Jaime Natan Eisig

Lugol's Dye Spray Chromoendoscopy Establishes Early Diagnosis of Esophageal Cancer in Patients with Primary Head and Neck Cancer

OBJECTIVE:Patients with primary head and neck cancer show a predisposition to develop esophageal cancer. The aim of this study was to investigate in these patients: the prevalence of esophageal cancer comparing the value of chromoendoscopy using Lugols solution examination to standard endoscopy, in the early diagnosis of esophageal cancer.METHODS:Prospective observational study at a state general university hospital in Sao Paulo, Brazil. 326 consecutive adult patients with primary head and neck cancer were evaluated. A standard endoscopy was performed, followed by a 2% lugols dye spray chromoendoscopy and histopathologic study. The prevalence of esophageal cancer was defined. The results of the two endoscopic methods were compared.RESULTS:Twenty-four patients with esophageal cancer and high-grade intraepithelial neoplasia were detected and had a prevalence of 7.36%. Chromoendoscopy and standard endoscopy were equivalent to the diagnosis of advanced and invasive esophageal cancer. However, standard endoscopy diagnosed 55% of high-grade intraepithelial neoplasia, in comparison to chromoendoscopy that detected 100%.CONCLUSIONS:Patients with primary head and neck cancer should be considered as high risks for the presence of esophageal cancer. Lugols dye chromoendoscopy diagnosed high-grade intraepithelial neoplasia, which went unnoticed with standard endoscopy. It permits a more exact detection of lesion boundaries and facilitates a more precise targeting of biopsy fragments.

Factors Related to Helicobacter pylori Prevalence in an Adult Population in Brazil

Background:  The prevalence of Helicobacter pylori is higher in developing countries. Sanitary facilities, crowding and ethnic group are some of the factors related to H. pylori infection. The aim of this study was to investigate in blood donors, free of dyspeptic symptoms, the prevalence and factors influencing H. pylori infection.

No Correlation of babA2 with vacA and cagA Genotypes of Helicobacter pylori and Grading of Gastritis from Peptic Ulcer Disease Patients in Brazil

Background.  The babA2 gene, which encodes a blood‐group antigen‐binding adhesin that mediates attachment of Helicobacter pylori to human Lewisb antigens on gastric epithelial cells, has been associated with a higher risk of peptic ulcer and gastric cancer. The purpose of this study was to ascertain the frequency of babA2 genotype in H. pylori strains of patients with peptic ulcer and to correlate with other virulence factors.

Helicobacter pylori antibiotic resistance in Brazil: clarithromycin is still a good option

CONTEXT The antibiotic susceptibility is the cornerstone for the eradication therapies of Helicobacter pylori. OBJECTIVES To evaluate the prevalence of primary resistance of H. pylori was evaluated in an urban Brazilian population. METHODS H. pylori isolates were obtained from patients submitted to an upper gastrointestinal endoscopy for the evaluation of dyspeptic symptoms. Biopsies from antrum, corpus and fundus were taken to determine the antibiotic susceptibility of H. pylori isolates. The minimal inhibitory concentration of furazolidone and bismuth were routinely determined by agar dilution method and the minimal inhibitory for amoxicillin, clarithromycin, tetracycline, levofloxacin, and metronidazole were routinely determined with the E-test. RESULTS Fifty-four patients were included. In vitro antimicrobial susceptibility of H. pylori strains were obtained from 39 patients. Resistance to metronidazole was detected in 20 patients (51%), to clarithromycin in 3 patients (8%), to levofloxacin in 9 patients (23%) and to bismuth in 2 patients (5%). There was no observed resistance to amoxicillin, tetracycline or furazolidone. CONCLUSION Due to the low amoxicillin and clarithromycin resistance observed in this study, therapies using these antimicrobials remain appropriated first-line H. pylori therapy.

Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

BackgroundThe treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy.If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen.MethodsPatients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment.ResultsOne hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08).ConclusionsThe use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects.Trial registrationCurrent Controlled Trials ISRCTN04714018

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

BackgroundIncreasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen.MethodsThis study included 48 patients with peptic ulcer disease. Helicobacter pylori infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use.ResultsOnly one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI- 89%–99%) and 88% (88–92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-naïve patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002).ConclusionAn empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of Helicobacter pylori, particularly in patients that have failed one prior eradication therapy.

Guidelines for the diagnosis and management of gastroesophageal reflux disease: an evidence-based consensus

A doenca do refluxo gastroesofagico e uma das enfermidades mais comuns na pratica medica. Numerosas diretrizes e recomendacoes de conduta para seu diagnostico e tratamento tem sido publicadas em varios paises, mas no Brasil ainda nao havia sido realizado um trabalho de consenso baseado em padroes de Medicina baseada em evidencias. Com esse objetivo, estabeleceu-se um grupo brasileiro representativo de especialistas (Grupo de Consenso da DRGE - doenca do refluxo gastroesofagico) para estabelecer diretrizes de conduta de Medicina baseada em evidencias para a doenca do refluxo gastroesofagico que pudessem ser utilizadas tanto por medicos em cuidados primarios de saude, como por especialistas, seguradoras e agencias regulatorias. Foram propostas 30 questoes e a busca das respostas baseou-se em pesquisa sistematica da literatura para a identificacao dos temas e respectivos graus de evidencia. Foram selecionadas 11.069 publicacoes sobre doenca do refluxo gastroesofagico, das quais 6.474 sobre diagnostico e 4.595 sobre terapeutica. Em relacao ao diagnostico, 51 trabalhos alcancaram as exigencias de Medicina baseada em evidencias: 19 foram classificadas como grau A e 32 como grau B. Em relacao a terapeutica, 158 alcancaram as exigencias de Medicina baseada em evidencias: 89 foram classificadas como grau A e 69 como grau B. No item Diagnostico as respostas sustentadas por publicacao de graus A e B foram aceitas. No item Tratamento, somente publicacoes grau A foram aceitas: as respostas apoiadas por publicacoes grau B foram submetidas a votacao pelo Grupo de Consenso. A presente publicacao apresenta as respostas as questoes propostas com os trabalhos mais representativos seguidos por comentarios pertinentes. Exemplos: 1) em pacientes com manifestacoes atipicas a pHmetria convencional pouco contribui para o diagnostico de doenca do refluxo gastroesofagico. A sensibilidade, entretanto, aumenta com o emprego de pHmetria de duplo canal. 2) Em pacientes com manifestacoes atipicas a impedância-pHmetria contribui substancialmente para o diagnostico de doenca do refluxo gastroesofagico. O exame, entretanto, e oneroso e pouco disponivel em nosso pais. 3) A avaliacao dos sinais histologicos de esofagite eleva a probabilidade diagnostica da doenca do refluxo gastroesofagico, considerando-se que a observacao das dimensoes do espaco intercelular da mucosa esofagica aumenta a probabilidade de certeza diagnostica e tambem permite a analise da resposta terapeutica. 4) Nao ha diferenca na resposta clinica ao tratamento com inibidor da bomba protonica administrado em duas doses diarias quando comparado a uma unica dose diaria. 5) A longo prazo (>1 ano) a erradicacao do H .pylori em pacientes com doenca do refluxo gastroesofagico nao reduz a presenca de sintomas ou a elevada recurrencia da enfermidade, embora reduza os sinais histologicos de inflamacao. E muito provavel que nao ocorra associacao entre a erradicacao do H. pylori e as manifestacoes da doenca do refluxo gastroesofagico. 6) A presenca de hernia hiatal exige doses maiores de IBP para o tratamento clinico. A ocorrencia de migracao permanente da juncao esofago-gastrica e as dimensoes da hernia (>2 cm) sao fatores de pior prognostico na doenca do refluxo gastroesofagico. Nesses casos, as hernias hiatais associadas a doenca do refluxo gastroesofagico, especialmente as fixas e maiores do que 2 cm devem ser consideradas para tratamento cirurgico. Os resultados da fundoplicatura laparoscopica tem se mostrado adequados.Gastroesophageal reflux disease (GERD) is one of the most common disorders in medical practice. A number of guidelines and recommendations for the diagnosis and management of GERD have been published in different countries, but a Brazilian accepted directive by the standards of evidence-based medicine is still lacking. As such, the aim of the Brazilian GERD Consensus Group was to develop guidelines for the diagnosis and management of GERD, strictly using evidence-based medicine methodology that could be clinically used by primary care physicians and specialists and would encompass the needs of physicians, investigators, insurance and regulatory bodies. A total of 30 questions were proposed. Systematic literature reviews, which defined inclusion and/or exclusion criteria, were conducted to identify and grade the available evidence to support each statement. A total of 11,069 papers on GERD were selected, of which 6,474 addressed the diagnosis and 4,595, therapeutics. Regarding diagnosis, 51 met the requirements for the analysis of evidence-based medicine: 19 of them were classified as grade A and 32 as grade B. As for therapeutics, 158 met the evidence-based medicine criteria; 89 were classified as grade A and 69 as grade B. In the topic Diagnosis, answers supported by publications grade A and B were accepted. In the topic Treatment only publications grade A were accepted: answers supported by publications grade B were submitted to the voting by the Consensus Group. The present publication presents the most representative studies that responded to the proposed questions, followed by pertinent comments. Follow examples. In patients with atypical manifestations, the conventional esophageal pH-metry contributes little to the diagnosis of GERD. The sensitivity, however, increases with the use of double-channel pH-metry. In patients with atypical manifestations, the impedance-pH-metry substantially contributes to the diagnosis of GERD. The examination, however, is costly and scarcely available in our country. The evaluation of the histological signs of esophagitis increases the diagnostic probability of GERD; hence, the observation of the dimensions of the intercellular space of the esophageal mucosa increases the probability of diagnostic certainty and also allows the analysis of the therapeutic response. There is no difference in the clinical response to the treatment with PPI in two separate daily doses when compared to a single daily dose. In the long term (>1 year), the eradication of H. pylori in patients with GERD does not decrease the presence of symptoms or the high recurrence rates of the disease, although it decreases the histological signs of gastric inflammation. It seems very likely that there is no association between the eradication of the H. pylori and the manifestations of GERD. The presence of a hiatal hernia requires larger doses of proton-pump inhibitor for the clinical treatment. The presence of permanent migration from the esophagogastric junction and the hernia dimensions (>2 cm) are factors of worse prognosis in GERD. In this case, hiatal hernias associated to GERD, especially the fixed ones and larger than 2 cm, must be considered for surgical treatment. The outcomes of the laparoscopic fundoplication are adequate.

A FURAZOLIDONE-BASED QUADRUPLE THERAPY FOR HELICOBACTER PYLORI RETREATMENT IN PATIENTS WITH PEPTIC ULCER DISEASE

PURPOSE Many of the currently used eradication regimens against Helicobacter pylori fail to cure the infection either due to antimicrobial resistance or to poor patient compliance. The infection leads to increased risk of developing potentially severe complications, such as gastric cancer. This study was aimed at assessing the efficacy and safety of a quadruple therapy with furazolidone for H. pylori retreatment. METHODS Patients who had failed one or more eradication regimens against H. pylori infection underwent upper gastrointestinal endoscopy. Biopsy specimens were taken from the gastric antrum and corpus for histology and for a urease test and. Patients received omeprazole 20 mg, bismuth citrate 240 mg, tetracycline 500 mg, and furazolidone 200 mg, all twice daily for 7 days. Therapeutic success was evaluated by endoscopy and biopsies 8 weeks after the end of treatment. RESULTS Sixty two patients were enrolled, and 58 completed the study. Under this protocol, H. pylori eradication was achieved in 39/58 patients (67%). Mild adverse events were reported. CONCLUSION The short quadruple therapy course with furazolidone is well tolerated, inexpensive, and effective in retreatment for H. pylori infection. It is a good option for developing countries.

Oral cavity is not a reservoir for Helicobacter pylori in infected patients with functional dyspepsia

INTRODUCTION Helicobacter pylori infection is very prevalent in Brazil, infecting almost 65% of the population. The aim of this study was to evaluate the presence of this bacterium in the oral cavity of patients with functional dyspepsia (epigastric pain syndrome), establish the main sites of infection in the mouth, and assess the frequency of cagA and vacA genotypes of oral H. pylori. METHODS All 43 outpatients with epigastric pain syndrome, who entered the study, were submitted to upper gastrointestinal endoscopy to rule out organic diseases. Helicobacter pylori infection in the stomach was confirmed by a rapid urease test and urea breath tests. Samples of saliva, the tongue dorsum and supragingival dental plaque were collected from the oral cavity of each subject and subgingival dental plaque samples were collected from the patients with periodontitis; H. pylori infection was verified by polymerase chain reaction using primers that amplify the DNA sequence of a species-specific antigen present in all H. pylori strains; primers that amplify a region of urease gene, and primers for cagA and vacA (m1, m2, s1a, s1b, s2) genotyping. RESULTS Thirty patients harbored H. pylori in the stomach, but it was not possible to detect H. pylori in any oral samples using P1/P2 and Urease A/B. The genotype cagA was also negative in all samples and vacA genotype could not be characterized (s-m-). CONCLUSION The oral cavity may not be a reservoir for H. pylori in patients with epigastric pain syndrome, the bacterium being detected exclusively in the stomach.

Eosinophilic esophagitis in patients with typical gastroesophageal reflux disease symptoms refractory to proton pump inhibitor

BACKGROUND: TREATMEN The contribution of eosinophilic esophagitis (EoE) to refractory gastroesophageal reflux disease (GERD) remains unknown. When EoE and GERD overlap, the clinical, endoscopic and histological findings are nonspecific and cannot be used to distinguish between the two disorders. Limited data are available on this topic, and the interaction between EoE and GERD is a matter of debate. AIM: We have conducted a prospective study of adult patients with refractory GERD to evaluate the overlap of reflux and EoE. METHODS: Between July 2006 and June 2008, we consecutively and prospectively enrolled 130 male and female patients aged 18 to 70 years old who experienced persistent heartburn and/or regurgitation more than twice a week over the last 30 days while undergoing at least six consecutive weeks of omeprazole treatment (at least 40 mg once a day). The patients underwent an upper digestive endoscopy with esophageal biopsy, and intraepithelial eosinophils were counted after hematoxylin/eosin staining. The diagnosis of EoE was based on the presence of 20 or more eosinophils per high-power field (eo/HPF) in esophageal biopsies. RESULTS: Among the 103 studied patients, 79 (76.7%) were females. The patients had a mean age of 45.5 years and a median age of 47 years. Endoscopy was normal in 83.5% of patients, and erosive esophagitis was found in 12.6%. Only one patient presented lesions suggestive of EoE. Histological examination revealed >20 eo/HPF in this patient. CONCLUSION: Our results demonstrated a low prevalence of EoE among patients with refractory GERD undergoing omeprazole treatment.