Thesis (PhD (Pathology. Anatomical Pathology))--University of Stellenbosch, 2006. / Patients with chronic gastro-oesophageal reflux disease are predisposed to Barrett’s metaplasia and oesophageal adenocarcinoma. The availability of molecular markers that can objectively identify patients with Barrett’s oesophagus at increased risk of carcinoma is highly desirable. A literature search was conducted to identify potentially useful biomarkers for genotype-phenotype correlation studies in South African patients with Barrett’s oesophagus. The COX-2, c-myb and c-myc genes selected for mRNA expression analysis were analysed in 26 patients with Barrett’s metaplasia (BM) without dysplasia; 14 with Barrett’s oesophagus and dysplasia (BD); 2 patients with Barrett’s adenocarcinoma (BAC); 19 with erosive oesophagitis (ERD); 25 with non-erosive oesophagitis (NERD) and 19 control individuals with a normal gastroscopy and no gastro-oesophageal reflux disease (GORD) symptoms. In the BD/BAC group, 69% (11/16) showed increased c-myb mRNA expression compared with 35% (9/26) in the BM group (p = 0.03). A statistically significant difference (p = 0.002) in c-myb expression was also observed between Barrett’s patients (20/42, 48%) and the control groups (9/63, 14%). In the BD patients, 21% (3/14) had increased c-myc mRNA expression compared with none in those with BM (p < 0.05) and BAC. No significant differences in mRNA expression levels were observed between ethnic groups for the genes analysed. In an attempt to determine whether the low expression level of c-myc in the study cohort may be related to possible gene-gene interaction, DNA samples of 199 individuals were subjected to genotyping of the functional GT-repeat polymorphism in the promoter region of the NRAMP1/SLC11A1 gene. Both these genes are involved in iron metabolism and c-myc is known to repress NRAMP1/SLC11A1. Genotype and allele frequencies were similar in all the groups studied with the 3/3 genotype being the most common. However, none of the three above-mentioned BD patients with increased c-myc mRNA expression had the 3/3 genotype. Therefore, although small in number, c-myc-NRAMP1/SLC11A1 interaction may be of adverse significance in patients with allele 2. TP53 mutation analysis was performed on 68 Barrett’s patients, and TP53 immuno-staining on oesophageal biopsy specimens of 55 subjects. Sporadic TP53 mutations were not identified in any of the patients with BM or dysplasia without BAC. Immuno-histochemistry staining of 2+ and 3+ intensity was similar in patients with metaplasia and dysplasia (58%). The low mutation frequency and relative non-specificity of TP53 immunostaining observed in Barrett’s patients seem to preclude its widespread use as a screening tool. TP53 mutation detection may however be useful for risk stratification once dysplasia has been diagnosed, as mutations G245R and D281Y were identified in two patients with BAC. Of the genes studied in the South African population, c-myb represents the most useful marker for early detection of an increased cancer risk in Barrett’s patients. In future, patients with Barrett’s oesophagus may benefit from genetic assessment to complement existing cancer surveillance and treatment strategies.

A Doença do Refluxo Gastroesofágico (DRGE), comumente observada em crianças e adolescentes, é uma das causas intrínsecas mais frequentes do desgaste erosivo. O objetivo dessa pesquisa foi realizar um estudo exploratório e analítico em crianças e adolescentes com idade entre 10 e 15 anos com DRGE e identificar possíveis diferenças entre grupos Casos e Controles quanto à presença de halitose, fluxo salivar, pH, capacidade tampão da saliva, lesões de desgaste erosivo e cárie dentária, classificação socioeconômica e qualidade de vida. Trinta voluntários participaram da pesquisa, sendo 15 do grupo Caso e 15 do grupo Controle. Informações sexo e idade foram coletadas durante a anamnese. A presença de halitose foi verificada por meio de avaliação organoléptica. A avaliação salivar foi realizada pelo fluxo salivar estimulado e o pH e a capacidade tampão (técnica de Ericsson), medidos com um pHmetro digital. Para a classificação econômica, utilizou-se o Critério de Classificação Econômica Brasil 2014 (CCEB/2014). Os voluntários responderam um questionário sobre qualidade de vida, validado no brasil (Child-OIDP) para faixa etária de 11-14 anos de idade. Além disso, foi realizado exame clínico para detecção de desgaste erosivo e cárie dentária de acordo com os índices BEWE e ICDAS, respectivamente. Os dados foram analisados pelo software STATA 9. As variáveis categorizadas sexo, idade, halitose e classificação socioeconômica e as variáveis numéricas fluxo salivar, capacidade tampão e pH não apresentaram diferença estatística entre os grupos (p > 0,05). O grupo Caso apresentou diferença significativa comparado ao grupo Controle para as variáveis BEWE e ICDAS. Apenas o desgaste erosivo e a presença de lesões de cárie foram associados a DRGE. O BEWE e o ICDAS podem ser considerados métodos auxiliares para o diagnóstico de pacientes com refluxo patológico. A relação interdisciplinar entre os profissionais de saúde, em especial, cirurgiões dentistas e médicos gastroenterologistas, é essencial para melhor conduta médica-odontológica de pacientes com Doença do Refluxo Gastroesofágico. / Gastroesophageal Reflux Disease (GERD), commonly observed in children and adolescents is one of the most common intrinsic causes of the erosive wear. The aim of this research was to conduct an exploratory and analytical study in children and adolescents aged between 10 and 15 years with GERD and to identify possible differences between Cases and Controls groups for the presence of halitosis, salivary flow, pH, saliva buffering capacity, erosive wear and dental caries, socioeconomic classification and quality of life. Thirty volunteers participated in this study, but fifteen were in the Case group and fifteen were in the Control group. Information about age and sex were collected during the anamnesis. The presence of halitosis was verified by organoleptic evaluation. The salivary tests were performed by saliva stimulated salivary flow; pH and buffering capacity (by Ericsson technique) were measured with a digital pH meter. Economic classification was evaluated by Economic Classification Criteria Brazil 2014 (CCEB/2014). The volunteers answered a questionnaire about quality of life, validated in Brazil (Child-OIDP) for the age group of 11-14 years. Furthermore, the clinical examination was conducted to erosive wear and caries detection in accordance with BEWE and ICDAS index, respectively. The data were analysed by Stata 9.0 software. Categorical variables sex, age, halitosis and socioeconomic classification and numeric variables salivary flow, buffer capacity and pH had not statistical difference between groups (p > 0.05). The Case group had significant difference compared to the Control group using BEWE and ICDAS variables. Only erosive tooth wear and carious lesions were associated with GERD. The BEWE and ICDAS can complement the methods for the diagnosis of patients with pathological reflux. The interdisciplinary relationship between dentists and gastroenterologists is essential for better medical and dental management of patients with Gastroesophageal Reflux Disease.

INTRODUÇÃO: Há relatos de ocorrência de displasia e adenocarcinoma esofágico em pacientes com esôfago de Barrett submetidos a tratamento cirúrgico com fundoplicatura bem sucedido, comprovado pela realização de pHmetria esofágica prolongada sem evidência de acidez em esôfago, o que sugere que pode ocorrer refluxo distal ao cateter de pHmetria, não detectado por esse método. Essa hipótese motivou o desenvolvimento de metodologia para avaliar a presença de refluxo 1cm acima da borda superior do esfíncter inferior do esôfago (EIE). OBJETIVO: Comparar a exposição ácida em 3 diferentes níveis: 5cm acima da borda superior EIE, 1cm acima da borda superior do EIE e em região intra-esfincteriana. CASUÍSTICA E MÉTODO: 11 pacientes com esôfago de Barrett, submetidos à fundoplicatura à Nissen para tratamento do refluxo gastroesofágico, sem sintomas de refluxo e com endoscopia e estudo radiográfico contrastado de esôfago sem sinais de recidiva, foram selecionados. Foram submetidos à manometria esofágica para avaliar a localização e a extensão do EIE. Realizou-se então pHmetria esofágica com 4 canais: canal A: 5cm acima da borda superior do EIE; canal B: 1cm acima; canal C: intraesfincteriano, na porção média entre a borda superior e inferior do EIE; canal D: em posição intragástrica. Avaliou-se o escore de DeMeester no canal A, para detectar refluxo patológico. Comparou-se o número de episódios de refluxo ácido, o número de episódios de refluxo prolongado e a fração de tempo com pH < 4,0 nos canais A e B. Comparou-se a fração de tempo de pH < 4,0 nos canais B e C. A fração de tempo com pH < 4,0 no canal D foi usada como parâmetro para não migração proximal do cateter. RESULTADOS: Houve maior número de episódios de refluxo e maior fração de tempo com pH < 4,0 no canal B do que no canal A, com significância estatística, sendo a mediana do tempo de exposição ácida menor que 1,5%. Por outro lado, houve menor fração de tempo com pH < 4,0 no canal B do que no canal C, sugerindo competência do esfíncter em conter o refluxo gastroesofágico. Um paciente apresentou refluxo patológico no canal A, apesar de não ter evidência até então de refluxo. Dois casos de adenocarcinoma esofágico foram diagnosticados nos pacientes do grupo estudado. CONCLUSÕES: A região 1cm acima da borda superior do EIE está mais exposta a acidez do que a região 5cm acima da borda superior do EIE, embora a exposição ácida seja em níveis bem reduzidos. A região 1cm acima da borda superior do EIE está menos exposta a acidez do que a região intraesfincteriana, demonstrando eficácia da fundoplicatura em conter o refluxo nesse nível / INTRODUCTION: There are reports of dysplasia and esophageal adenocarcinoma occurring in patients with Barrett´s esophagus after successful surgical treatment with fundoplication, confirmed with prolonged esophageal pH monitoring showing no acid in esophagus, suggesting that there might be reflux distal to the catheter, not detected by this method. This hypothesis led to the development of methodology to evaluate the occurrence of reflux 1cm above the upper border of the lower esophageal sphincter (LES). OBJECTIVE: Compare the acid exposition in three different levels: 5cm above the upper border of the LES, 1cm above the upper border of the LES and in the intrasphincteric region. CASUISTIC AND METHODS: 11 patients with Barrett´s esophagus, submitted to Nissen fundoplication as treatment for gastroesophageal reflux, with no symptoms of reflux and with endoscopy and contrasted esophageal radiograph, were selected. The patients underwent esophageal manometry to evaluate the location and extension of the LES. After that, they underwent a 4-channel pH monitoring: channel A: 5cm above the upper border of the LES; channel B: 1cm above the upper border of the LES; channel C: intrasphincteric, in the mid-portion between the upper and lower border of the LES; channel D: intragastric. The DeMeester score was assessed in channel A, to detect pathologic reflux. The number of reflux episodes, the number of prolonged episodes and the fraction of time with pH < 4,0 were compared in channels A and B. The fraction of time with pH < 4,0 was compared in channels B and C. The fraction of time with pH < 4,0 in channel D was used as a parameter to ensure no proximal migration of the catheter. RESULTS: There were more episodes of reflux and a higher fraction of time with pH < 4,0 in channel B than in channel A, with statistical significance. On the other hand, there was lesser fraction of time with pH < 4,0 in channel B than in channel C, suggesting competence of the sphincter in preventing gastroesophageal reflux. One patient presented pathologic reflux in channel A, besides no other evidence of that. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. CONCLUSIONS: the region 1cm above the upper border of the LES is more exposed to acid than the region 5cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1cm above the upper border of the LES is less exposed to acid than the intrasphincteric region

Introdução: O tratamento cirúrgico da doença do refluxo gastroesofágico (DRGE) possui excelente resultado na maioria dos pacientes. Porém, um grupo significante de indivíduos apresenta complicações ou recidiva dos sintomas, com impacto na qualidade de vida. Objetivos: Avaliar o grau de satisfação dos pacientes submetidos à fundoplicatura laparoscópica à Nissen, e comparar os resultados da aplicação do questionário GERD-HRQL de qualidade de vida pessoalmente e por via telefônica. Identificar fatores pré e pós-operatórios associados ao resultado do tratamento cirúrgico. Métodos: Foram selecionados 178 pacientes operados entre 2005 e 2009, no serviço de cirurgia do esôfago do HCFMUSP. Os pacientes foram convocados para consulta ambulatorial. Foram levantados os prontuários médicos para obtenção de dados pré-operatórios. No estudo foi feita a análise de dados epidemiológicos, cirúrgicos, endoscópicos e manométricos. Os pacientes foram divididos em grupos, e foi aplicado o questionário de qualidade de vida GERD- HRQL. Foi avaliada também a nota de melhora dos sintomas de 0 a 10, a intenção de fazer novamente a cirurgia e o uso atual de omeprazol. Os pacientes que não puderam comparecer ao ambulatório foram entrevistados por telefone. Resultados: 90 pacientes foram incluídos no estudo, 45 no grupo A (entrevista ambulatorial) e 45 no grupo B (entrevista telefônica). Houve diferença significante entre a pontuação média no questionário GERD-HRQL dos pacientes do grupo A (6,29) e B (14,09), p=0,002. Esse resultado também foi significante quando separados homens (p=0,018) e mulheres (p=0,049) de ambos os grupos. Porém, a nota de melhora dos sintomas (p=0,642) e a intenção de fazer novamente a cirurgia (p=0,714) foram iguais. Analisando-se somente os pacientes do grupo A, a correlação linear de Pearson não mostrou diferença estatística entre a pontuação no questionário GERD-HRQL e idade (p=0,953), IMC pré-operatório (p=0,607), IMC pós-operatório (p=0,498), pressão do esfíncter inferior do esôfago (PEM, p=0,651; PRM, p>0,999) e amplitude média de contração do esôfago distal (p=0,997). A correlação da pontuação média no questionário GERD-HRQL com número de pontos na hiatoplastia (p=0,857), presença de esofagite erosiva pré-operatória (p=0,867), tamanho da hérnia hiatal (p=0,867) e presença de distúrbio motor do esôfago (p=0,207) também não mostrou significância estatística. A presença de esôfago de Barrett maior que 1cm correlacionou-se com menor pontuação no questionário GERD-HRQL (p=0,035). O uso rotineiro de omeprazol foi marcador de menor satisfação com a cirurgia (p=0,034). Conclusões: A satisfação dos pacientes com o tratamento cirúrgico é de forma geral elevada. A aplicação do questionário GERD-HRQL mostrou pior qualidade-de-vida dos pacientes entrevistados por telefone, em comparação aos pacientes entrevistados pessoalmente no ambulatório. O uso rotineiro de omeprazol após a cirurgia esteve associado à menor satisfação com o tratamento cirúrgico da DRGE Não foram identificados fatores pré-operatórios que possam determinar pior resultado da fundoplicatura laparoscópica à Nissen, porém a presença de esôfago de Barrett no pré-operatório foi um marcador de maior satisfação dos pacientes operados / Introduction: The surgical treatment of gastroesophageal reflux disease (GERD) has excellent results in most patients. However, a significant group develops complications or recurrence of symptoms, with impact on quality-of- life. Objectives: Evaluate the satisfaction of patients submitted to laparoscopic Nissen fundoplication, and compare the results of the GERD-HRQL quality of life questionnaire applied in person and by telephone. Identify pre and postoperative factors associated with the outcome of the surgical treatment.. Methods: 178 patients operated by the esophageal surgery division at Hospital das Clínicas da Faculdade de Medicina da USP, between 2005 and 2009, were selected. Patients were invited to an ambulatory interview. Charts were reviewed, and preoperative data was obtained. Epidemiological, surgical, endoscopic, and manometric parameters were studied. Patients were divided in groups, and the GERD-HRQL questionnaire was used. We also evaluated the score of symptom improvement between 0 and 10, if the patient would do the surgery again and current use of omeprazole. Patients who could not come to the ambulatory were interviewed by telephone. Results: 90 patients were enrolled in the study, 45 in group A (ambulatory interview) and 45 in group B (telephonic interview). There was significant statistical difference between the average score in the GERD-HRQL questionnaire in groups A (6,29) and B (14,09), p=0,002. This result was also significant among men (0,018) and women (0,049) in both groups. However, the score of symptom improvement (p=0,642) and the intention of doing the surgery again (p=0,714) were equivalent. In group A patients, Pearson\'s linear correlation did not show statistical difference between the GERD-HRQL score and age (p=0,953), preoperative BMI (p=0,607), postoperative BMI (p=0,997), inferior esophageal sphincter pressure (PEM, p=0,651; PRM, p>0,999) and distal esophageal contraction pressure (p=0,997). The correlation between GERD-HRQL score and number of stitches in hiatoplasty (p=0,857), presence of preoperative erosive esophagitis (p=0,867), size of hiatal hernia (p=0,867) and presence of motor esophageal disturbances (p=0,207) did not show statistical significance. The presence of Barrett\'s esophagus larger than 1cm correlated with a lower score on GERD-HRQL questionnaire (p=0,035). The routine use of omeprazole was a marker of lower satisfaction with the surgical treatment (p=0,034). Conclusions: Patient satisfaction with surgical treatment is generally high. The GERD-HRQL questionnaire showed poorer quality-of-life of patients interviewed by telephone, compared to patients interviewed at the ambulatory. The routine use of omeprazole after surgery was associated with lower satisfaction with the surgical treatment. No preoperative factors were identified that could determine worst outcome after laparoscopic Nissen fundoplication, but the presence of Barrett\'s esophagus preoperatively was a marker of increased patient\'s satisfaction

Gastrointestinal symptoms have a prevalence of 20-40% in the general adult population in the Western world. These symptoms are generally considered to be poor predictors of organic findings [e.g. peptic ulcer disease (PUD) or malignancy]. Approximately 50% of patients seeking care for such symptoms have no organic explanation for these upon investigation. When other organic or other functional conditions are excluded [e.g. PUD, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS)] the remaining patients are labelled as having functional dyspepsia (persistent or recurrent pain and/or discomfort centred in the upper abdomen). Management of functional dyspepsia remains a challenge, reflecting the heterogeneity of the patients and the uncertain role of drug treatment. Also, prognostic factors for treatment success are largely unknown. I have therefore performed a series of studies to shed light on these issues: The first study (Paper I) was performed in a randomly selected adult population (n=1,001) assessing upper and lower gastrointestinal symptoms at two occasions with 1 to 6 month intervals. The results show that gastrointestinal symptoms are common (57%) and fluctuate to some extent in the shorter term. Troublesome dyspeptic symptoms remain in two out of three individuals. This proportion was similar whether or not organic findings were present. In the second study (Paper II) 799 patients with dyspeptic symptoms were evaluated with regard to whether gastrointestinal symptoms, identified by self-administered questionnaires, correlate with endoscopic diagnoses and discriminate organic from non-organic (functional) dyspepsia. The impact of dyspeptic symptoms on health-related well-being was also evaluated. Approximately 50% of these dyspeptic patients were found to have functional dyspepsia at upper endoscopy. A difference was discovered in the symptom profile between patients with organic and functional dyspepsia. Predicting factors for functional dyspepsia were found. This study shows that use of self-administered symptom questionnaires may aid in clinical decision making for patient management, e.g. by reducing the number of endoscopies, although probabilities of risks for organic dyspepsia are difficult to transfer to management of the individual patient. The results also indicate that the health-related well-being in patients with functional and organic dyspepsia is impaired to the same extent, illustrating the need for effective treatment of patients with functional dyspepsia, a group not well served by currently available treatment modalities. The aim of the third study (Paper III) was to develop and evaluate a selfadministered questionnaire focusing on upper abdominal and reflux complaints to allow for identification of patients with heartburn and factors that might predict symptom relief with omeprazole both in GERD and functional dyspepsia patients. The diagnostic validity of the questionnaire was tested against endoscopy and 24-hour pH monitoring. The questionnaire had a sensitivity of 92%, but a low specificity of 19%. Symptom relief by omeprazole was best predicted by the presence of predominant heartburn described as ‘a burning feeling rising from the stomach or lower chest up towards the neck’ and ‘relief from antacids’. These results indicate that this questionnaire which used descriptive language, appeared to be useful in identifying heartburn and predicting responses to omeprazole in patients with upper gastrointestinal symptoms. The fourth study (Paper IV) was a pilot study investigating the symptom response to omeprazole 20 mg twice daily or placebo for a duration of 14 days in 197 patients with functional dyspepsia. We concluded that a subset of patients with functional dyspepsia, with or without heartburn, would respond to therapy with omeprazole. In the final study (Paper V) the aim was to identify prognostic factors for the treatment success to a 4-week course of omeprazole 10 or 20 mg once daily in 826 patients with functional dyspepsia. The most highly discriminating predictor of treatment success was the number of days without dyspeptic symptoms during the first week of treatment. Fewer days with symptoms during the first week indicated higher response rates at four weeks. In addition, positive predictors of treatment response to omeprazole were identified as age &gt;40 years, bothersome heartburn, low scores of bloating and diarrhoea, history of symptoms for &lt;3 months and low impairment of vitality at baseline. The results indicate that early response during the first week to treatment with a proton pump inhibitor seems to predict treatment success after four weeks in patients with functional dyspepsia. Conclusion: These studies have shown that a large proportion of adult individuals in society, both those who seek and those who do not seek medical care, suffer from symptoms located in the upper part of the abdomen regardless of whether an organic cause is present. A subset of patients without organic findings and other functional conditions, i.e. functional dyspepsia, respond to therapy with omeprazole irrespective of the presence or absence of heartburn . An excellent way to predict the response to a full course of omeprazole in functional dyspepsia is to assess the early response (first week) to treatment. These findings allow for better and faster targeting of acid inhibitory therapy in functional dyspepsia, which potentially can result in more effective clinical management of these patients and savings of health care resources.

Μελέτη της αναπνευστικής λειτουργίας με εργοσπιρομετρία σε ασθενείς με γαστροοισοφαγική παλινδρομική νόσο. Εισαγωγή: Η Γαστροοισοφαγική Παλινδρομική Νόσος (ΓΟΠΝ) έχει συσχετισθεί με πλειάδα πνευμονικών εκδηλώσεων αλλά είναι ασαφές εάν η γαστροοισοφαγική παλινδρόμηση προκαλεί οποιαδήποτε δυσλειτουργία στην πνευμονική λειτουργία. Η εργοσπιρομετρία είναι μια εξειδικευμένη μέθοδος η οποία χρησιμοποιείται για να διερευνήσει την αναπνευστική λειτουργία κατά την άσκηση. Σκοπός: Σκοπός της μελέτης ήταν να αποκαλυφθεί οποιαδήποτε ανωμαλία της πνευμονικής λειτουργίας σε ασθενείς με ΓΟΠΝ και αναπνευστικά συμπτώματα. Μέθοδος: Μελετήσαμε 34 ασθενείς με ΓΟΠΝ (ηλικίας 21-63, 24 άνδρες/10 γυναίκες) και εξωοισοφαγικά αναπνευστικά συμπτώματα (συριγμός ή/και βήχας) πριν και μετά από 12 εβδομάδες θεραπεία με διπλή δόση ομεπραζόλης. Κανείς ασθενής δεν παρουσίασε παθολογική σπιρομέτρηση. Εργομετρία διενεργήθηκε σε όλους του ασθενείς πριν την θεραπεία και μετά την θεραπεία. Γαστροσκόπηση διενεργήθηκε σε όλους τους ασθενείς πριν την θεραπεία και σε αυτούς με οισοφαγίτιδα επανελήφθη μετά την θεραπεία. Καταγραφήκαν οι ακόλουθες εργομετρικές παράμετροι: VO2rest, VO2max, VCO2rest, VCO2max, O2–puls rest, O2–puls max, HR (heart rate) rest, HRmax, PETCO2rest, PETCO2max, VE/VCO2 SLOPE πριν και μετά την θεραπεία. Αποτελέσματα: Είκοσι τέσσερις ασθενείς (70.6%) είχαν οισοφαγίτιδα (βαθμού Α-D), 16 ασθενείς είχαν διαφραγματοκήλη (47.1%), και σε 13 ασθενείς (38.23 %) ανιχνεύθηκε Helicobacter pylori.Οι εργομετρικές παράμετροι ήταν εντός φυσιολογικών ορίων σε όλους τους ασθενείς, κανείς ασθενής δεν παρουσίασε οποιαδήποτε ανωμαλία κατά την άσκηση. Είκοσι οκτώ ασθενείς επανελέγχθηκαν. Καμία βελτίωση σε οποιαδήποτε εργομετρική παράμετρο μετά την θεραπεία δεν παρατηρήθηκε παρά την ύφεση των οισοφαγικών και των εξωοισοφαγικών συμπτωμάτων σε όλους τους ασθενείς. Καμία στατιστικώς σημαντική διαφορά δεν παρατηρήθηκε πριν και μετά την θεραπεία μεταξύ ασθενών μεγαλύτερων των 40 ετών και νεότερων των 40 ετών, καπνιστών και μη καπνιστών, Hp(+) και Hp(-) ασθενών, όπως επίσης και μεταξύ ασθενών με και χωρίς οισοφαγίτιδα, και μεταξύ ασθενών με και χωρίς διαφραγματοκήλη. Συμπεράσματα: Ασθενείς με ΓΟΠΝ, αναπνευστικές εκδηλώσεις και φυσιολογική σπιρομέτρηση, δεν παρουσιάζουν διαταραχές κατά την εργομετρία (δοκιμασία άσκησης). Επίσης δεν παρατηρείται καμιά κλινικά αξιόλογη μεταβολή στις εργομετρικές τιμές μετά την θεραπεία ούτε διαφορά στις εργομετρικές τιμές σύμφωνα με την ηλικία, το κάπνισμα, την παρουσία H.pylori, οισοφαγίτιδας ή διαφραγματοκήλης. / Evaluation of respiratory function with cardiopulmonary exercise test in patients with gastroesophageal reflux disease. Introduction: Gastroesophageal reflux disease (GERD) has been associated with a variety of pulmonary manifestations but it is unclear if gastroesophageal reflux causes any abnormality in pulmonary function. Cardiopulmonary exercise test (CPET) is a specialized method which is used to evaluate respiratory function during exercise. Aim: The aim of this study was to reveal any abnormality of pulmonary function in patients with GERD and respiratory symptoms. Method: We evaluated 34 patients with GERD (age 21-63, 24 men) and extraesophageal respiratory symptoms (wheezing and/or cough) before therapy and after twelve weeks treatment with double dose omeprazole. No patient presented abnormal spirometry. CPET was performed in all patients at baseline and after completion of 12 week treatment. The following CPET parameters: VO2rest, VO2max, VCO2rest, VCO2max, O2–pulse rest, O2–pulse max, HR (heart rate) rest, HRmax, PETCO2rest, PETCO2max, VE/VCO2 slope were recorded pre-treatment and post-treatment. Results: Twenty four patients (70.6%) had esophagitis (grade I-IV), 16 patients had hiatal hernia (47.1%) and in 13 patients (38,2%) Helicobacter pylori was positive. All patients completed the CPET. No one presented shortness of breath or respiratory symptoms. CPET parameters were within normal limits in all patients. Twenty eight patients were reevaluated. No improvement in any CPET parameter post treatment was observed despite remission of esophageal and extraesophageal symptoms in all patients. No statistically significant difference was observed pre and post-treatment, between older and younger than 40 year old patients, smokers and non smokers, Hp(+) and Hp(-) patients and those with and without hiatal hernia and esophagitis. Conclusions: Patients with GERD and respiratory manifestations and normal spirometry present no pulmonary dysfunction during CPET. Also no alterations in CPET values post-treatment neither differences in CPET values according to age, smoking, Hp status, presence of oesophagitis or hiatal hernia were observed.

Introdução: A fisiopatologia da Doença do Refluxo Gastroesofágico (DRGE) é multifatorial, sendo a motilidade esofágica um dos fatores implicados na sua gênese. Todavia, ainda não há consenso sobre a existência de associação entre dismotilidade e Hérnia Hiatal (HH) em pacientes com DRGE. Esse estudo tem como objetivo estabelecer a prevalência de Dismotilidade Esofágica (DE) em pacientes com HH e avaliar se a herniação é fator relacionado à DE. Métodos: Foram estudados 356 pacientes com diagnóstico clínico de DRGE submetidos à Endoscopia Digestiva Alta e Manometria Esofágica. Hérnia Hiatal foi definida endoscopicamente por uma distância igual ou maior que 2 cm entre o pinçamento diafragmático e a junção escamo-colunar e Dismotilidade Esofágica quando a ME identificou amplitude das ondas peristálticas no esôfago distal < 30 mmHg e/ou menos de 80% de contrações efetivas. Foi feita a divisão dos pacientes para a análise estatística em 2 grupos, com e sem HH. Resultados: Pacientes com DRGE portadores de HH tiveram prevalência de DE igual a 14,8% e os sem HH, prevalência de 7,7% (p = 0,041). O grupo de pacientes com HH apresentou também maior frequência de esofagite erosiva (47,5% contra 24,2%, p <0,001), menor valor de pressão no EEI (10,4 versus 13,10; p < 0,001) e maior frequência de indivíduos com valores de pH-metria anormais (p < 0,001). A razão bruta de prevalências de DE, segundo a presença de HH, foi 1,92 (IC: 1,04 - 3,53; p = 0,037), porém essa associação não persistiu quando controlada por idade, esofagite, pH-metria alterada e EEI alterado (RP ajustada: 1,69; IC: 0,68 – 4,15; p = 0,257). Conclusão: Apesar da prevalência de DE no grupo HH ter sido maior do que no grupo sem HH, a associação entre HH e DE em indivíduos com DRGE desaparece ao se controlar por co-variáveis relevantes, levando a crer que neste tipo de paciente, HH não é fator de risco independente destas variáveis. / Introduction: The pathophysiology of gastroesophageal reflux disease is multifactorial, where esophageal motility is one of the factors implicated in its genesis. However, there is still no consensus on the existence of an association between esophageal dysmotility and hiatal hernia in patients with gastroesophageal reflux disease. The objective of this study was to establish the prevalence of esophageal dysmotility in patients with hiatal herina and to determine if herniation is a factor related to esophageal dysmotility. Methods: The study included 356 patients with a clinical diagnosis of gastroesophageal reflux disease submitted to upper digestive endoscopy and esophageal functional dagnostics. Hiatal Hernia was defined endoscopically by a distance equal to or greater than 2 cm between the diaphragmatic constriction and the squamo-columnar junction and esophageal dysmoyility when the esophageal manometry identified the amplitude of the peristaltic waves in the distal esophagus are < 30 mmHg and/or less than 80% of effective contractions. For statistical analysis, the patients were divided into 2 grups: with and without HH. Results: Gastroesophageal reflux disease patients with hiatal hernia had a prevalence of esophageal dysmotility equal to 14.8% and those without hiatal hernia, a prevalence of 7.7% (p = 0.041). The group of patients with hiatal hernia also showed a greater frequency of erosive esophagitis (47.5% versus 24.2%, p <0.001), lower low esophageal sphincter pressure (10.4 versus 13.10; p < 0.001) and greater frequency of individuals with abnormal pH-metry values (p < 0.001). The crude prevalence ratios for esophageal dysmotility, according to the presence of hiatal hernia, was 1.92 (CI: 1.04 - 3.53; p = 0.037), but this association did not persist when controlled for age, esophagitis, altered pH-metry and altered low esophageal sphincter (adjusted PR: 1.69; CI: 0.68 – 4.15; p = 0.257). Conclusion: Despite the prevalence of esophageal dysmotility in the hiatal hernia group being higher than that in the group without hiatal hernia, the association between hiatal hernia and esophageal dysmotility in individuals with gastroesophageal reflux disease disappeared on controlling for relevant co-variables, leading us to believe that in this type of patient, hiatal hernia is not a risk factor independent of these variables.

Objetivos: Avaliar a associação entre a dismotilidade esofágica, caracterizada como Motilidade Esofágica Ineficaz (MEI), com a presença de refluxo ácido patológico avaliado pela pH-metria de 24 horas, controlando por Esfíncter Esofágico Inferior (EEI) estruturalmente defeituoso, Hérnia Hiatal (HH) e Esofagite, em pacientes em investigação de Doença do Refluxo Gastroesofágico. Métodos: Foram estudados 311 pacientes referenciados para investigação de DRGE em laboratório de motilidade esofágica. Os pacientes foram submetidos à Endoscopia Digestiva Alta (EDA), Manometria Esofágica, pHmetria Esofágica de 24 horas e a uma entrevista sobre os sintomas clínicos apresentados. Foram comparados os grupos de pH-metria negativa com o de pH-metria positiva quanto à presença dos fatores de risco – MEI, EEI defeituoso, HH e Esofagite. A associação entre MEI e pH-metria positiva foi primeiramente avaliada através de análise univariada e, posteriormente, através de análise de regressão logística (multivariada). Resultados: Do total de 311 pacientes estudados, 208 preencheram os critérios de inclusão. A idade média foi 47 anos, com 88 pacientes apresentando pH-metria normal e 120 pH-metria positiva. Após a análise univariada, foi observado que a ocorrência de MEI, EEI defeituoso e HH foi significativamente maior no grupo de pH-metria positiva. Após análise de regressão logística, a ocorrência de MEI e EEI defeituoso permaneceram significativamente maior no grupo de pH-metria positiva. Conclusões: MEI está associada à presença de refluxo ácido anormal, avaliado através de pH-metria esofágica de 24 horas, independentemente da presença de EEI defeituoso, HH ou Esofagite. / Objectives: To assess the association between esophageal dysmotility, characterized as inefficient esophageal motility (IEM), and the presence of pathological acid reflux due to a structurally defective lower esophageal sphincter (LES), hiatus hernia (HH), or esophagitis in patients suspected of having gastroesophageal Reflux reflux disease (GERD). Methods: Three hundred and eleven patients referred for GERD diagnostic procedures in a gastroesopahgeal motility laboratory were included in the study. Patients underwent upper endoscopy (UE), esophageal manometry, 24-hour esophageal pH-metry and an interview regarding their clinical symptoms. The following risk factors of patients in the negative pH-metry group were compared to those in the positive pH-metry group: IEM, defective LES, HH, and esophagitis. The association between IEM and positive pH-metry results was first assessed by means of univariate analysis and later determined with logistic regression analysis (multivariate). Results: Of the total 311 patients studied, 208 met the inclusion criteria (mean age 47 years); 88 had normal pH-metry reslults and 120 had positive pH-metry results. Univariate analysis revealed that the occurrence of IEM, defective LES, and HH was significantly greater in the positive pH-metry group. Following logistic regression analysis, the occurrence of IEM remained significantly greater in the positive pH-metry group. Conclusions: IEM is associated with the presence of abnormal acid reflux, as assessed by 24-hour esophageal pH-metry, regardless of the presence of defective LES, HH, or esophagitis.

Objetivos: Avaliar a associação entre a dismotilidade esofágica, caracterizada como Motilidade Esofágica Ineficaz (MEI), com a presença de refluxo ácido patológico avaliado pela pH-metria de 24 horas, controlando por Esfíncter Esofágico Inferior (EEI) estruturalmente defeituoso, Hérnia Hiatal (HH) e Esofagite, em pacientes em investigação de Doença do Refluxo Gastroesofágico. Métodos: Foram estudados 311 pacientes referenciados para investigação de DRGE em laboratório de motilidade esofágica. Os pacientes foram submetidos à Endoscopia Digestiva Alta (EDA), Manometria Esofágica, pHmetria Esofágica de 24 horas e a uma entrevista sobre os sintomas clínicos apresentados. Foram comparados os grupos de pH-metria negativa com o de pH-metria positiva quanto à presença dos fatores de risco – MEI, EEI defeituoso, HH e Esofagite. A associação entre MEI e pH-metria positiva foi primeiramente avaliada através de análise univariada e, posteriormente, através de análise de regressão logística (multivariada). Resultados: Do total de 311 pacientes estudados, 208 preencheram os critérios de inclusão. A idade média foi 47 anos, com 88 pacientes apresentando pH-metria normal e 120 pH-metria positiva. Após a análise univariada, foi observado que a ocorrência de MEI, EEI defeituoso e HH foi significativamente maior no grupo de pH-metria positiva. Após análise de regressão logística, a ocorrência de MEI e EEI defeituoso permaneceram significativamente maior no grupo de pH-metria positiva. Conclusões: MEI está associada à presença de refluxo ácido anormal, avaliado através de pH-metria esofágica de 24 horas, independentemente da presença de EEI defeituoso, HH ou Esofagite. / Objectives: To assess the association between esophageal dysmotility, characterized as inefficient esophageal motility (IEM), and the presence of pathological acid reflux due to a structurally defective lower esophageal sphincter (LES), hiatus hernia (HH), or esophagitis in patients suspected of having gastroesophageal Reflux reflux disease (GERD). Methods: Three hundred and eleven patients referred for GERD diagnostic procedures in a gastroesopahgeal motility laboratory were included in the study. Patients underwent upper endoscopy (UE), esophageal manometry, 24-hour esophageal pH-metry and an interview regarding their clinical symptoms. The following risk factors of patients in the negative pH-metry group were compared to those in the positive pH-metry group: IEM, defective LES, HH, and esophagitis. The association between IEM and positive pH-metry results was first assessed by means of univariate analysis and later determined with logistic regression analysis (multivariate). Results: Of the total 311 patients studied, 208 met the inclusion criteria (mean age 47 years); 88 had normal pH-metry reslults and 120 had positive pH-metry results. Univariate analysis revealed that the occurrence of IEM, defective LES, and HH was significantly greater in the positive pH-metry group. Following logistic regression analysis, the occurrence of IEM remained significantly greater in the positive pH-metry group. Conclusions: IEM is associated with the presence of abnormal acid reflux, as assessed by 24-hour esophageal pH-metry, regardless of the presence of defective LES, HH, or esophagitis.

Introdução: A fisiopatologia da Doença do Refluxo Gastroesofágico (DRGE) é multifatorial, sendo a motilidade esofágica um dos fatores implicados na sua gênese. Todavia, ainda não há consenso sobre a existência de associação entre dismotilidade e Hérnia Hiatal (HH) em pacientes com DRGE. Esse estudo tem como objetivo estabelecer a prevalência de Dismotilidade Esofágica (DE) em pacientes com HH e avaliar se a herniação é fator relacionado à DE. Métodos: Foram estudados 356 pacientes com diagnóstico clínico de DRGE submetidos à Endoscopia Digestiva Alta e Manometria Esofágica. Hérnia Hiatal foi definida endoscopicamente por uma distância igual ou maior que 2 cm entre o pinçamento diafragmático e a junção escamo-colunar e Dismotilidade Esofágica quando a ME identificou amplitude das ondas peristálticas no esôfago distal < 30 mmHg e/ou menos de 80% de contrações efetivas. Foi feita a divisão dos pacientes para a análise estatística em 2 grupos, com e sem HH. Resultados: Pacientes com DRGE portadores de HH tiveram prevalência de DE igual a 14,8% e os sem HH, prevalência de 7,7% (p = 0,041). O grupo de pacientes com HH apresentou também maior frequência de esofagite erosiva (47,5% contra 24,2%, p <0,001), menor valor de pressão no EEI (10,4 versus 13,10; p < 0,001) e maior frequência de indivíduos com valores de pH-metria anormais (p < 0,001). A razão bruta de prevalências de DE, segundo a presença de HH, foi 1,92 (IC: 1,04 - 3,53; p = 0,037), porém essa associação não persistiu quando controlada por idade, esofagite, pH-metria alterada e EEI alterado (RP ajustada: 1,69; IC: 0,68 – 4,15; p = 0,257). Conclusão: Apesar da prevalência de DE no grupo HH ter sido maior do que no grupo sem HH, a associação entre HH e DE em indivíduos com DRGE desaparece ao se controlar por co-variáveis relevantes, levando a crer que neste tipo de paciente, HH não é fator de risco independente destas variáveis. / Introduction: The pathophysiology of gastroesophageal reflux disease is multifactorial, where esophageal motility is one of the factors implicated in its genesis. However, there is still no consensus on the existence of an association between esophageal dysmotility and hiatal hernia in patients with gastroesophageal reflux disease. The objective of this study was to establish the prevalence of esophageal dysmotility in patients with hiatal herina and to determine if herniation is a factor related to esophageal dysmotility. Methods: The study included 356 patients with a clinical diagnosis of gastroesophageal reflux disease submitted to upper digestive endoscopy and esophageal functional dagnostics. Hiatal Hernia was defined endoscopically by a distance equal to or greater than 2 cm between the diaphragmatic constriction and the squamo-columnar junction and esophageal dysmoyility when the esophageal manometry identified the amplitude of the peristaltic waves in the distal esophagus are < 30 mmHg and/or less than 80% of effective contractions. For statistical analysis, the patients were divided into 2 grups: with and without HH. Results: Gastroesophageal reflux disease patients with hiatal hernia had a prevalence of esophageal dysmotility equal to 14.8% and those without hiatal hernia, a prevalence of 7.7% (p = 0.041). The group of patients with hiatal hernia also showed a greater frequency of erosive esophagitis (47.5% versus 24.2%, p <0.001), lower low esophageal sphincter pressure (10.4 versus 13.10; p < 0.001) and greater frequency of individuals with abnormal pH-metry values (p < 0.001). The crude prevalence ratios for esophageal dysmotility, according to the presence of hiatal hernia, was 1.92 (CI: 1.04 - 3.53; p = 0.037), but this association did not persist when controlled for age, esophagitis, altered pH-metry and altered low esophageal sphincter (adjusted PR: 1.69; CI: 0.68 – 4.15; p = 0.257). Conclusion: Despite the prevalence of esophageal dysmotility in the hiatal hernia group being higher than that in the group without hiatal hernia, the association between hiatal hernia and esophageal dysmotility in individuals with gastroesophageal reflux disease disappeared on controlling for relevant co-variables, leading us to believe that in this type of patient, hiatal hernia is not a risk factor independent of these variables.