodo sentinela em 83,13% das pacientes e a localização mais freqüente destes linfonodos foi na cadeia ilíaca externa. A sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo foram, respectivamente, 80%, 100%, 100% e 97,67% no histopatológico de congelação. Além disso, observou-se que linfocintigrafia pré operatória detecta um número consideravelmente menor de linfonodos sentinelas quando comparado ao mapeamento linfático intra-operatório com o gama probe. No segundo estudo observou-se que somente uma paciente apresentou reação anafilática. Treze pacientes apresentaram queda de oximetria de pulso (menor que 96% de saturação) após a injeção do azul patente no colo do útero, que durou em média cinco minutos e sem repercussões clínicas; essa queda se associou de forma limítrofe com tumores maiores e localizados ao redor do orifício externo do canal cervical. Conclusões: Concluiu-se que a combinação do azul patente com o tecnécio99m demonstrou excelentes resultados na detecção do linfonodo sentinela; a linfocintigrafia pré-operatória não oferece qualquer vantagem em relação ao mapeamento linfático intra-operatório com azul patente e tecnécio99m. Não houve repercussões clínicas devido à queda da oximetria de pulso e essas alterações se correlacionaram, embora com significância limítrofe, com tumores maiores e localizados ao redor do orifício cervical externo.
Abstract: Objectives: To evaluate sentinel lymph node detection in cervical cancer patients using a combination of patent blue dye and technetium99m and assess complications associated with the use of patent blue dye. Subjects and methods: This study investigated a case series that selected 56 women diagnosed with FIGO stage Ia2, Ib1, Ib2 and IIa cervical cancer who underwent a procedure for sentinel lymph node identification. The study was conducted from May 2006 to December 2007 and was described in two articles. The first article was about a study of sentinel lymph node detection in cervical cancer using a combination of patent blue dye and technetium99m. It assessed the agreement between preoperative lymphoscintigraphy and intraoperative lymphatic mapping with a gamma probe. The second article focused on the evaluation of changes in pulse oximetry readings in patients undergoing surgery after patent blue injection. Results: In the first article, at least one sentinel lymph node was identified in 83.13% of the patients and the most frequent site for finding sentinel lymph nodes was the external iliac chain. The sensitivity, specificity, positive predictive value and negative predictive value were 80%, 100%, 100% and 97.67% respectively on histopathology examination of frozen biopsy. In addition, it was observed that preoperative lymphoscintigraphy detected a substantially lower number of sentinel lymph nodes when compared to intraoperative lymphatic mapping with a gamma probe. In the second study, only one patient presented with an anaphylactic reaction. Thirteen patients showed a decrease in pulse oximetry readings (less than 96% saturation) after patent blue injection into the cervix, which lasted an average of five minutes and had no clinical repercussions. There was a borderline association between this decline in oxygen saturation values and tumors that were larger and located around the external cervical os. Conclusions: It was concluded that a combination of patent blue dye and technetium99m demonstrated excellent results in the detection of sentinel lymph nodes. Preoperative lymphoscintigraphy offers no advantage in relation to intraoperative lymphatic mapping with patent blue dye and technetium99m. There were no clinical repercussions due to lower oxygen saturation values. These changes correlated with tumors that were larger and located around the external cervical os, although the significance of this correlation was borderline.
Doutorado
Ciencias Biomedicas
Doutor em Tocoginecologia

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
estudar o linfonodo sentinela em pacientes portadoras de cÃncer na mama localmente avanÃado e que foram submetidos a quimioterapia neoadjuvante, compararando-o com os linfonodos axilares nÃo-sentinelas. Verificar a taxa de identificaÃÃo do linfonodo sentinela nestas pacientes, assim como estimar a sensibilidade, especificidade, falso-negativo, valor preditivo negativo e acurÃcia do mÃtodo. Metodologia: estudo transversal de validaÃÃo de teste diagnÃstico, envolvendo 34 pacientes oriundas do AmbulatÃrio da Maternidade-Escola Assis Chateaubriand. As pacientes portadoras de cÃncer na mama localmente avanÃado foram submetidas a quimioterapia neoadjuvante e aquelas que apresentaram axila clinicamente negativa para metÃstase de cÃncer de mama foram submetidas a biopsia do linfonodo sentinela e linfadenectomia axilar, utilizando administraÃÃo subareolar de azul patente, e este, apÃs sua identificaÃÃo, foi estudado mediante o exame de citologia de contato e parafina e comparado com conteÃdo linfÃtico axilar nÃo-sentinela. Realizada anÃlise descritiva e anÃlise dos testes utilizando teste t de Student, as proporÃÃes dos testes foram consideradas significativamente diferentes quando a probabilidade de estas serem semelhantes foi menor ou igual a 0,05. Resultados: Quando foi testada a citologia de contato intra-operatÃrio e parafina linfonodo sentinela e padrÃo-ouro os linfonodos sentinelas e nÃo-sentinelas, a taxa de identificaÃÃo do linfonodo sentinela foi de 85,3%. A sensibilidade foi de 84,62% e a especificidade de 100%. O valor preditivo negativo de 87,99% e taxa de falso-negativo de 12,01%. A acurÃcia foi de 92,77%. Dado observado na amostra foi a diferenÃa significativa do nÃmero mÃdio do total de linfonodos observados entre o grupo de pacientes com tempo de intervenÃÃo cirÃrgica Ãtimo p=0,037. Quando foi testada apenas a citologia de contato intraoperatÃria do linfonodo sentinela e padrÃo-ouro, a parafina dos linfonodos sentinelas e nÃo-sentinelas a sensibilidade foi de 62,50%, a especificidade de 100%, valor preditivo negativo de 75,04%, falso-negativo de 24,96% e acurÃcia de 82,38%. ConclusÃo: a citologia de contato intraoperatÃrio do linfonodo sentinela para pacientes com cÃncer de mama localmente avanÃados com axila clinicamente negativa apÃs quimoterapia neoadjuvante apresenta baixa sensibilidade e taxa de falso-negativo elevada.
Aims: investigating sentinel lymph node in patients with locally advanced breast cancer whom were administered neoadjuvant chemotherapy, by contrast to non-sentinel axillary lymph nodes. Verifying the identification of sentinel lymph node rate in these patients, as well as estimating methodâs sensibility, specificity, false-negative and accuracy. Methodology: transversal study for validation of a diagnostic test, with 34 patients from Maternidade-Escola Assis Chateaubriandâs ambulatory. The locally advanced breast cancer patients were treated with neoadjuvant chemotherapy, and the ones with cancer metastasis clinically negative axilla were submitted to sentinel lymph node biopsy and axillary lymphadenectomy, using subareolar patent blue, and, after its identification, it was studied with contact cytology and paraffin and it was compared with non-sentinel axillary lymph content. The descriptive analysis of tests used Studentâs t-test, and tests proportions were considered significantly different when their similarity possibility was less or equal to 0.05. Results: When intraoperatory contact cytology study, paraffin sentinel lymph node and gold standar, sentinel and non-sentinel lymph nodes, the sentinel lymph node identification rate was 85.3%. Sensibility was 84.62%, and specificity was 100%. The predictive negative value was 87.99%, and the false-negative rate was 12.01%. Accuracy rate was 92.77%. The study points the significant difference of total lymph nodes mean number observed among the group with optimal time of surgical intervention p=0.037. When only the intraoperatory contact cytology of sentinel lymph node and gold pattern, the paraffin of sentinel and non-sentinel lymph nodes, sensibility was 62.50%, specificity 100%, predictive negative value 75.04%, false-negative 24.96%, and accuracy 82.38%. Conclusion: intraoperatory contact cytology of sentinel lymph node to locally advanced breast cancer patients with clinically negative axilla after neoadjuvant chemotherapy presents low sensibility and high false-negative rates.

El carcinoma papil·lar de tiroide (CPT) és el càncer tiroïdal més freqüent. Malgrat que el seu pronòstic és habitualment bo, alguns pacients presenten disseminació de la malaltia i recurrència. L’impacte pronòstic de l’afectació ganglionar cervical sembla relacionar-se amb la seva extensió. El sistema d’estratificació TNM és imprecís quantificant aquest grau d’afectació ganglionar. L’abordatge quirúrgic de les metàstasis limfàtiques en el CPT és controvertit. Les recomanacions vigents proposen realitzar buidament ganglionar als malalts amb metàstasis demostrades i en situacions de risc de mal pronòstic. Per tant, resulta clau conèixer amb precisió l’estat ganglionar real. Amb aquest objectiu s’ha proposat la tècnica de la biòpsia selectiva del gangli sentinella (BSGS), comú en d’altres carcinomes. Aquesta metodologia pressuposa, per a cada tumor, una seqüència d’afectació limfàtica previsible. Això permet un abordatge quirúrgic més dirigit i centrar els esforços en l’anàlisi morfològica exhaustiva dels ganglis amb major probabilitat d’afectació. És fonamental que el diagnòstic intraquirúrgic de l’estat ganglionar sigui el més acurat possible, evitant falsos negatius. Per a minimitzar els errors diagnòstics de la morfologia convencional, s’ha implementat en el càncer de mama l’assaig molecular OSNA (One-Step Nucleic Acid Amplification). És un assaig quantitatiu, reproduïble i fiable, alternatiu a la histologia i que pot resoldre els errors diagnòstics de la morfologia. Alhora, estratifica el resultat depenent de la càrrega tumoral (negatiu, micrometàstasi o macrometàstasi). La present tesi doctoral ha estat estructurada en 4 articles científics i ha tingut com a objectiu final demostrar tant l’efectivitat de la BSGS en el CPT, escassament reportada, com avaluar per primera vegada la implementació d’OSNA en aquest context. El primer treball va demostrar, en una sèrie de 43 pacients, els bons resultats de la BSGS amb anàlisi intraoperatòria convencional (citologia/histologia), permetent millorar l’estratificació ganglionar i demostrant metàstasis ocultes en 50% dels casos. Va evidenciar el problema dels falsos negatius, fet que ens va suggerir la necessitat de cercar un sistema d’anàlisi alternatiu. El segon treball va pretendre, buscant una solució al problema, testar l’aplicabilitat d’OSNA per a l’anàlisi dels ganglis en el CPT. Es va plantejar un estudi preliminar comparatiu amb OSNA i morfologia convencional en paral·lel per a la valoració dels ganglis ressecats en 5 pacients amb evidència clínica de metàstasis. Un cop demostrada l’aplicabilitat d’OSNA en aquests ganglis, ens vàrem plantejar un tercer treball amb l’objectiu d’avaluar definitivament l’impacte de la introducció d’OSNA intraoperatori en una sèrie de 35 pacients sense evidència clínica de metàstasi. L’estudi va demostrar que el binomi BSGS+OSNA era factible. Addicionalment, la naturalesa quantitativa de l’assaig ens permeté plantejar un abordatge quirúrgic personalitzat depenent de la càrrega tumoral en el gangli sentinella. Finalment, el quart treball comparava amb OSNA algunes dades morfològiques proposades com a criteris de càrrega metastàtica ganglionar i qüestionava, segons aquesta metodologia, la validesa d’alguna d’elles. En resum, la tesi demostra l’aplicabilitat clínica d’OSNA per a millorar el rendiment de la BSGS en CPT. Addicionalment, OSNA permet un millor coneixement del potencial oncològic real de les metàstasis, aportant un valor quantitatiu i estandarditzable. A dia d’avui, tot i que les dades presentades son prometedores i encoratgen a no abandonar aquesta línia de recerca, el paper definitiu d’OSNA com a peça integrant dels algoritmes de maneig clínic en el CPT és un camp encara per explorar.
El carcinoma papilar (CPT) es el cáncer tiroideo más frecuente. Pese a tener un pronóstico generalmente bueno, algunos pacientes presentan una evolución agresiva con enfermedad diseminada y mayor riesgo de recurrencia. El impacto pronóstico de la afectación ganglionar cervical parece relacionarse con su extensión. El sistema de estratificación TNM es impreciso en la cuantificación del grado de afectación ganglionar. El abordaje quirúrgico de las metástasis linfáticas en el CPT es controvertido. Las recomendaciones vigentes proponen realizar vaciamiento ganglionar a aquellos pacientes con metástasis pre/intraquirúrgicamente demostradas y/o en situaciones de riesgo de mal pronóstico. Por ello, es clave conocer con la mayor precisión la afectación ganglionar real. Con este fin se ha propuesto la técnica de la biopsia selectiva del ganglio centinela (BSGC), de uso común en el cáncer de mama. Esta metodología presupone, para cada tumor, una secuencia de afectación linfática previsible. Esto permite un abordaje quirúrgico más dirigido y centrar los esfuerzos en el análisis morfológico exhaustivo de aquellos ganglios con mayor probabilidad de afectación. Es fundamental que el diagnóstico intraquirúrgico del estado ganglionar sea lo más exacto posible, evitando falsos negativos. Para minimizar los errores diagnósticos del estudio morfológico convencional, se ha implementado en el cáncer de mama el ensayo molecular OSNA (One-Step Nucleic Acid Amplification). Es un ensayo cuantitativo, reproducible y fiable, alternativo a la histología y que puede subsanar los errores diagnósticos de la morfología. Asimismo, estratifica el resultado según la carga tumoral (negativo, micrometástasis o macrometástasis). La presente tesis doctoral se ha estructurado en 4 artículos científicos y ha tenido como objetivo final demostrar tanto la efectividad de la técnica de la BSGS en los pacientes con CPT, escasamente reportada en la literatura, como evaluar por primera vez la implementación de la metodología OSNA en este contexto. El primer trabajo demostró, en una serie de 43 pacientes, los buenos resultados de la BSGS con análisis intraoperatorio convencional (citología/histología), permitiendo mejorar la estratificación ganglionar y demostrando metástasis ocultas en más del 50% de los casos. Se evidenció el problema ya conocido de los falsos negativos, sugiriéndose la necesidad de explorar un sistema de análisis alternativo. El segundo trabajo pretendió, buscando una solución a este problema, testar la aplicabilidad de OSNA para el análisis de los ganglios en el CPT. Se planteó, con buenos resultados finales, un estudio preliminar comparativo con OSNA y morfología convencional en paralelo para la valoración de los ganglios resecados en 5 pacientes con evidencia clínica de metástasis. Una vez demostrada la aplicabilidad de OSNA para el análisis de estos ganglios, nos planteamos un tercer trabajo con el objetivo de evaluar definitivamente el impacto de la introducción de OSNA intraoperatorio en una serie de 35 pacientes sin evidencia clínica de metástasis. El estudio demostró que el binomio BSGS+OSNA era factible. Adicionalmente, la naturaleza cuantitativa del ensayo nos permitió plantear un abordaje quirúrgico personalizado según la carga tumoral en el ganglio centinela. Finalmente, el cuarto trabajo comparaba con OSNA algunos datos morfológicos propuestos como criterios de carga metastásica ganglionar y cuestionaba, según esta metodología, la validez de alguno de ellos. En resumen, la tesis demuestra la aplicabilidad clínica de OSNA para mejorar el rendimiento de la BSGS en CPT. Adicionalmente, OSNA permite un mejor conocimiento del potencial oncológico real de las metástasis, aportando un valor cuantitativo y estandarizado. A día de hoy, pese a que los prometedores resultados animan a no abandonar esta línea de investigación, el papel definitivo de OSNA como pieza integrante de los algoritmos de manejo clínico en el CPT es un campo aún por explorar.
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Despite usually having a good prognosis, some patients present an aggressive course with disseminated disease and a higher risk of recurrence. The prognostic impact of cervical lymph node involvement appears to be related to its extent. The TNM stratification system is imprecise in estimating the lymph node extension. The surgical approach to nodal metastases in PTC is controversial. Current recommendations propose to perform cervical lymphadenectomy in those patients with metastases demonstrated before or during surgery and/or in cases of poor prognosis. Therefore, it is essential to accurately know the lymph node involvement. With this objective, the selective sentinel lymph node biopsy (SSLNB) technique, commonly used in other carcinomas such as breast cancer, has been proposed. This methodology presupposes, for each tumour, a predictable lymphatic involvement sequence. This allows a more personalized surgical approach and focuses efforts on the exhaustive morphological analysis of those nodes likely to be affected. The accuracy in the intra-operative diagnosis of the sentinel lymph node status is mandatory for the success of this technique, avoiding as much as possible false negative results. To minimize the diagnostic errors of the conventional morphological study, the OSNA (One-Step Nucleic Acid Amplification) molecular assay has been implemented in breast cancer. It is a quantitative, reproducible and reliable test, alternative to histology that can avoid the diagnostic errors of the morphology assessment. At the same time, it stratifies the result according to the tumour load (negative, micrometastasis or macrometastasis). The present PhD project has been structured in 4 papers. The main objectives have been to demonstrate: 1) the effectiveness of the SSLNB technique in patients with PTC, rarely reported in the literature, and 2) the usefulness, for the first time, of the implementation of OSNA in this context. The first paper demonstrated, in a series of 43 patients, the effectiveness of the SSLNB with conventional intraoperative analysis (cytology / histology). The technique improves lymph node stratification and shows occult metastases in more than 50% of cases. The already known problem of false negatives became evident, suggesting the necessity to explore an alternative analysis system. The second work aimed, in order to minimize this problem, to test the applicability of OSNA for the analysis of the lymph nodes in PTC. With that purpose in mind, a comparative preliminary study with OSNA and conventional morphology for the evaluation of the resected nodes in 5 patients with clinical evidence of nodal metastasis was performed. Once demonstrated by this second study the applicability of OSNA for the analysis of the lymph nodes in PTC, we developed a third study with the aim to finally evaluate the value of the intraoperative OSNA in a series of 35 patients without clinical evidence of nodal metastasis. The study showed that SSLNB + OSNA was feasible. Additionally, the quantitative nature of the assay allowed us to propose a personalized surgical approach according to the tumour burden on the sentinel node. Finally, in the fourth paper we compared some morphological data proposed as criteria for lymph node metastatic load with OSNA and we questioned, according to this methodology, the validity of some of them. In summary, our work demonstrates the clinical applicability of OSNA to improve the performance of the SSLNB in PTC. Additionally, OSNA allows a better understanding of the real oncological potential of metastases, providing a quantitative and standardized value. Today, despite the promising results that encourage to continue with this research, the definitive role of OSNA as an integral part of the clinical management algorithms in PTC is a field still to be explored.

A fluorescência é uma técnica amplamente empregada na área de diagnóstico médico, com aplicações distintas. Uma de suas aplicações é a detecção de um determinado marcador que pode ser injetado no paciente. A indocianina verde (ICG) é um exemplo de marcador fluorescente que pode ser empregado para auxiliar na identificação do linfonodo sentinela. A excitação é realizada em 780 nm e a emissão detectada ao redor de 850 nm. Tais comprimentos de onda são muito favoráveis para aplicação médica por apresentarem pouca absorção por tecidos biológicos. O objetivo deste trabalho foi desenvolver um sistema de imagens por fluorescência de ICG. Este sistema é basicamente constituído por um dispositivo de iluminação e de aquisição e tratamento de imagem. Dois protótipos foram construídos e testados, um com excitação Laser e o segundo a LED. O dispositivo de iluminação oferece uma iluminação uniforme em uma área de 10 por 15 cm a uma distância de 30 cm. A fluorescência é captada por um sistema composto por duas câmeras perpendiculares uma à outra e um espelho dicroico angulado 45° a ambas, cuja função é separar a imagem por bandas. Uma das câmeras capta a imagem refletida do espelho no espectro visível e a outra capta a imagem transmitida pelo espelho no infravermelho. As imagens obtidas pelas câmeras recebem tratamento em uma rotina desenvolvida em plataforma LabVIEW® para destacar a região com fluorescência sobreposta na imagem sob iluminação branca em tempo real, sendo possível salvar figuras ou vídeos, dependendo da necessidade do operador. O equipamento foi testado no Hospital de Câncer de Barretos em pacientes para ressecção cirúrgica de tumores de cabeça e pescoço e de melanoma e apresentou resultados promissores.
Fluorescence is a widely used technique in medical diagnostic, with several applications. One of its applications is the screening of a particular marker that can be injected into the patient. The indocyanine green (ICG) is an example of fluorescent marker that can be used to assist the identification of the sentinel lymph node. The excitation is performed at 780 nm and the emission is detected around 850 nm. Such wavelengths are very suitable for medical applications due to their little absorption by biological tissues. The objective of this study was to develop a system of fluorescence imaging of ICG. This system is basically constituted by an irradiation and image acquisition device and a routine for image processing. Two prototypes were built and tested, the first one with Laser excitation and the second with LED. The lighting device provides uniform illumination in an area of 10 by 15 cm at a distance of 30 cm. The fluorescence is collected by a system with two cameras orthogonal to each other and a dichroic mirror angled 45 ° to both, whose function is to separate the image in bands. One of the cameras captures the image reflected from the mirror in the visible spectrum and the other captures the image absorbed by the mirror in the infrared. The images obtained by the cameras receive treatment on a routine developed in LabVIEW® platform to highlight the fluorescent region overlapping the image under white light in real time, making it possible to save pictures or videos, depending on the needs of the operator. The equipment was tested in Barretos\' Cancer Hospital in patients for surgical resection of head and neck tumors and melanoma tumors and presented promising results.

Objetivo: determinar a viabilidade da identificação do linfonodo-sentinela em pacientes com câncer invasor de colo uterino estádio Ib1. Material e Métodos: 16 pacientes consecutivas com câncer de colo uterino agendadas para histerectomia radical com linfadenectomia pélvica bilateral realizaram estudo para detecção de linfonodo-sentinela. Onze pacientes injetaram 1 mCi de tecnécio 99 (99Tc) em quatro pontos do estroma superficial do colo uterino ao redor do tumor, às 12, 3, 6 e 9 h ( 16 horas antes da cirurgia ). No dia da cirurgia, as pacientes foram submetidas ao mapeamento linfático com gamma-probe e azul patente injetado nos mesmos pontos que o 99Tc.Cinco pacientes realizaram a detecção apenas com azul patente. Resultados: foi detectado pelo menos um (1 a 3 por paciente) linfonodo-sentinela em cada uma das 15 pacientes (93,7 %) que realizaram a técnica combinada.Foi detectado pelo menos 1 linfonodo-sentinela em 4 pacientes ( 80% )com azul patente apenas. A maioria dos linfonodos-sentinela foi localizada nas regiões: obturadora (37 %), ilíaca externa (22,2 %) e inter-ilíacas (18,5 %). Seis pacientes (40 %) tiveram linfonodos-sentinela bilaterais. Dos 27 linfonodos-sentinela detectados, 11 (40,7 %) foram detectados pelo corante, 9 (33,3%) pela radioatividade e 7 (26 %) pela radioatividade e corante. O índice de detecção intra-operatória com o gamma-probe foi de 90,9 % ( 11 pacientes ). Destes, 7 linfonodos foram azul e quente (31,8 %), 6 linfonodos foram apenas azuis (27,2 %) e 9 linfonodos foram apenas quentes (40,9 %). A sensibilidade, especificidade e valor preditivo negativo para a detecção do linfonodo-sentinela foram 100%, 85,7 % e 100 % respectivamente. Conclusão: A combinação do radiofármaco 99Tc e azul patente é efetiva na detecção do linfonodosentinela em câncer de colo uterino inicial.
Objective: to establish the feasibility of sentinel lymph node identification in patients with stages Ib1 invasive cervical cancer. Material and Methods: 16 consecutive patients with cervical cancer, were scheduled for radical hysterectomy with bilateral pelvic lymphadenectomy, were submitted to sentinel lymph node detection. Eleven patients was injected 1 mCi of technetium-99 (99Tc) into four points of the superficial cervical stroma around the tumor, at the 12, 3, 6 and 9 o’clock positions (sixteen hours before surgery ). On the day of the surgery, the patients were submitted to gamma-probe-guided lymphatic mapping and patent blue dye was injected into the same points as the 99Tc. Five patients were submitted to detection with patent blue only. Results: at least one sentinel lymph node (one to three per patient) was detected in each of the 15 patients (93.7%) in whom a combination of both methods was used. At least one sentinel lymph node was detected in four patients ( 80 % ) with patent blue only. Most sentinel lymph nodes were identified in the obturator (37%), external iliac (22.2%) and interiliac (18.5%) regions. Six patients (40%) had bilateral sentinel lymph nodes. Of the 27 sentinel lymph nodes detected, 11 (40.7%) were identified by the blue-dye technique, 9 (33.3%) by radiation, and 7 (26%) by radiation and by the blue-dye technique. The intraoperative detection rate was 90.9% with gamma-probe only ( 11 patients ). Of these, 7 lymph nodes were blue-stained and hot (31.8), 6 were just blue-stained (27.2%) and 9 were just hot (40.9%). Sensitivity, specificity and the negative predictive value for sentinel lymph node detection were 100%, 85,7% and 100 % respectively. Conclusion: the combination of 99Tc and patent blue dye is effective in the detection of sentinel lymph nodes in early-stage cervical cancer.

Introdução: o status dos linfonodos axilares permanece um dos mais importantes fatores prognósticos no carcinoma de mama em estágios iniciais, além de definir o uso de terapias complementares. A biópsia de linfonodo sentinela (BLNS) surgiu com a finalidade de estadiar a axila com o mínimo de morbidade, tendo como objetivo a identificação e o estudo patológico do primeiro linfonodo axilar proveniente da drenagem linfática da mama. Pacientes com axila clinicamente negativa têm indicação de biópsia de linfonodo sentinela como método de estadiamento da axila, e quando o resultado era positivo para metástase recomendava-se o esvaziamento axilar. Por recomendação do ACOSOG Z0011, o esvaziamento axilar (EA) após uma biópsia de linfonodo sentinela positivo não é necessário. Esse estudo demonstrou não haver benefício em realizar o EA na presença de LNS positivo na sobrevida global ou na sobrevida livre de doença. Objetivos: Avaliar a taxa de recidiva e morte em pacientes submetidas à cirurgia conservadora de mama e BLNS positiva com posterior esvaziamento axilar no Hospital de Clínicas de Porto Alegre; e, como objetivo secundário, avaliar as características clínicas e patológicas dessa população. Método: foi realizado um estudo de coorte retrospectiva, incluindo pacientes com diagnóstico de carcinoma de mama invasor submetidas à cirurgia conservadora da mama e BLNS, cujo resultado foi positivo para presença de metástases, e foram submetidas ao EA o período de janeiro de 2004 a dezembro de 2008. Resultados: foram incluídas 144 pacientes submetidas à biópsia de linfonodo sentinela e CCM; 33 tiveram o achado de biópsia de linfonodo sentinela positivo para metástase, e dessas 33 pacientes restaram 27 para análise dos dados. A taxa de sucesso na identificação do LNS foi de 0,96. A idade média das pacientes foi de 53,8 anos, o número de LNS ressecados foi de 1,6 por paciente; a média do tamanho tumoral foi de 2,3 cm. Seis pacientes apresentaram doença axilar residual correspondendo a 22,2% da amostra e tiveram um risco relativo de morte de 3 vezes mais para aquelas sem doença axilar residual e 50% a mais de desenvolvimento de metástases. Conclusão: O comprometimento axilar é importante fator no prognóstico das pacientes com câncer de mama, quanto maior o comprometimento da axilar pior será o desfecho de sobrevida livre de doença e de morte. Acreditamos que se pode aplicar a conduta do ACOSOG Z0011 também nas pacientes do HCPA devido à alta sensibilidade do método no nosso meio.
Introduction: The status of axillary lymph nodes remains one of the most important prognostic factors in breast carcinoma in the early stages, in addition it helps to defining the use of complementary therapies. Sentinel lymph node biopsy (SLNB) was developed with the purpose of staging the axilla with minimal morbidity, aiming at the identification and pathological study of the first axillary lymph node from the lymphatic drainage of the breast. Patients with clinically negative lymph node have indication of SLNB as a method of axillary staging, and with a positive finde for metastasis the axilar clereance was performed. Nowadays, due to the ACOSOG Z0011 Study, the axillary dissection (AD) after a positive SLNB for metastasis was put in check. This estudy have as a result no difference in global survive ou disease free survive if ALND was not performed in a positive SLNB. In the present study, we intend to evaluate the clinical and histopathological characteristics of patients submitted to breast conservative surgery and sentinel lymph node biopsy with a positive result for metastasis. Main objective: Evaluate the rate of recurrence and death in patients submitted to conservative breast surgery and BLNS with posterior axillary emptying at Hospital de Clínicas, Porto Alegre. It is a secondary objective to evaluate the clinical and pathological characteristics of this population. Material and Methods: A retrospective cohort study was performed, including 144 patients diagnosed with invasive breast carcinoma submitted to conservative breast surgery and SLNB, whose results were positive for metastases, and were submitted to AD, at the Mastology Unit of the Hospital de Clinicas de Porto Alegre (HCPA), from January 2004 to December 2008. Results: Of 144 patients submitted to SLNB and BCS, 33 had SLNB positive for metastasis, of these 33 patients remained 27 for data analysis. The success rate in LNS identification was 0.96. The mean age of the patients was 53.8 years, the number of resected SLN was 1.6 per patient; The mean tumor size was 2.3 cm. Six patients had residual axillary disease corresponding to 22.2% of the sample and had a relative risk of death of 3 times more for those without residual axillary disease and 50% more for the development of metastases. Conclusion: Axillary involvement is an important factor in the prognosis of patients with breast cancer, and the greater the axillary impairment, the worse the diseasefree survival outcome and death. We believe that the ACOSOG Z0011 trial can also be applied to HCPA patients who meet the inclusion criteria for this purpose, due to the high sensitivity of the method in our environment.

INTRODUÇÃO: O status axilar é o fator prognóstico mais importante em câncer de mama. A biópsia de linfonodo sentinela (BLS) tornou-se o procedimento padrão no estadiamento axilar em pacientes com axila clinicamente negativa. O procedimento recomendado para pacientes com metástase em linfonodo sentinela (LS) inclui a linfadenectomia axilar completa (LAC). Porém questiona-se a necessidade da LAC em todos os pacientes com metástase em LS (MLS), particularmente naqueles com baixo risco de metástase em linfonodos axilares adicionais (Não-LS). Estimar de forma precisa a probabilidade de MLS e metástase em Não-LS (MNão-LS) pode auxiliar em muito o processo de decisão terapêutica. Os dados publicados referentes aos fatores preditivos de MLS e MNão-LS são de certa forma escassos. A forma de como esses dados são apresentados – geralmente expressos como razão de chance (odds-ratio) – dificulta o cálculo de probabilidade de MLS ou MNão-LS para um paciente em específico. Nesta tese, dois modelos de previsão computadorizados de fácil utilização foram desenvolvidos, utilizando-se um grande número de casos, para facilitar o cálculo de probabilidade de MLS e MNão-LS. MÉTODOS: Todos os dados clínico-patológicos foram coletados do banco de dados prospectivo de LS do Memorial Sloan-Kettering Cancer Center (MSKCC), Nova York, EUA. Os projetos de desenvolvimento de ambos os modelos foram aprovados pelo Institutional Review Board do MSKCC. Dois modelos foram desenvolvidos: Modelo de MLS (Modelo LS) e Modelo de metástase em Não-LS (Modelo Não-LS). No Modelo LS, os achados clínico-patológicos de 4.115 procedimentos subseqüentes de BLS (amostra de modelagem) foram submetidos à análise de regressão logística multivariada para se criar um modelo de previsão de MLS. Um software baseado nesse modelo foi desenvolvido utilizando-se as variáveis: idade, tamanho do tumor, tipo histológico, invasão vásculo-linfática (IVL), localização do tumor e multifocalidade. Esse modelo foi validado em uma amostra distinta (amostra de validação) com 1.792 BLSs subseqüentes. No Modelo Não-LS, os achados patológicos do tumor primário e das MLS, obtidas de 702 procedimentos de BLS (amostra de modelagem) em pacientes submetidos à LAC, foram submetidos à análise de regressão logística multivariada para se criar um modelo de previsão de MNão-LS. Um nomograma e um software baseados nesse modelo foram desenvolvidos utilizando-se as variáveis: tamanho do tumor, tipo histológico, grau nuclear, IVL, multifocalidade, receptor de estrógeno, método de detecção da MLS, número de LS positivos, número de LS negativos. Esse modelo foi validado em uma amostra distinta (amostra de validação) com 373 casos subseqüentes. RESULTADOS: O software do Modelo LS na amostra de modelagem mostrou-se adequado, com a área sob a curva de características operacionais (ROC) de 0,76. Quando aplicado na amostra de validação, o Modelo LS também previu de forma acurada as probabilidades de MLS (ROC = 0,76). O software e o nomograma do Modelo Não-LS na amostra de modelagem apresentaram uma área ob a curva ROC de 0,76 e, na amostra de validação, 0,77. CONCLUSÕES: Dois softwares de fácil utilização foram desenvolvidos, utilizando-se informações comumente disponíveis pelo cirurgião para calcular para o paciente a probabilidade de MLS e MNão-LS de forma precisa, fácil e individualizada. O software do Modelo LS não deve ser utilizado, porém, para se evitar a BLS. Para download dos softawares clique em: www.mastologia.com .
INTRODUCTION: Axillary lymph node status is the most significant prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) has become the standard of care as the axillary staging procedure in clinically node negative patients. The standard procedure for patients with sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND). However, many experts question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of additional lymph node (Non-SLN) metastasis. Accurate estimates of the likelihood of SLN metastases and additional disease in the axilla could greatly assist in decision-making treatment. The published data on predictive factors for SLN and Non-SLN metastases is somewhat scarce. It is also difficult to apply these data – usually expressed as odds ratio – to calculate the probability of SLN or Non-SLN metastases for a specific patient. In this thesis, two user-friendly computerized prediction models based on large datasets were developed, to assist the prediction of the presence of SLN and Non-SLN metastases. METHODS: All clinical and pathological data were collected from the prospective SLN database of Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA. The development projects of both models were approved by the Institutional Review Board of MSKCC. Two models were developed: Model for predicting SLN metastases (SLN Model) and Model for predicting Non-SLN metastases (Non-SLN Model). In the SLN Model, clinical and pathological features of 4,115 sequential SLNB procedures (modeling sample) were assessed with multivariable logistic regression to predict the presence SLN metastases. A software based on the logistic regression model was created using age, tumor size, tumor type, lymphovascular invasion, tumor location and multifocality. This model was subsequently applied to another set of 1,792 sequential SLNBs (validation sample). In the Non-SLN Model, pathological features of the primary tumor and SLN metastases, identified in 702 SLNBs (modeling sample) on patients who underwent complete ALND, were assessed with multivariable logistic regression to predict the presence of additional disease in the Non-SLNs of these patients. A nomogram and a software were created using tumor size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. This model was subsequently applied to another set of sequential 373 procedures (validation sample). RESULTS: The software of the SLN Model for the modeling sample was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the validation sample, the SLN-Model accurately predicted likelihood of SLN metastases (ROC = 0.76). The software and nomogram of the Non-SLN Model was also accurately predicted likelihood of Non-SLN metastases, with an area under ROC curve of 0.76 for the modeling sample, and 0.77 for the validation sample. CONCLUSION: Two user-friendly softwares were developed, using information commonly available to the surgeon to easily and accurately calculate the likelihood of having SLN metastases or additional, Non-SLN metastases for individual patients. However, the software of the SLN Model should not be used to avoid SLNB. Click on www.mastologia.com to download these softwares.

Introducció: El tractament d'elecció del carcinoma escamós de cavitat oral en estadis inicials (T1-2N0) es basa en la resecció quirúrgica del tumor primari, acceptant-se tres opcions per al tractament del coll clínicament negatiu: l'observació clínica, el buidament ganglionar cervical i la biòpsia del gangli sentinella. L'aplicació de la biòpsia del gangli sentinella en el territori cervicofacial es basa en l'elevada seqüencialització del flux limfàtic local, havent-se evidenciat a més patrons de drenatge específics per a cada localització tumoral. No obstant això, els estudis prequirúrgics basats en la detecció de radiotraçador (gammagrafia planar o SPECT-CT) permeten evidenciar en ocasions l'existència de vies de drenatge limfàtic cap a territoris inesperats (més enllà dels nivells I a III o al coll contralateral per tumors de lateralitat ben definida). Si bé aquesta troballa no implica necessàriament la presència de dipòsits tumorals, les repercussions clíniques de la mateixa són desconegudes, dificultant així arribar a un consens per establir recomanacions a les guies de pràctica clínica. Hipòtesi i Objectius: L'objectiu principal d'aquest estudi consisteix a avaluar la rellevància de l'anàlisi dels dipòsits de radiotraçador en territoris ganglionars inesperats (definits com aquells localitzats en territoris contralaterals per tumors de lateralitat ben definida o en nivells més enllà dels nivells I a III). S'estableix com a hipòtesi que l'anàlisi dels ganglis sentinella als territoris atípics està justificada per la potencial presència de dipòsits tumorals, contribuint a establir la major precisió diagnòstica de la biòpsia de gangli sentinella davant el buidament ganglionar electiu i el watchful waiting. Material i Mètodes: Es descriuen i analitzen els resultats de les fases de validació i aplicació de la tècnica del gangli sentinella per al carcinoma escamós de cavitat en estadis inicials pel servei de Cirurgia Oral i Maxil•lofacial de l'Hospital Universitari Vall d'Hebron (Barcelona) durant el període 2005-2013, realitzant un seguiment de la mostra fins a l’agost de 2019. Resultats: Dels 75 pacients que van complir els criteris d'inclusió, 19 presentaven disseminació ganglionar cervical. Mitjançant una anàlisi basada en l'aplicació de diferents escenaris simulats sobre la cohort estudiada es va evidenciar una major capacitat diagnòstica del protocol del gangli sentinella amb anàlisi dels ganglis situats en territoris inesperats en comparació amb la biòpsia de gangli sentinella ometent aquests últims, un protocol estàndard de buidament ganglionar supraomohioideu o el watchful waitings. Una anàlisi detallada dels resultats desglossant els pacients malalts en tres categories (FN, VP- i VP +) resulta necessària per comparar de forma exhaustiva la precisió diagnòstica dels diferents abordatges acceptats per al tractament del coll N0. Conclusions: La biòpsia del gangli sentinella amb anàlisi dels ganglis en territoris inesperats defineix amb major precisió que les seves alternatives l'extensió de la disseminació cervical, permetent ajustar l'abordatge terapèutic a l'extensió real de la malaltia.
Introducción: El tratamiento de elección del carcinoma escamoso de cavidad oral en estadios iniciales (T1-2N0) se basa en la resección quirúrgica del tumor primario, aceptándose tres opciones para el manejo del cuello clínicamente negativo: la observación clínica, el vaciamiento ganglionar cervical y la biopsia del ganglio centinela. La aplicación de la biopsia del ganglio centinela en el territorio cervicofacial se basa en la elevada secuencialización del flujo linfático local, habiéndose evidenciado además patrones de drenaje específicos para cada localización tumoral. No obstante, los estudios prequirúrgicos basados en la detección de radiotrazador (gammagrafía planar o SPECT-CT) permiten evidenciar en ocasiones la existencia de vías de drenaje linfático hacia territorios inesperados (más allá de los niveles I a III o en el cuello contralateral para tumores de lateralidad bien definida). Si bien dicho hallazgo no implica necesariamente la presencia de depósitos tumorales, las repercusiones clínicas del mismo son desconocidas, dificultando así alcanzar un consenso para establecer recomendaciones en las guías de práctica clínica. Hipótesis y Objetivos: El objetivo principal de este estudio consiste en evaluar la relevancia del análisis de los depósitos de trazador en territorios ganglionares inesperados (definidos como aquellos localizados en territorios contralaterales para tumores de lateralidad bien definida o en niveles más allá de los niveles I-III). Se establece como hipótesis que el análisis de los ganglios centinela en los territorios atípicos está justificado por la potencial presencia de depósitos tumorales, contribuyendo a establecer la mayor precisión diagnóstica de la biopsia del ganglio centinela frente al VGC electivo y el watchful waiting. Material y Métodos: Se describen y analizan los resultados de las fases de validación y aplicación de la técnica del ganglio centinela para el carcinoma escamoso de cavidad en estadios iniciales por el servicio de Cirugía Oral y Maxilofacial del Hospital Universitario Vall d'Hebron (Barcelona) durante el periodo 2005-2013, realizándose un seguimiento de la muestra hasta Agosto de 2019. Resultados: De los 75 pacientes que cumplieron los criterios de inclusión, 19 presentaban diseminación ganglionar cervical. Mediante un análisis basado en la aplicación de distintos escenarios simulados sobre la cohorte a estudio se evidenció una mayor capacidad diagnóstica del protocolo del ganglio centinela con análisis de los ganglios ubicados en territorios inesperados frente a la biopsia del ganglio centinela omitiendo estos últimos y frente a un protocolo estándar de vaciamiento ganglionar supraomohioideo o watchful waiting. Un análisis pormenorizado de los resultados desglosando los pacientes enfermos en tres categorías (FN, VP- y VP+) resulta necesario para comparar de forma exhaustiva la precisión diagnóstica de los distintos abordajes aceptados para el manejo del cuello N0. Conclusiones: La biopsia del ganglio centinela con análisis de los ganglios en territorios inesperados define con mayor precisión que sus alternativas la extensión de la diseminación cervical, permitiendo ajustar el abordaje terapéutico a la extensión real de la enfermedad.
Introduction: Early stage oral squamous cell carcinoma (T1-2N0 OSCC) is routinely treated by means of surgical resection of the primary tumor. Current guidelines accept three scenarios for the management of the clinically negative neck: watchful waiting, elective neck dissection or sentinel lymph node biopsy (SLNB). The use of SLNB in head and neck malignancies is based on the fact that the dissemination of metastatic cells to the regional lymph nodes occurs in a sequential fashion and that only a limited group of nodes are at high risk of harbouring metastatic cancer for each specific primary tumour. However, presurgical studies based on the detection of radiotracer (planar scintigraphy or SPECT-CT) sometimes reveal the existence of lymphatic drainage routes to unexpected territories (beyond levels I to III or in the contralateral neck for tumors without midline involvement). Although this finding does not necessarily imply the presence of tumor deposits, its clinical repercussions are unknown, thus making it difficult to reach a consensus to establish recommendations in clinical practice guidelines. Hypothesis and Objectives: The main objective of this study is to assess the relevance of the analysis of radiotracer deposits in unexpected nodal territories (defined as those located in the contralateral neck for tumors without midline involvement or beyond levels I to III). The working hypothesis is that the analysis of sentinel nodes in atypical territories is justified by the potential presence of tumor deposits and that it is vital to establish SLNB's diagnostic superiority compared to elective VGC and watchful waiting. Material and Methods: This study is based on the validation and application phases of the sentinel lymph node biopsy for squamous cavity carcinoma in early stages run by the Oral and Maxillofacial Surgery service at the Vall d'Hebron Hospital (Barcelona) during the period 2005-2013. Results: 19 of the 75 patients who met the inclusion criteria suffered from cervical lymph node dissemination. An analysis based on the application of different simulated scenarios showed a greater diagnostic accuracy when atypical sentinel nodes were analyzed compared to a standard supraomohyoid neck dissection, watchful waiting or a SLNB protocol omitting atypical nodes. A comprehensive analysis of the results, dividing ill patients into three categories is necessary to compare the diagnostic precision of the different approaches of the N0 neck for oral squamous cell carcinoma. Conclusions: Inclusion of atypical sentinel lymph nodes is key to define the extent of cervical dissemination with greater precision than other accepted approaches, allowing to precisely adjust the treatment to the real extent of the disease.

Orientador: René Aloísio da Costa Vieira
Resumo: Introdução: O câncer de mama representa o tipo de câncer mais comum entre as mulheres no mundo. A presença e a extensão do envolvimento linfonodal axilar é um importante fator prognóstico, com grande impacto na decisão terapêutica. Por outro lado, a linfadenectomia axilar (LA) associa-se a considerável morbidade. Neste sentido, a biópsia do linfonodo sentinela (BLS) constitui modalidade atualmente aceita para uso em tumores T1 e T2, associados a axila negativa. Fato é que pacientes com tumores T3 e T4 e axila negativa são, muitas vezes, submetidas a LA de maneira desnecessária, visto o limitado número de pacientes em séries publicadas. Assim, o objetivo deste estudo é avaliar a negatividade e segurança da BLS em tumores T3 e T4, associados à axila clinicamente negativa, baseada em série de casos institucionais e revisão sistemática da literatura. Material e métodos: Estudo retrospectivo, observacional de pacientes tratadas de câncer de mama no ambulatório de Mastologia e Reconstrução Mamária do Hospital de Câncer de Barretos (HCB), Fundação Pio XII, nos anos de 2008 a 2015, realizado em pacientes portadoras de tumores T3/T4 e axila clinicamente N0 submetidas a BLS. Realizou-se, também, revisão sistemática da literatura em 5 bases. Utilizou-se a metodologia PICO, considerando P = breast cancer, I = lymph node sentinela, C = T3 and T4 tumors e O = axillary preservation. Para avaliação dos artigos, foi utilizada a metodologia PRISMA. Resultados: Foram analisadas 73 pacientes; de... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Introduction: Breast cancer represents the most common type of cancer among women in the world. The presence and extent of axillary lymph node involvement represents an important prognostic factor, with an impact on therapy. On the other hand, axillary lymph node dissection (ALND) is associated with considerable morbidity. In this sense, sentinel lymph node biopsy (SLNB) is currently accepted modality for tumors T1 and T2 with negative axilla (N0). The fact is that many patients with T3-T4 tumors with negative axilla, are often submitted to unnecessarily ALND. There are limited number of patients in published series and selected cases may have axillary preservation. Thus, the objective of this study is to evaluate the negativity and safety of SLNB in T3 and T4 tumors, associated to the clinically N0, based on a series of institutional cases and a systematic review of the literature. Materials and Methods: A retrospective, observational study of patients treated for breast cancer at a tertiary cancer center between 2008 and 2015, with T3 / T4 tumors and N0 who underwent SLNB. A systematic review of literature was also carried out in 5 bases through the PICO methodology, considering: P = breast cancer; I = sentinel lymph node; C = T3 and T4 tumors and O = axillary preservation. Results: We analyzed 73 patients, 9 of whom were cT3 and after surgery they became pT2, 47 pT3 patients and 17 T4b patients. SLNB was identified in all cases and was negative for macrometastasis in 60.3%... (Complete abstract click electronic access below)
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INTRODUÇÃO: O aprimoramento dos métodos de rastreamento e a conscientização da população geral contribuíram para o diagnóstico cada vez mais precoce do câncer de mama e proporcionou, juntamente com o avanço na terapêutica, altas taxas de sobrevida. O estado do acometimento axilar por metástase é um dos principais fatores prognósticos em pacientes com câncer de mama, particularmente naquelas com diagnóstico em estádio inicial. Na última década, esforços científicos foram direcionados para simplificar a amostragem dos linfonodos axilares, diminuindo a morbidade, mas respeitando os princípios oncológicos. Nesse sentindo, a biópsia do linfonodo sentinela foi considerada o avanço mais importante. Ao se obter um método preditor do estado axilar, que apresente os benefícios da abordagem padrão dissecção axilar e biópsia de linfonodo sentinela porém sem seus efeitos colaterais e que seja facilmente reproduzível, realizaremos um grande avanço na avaliação e terapêutica do câncer de mama inicial. MÉTODOS: Foi realizado estudo transversal retrospectivo com base nos prontuários de pacientes com câncer de mama invasivo, não metastático, com qualquer idade, atendidas entre 1999 e 2007 no Setor de Mastologia da Disciplina de Ginecologia do Departamento de Obstetrícia e Ginecologia da Faculdade de Medicina da Universidade de São Paulo e Clínica Professor José Aristodemo Pinotti, cujo estudo histopatológico e imunoistoquímico foi supervisionado por um único médico patologista. Realizamos uma subdivisão imunoistoquímica dos tumores, sendo considerado luminal A os tumores com receptores hormonais positivos e HER 2 negativo; luminal B os com receptores hormonais positivos e HER 2 positivo; HER 2 as pacientes com receptores hormonais negativos e HER 2 positivo e triplo negativo aquelas com receptores hormonais e HER 2 negativos. Correlacionamos esses subtipos com as variáveis clínicas idade e tamanho tumoral para predizer a probabilidade de acometimento linfonodal axilar. RESULTADOS: Duzentos e trinta e nove casos foram analisados. No subtipo luminal A, a possibilidade de metástase foi maior quanto menor a idade da paciente e maior o tamanho do tumor. Essa foi a única associação que apresentou diferença estatisticamente significante. As pacientes que possuíam tumores triplo negativo tiveram, aproximadamente, 90% menos chance de metástase linfonodal que as pacientes com tumor luminal A. CONCLUSÕES: As pacientes com tumor luminal A apresentaram, significativamente, maior probabilidade de metástase linfonodal axilar. As pacientes com de tumores triplo negativo, com idade superior a 55 anos ou tumores menores que 2 cm, revelaram menor probabilidade de metástase axilar
INTRODUTION: The improvement of screening methods and awareness of general population contributed to the increasingly early diagnosis of breast cancer and provided, together with advances in therapy, high survival rates. The status of axillary involvement is a major prognostic factor in patients with breast cancer, particularly those with early stage. In the last decade, research efforts were directed to simplify the sampling of axillary lymph nodes, decreasing the morbidity, but respecting the oncological principles. In this sense, the sentinel lymph node biopsy was considered the most important advance. If we obtain a method to predict the axillary status, with the benefits of the standard approach - axillary dissection and sentinel lymph node biopsy - without its side effects and easily reproducible, we will hold a major advance in the assessment and treatment of early breast cancer. METHODS: We conducted a retrospective cross-sectional study based on records of patients with invasive breast cancer, non metastatic, with any age, treated between 1999 and 2007 in the breast cancer Sector of the Gynecology Discilpine of the Department of Obstetrics and Gynecology, Faculty of Medicine, University of São Paulo and Private Clinic of Professor José Aristodemo Pinotti, whose histopathological studies were supervised by a single pathologist. We performed an immunohistochemical subdivision of the tumors, and considered luminal A tumors with positive hormonal receptors and negative HER 2, luminal B with positive hormonal receptors and positive HER 2, HER 2 patients with negative hormonal receptors and positive HER 2 and the triple-negative those with negative hormonal receptors and HER 2. Those subtypes were correlated with the clinical variables age and tumor size in predicting the likelihood of axillary lymph node involvement. RESULTS: Two hundred and nine cases were analyzed. In the luminal A, the possibility of axillary metastasis was higher in the younger patients and larger tumors. That was the only combination that showed statistically significant difference. The patients who had triplenegative tumors had approximately 90% less chance of lymph node metastasis than patients with tumors luminal A. CONCLUSIONS: The patients with luminal A tumors showed a significantly association with greater likelihood of axillary lymph node metastasis. The patients with triple negative tumors, age over 55 years or tumors smaller than 2 cm showed a lower likelihood of axillary lymph node metastasis

El valor clínic de la biòpsia selectiva del gangli sentinella (BSGS) en pacients amb melanoma gruixut (Breslow > 4 mm) no ha estat prou estudiada. L'objectiu principal d'quest treball és avaluar si la BSGS augmenta la supervivència en pacients amb melanoma gruixut i com a objectiu secundari, investigar la relació entre la supervivència i l'estat del gangli sentinella (GS). Altres objectius secundaris són identificar quines variables estan associades amb l'afectació de l'GS i analitzar el paper de la dissecció completa dels ganglis limfàtics en pacients amb una BSGS positiva. Es van incloure pacients amb melanomes gruixuts (> 4 mm) registrats en les bases de dades de melanoma dels hospitals participants entre 1997 i 2015. Els pacients van ser aparellats pel mètode de la puntuació de propensió segons el sexe, l'edat, la localització del tumor primari, les característiques histològiques del melanoma, l'any de diagnòstic, l'hospital i la realització de teràpia adjuvant amb interferó. Per identificar els factors associats amb l'afectació del GS, vam realitzar un estudi de cohorts retrospectiu multicèntric que va incloure a tots els pacients amb melanoma gruixut que s'havien sotmès a la BSGS. Per analitzar el paper de la limfadenectomia selectiva (LS) en pacients amb melanoma gruixut i una BSGS positiva, vàrem crear un model multivariat de riscos proporcionals de Cox per a la supervivència específica del melanoma (SEM) i la supervivència lliure de malaltia (SLM) i compararem els pacients que havien rebut LS i els que no. La BSGS enfront de l'observació es va associar amb una millor SLM (raó de risc ajustada [AHR], 0,74; interval de confiança [IC] de el 95%: 0,61-0,90); p = 0.002) i supervivència global (AHR, 0.75; IC 95%, 0,60-0,94; p = 0.013) però no SEM (AHR, 0.84; IC 95%, 0.65-1.08; p = 0,165). Els pacients amb BSGS negativa van tenir una millor SEM als 5 i 10 anys en comparació amb els pacients amb una BSGS positiva (65.4% vs 51.9% i 48.3% vs 38.8%; p = 0.01, respectivament). L'anàlisi de regressió logística va mostrar que l'edat, el subtipus histològic, la ulceració, les satelitosis microscòpiques i la invasió limfovascular es van associar amb l'afectació ganglionar. L'arbre de decisió CHAID (detecció automàtica d'interaccions mitjançant chi-quadrat) va mostrar que la ulceració és el predictor més important deafectació de l'GS. Per als melanomes no ulcerats, els subtipus histològics de melanoma lentigen maligne i altres subtipus poc freqüents es van associar amb una baixa taxa d'afectació de GS (4,3%). No es van observar diferències significatives per SLM i SEM entre els grups als quals s'havia realitzat LS i els que no. L'estat dels ganglis no sentinella en la LS es va associar amb diferències en les taxes de SLM i SEM. En conclusió, la biòpsia SLN es va associar a una millor SLM però no a una millor SEM, en pacients amb melanoma gruixut després de l'ajust per factors pronòstics clàssics. La BSGS és útil per estratificar aquests pacients en diferents grups de risc. Hi ha subgrups de pacients amb melanoma gruixut i una baixa probabilitat d'afectació de l'GS. La LS no ofereix beneficis de supervivència, però proporciona informació pronòstica.
El valor clínico de la biopsia selectiva del ganglio linfático centinela (BSGC) en pacientes con melanoma grueso (Breslow> 4 mm) no ha sido suficientemente estudiada. El objetivo principal del trabajo es evaluar si la biopsia BSGC aumenta la supervivencia en pacientes con melanoma grueso y como objetivo secundario, investigar la relación entre la supervivencia y el estado del ganglio centinela (GC). Otros objetivos secundarios son identificar qué variables están asociadas con la afectación del GC y analizar el papel de la disección completa de ganglios linfáticos en pacientes con una BSGC positiva. Se incluyeron pacientes con melanomas gruesos (> 4 mm) registrados en las bases de datos de melanoma de los hospitales participantes entre 1997 y 2015. Los pacientes fueron emparejados por el método de la puntuación de propensión según el sexo, la edad, la localización del tumor primario, las características histológicas del melanoma, el año de diagnóstico, el hospital y la realización de terapia adyuvante con interferón. Para identificar los factores asociados con la afectación del GC, realizamos un estudio de cohorte retrospectivo multicéntrico que incluyó a todos los pacientes con melanoma grueso que se habían sometido a la BSGC. Para analizar el papel de la linfadenectomía selectiva (LS) en pacientes con melanoma grueso y una BSGC positiva, creamos un modelo multivariado de riesgos proporcionales de Cox para la supervivencia específica del melanoma (SEM) y la supervivencia libre de enfermedad (SLE) y comparamos a los pacientes que habían recibido LS y los que no. La BSGC frente a la observación se asoció con una mejor SLE (razón de riesgo ajustada [AHR], 0,74; intervalo de confianza [IC] del 95%: 0,61-0,90); p = 0.002) y supervivencia global (AHR, 0.75; IC 95%, 0.60-0.94; p = 0.013) pero no SEM (AHR, 0.84; IC 95%, 0.65-1.08; p = 0.165). Los pacientes con BSGC negativa tuvieron una mejor SEM de 5 y 10 años en comparación con los pacientes con BSGC positiva (65.4% vs. 51.9% y 48.3% vs 38.8%; p = 0.01, respectivamente). El análisis de regresión logística mostró que la edad, el subtipo histológico, la ulceración, la satelitosis microscópica y la invasión linfovascular se asociaron con la enfermedad ganglionar. El árbol de decisión CHAID (detección automática de interacciones mediante chi-cuadrado) mostró que la ulceración es el predictor más importante de afectación del GC. Para los melanomas no ulcerados, los subtipos histológicos de melanoma lentigo maligno y otros subtipos poco frecuentes se asociaron con una baja tasa de afectación de GC (4,3%). No se observaron diferencias significativas para SLE y SEM entre los grupos a los que se había realizado LS y los que no. El estado de los ganglios no centinela en la LS se asoció con diferencias en las tasas de SLE y SEM. En conclusión, la biopsia SLN se asoció con una mejor SLE pero no con una mejor SEM en pacientes con melanoma grueso después del ajuste por factores pronósticos clásicos. La BSGC es útil para estratificar a estos pacientes en diferentes grupos de pronóstico. Existen subgrupos de pacientes con melanoma grueso con una baja probabilidad de afectación del GC. La LS no ofrece beneficios de supervivencia, pero proporciona información pronóstica.
The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The main aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. Other secondary objectives include the identification of variables associated with SLN involvement and analyze the role of complete lymph node dissection in patients with a positive SLN biopsy. Patients with thick melanomas (>4 mm) registered in the participating hospitals’ melanoma databases between 1997 and 2015 were included. Patients were matchedinto pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital, and adjuvant interferon therapy. To identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving all patients with thick melanoma who had undergone SLN biopsy. To analyze the role of complete lymph node dissection (CLND) in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and diseasefree survival (DFS) and compared patients who had undergone CLND with who had not. The SLN biopsy vs. observation was associated with better DFS (adjusted hazard ratio [AHR], 0.74; 95% confidence interval [CI] 0.61-0.90); p = 0.002) and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = .013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared to SLN-positive patients (65.4% vs. 51.9% and 48.3% vs 38.8%; p = 0.01, respectively). The logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, lentigo maligna melanoma and other rare histologic subtypes were associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates. In conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. We also identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information.

O câncer de mama é a neoplasia maligna que mais acomete as mulheres na população brasileira. Atualmente o tratamento para o câncer de mama está fundamentado em três pilares: radioterapia, cirurgia em suas diversas técnicas, quimioterapia/hormonioterapia. A qualidade de vida pode ser afetada de uma forma geral, envolvendo os aspectos físicos, psicológicos, sociológicos, emocionais, entre outros. O objetivo deste estudo foi comparar a função do membro superior em pacientes com câncer de mama que foram submetidas à biópsia de linfonodo sentinela com as submetidas à dissecção axilar, e que não foram acompanhadas por um protocolo de reabilitação pré-estabelecido. Pacientes e métodos: foram avaliadas 36 pacientes que passaram por dissecção axilar (grupo DA), 29 que foram submetidas à biópsia de linfonodo sentinela (grupo BLS) e 11 sujeitos normais (grupo SN). Resultados: Verificamos que o grupo DA apresenta um risco de ter perda funcional para os movimentos de flexão e abdução de ombro na ordem de 5 e 3,7 vezes maior que o grupo BLS, respectivamente. Encontramos também que pacientes submetidas à BLS evoluem com disfunção significativa para a flexão e abdução de ombro quando não submetidas à intervenção fisioterápica. Conclusão: A DA apresenta uma maior disfunção em membro superior quando comparada com BLS. A reabilitação de pacientes submetidas à BLS não pode ser ignorada, pois esta intervenção cirúrgica pode levar a disfunção significativa do membro superior ipsilateral
Breast cancer is a malignancy that affects more women in the Brazilian population. Currently the treatment for breast cancer is based on three pillars: radiotherapy, surgery in its various techniques, chemotherapy / hormone therapy. Quality of life may be affected in general, involving the physical, psychological, sociological, emotional, and others. The aim of this study was to compare the upper limb function in patients with breast cancer who underwent sentinel lymph node biopsy with axillary dissection underwent, and were not accompanied by a rehabilitation protocol pre-established. Patients and methods: we evaluated 36 patients who underwent axillary dissection (group DA), 29 who underwent sentinel lymph node biopsy (SNB group) and 11 normal subjects (group SN). Results: We found that the DA group presents a risk of loss of function for flexion and shoulder abduction in the order of 5 and 3.7 times higher than the BLS group, respectively. We also found that patients who underwent SNB evolve with significant dysfunction for flexion and shoulder abduction when not undergoing physiotherapy intervention. Conclusion: The DA has a higher dysfunction in upper limb when compared with BLS. The rehabilitation of patients who underwent SNB can not be ignored because this surgery can lead to significant dysfunction of the ipsilateral upper limb

Antecedents: El càncer de mama és el tumor més freqüent en les dones occidentals. En les últimes dècades s'ha reconegut i estudiat l'heterogeneïtat dels carcinomes de mama, i mitjançant l'ús d'anàlisi de l'expressió gènica, s'han pogut identificar diversos subtipus moleculars i en la pràctica clínica diària s'ha adaptat l'ús de marcadors immunohistoquímics per identificar-los de manera rutinària. La quimioteràpia neoadjuvant (QNA) s'ha utilitzat àmpliament per tractar el càncer de mama i la resposta d'un tumor al tractament sistèmic es relaciona amb un increment en la supervivència a llarg termini. Així mateix estat dels ganglis limfàtics axil·lars continua sent el factor pronòstic més important per a les pacients amb càncer de mama en estadi d'hora. Mètodes: estudi de cohort retrospectiu i descriptiu, que incloc 92 pacients diagnosticades de càncer de mama invasiu estadis CT2-cT3 cN0, les quals van ser sotmeses a QNA i posteriorment a cirurgia amb biòpsia selectiva del gangli sentinella (BSGS) pel mètode de Osna a l'Hospital Universitari Sant Joan de Reus . De la base de dades del servei d'Anatomia Patològica es van recopilar dades com el grau tumoral, el tipus histològic, la resposta patològica del tumor a la QNA, el nombre total de GC obtinguts, el nombre de còpies d'àcid ribonucleic missatger (ARNm) de CK19 i l'estat dels ganglis axil·lars no sentinelles. Resultats: El subtipus tumoral intrínsec més observat va ser el Luminal B (61,96%). La resposta patològica del tumor al tractament sistèmic va ser parcial en 59 casos (65,22%), completa en 28 (30,44%) i no es va observar resposta en 5 casos (4,35%). El Gc va ser positiu en 38 pacients i en 6 d'elles es van trobar més ganglis axil·lars no sentinelles positius. Totes elles van presentar tumors del subtipus Luminal B amb una resposta patològica parcial. Conclusió: Les pacients que presenten el GC positiu però mostren una RPC a la mama poden tenir una baixa probabilitat de presentar mes ganglis no sentinelles afectes a l'aixella.
Antecedentes: El cáncer de mama es el tumor más frecuente en las mujeres occidentales. En las últimas décadas se ha reconocido y estudiado la heterogeneidad de los carcinomas de mama, y mediante el uso de análisis de la expresión génica , se han podido identificar varios subtipos moleculares y en la práctica clínica diaria se ha adaptado el uso de marcadores inmunohistoquímicos para identificarlos de manera rutinaria. La quimioterapia neoadyuvante (QNA) se ha utilizado ampliamente para tratar el cáncer de mama y la respuesta de un tumor al tratamiento sistémico se relaciona con un incremento en la supervivencia a largo plazo. Así mismo estado de los ganglios linfáticos axilares continúa siendo el factor pronóstico más importante para las pacientes con cáncer de mama en estadio temprano. Métodos:estudio de cohorte retrospectivo y descriptivo, que incluyo 92 pacientes diagnosticadas de cáncer de mama invasivo estadios cT2-cT3 cN0, las cuales fueron sometidas a QNA y posteriormente a cirugía con biopsia selectiva del ganglio centinela (BSGC) por el método de OSNA en el Hospital Universitario Sant Joan de Reus. De la base de datos del servicio de Anatomía Patológica se recopilaron datos como el grado tumoral, el tipo histológico, la respuesta patológica del tumor a la QNA, el número total de GC obtenidos, el número de copias de ácido ribonucleico mensajero (ARNm) de CK19 y el estado de los ganglios axilares no centinelas. Resultados:El subtipo tumoral intrínseco más observado fue el Luminal B (61,96%).La respuesta patológica del tumor al tratamiento sistémico fue parcial en 59 casos (65,22%), completa en 28 (30,44%) y no se observó respuesta en 5 casos (4,35%). El Gc fue positivo en 38 pacientes y en 6 de ellas se hallaron más ganglios axilares no centinelas positivos. Todas ellas presentaron tumores del subtipo Luminal B con una respuesta patológica parcial. Conclusión:Las pacientes que presentan el GC positivo pero muestran una RPc en la mama pueden tener una baja probabilidad de presentar mas ganglios no centinelas afectos en la axila.
Background: Breast cancer is the most frequent tumor in Western women. In the last decades the heterogeneity of breast carcinomas has been recognized and studied, and through the use of gene expression analysis, several molecular subtypes have been identified and the use of immunohistochemical markers has been adapted in daily clinical practice identify them routinely. Neoadjuvant chemotherapy (NAC) has been widely used to treat breast cancer and the response of a tumor to systemic treatment is related to an increase in long-term survival. Likewise, axillary lymph node status continues to be the most important prognostic factor for patients with early-stage breast cancer. Methods: retrospective and descriptive cohort study, which included 92 patients diagnosed with invasive breast cancer cT2-cT3 cN0 stages, who underwent NAC and then surgery with selective biopsy of sentinel lymph node (SLNB) by the OSNA method at the University Hospital Sant Joan de Reus . From the database of the Pathology deparment, data were collected such as the tumor grade, the histological type, the pathological response of the tumor to the NAC, the total number of SLN obtained, the number of copies of messenger ribonucleic acid (mRNA) from CK19 and the status of axillary nodes sentinels. Results: The most observed intrinsic tumoral subtype was Luminal B (61.96%) .The pathological response of the tumor to systemic treatment was partial in 59 cases (65.22%), complete in 28 (30.44%) and not response was observed in 5 cases (4.35%). The Gc was positive in 38 patients and in 6 of them more axillary no sentinel lymph nodes were found. All of them presented tumors of the Luminal B subtype with a partial pathological response. Conclusion: Patients who present positive GC but show an RPc in the breast may have a low probability of presenting more no sentinel lymph nodes affected in the axilla.

INTRODUÇÃO: O mapeamento do linfonodo sentinela (MLNS) é largamente utilizado em pacientes com melanoma cutâneo, câncer de mama e outras neoplasias malignas sólidas com a finalidade de estadiá-las e indicar esvaziamento linfático apenas na presença de metástase. Nos últimos anos aumentou o interesse pelo uso do MLNS em pacientes com carcinoma papilífero de tireoide (CPT) sem metástases linfáticas detectáveis clinicamente (estádio cN0), devido à alta frequência de metástases ocultas nesses pacientes. O MLNS pode evitar o esvaziamento linfático do compartimento central (ECC) em portadores de CPT sem metástase. Mesmo que não se planeje o ECC eletivo, o MLNS pode também ser usado para estadiar adequadamente o pescoço e indicar tratamento posterior com radioiodoterapia em casos com metástase. Esse estudo tem como objetivo verificar: 1) a efetividade da técnica do MLNS nos pacientes com CPT; 2) a acurácia do MLNS em diagnosticar as metástases linfáticas; 3) se o MLNS pode modificar o estadiamento dos pacientes com CPT cN0. MÉTODOS: Trata-se de estudo de acurácia, prospectivo longitudinal de 38 casos consecutivos de CPT clinicamente N0, atendidos em um único centro, no período de 2010 a 2015. Todos foram submetidos à tireoidectomia total, MLNS com radiofármaco e ECC eletivo. Os resultados relativos ao MLNS foram comparados com o exame anatomopatológico do conteúdo do ECC. RESULTADOS: O tempo médio de seguimento dos doentes foi de 36 ± 13 meses. Os LNS foram localizados com maior frequência nos níveis VI e III. O LNS foi detectado em 95% da casuística e os valores de avaliação de testes diagnósticos foram: 1 falso negativo, 95% de sensibilidade, 100% de especificidade, 94% de valor preditivo negativo e 97% de acurácia. O MLNS foi capaz de reestadiar 49% dos pacientes inicialmente N0 para pN positivo. Quanto ao grupo de estadiamento AJCC (que leva em conta a idade), 3% dos pacientes foram reestadiados para estádio III e 18% para estádio IV. CONCLUSÕES: 1) a técnica de MLNS utilizada nos pacientes com CPT foi efetiva em 95% dos procedimentos realizados; 2) a acurácia do MLNS em diagnosticar as metástases linfáticas cervicais foi de 97%; 3) o MLNS re-estadiou os portadores de CPT, classificados clinicamente como N0, para pN positivo em 49% da casuística, e para estádio III e IVa em 21%
INTRODUCTON: Sentinel lymph node mapping (SLNM) is widely perfomed in melanoma, breast cancer and other solid tumors, to adequately stage these diseases. More recently, the interest in SLNM for clinically N0 Papillary Thyroid Cancer (PTC) has increased due to the high rate of occult metastases in these patients, to avoid unnecessary central neck dissection (CND), and its complications. Even if routine elective CND is not planned, SLNM can be used to adequately stage the neck, and to indicate further treatment with radioiodine in cases with neck metastases, for instance. This study aims to evaluate 1) SLNM effectiveness in PTC patients, 2) SLNM accuracy to diagnosis lymph node metastases and 3) if SLNM can upstage cN0 PTC patients. METHODS: This is a prospective longitudinal, diagnostic test accuracy study with 38 consecutive cN0 PTC patients, treated in a single center between 2010 and 2015. Surgical treatment in all cases included total thyroidectomy and elective CND after SLNM. Results of SLNM were compared to CND pathological findings, in order to verify if sentinel lymph node (SLN) predicted the occurrence of PTC occult lymph node metastasis. RESULTS: The mean patients\' follow-up was 36 ± 13 months. 133 SLN were found in the neck, on levels VI and III. The SLN was identified in 95% of the patients with 1 false negative, 95% sensitivity, 94% negative predictive value and 97% accuracy. The SLNM upstaging from cN0 to pN+ was 49%, with 3% stage III and 18% stage IVa. CONCLUSION: 1) SLNM was effective in 95% of procedures, 2) SLNM accuracy was 97%, 3) SLNM upstaging from cN0 to pN+ was 49%, and to stage III and IVa was 21%