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INTRODUCTION: The diagnosis of esophageal varices in cirrhotic patients is made by the upper gastrointestinal endoscopy. Multiple non-invasive predictors have been studied for the diag-nosis of esophageal varices. The objective of this study is to testthe FIB4 index as screening of esophageal varices in patients with liver cirrhosis. MATERIALS AND METHODS: A cross-sectional analytic study was developed in four national hospital using hepatic cirrhosis patient's medi-cal files. We assessed the information using univariate and bivariate analysis, sensitivity, speci-ficity, predictive positive and negative value, the positive and negative likelihood ratio calcu-lation of the esophageal varices screening and its size. We built ROC curve for every analysis group. RESULTS: The study included 289 liver cirrhosis patients. Most of the patients were male (54.33%). 77.85% patients had esophageal varices. The distribution of varices was 19.03%, 35.99% and 22.84% for large, medium and small varices, respectively. In the FIB-4 index analysis for the presence of varices, it was found a sensitivity of 81.3%, specificity of 37.5% (AUC: 0.57). The calculation for variceal size showed a sensitivity of 81.8%, specificity of 23.9% (AUC: 0.50). In the analysis of FIB-4 index for prophylaxis groups was found a sensitivity of 81.8% and a specificity of 28.5% (AUC: 0.54). CONCLUSIONS: The FIB-4 index has no good performance in the screening for the presence of esophageal varices and its size in liver cirrhosis patients. / Revisión por pares

The definition of clinical target volume (CTV) margins around gross tumor volume (GTV) for radiotherapy of esophageal cancer (EC) and many solid tumors is still a challenge hence the currently available in-vivo imaging techniques still fail to detect areas of microscopic tumor extension (MTE). Many parameters of the tumor microenvironment (TME), e.g., tumor cell proliferation, cancer stem cells, hypoxia, kinases, immune architecture and patient-specific parameters are hypothesized as inducers of MTE in esophageal cancer and other tumors. The correlation of these TME biomarkers with MTE before, during or after radiochemotherapy (RCHT) is crucial in the era of image-guided, adaptive high-precision photon or particle therapy. In this thesis, two study cohorts were used to assess some selected TME biomarkers and their predictive value on MTE for an improved CTV definition. The first study used immunohistochemistry analysis for the assessment of TME marker namely HIF-1α, Ki67, p53, CXCR4 and PD1 in a cohort of retrospectively collected formalin-fixed paraffin-embedded (FFPE) blocks of EC patients treated with either neoadjuvant radiochemotherapy plus resection (NRCHT+R) or resection alone (R). The subsequent study employing a multiplex-immunofluorescence technique assessed the expression of various markers, i.e., FAK, ILK, CD44, HIF-1α and Ki67, in a cohort of prospectively prepared FFPE resection specimens of EC patients with implantable fiducial gold markers at the proximal and distal tumor borders illustrating the GTV prior to NRCHT+R and correlated those markers to the MTE. The findings from our first study showed upregulation of HIF-1α, Ki67, p53, CXCR4 and PD1, within squamous cell carcinoma (SCC) and adenocarcinoma (AC) patients treated with R compared to those having undergone NRCHT+R. In the second study higher expression of FAK+, CD44+, HIF-1+, and Ki67+ cells in tumor-nests than in tumor-stroma of both SCC and AC patients was found, although ILK+ cells were higher in tumor stroma. In addition, MTE reaching up to 31 mm beyond the fiducial markers was found in three patients (all cT3N1) with a stronger expression of FAK+, CD44+ and ILK+ cells in tumor-nests in between the fiducial markers (former GTV) and beyond those (former CTV), even after NRCHT. In conclusion, there is thus far no evidence that the TME influences the CTV margin on an individual patient basis, hence differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not detected.

Made available in DSpace on 2016-01-26T12:51:37Z (GMT). No. of bitstreams: 1 eumildodecampos junior_tese.pdf: 1761590 bytes, checksum: 07f0e6564f9169c180cc6baf09d6de84 (MD5) Previous issue date: 2011-12-16 / Dysphagia caused by chagasic megaesophagus compromises the clinical status and quality of life of patients. In this context, the Serra Dória s operation is a useful procedure in cases of advanced or recurrent disease. Little is known about the cardiovascular complications related to this surgery. Objective: This study aim to identify preoperative risk factors associated with cardiovascular complications after Serra Dória s operation in patients with megaesophagus caused by Chagas disease at the hospital period to document the data in order to better preoperative evaluating of these of these patients. Methods: This is a retrospective study evaluating patients who underwent the Serra Dória s operation at the General Surgery Service of Hospital de Base (FUNFARME), Faculty of Medicine of Sao Jose do Rio Preto (FAMERP) from 1998 to 2010. Initially, we assessed 103 medical records and excluded from the study 16 patients with idiopathic achalasia and 11 incomplete charts; therefore, the study population consisted of 76 patients with chagasic megaesophagus who underwent Serra Dória s procedure. The study was approved by the Ethics in Research Committee No. 254/2011. The following preoperative variables were included in the multivariate stepwise regression analysis: the model: age, sex, degrees of megaesophagus, operation for recurrence of symptoms, need for transfusion of red blood cells, blood pressure, electrolytes, comorbidities, electrocardiographic findings and degree of surgical risk. Cardiovascular complications were as follows: levels of hypotension and hypertension and cardiac arrhythmias without hemodynamic instability observed during the surgery and in the postoperative period. Student s t test was used in the comparison of continuous variables, whereas the chi-squared test was used in the comparison of categorical variables. Variables associated with the presence of cardiovascular complications at the p<0.05 were included in multivariate logistic stepwise regression. Those that remained associated with the presence of cardiovascular complications were considered independent variables to predict the appearance of cardiovascular complications. Results: The mean age was 61 ±10 years with male predominance (42, 55%). Most patients were classified as advanced megaesophagus (65, 86%); 36(47%) of them had relapsed megaesophagus. In 22(29%) of cases there was at least one comorbidity, with hypertension being the most frequently found (25, 30%). In 34(45%) patients the surgical risk was classified as moderate to severe. Among the electrocardiographic findings found preoperatively, sinus rhythm was found in 68(89%) patients, and right bundle-branch block in 28(37%). Cardiovascular complication was observed in 29(38%) patients, with prevalence of hypotension in various levels (14, 41%), followed by cardiac arrhythmias in 12(35%). The largest number of cardiovascular complications occurred during the immediate postoperative period. Variables associated with the presence of complications in the univariate model were age (p=0.003) and left bundle-branch block (p= 0.02). However, only the aged above 61 years of age was an independent predictor of cardiovascular complications in the postoperative Serra Dória s operation. Conclusion: Age is an independent predictor of cardiovascular complications following the Serra Dória s procedure. / A disfagia causada pelo megaesôfago chagásico compromete o estado geral e a qualidade de vida dos pacientes. Neste contexto, a cirurgia de Serra Dória é um procedimento útil nos casos avançados ou de recidiva da doença. Pouco se sabe a respeito das complicações cardiovasculares relativas a esta cirurgia. Objetivo: O estudo buscou identificar fatores de risco pré-operatórios associados às complicações cardiovasculares após a cirurgia de Serra Dória no período hospitalar para documentar os dados visando melhorar a avaliação pré-operatória destes pacientes. Casuística e Métodos: Estudo retrospectivo que analisou pacientes submetidos à cirurgia de Serra Dória no Serviço de Cirurgia Geral do Hospital de Base (FUNFARME) da Faculdade de Medicina de São Jose do Rio Preto (FAMERP) no período de 1998 a 2010. Inicialmente foram analisados 103 prontuários e excluídos do estudo 16 portadores de acalasia idiopática e 11 prontuários incompletos; portanto, a amostra consistiu de 76 pacientes portadores de megaesôfago chagásico submetidos à cirurgia de Serra Dória. O estudo foi aprovado pelo Comitê de Ética e Pesquisa parecer nº 254/2011. As seguintes variáveis pré-operatórias foram incluídas na análise de regressão logística multivariada passo-a-passo: idade, sexo, graus do megaesôfago, operação por recidiva dos sintomas, necessidade de transfusão de hemácias, níveis de pressão arterial, eletrólitos, comorbidades, achados eletrocardiográficos e grau de risco cirúrgico. As complicações cardiovasculares consideradas foram: níveis de hipotensão e hipertensão arterial e arritmias cardíacas com ou sem instabilidade hemodinâmica, observadas durante o período transoperatório, pós-operatório imediato e enfermaria. Para análise das variáveis contínuas utilizou-se o Test t de student não pareado, e para as variáveis descontínuas, o teste de qui-quadrado. Variáveis associadas à presença de complicações cardiovasculares com p <0,05 foram incluídas no modelo multivariado de regressão logística passo-a-passo. Aquelas que se mantiveram associadas à presença de complicações cardiovasculares foram consideradas variáveis de predição independente para o aparecimento dessas complicações. Resultados: A idade média da amostra foi de 61 ± 10 anos com predomínio do sexo masculino (42, 55%). A maioria dos pacientes apresentou megaesôfago avançado (65, 86%), e 36(47%) com recidiva dos sintomas que necessitaram de novo procedimento. Em 22(29%) dos casos houve pelo menos uma comorbidade, sendo a hipertensão arterial a mais frequente (25, 30%). O risco cirúrgico em 34(45%) pacientes foi considerado como moderado a grave. Nos achados eletrocardiográficos do pré-operatório, os mais frequentemente encontrados foram 68(89%) com ritmo sinusal seguido pelo bloqueio completo do ramo direito do feixe de His em 28(37%). Observou-se complicação cardiovascular em 29(38%) pacientes, com predomínio de hipotensão arterial em vários níveis (14, 41%), seguida de arritmias cardíacas em 12(35%). O maior número de complicações cardiovasculares ocorreu no período pós-operatório imediato. As variáveis associadas à presença de complicações no modelo univariado foram a idade (p=0,003) e o bloqueio de ramo esquerdo do feixe de His (p=0,02). No modelo multivariado, apenas a idade igual ou superior a 61 anos mostrou-se variável de predição independente para o aparecimento de complicações cardiovasculares no pós-operatório da cirurgia de Serra Dória. Conclusão: A idade é um fator de predição independente de complicações cardiovasculares após a cirurgia de Serra Dória.

Les complications respiratoires restent la première cause des complications postopératoiresen chirurgie thoracique oncologique. Le développement des ces complications sont le plussouvent de nature infectieuse. Leur fréquence reste élevée (30 %) et représente la premièrecause de mortalité hospitalière. Des données récentes suggèrent que ces complicationsrespiratoires soient liées à une colonisation périopératoire des voies aériennes. Plusieurstravaux fondés sur l’analyse phénotypique de mise en culture traditionnelle démontrentl’existence d’une colonisation bronchique proximale chez près de 40 % des malades.Néanmoins, les liens entre colonisation et complications respiratoires restent controversés.Une des principales limites demeure les méthodes de cultures employées qui ne permettentl’identification que d’une faible partie (< 1%) des espèces microbiologiques potentiellementexistantes dans la biosphère. Nous avons formulé l’hypothèse que des techniques debiologie moléculaire d’amplification universelle des ADN présents dans les échantillonssuivies du clonage des produits de PCR et du séquençage de ces clones, appliquées à deséchantillons obtenus des bronches distales et de biopsies pulmonaires, permettraientl’identification de pathogènes bactériens, viraux ou émergents. Nos résultats suggèrent quel’identification précise et exhaustive de ces colonisations ne peut être réalisée que par uneapproche moléculaire moderne, innovante et systématique. Cette approche permetd’envisager, d’une part, un lien plus précis entre colonisation et complications respiratoires etd’autre part, l’identification de pathogènes difficilement cultivables ou émergents. / Postoperative respiratory complications remain the most frequent and seriouscomplications, as well as being the primary cause of hospital death after thoracic oncologicsurgery. Their incidence is relatively high and concern near 30 % of patients submitted forsurgery. These complications are notoriously infectious and airways colonizations (AWC)have been suggested to be an essential first step in the pathogenesis of this respiratorymorbidity. Previous studies have documented that AWC are presents in near 40 % of cases.However, correlation between AWC and respiratory complications remains controversial.One of the limits is the traditional phenotypic methods of cultures that precludes for definitiveconclusions when considering that majority of microbiological species required modern andinnovating techniques of culture to be identified. Recent data have demonstrated that 99% oforganisms seen microscopically are not cultivated by routine techniques and requiredmolecular techniques to be identified. We have postulated that instead of culture test,molecular detection (DNA genes amplification and sequencing of the bacterial 16S ribosomalRNA) applied to distal bronchial samples or to lung biopsies, should allow identifyingbacteria, virus or emerging pathogens. Our results suggest that molecular cultureindependenttechniques applied in the context of AWC will provide in the future a greatopportunity to precise correlation between colonization and respiratory complications and tothe other hand, to discover new and/or emerging pathogens that are currently unknown.

Contexte & Objectifs : La manométrie perfusée conventionnelle et la manométrie haute résolution (HRM) ont permis le développement d’une variété de paramètres pour mieux comprendre la motilité de l'œsophage et quantifier les caractéristiques de la jonction œsophago-gastrique (JOG). Cependant, l'anatomie de la JOG est complexe et les enregistrements de manométrie détectent à la fois la pression des structures intrinsèques et des structures extrinsèques à l'œsophage. Ces différents composants ont des rôles distincts au niveau de la JOG. Les pressions dominantes ainsi détectées au niveau de la JOG sont attribuables au sphincter œsophagien inférieur (SOI) et aux piliers du diaphragme (CD), mais aucune des technologies manométriques actuelles n’est capable de distinguer ces différents composants de la JOG. Lorsqu’on analyse les caractéristiques de la JOG au repos, celle ci se comporte avant tout comme une barrière antireflux. Les paramètres manométriques les plus couramment utilisés dans ce but sont la longueur de la JOG et le point d’inversion respiratoire (RIP), défini comme le lieu où le pic de la courbe de pression inspiratoire change de positif (dans l’abdomen) à négatif (dans le thorax), lors de la classique manœuvre de « pull-through ». Cependant, l'importance de ces mesures reste marginale comme en témoigne une récente prise de position de l’American Gastroenterology Association Institute (AGAI) (1) qui concluait que « le rôle actuel de la manométrie dans le reflux gastro-œsophagien (RGO) est d'exclure les troubles moteurs comme cause des symptômes présentés par la patient ». Lors de la déglutition, la mesure objective de la relaxation de la JOG est la pression de relaxation intégrée (IRP), qui permet de faire la distinction entre une relaxation normale et une relaxation anormale de la JOG. Toutefois, puisque la HRM utilise des pressions moyennes à chaque niveau de capteurs, certaines études de manométrie laissent suggérer qu’il existe une zone de haute pression persistante au niveau de la JOG même si un transit est mis en évidence en vidéofluoroscopie. Récemment, la manométrie haute résolution « 3D » (3D-HRM) a été développée (Given Imaging, Duluth, GA) avec le potentiel de simplifier l'évaluation de la morphologie et de la physiologie de la JOG. Le segment « 3D » de ce cathéter de HRM permet l'enregistrement de la pression à la fois de façon axiale et radiale tout en maintenant une position fixe de la sonde, et évitant ainsi la manœuvre de « pull-through ». Par conséquent, la 3D-HRM devrait permettre la mesure de paramètres importants de la JOG tels que sa longueur et le RIP. Les données extraites de l'enregistrement fait par 3D-HRM permettraient également de différencier les signaux de pression attribuables au SOI des éléments qui l’entourent. De plus, l’enregistrement des pressions de façon radiaire permettrait d’enregistrer la pression minimale de chaque niveau de capteurs et devrait corriger cette zone de haute pression parfois persistante lors la déglutition. Ainsi, les objectifs de ce travail étaient: 1) de décrire la morphologie de la JOG au repos en tant que barrière antireflux, en comparant les mesures effectuées avec la 3D-HRM en temps réel, par rapport à celle simulées lors d’une manœuvre de « pull-through » et de déterminer quelles sont les signatures des pressions attribuables au SOI et au diaphragme; 2) d’évaluer la relaxation de la JOG pendant la déglutition en testant l'hypothèse selon laquelle la 3D-HRM permet le développement d’un nouveau paradigme (appelé « 3D eSleeve ») pour le calcul de l’IRP, fondé sur l’utilisation de la pression radiale minimale à chaque niveau de capteur de pression le long de la JOG. Ce nouveau paradigme sera comparé à une étude de transit en vidéofluoroscopie pour évaluer le gradient de pression à travers la JOG. Méthodes : Nous avons utilisé un cathéter 3D-HRM, qui incorpore un segment dit « 3D » de 9 cm au sein d’un cathéter HRM par ailleurs standard. Le segment 3D est composé de 12 niveaux (espacés de 7.5mm) de 8 capteurs de pression disposés radialement, soit un total de 96 capteurs. Neuf volontaires ont été étudiés au repos, où des enregistrements ont été effectués en temps réel et pendant une manœuvre de « pull-through » du segment 3D (mobilisation successive du cathéter de 5 mm, pour que le segment 3D se déplace le long de la JOG). Les mesures de la longueur du SOI et la détermination du RIP ont été réalisées. La longueur de la JOG a été mesurée lors du « pull-through » en utilisant 4 capteurs du segment 3D dispersés radialement et les marges de la JOG ont été définies par une augmentation de la pression de 2 mmHg par rapport à la pression gastrique ou de l’œsophage. Pour le calcul en temps réel, les limites distale et proximale de la JOG ont été définies par une augmentation de pression circonférentielle de 2 mmHg par rapport à la pression de l'estomac. Le RIP a été déterminée, A) dans le mode de tracé conventionnel avec la méthode du « pull-through » [le RIP est la valeur moyenne de 4 mesures] et B) en position fixe, dans le mode de représentation topographique de la pression de l’œsophage, en utilisant l’outil logiciel pour déterminer le point d'inversion de la pression (PIP). Pour l'étude de la relaxation de la JOG lors de la déglutition, 25 volontaires ont été étudiés et ont subi 3 études de manométrie (10 déglutitions de 5ml d’eau) en position couchée avec un cathéter HRM standard et un cathéter 3D-HRM. Avec la 3D-HRM, l’analyse a été effectuée une fois avec le segment 3D et une fois avec une partie non 3D du cathéter (capteurs standard de HRM). Ainsi, pour chaque individu, l'IRP a été calculée de quatre façons: 1) avec la méthode conventionnelle en utilisant le cathéter HRM standard, 2) avec la méthode conventionnelle en utilisant le segment standard du cathéter 3D-HRM, 3) avec la méthode conventionnelle en utilisant le segment « 3D » du cathéter 3D-HRM, et 4) avec le nouveau paradigme (3D eSleeve) qui recueille la pression minimale de chaque niveau de capteurs (segment 3D). Quatorze autres sujets ont subi une vidéofluoroscopie simultanée à l’étude de manométrie avec le cathéter 3D-HRM. Les données de pression ont été exportés vers MATLAB ™ et quatre pressions ont été mesurées simultanément : 1) la pression du corps de l’œsophage, 2cm au-dessus de la JOG, 2) la pression intragastrique, 3) la pression radiale moyenne de la JOG (pression du eSleeve) et 4) la pression de la JOG en utilisant la pression minimale de chaque niveau de capteurs (pression du 3D eSleeve). Ces données ont permis de déterminer le temps permissif d'écoulement du bolus (FPT), caractérisé par la période au cours de laquelle un gradient de pression existe à travers la JOG (pression œsophagienne > pression de relaxation de la JOG > pression gastrique). La présence ou l'absence du bolus en vidéofluoroscopie et le FPT ont été codés avec des valeurs dichotomiques pour chaque période de 0,1 s. Nous avons alors calculé la sensibilité et la spécificité correspondant à la valeur du FPT pour la pression du eSleeve et pour la pression du 3D eSleeve, avec la vidéofluoroscopie pour référence. Résultats : Les enregistrements avec la 3D-HRM laissent suggérer que la longueur du sphincter évaluée avec la méthode du « pull-through » était grandement exagéré en incorporant dans la mesure du SOI les signaux de pression extrinsèques à l’œsophage, asymétriques et attribuables aux piliers du diaphragme et aux structures vasculaires. L’enregistrement en temps réel a permis de constater que les principaux constituants de la pression de la JOG au repos étaient attribuables au diaphragme. L’IRP calculé avec le nouveau paradigme 3D eSleeve était significativement inférieur à tous les autres calculs d'IRP avec une limite supérieure de la normale de 12 mmHg contre 17 mmHg pour l’IRP calculé avec la HRM standard. La sensibilité (0,78) et la spécificité (0,88) du 3D eSleeve étaient meilleurs que le eSleeve standard (0,55 et 0,85 respectivement) pour prédire le FPT par rapport à la vidéofluoroscopie. Discussion et conclusion : Nos observations suggèrent que la 3D-HRM permet l'enregistrement en temps réel des attributs de la JOG, facilitant l'analyse des constituants responsables de sa fonction au repos en tant que barrière antireflux. La résolution spatiale axiale et radiale du segment « 3D » pourrait permettre de poursuivre cette étude pour quantifier les signaux de pression de la JOG attribuable au SOI et aux structures extrinsèques (diaphragme et artéfacts vasculaires). Ces attributs du cathéter 3D-HRM suggèrent qu'il s'agit d'un nouvel outil prometteur pour l'étude de la physiopathologie du RGO. Au cours de la déglutition, nous avons évalué la faisabilité d’améliorer la mesure de l’IRP en utilisant ce nouveau cathéter de manométrie 3D avec un nouveau paradigme (3D eSleeve) basé sur l’utilisation de la pression radiale minimale à chaque niveau de capteurs de pression. Nos résultats suggèrent que cette approche est plus précise que celle de la manométrie haute résolution standard. La 3D-HRM devrait certainement améliorer la précision des mesures de relaxation de la JOG et cela devrait avoir un impact sur la recherche pour modéliser la JOG au cours de la déglutition et dans le RGO. / Background & Aims: Conventional water-perfused manometry and high resolution manometry permitted the development of a variety of manometric methodologies and metrics to understand the motility of the esophagus and to quantify esophagogastric junction (EGJ) characteristics. However, the anatomy in the area of the EGJ is complex and intraluminal manometry recordings detect pressure signals referable both to intrinsic esophageal structures and to adjacent extrinsic structures impinging on the esophagus. Both have distinct sphincteric mechanisms within the EGJ. The dominant pressure signals detected near the EGJ are attributable to the lower esophageal sphincter (LES) and the crural diaphragm (CD). However, neither of these technologies were able to distinguish between the different components of the EGJ. When analyzing EGJ characteristics as a reflection of its competence against reflux, the more widely used manometric parameters are the EGJ length and the respiratory inversion point (RIP), defined as the location at which inspiratory pressure deflections change from positive (abdomen) to negative (chest). However, the significance of these metrics has not gained wide acceptance in the gastroenterology community as evident in a recent American Gastroenterology Association Institute (AGAI) Position Statement (1) concluding that ‘The current role of manometry in gastroesophageal reflux disease (GERD) is to exclude motor disorders as a cause of the continued symptoms’. During deglutition, the objective quantitative measurement of EGJ relaxation, the integrative relaxation pressure (IRP), permits one to distinguish between normal and abnormal EGJ relaxation. However, comparison between spatial pressure variation plots and relaxation pressures derived from circumferentially averaged pressures suggest a persistent high pressure at the hiatal center during a period that flow is known to be occurring whereas this was not seen using nadir radial pressure data. Recently, a 3D-high resolution manometry (3D-HRM) assembly (Given Imaging, Duluth, GA) has been developed with the potential to simplify the assessment of EGJ pressure morphology and physiology. The 3D segment of the array permits high resolution recording both axially and radially while maintaining a stationary sensor position. Consequently, 3D-HRM should allow for the measurement of important EGJ parameters such as length and RIP. Data extracted from the 3D-HRM recording may also allow differentiating pressure signals within the EGJ attributable to the intrinsic sphincter and to the surrounding elements. Moreover, 3D-HRM preserves the individual pressure values of each radially dispersed sensor within the array, permitting one to overcome the apparent persistent high pressure during the deglutitive relaxation. Thus, the aims of this work were 1) to describe the EGJ pressure morphology at rest, comparing measures made with real time 3D-HRM to simulations of a conventional pull-through protocol and to define the pressure signatures attributable to the diaphragmatic and LES pressure components within the 3D-HRM recording; 2) to assess deglutitive EGJ relaxation by testing the hypothesis that the 3D-HRM array using an analysis paradigm based on finding the minimal radial pressure at each axial level (3D-eSleeve) should provide a representation of the luminal pressure gradient across the EGJ that is more relevant to predicting periods of trans-sphincteric flow using barium transit on fluoroscopy as the comparator. We also sought to adapt the IRP metric to the 3D-HRM array using the 3D-eSleeve principle (3D-IRP) and compare normative values obtained with this new paradigm to standard IRP calculations. Methods: Patients were studied with a 3D-HRM assembly. The 3D-HRM assembly incorporated a 9 cm 3D-HRM segment into an otherwise standard HRM assembly; the 3D segment was comprised of 12 rings of 8 radially dispersed independent pressure sensors, spaced 7.5mm apart. At rest, 9 volunteers were studied and recordings were done during a station pull-through of the 3D-HRM segment withdrawing it across the EGJ at 5 mm increments with each position held for 30s (sufficient to capture several respiratory cycles). Conventional measures of ‘LES length’ were made using 4 radially dispersed sensors within the 3D-HRM array, defining the margins of the sphincter by a 2 mmHg pressure increase relative to gastric or esophageal pressure. In the 3D-HRM, the proximal and distal limits of the EGJ were defined as the axial locations first detecting a 360° circumferential pressure increase of 2 mmHg relative to the stomach. RIP was determined, A) in the tracing mode: using the pull-through of 4 single sensors spaced 7.5 mm apart [RIP is the average value of 4 radially dispersed sensors] and B) in a stationary position using the software pressure inversion point (PIP) tool. In the esophageal pressure topography (EPT) mode, the tracing changed progressively from a thoracic pattern to an abdominal pattern, and the RIP was localized within the inversion zone with the PIP tool tracing. For the study of the EGJ deglutitive relaxation, 25 volunteers underwent 3 consecutive 10-swallows protocols of 5 ml of water in the supine position with both the standard (once) and 3D-HRM (twice) devices in random sequence. During the 3D-HRM studies, the EGJ was measured once with the 3D-sleeve segment and once with a proximal (non-3D sleeve portion) of the device incorporating standard HRM sensors. For each subject, the IRP was calculated in four ways: 1) conventional method with the standard HRM device, 2) conventional method with a standard HRM segment of the 3D-HRM device, 3) conventional method using the 3D-HRM sleeve segment, and 4) a novel 3D-HRM eSleeve paradigm (3D-IRP) localizing the radial pressure minimum at each locus along the eSleeve. Fourteen additional subjects then underwent synchronized simultaneous videofluoroscopy and 3D-HRM (including two 5-ml barium swallows). Pressure data were exported to MATLAB™ and four pressures were measured simultaneously: 1) esophageal body pressure 2cm above EGJ, 2) intragastric pressure, 3) radially average eSleeve pressure and 4) 3D-eSleeve pressure. Data were plotted to determine the flow permissive time (FPT) characterized as periods during which a pressure gradient through the EGJ is present (esophageal pressure > EGJ relaxation pressure (radial average or 3D-eSleeve paradigm) > gastric pressure). FPT was calculated during a 10s time window after upper sphincter relaxation. The presence or absence of bolus transit or FPT was coded with dichotomous values for each 0.1 s. We calculated the corresponding sensitivity and specificity for both radial average and 3D-eSleeve analyses of FPT with bolus transit evident on fluoroscopy being the reference. Results: 3D-HRM recordings suggested that sphincter length assessed by a pull-through method greatly exaggerated the estimate of LES length by failing to discriminate among circumferential contractile pressure and asymmetric extrinsic pressure signals attributable to diaphragmatic and vascular structures. Real-time 3D EGJ recordings found that the dominant constituents of EGJ pressure at rest were attributable to the diaphragm. The 3D-IRP was significantly less than all other calculations of IRP with the upper limit of normal being 12 mmHg vs. 17 mmHg for the standard IRP. The sensitivity (0.78) and the specificity (0.88) of the 3D-eSleeve were also better than the standard eSleeve (0.55 and 0.85, respectively) for predicting flow permissive time verified fluoroscopically. Discussion & Conclusion: Our observations suggest that the 3D-HRM permits real-time recording of EGJ pressure morphology facilitating analysis of the EGJ constituents responsible for its function as a reflux barrier at rest. The axial and radial spatial resolution of the 9 cm 3D-HRM segment may permit further studies to differentiate pressure signals within the EGJ attributable to the LES and to extrinsic structures (diaphragm and vascular artifacts). These attributes of the 3D-HRM device suggest it to be a promising new tool in the study of GERD pathophysiology. During deglutition, we evaluated the feasibility of improving the measurement of IRP utilizing a novel 3D-HRM assembly and a novel 3D-eSleeve concept based on finding the axial maximum of the radial minimum pressures at each sensor ring along the sleeve segment. Our findings suggest that this approach is more accurate than standard HRM and other methods that utilize a radially averaged pressure within the EGJ. Although we can only speculate on how much this will improve clinical management, 3D-HRM will certainly improve the accuracy of EGJ relaxation measurements and this will certainly impact research endeavors focused on modeling EGJ function during swallowing and reflux.

The aim of this thesis is to present a complex information about the etiology, diagnosis and treatment of gastroesophageal reflux disease (GERD) and to further elucidate the function of the diaphragm as the external esophageal sphincter and as a part of the antireflux barrier in patients with GERD. The study included 87 patients with verified GERD. Patients were subjected to a set of postural and respiratory maneuvers - caudal position of chest, abdominal breathing and measuring of the maximal respiratory pressures, all performed on the basis of tolerance to position and maneuver. The high-resolution manometry (HRM) was chosen to record the changes in pressure in the lower esophageal sphincter and for the measurement of respiratory pressures was used the spirometric system MasterScope. It was found that postural and respiratory maneuvers, that activate the diaphragm, increase the pressure in the EGJ. The most significant increase occurred during the maximal inspiratory maneuver, which increased LES pressure up to 261.2 %. The results also show that patients with GERD have reduced the strength of respiratory muscles, especially inspirational muscles. Reaching only 66.5 % of predicted PImax. We have demonstrated that patients with GERD have significantly lower diaphragm muscle strength, what...

Introduction The main aim of this study is to present a complex review comprising etiological factors, diagnostic options and therapeutic methods related to globus pharyngeus, a persistent or intermittent sensation of a lump or foreign body in the throat. The second purpose is to investigate the reciprocal relationship between motor control with musculoskeletal system and pressure changes in the esophagus, especially in the upper esophageal sphincter. Methods 37 patients participated in the study. 24 of them suffered globus pharyngeus and 13 were patients with GERD but without the symptoms of globus pharyngeus. Because of the complex physiology of esophageal function and the inability of conventional manometry to fully describe this complexity, we found High-Resolution Manometry as a useful device for accomlishing the referred task. Patients were examined in four different postural situations which had to be modified when the attitude wasn't tolerated. The examination was followed by manual physiotherapy and exercises targeted to influence postural alignment. 10 patients with globus pharyngeus who agreed with a control manometry examination were familiarized with the results as a form of biofeedback. Results On the basis of the results of this research, it can be concluded that a high pressure...

No Brasil a principal causa de hipertensão portal é a esquistossomose mansônica na sua forma hepato-esplênica, classificada como pré-sinusoidal. Esta doença adquire grande importância epidemiológica, por acometer indivíduos jovens, com função hepática preservada, e por atingir uma grande parcela da população (cerca de 1 milhão de indivíduos). Destes, cerca de 12 a 52% irão apresentar hemorragia digestiva por ruptura de varizes de esôfago. Não existe até o momento nenhum tratamento que se estabeleça como de consenso para esta enfermidade, porém há uma preferência dos autores para o tratamento cirúrgico e, no Brasil, esta recai sobre a desconexão ázigo-portal e esplenectomia geralmente associada a escleroterapia endoscópica das varizes no pós-operatório. Não estão bem estabelecidas as alterações hemodinâmicas portais decorrentes do tratamento cirúrgico da hipertensão portal e sua influência no resultado deste tratamento. Com o objetivo de avaliar o impacto imediato da desconexão ázigo-portal e esplenectomia (DAPE) na pressão portal e os resultados do tratamento cirúrgico da hipertensão portal no que se refere à recidiva hemorrágica e ao calibre das varizes de esôfago, foram estudados 19 pacientes portadores de esquistossomose hepato-esplênica e hipertensão portal com história de hemorragia digestiva alta por ruptura de varizes esofágicas, com idade média de 37,9 anos. Durante a cirurgia foi avaliada a pressão portal, no início e no final do procedimento através da cateterização da veia porta por cateter de polietileno introduzido por veia jejunal. Todos os pacientes foram submetidos à endoscopia no pré e pós-operatório para avaliar a variação do calibre das varizes esofágicas. Os pacientes foram acompanhados ambulatorialmente e o tempo médio de seguimento foi de 26 meses. Como resultado obteve-se uma queda na pressão portal média de 31,3% após a DAPE (p=0,0001). No acompanhamento pós-operatório houve redução significativa do calibre das varizes esofágicas quando comparadas com a avaliação pré-operatória (p < 0,05). Apenas um paciente (8,3%) apresentou, durante o acompanhamento, recidiva hemorrágica porém, esta foi decorrente de úlcera gástrica e não de varizes esofágicas. Por fim chegou-se à conclusão de que a desconexão ázigo-portal e esplenectomia promoveu queda imediata na pressão portal, com conseqüente diminuição do calibre das varizes esofágicas, tendo sido eficaz no tratamento da hipertensão portal destes pacientes / The main cause of portal hypertension in Brazil is the hepato-splenic form of mansonic schistosomiasis, which is classified as pre-sinusoidal. It acquires major epidemiological importance because it occurs in young individuals and affects a huge parcel of the population (around 1 million people), 12 to 52% of whom will present digestive hemorrhage due to rupture of esophageal varices. There is no consensus treatment for this disease up to the moment, but there is a predilection for the surgical approach. In Brazil, the most employed technique is the esophagogastric devascularization with splenectomy (EGDS), generally associated to late postoperative endoscopical sclerotherapy of the esophageal varices. The hemodynamic alterations in the portal flow resulting from the surgery and their possible influences on the outcome are not well established. With the aim of evaluating the immediate impact of the EGDS upon the portal pressure as well as the results of the surgical treatment on the digestive hemorrhage recurrence and the caliber of the esophageal varices, 19 patients (11males, aged between 18 and 61 years) with hepato-splenic schistosomiasis, presenting portal hypertension and previous episodes of digestive hemorrhage were studied. None of the patients had received any treatment prior to the surgery. The portal pressure was assessed at the beginning and the end of the EGDS through catheterization of the portal vein with a polyethylene catheter introduced through a branch of a jejunal vein. All the patients were submitted to digestive endoscopy before and after the surgery (2 months), in order to classify the caliber of the esophageal varices according to Palmer\'s classification. They also entered the continuous program of endoscopical evaluation and sclerotherapy. The mean clinical follow up period was 26 months. Our results showed that the portal pressure had diminished in all the patients, with a mean decrease of 31.3% after the EGDS. In the postoperative follow up (1 month), the esophageal varices showed a statistically significant reduction in their calibers, when compared to the pre-surgical measurements (p=0.004). Only one patient presented digestive hemorrhage during the follow up period, but it was due to gastric ulcer and not to rupture of esophageal varices. These results have demonstrated that the EGDS promotes an immediate decrease in the portal pressure and a reduction in the caliber of the esophageal varices, thus contributing to the good results of this technique. With the association of EGDS and sclerotherapy of the esophageal varices, no hemorrhagic episodes were observed in this series, during the study