Fernando Fornari

Questionário de sintomas na doença do refluxo gastroesofágico

BACKGROUND: Structured questionnaires are valuable instruments to measure the impact of specific diseases in patients quality of life through a score and they are available such abroad as in Brazil. Nevertheless, questionnaires based on gastroesophageal reflux disease symptoms are not available in Portuguese. AIM: To develop and validate in Portuguese a specific questionnaire for gastroesophageal reflux disease symptoms. PATIENTS AND METHODS: Velanovichs original questionnaire was translated, one question about regurgitation symptom was included and the vocabulary was adjusted to be understood to the scholarity level of the analyzed population. The face validity to each question was evaluated by the members of a multidisciplinary panel and a symptoms questionnaire for gastroesophageal reflux disease was developed. The questionnaire was applied to patients with gastroesophageal reflux disease symptoms confirmed by prolonged pH esophageal monitoring. The reproducibility, the comprehension, the time spent to fill out the questionnaire and the correlation coefficient to Johnson-DeMeesters score were measured. RESULTS: The face validity was considered satisfactory by the panel and the questionnaire was applied to 124 patients, consecutively. The comprehension of the questionnaire and the time less than 5 minutes to fill out them were observed in all patients (100%). Reproducibility for 10 patients in two different occasions showed a high intra-class correlation coefficient of 0,833. The correlation to the Johnson-DeMeesters score was null. CONCLUSION: This study showed that the symptoms questionnaire for gastroesophageal reflux disease has face validity, excellent reproducibility, easy comprehension and was quickly answered by patients. The correlation with Johnson-DeMeesters score was null.

Is ineffective oesophageal motility associated with reflux oesophagitis

Objective To evaluate the association between ineffective oesophageal motility and reflux oesophagitis controlling for hiatal hernia, hypotensive lower oesophageal sphincter and male sex in patients with gastro-oesophageal reflux disease. Methods A total of 387 patients with reflux disease (mean age, 46 years, 42% men) were consecutively selected from a database. All patients underwent upper endoscopy, oesophageal manometry and 24u2009h oesophageal pH-metry in accordance with a standardized protocol. Reflux disease was confirmed either by endoscopy (oesophagitis grade I–IV according to Savary–Miller) or by pH-metry (increased acid exposure). Hiatal hernia was diagnosed endoscopically, whereas ineffective oesophageal motility and hypotensive lower oesophageal sphincter were characterized during manometry testing. The association between ineffective oesophageal motility and reflux oesophagitis was assessed by logistic regression analysis. Results A total of 166 patients with oesophagitis (mean age 45 years, 49% men) and 221 without oesophagitis (mean age 46 years, 37% men) were present. Prevalences of ineffective oesophageal motility, hiatal hernia, hypotensive lower oesophageal sphincter and male sex were significantly higher in patients with oesophagitis compared with those without oesophagitis (P<0.05). Ineffective oesophageal motility was independently associated with oesophagitis after multivariate logistic regression analysis (odds ratio=1.68; 95% confidence interval=1.04–2.70). Conclusion Ineffective oesophageal motility is associated with reflux oesophagitis, independently of hiatal hernia, hypotensive lower oesophageal sphincter and male sex.

Obese Patients Have Stronger Peristalsis and Increased Acid Exposure in the Esophagus

BackgroundObesity is a risk factor for GERD and a potential modulator of esophageal motility.AimTo assess whether obese patients differ from non-obese patients in terms of esophageal motility and reflux.MethodsPatients (nxa0=xa0332) were categorized in GERD and controls after clinical assessment, esophageal manometry, and pH monitoring. Non-obese (BMI 16–29.9) and obese (BMI 30–68) were compared in regard of distal esophageal amplitude (DEA), LES pressure (LESP), manometric diagnosis, and esophageal acid exposure (EAE).ResultsObese showed higher DEA in both controls (122xa0±xa053 vs. 97xa0±xa036xa0mmHg, pxa0=xa00.041) and GERD patients (109xa0±xa038 vs. 94xa0±xa046xa0mmHg, pxa0<xa00.001), higher LESP in GERD patients (20.5xa0±xa010.6 vs. 18.2xa0±xa010.6xa0mmHg, pxa0=xa00.049), higher frequency of nutcracker esophagus in controls (30 vs. 0%, pxa0=xa00.001), lower frequency of ineffective motility in GERD patients (6 vs. 20%, pxa0=xa00.001), and higher EAE in both controls [total EAE: 1.6% (0.7–5.1) vs. 0.9% (0.2–2.4), pxa0=xa00.027] and GERD patients [upright EAE: 6.5% (3.8–11.1) vs. 5.2% (1.5–10.6), pxa0=xa00.048]. Multiple linear regression showed that BMI was associated either with EAE (pxa0<xa00.001), DEA (pxa0=xa00.006), or LESP (in men, pxa0=xa00.007).ConclusionsObese patients differed from non-obese in terms of esophageal motility and reflux, regardless of the presence of GERD. Obese patients showed stronger peristalsis and increased acid exposure in the esophagus.

Exon 11 mutations, Ki67, and p16INK4A as predictors of prognosis in patients with GIST

Prognostic biomarkers for GIST are under investigation. The aim of this study was to assess whether exon 11 mutations, Ki67, and p16(INK4A) are predictors of prognosis in GIST. Consecutive GIST cases (n=84) had their specimens evaluated for exon 11 mutations and expression of Ki67 and p16(INK4A). Surgical cases were categorized according to NIH and Miettinens classification, and survival was analyzed from hospital database. GISTs were predominately gastric (45%) and with spindle cell morphology (74%). The risk category was very low or low in 28%, intermediate in 23%, and high in 49%. Exon 11 mutation was identified in 29 (48%) out of 60 cases studied. There were 12 point mutations, 10 deletions, 4 duplications, and 3 double mutations. A third of GISTs had either high Ki67 index (>3%) or negativity for p16(INK4A). In multivariate analysis, independent predictors of mortality were Ki67>3% (HR=7.3; P=0.036) and high mitotic index (HR=10.4; P=0.043). There was no association between exon 11 mutations and survival. This study suggests that Ki67>3% is an independent predictor of poor prognosis in patients with GIST. Exon 11 mutations and negativity for p16(INK4A) need further studies to address the prognostic value.

Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non-erosive reflux disease

Non‐erosive reflux disease (NERD) patients generally present with heartburn as the main symptom. Antidepressants might help to relieve heartburn by acting on the esophagus‐brain axis. We aimed to assess the effect of nortriptyline on behavioral and brain responses to painful esophageal acid infusion in NERD patients evaluated with functional magnetic resonance imaging (fMRI).

Heartburn during sleep: a clinical marker of gastro-oesophageal reflux disease in morbidly obese patients.

Abstractu2002 Gastro‐oesophageal reflux disease (GORD) and morbid obesity are entities with increasing prevalence. New clinical strategies are cornerstones for their management. The aim of this study was to assess the prevalence of heartburn during sleep (HDS) and whether this symptom predicts the presence of objective GORD parameters and increased heartburn perception in morbidly obese patients. Ninety‐one consecutive morbidly obese patients underwent clinical evaluation, upper gastrointestinal endoscopy and oesophageal pH monitoring. HDS was characterized when patients replied positively to the question, ‘Does heartburn wake you from sleep?’. A General Score for Heartburn (GSH) ranging between 0 and 5 was assessed with the question ‘How bad is your heartburn?’. HDS was reported by 33 patients (36%). More patients with HDS had abnormal acid contact time or reflux oesophagitis than patients without HDS (94%vs 57%, Pu2003<u20030.001). HDS had a positive predictive value of 94% (0.95 CI 82–98), sensitivity of 48% (0.95 CI 37–60%) and specificity of 93% (0.95 CI 77–98%) for detection of GORD. A higher proportion of patients with HDS perceived heartburn preceded by acid reflux in diurnal (39%vs 9%; Pu2003<u20030.001) periods during pH‐metry. HDS patients showed higher GSH (2.4u2003±u20030.5 vs 1.7u2003±u20030.4; Pu2003<u20030.0001) compared with patients who denied HDS but reported diurnal heartburn. HDS occurs in a significant minority of patients with morbid obesity and has high positive predictive value for GORD. Symptomatic reflux during the sleep seems to be a marker of increased heartburn perception in this population.

Comfort, safety and quality of upper gastrointestinal endoscopy after 2 hours fasting: a randomized controlled trial

BackgroundUpper gastrointestinal endoscopy has been performed after fasting 8 or more hours, which can be harmful to the patients. We assessed comfort, safety and quality of endoscopy under moderate sedation after 2xa0hours fasting for clear liquids.MethodsIn this clinical trial, patients referred for elective endoscopy were randomly assigned to a fasting period of 8xa0hours (F8) or a shorter fasting (F2), in which 200xa0ml of clear liquids were ingested 2xa0hours before the procedure. Endoscopists blinded to patients fasting status carried out the endoscopies. Comfort was rated by the patients, whereas safety and quality were determined by the endoscopists.ResultsNinety-eight patients were studied (aging 48.5u2009±u200916.5xa0years, 60% women): 50 patients (51%) in F2 and 48 in F8. Comfort was higher in F2 than F8 in regard to anxiety (8% vs. 25%; Pu2009=u20090.029), general discomfort (18% vs. 42%; Pu2009=u20090.010), hunger (44% vs. 67%; Pu2009=u20090.024), and weakness (22% vs. 42%; Pu2009=u20090.034). Regurgitation of gastric contents into the esophagus after endoscopic intubation did not differ between F2 and F8 (26% vs. 19%; Pu2009=u20090.471). There was no case of pulmonary aspiration. Gastric mucosal visibility was normal in most patients either in F2 or F8 (96% vs. 98%; Pu2009=u20090.999).ConclusionsElective upper GI endoscopy after 2xa0hours fasting for clear liquids was more comfortable and equally safe compared to conventional fasting. This preparation might be cautiously applied for patients in regular clinical conditions referred for elective endoscopy.Trial registrationSAMMPRIS ClinicalTrial.gov number, NCT01492296

Elimination of Angiostrongylus costaricensis larvae in feces from experimentally infected Swiss mice: circadian rhythm and correlation with survival.

Angiostrongylus costaricensis is a nematode which harbors mesentery arteries of rodents. In these animals, a circadian rhythm of elimination of first-stage larvae (L1) and a relation between the amount of L1 in feces and survival are unknown. We assessed fecal elimination of A. costaricensis L1 from experimentally infected Swiss mice and tried to correlate L1 elimination with survival. Thirteen Swiss mice were infected by gavage with ten A. costaricensis L3 larvae obtained from Phyllocaulis slugs. Feces were weighed at 7xa0a.m. and 7xa0p.m. starting from the 24th day post-infection until animal death. Feces sediment was examined in microscope for L1 counting. The mice were dead after a period ranging 19–61xa0days post-infection. Compared to diurnal samples, both feces’ weight (2.3u2009±u20090.7 vs. 1.8u2009±u20090.5xa0g; Pu2009<u20090.0001) and L1 total count [median 1,950 vs. 1,250; Pu2009=u20090.015] were higher in feces eliminated at night. No difference was observed between diurnal and nocturnal elimination when counting L1 by gram of feces (725 vs. 650xa0L1/g; Pu2009=u20090.821). A significant correlation was observed between survival and total number of L1 in feces (ru2009=u20090.84; Pu2009=u20090.0007). This study suggests that mice experimentally infected with A. costaricensis eliminate more L1 at night due to higher fecal volume at this period. The correlation between number of L1 in feces and survival suggests a phenomenon of tolerance to A. costaricensis infection in mice with longer survival.

Gastroesophageal Reflux Disease is Inversely Related with Glycemic Control in Morbidly Obese Patients

BackgroundThe link between diabetes mellitus and gastroesophageal reflux disease (GERD) is controversial. We assessed the relationship between glycemic control (GC) and GERD in morbidly obese patients.MethodsConsecutive patients with morbid obesity (nu2009=u200986) underwent manometry, pH-metry, endoscopy, and contrasted X-ray after responding to a GERD questionnaire and dosing fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients with poor GC (HbA1c, 6.1–10% and FPGu2009<u2009140xa0mg/dl) and those with very poor GC (HbA1cu2009>u200910% or FPGu2009>u2009140xa0mg/dl) were compared.ResultsThere were 63 patients with poor GC and 17 with very poor GC. Compared to patients with very poor GC, patients with poor GC showed higher heartburn scores [8 (0–12) vs. 0 (0–4); Pu2009=u20090.003]; higher total esophageal acid exposure [5.2% (2.5–10.5%) vs. 2.3% (0.8–7.5%); Pu2009=u20090.041]; lower distal esophageal amplitude (105u2009±u200938 vs. 134u2009±u200963xa0mmHg; Pu2009=u20090.019); higher expiratory gastroesophageal pressure gradient (GEPG, 7u2009±u20093.4 vs. 5.2u2009±u20093xa0mmHg; Pu2009=u20090.050); lower ventilatory gradient (inspiratory–expiratory GEPG, 10.9u2009±u20093.8 vs. 13.6u2009±u20094.1xa0mmHg; Pu2009=u20090.012); lower waist-to-hip ratio (0.95 vs. 1; Pu2009=u20090.040); and more hiatal hernia (38% vs. 6%; Pu2009=u20090.016).ConclusionsThis study suggests an inverse relation between glycemic control and GERD in morbidly obese patients. This can be partially explained by a lower frequency of hiatal hernia in patients with very poor glycemic control.

Endoscopic augmentation of the esophagogastric junction with polymethylmethacrylate: durability, safety, and efficacy after 6 months in mini-pigs

Background and aimsEndoscopic augmentation of the esophagogastric junction (EGJ) with polymethylmethacrylate (PMMA) has been reported in an experimental short-term study. We assessed whether endoscopic augmentation of the EGJ with PMMA is durable, safe, and efficacious after 6xa0months in mini-pigs.MethodsTen mini-pigs were studied under anesthesia. After a pilot study in two animals, eight mini-pigs underwent lower esophageal sphincter (LES) manometry and gastrostomy with measurement of gastric yield volume (GYV) and gastric yield pressure (GYP). Endoscopic implantation of PMMA was performed aiming for the submucosa of the EGJ. Six months later, LES manometry and GYV and GYP measurements were repeated and animals were sacrificed, followed by microscopic analyses of the EGJ.ResultsOut of 32 implants (four per animal), 29 (91%) were identified as submucosal nodules postmortem. PMMA deposits were found at microscopic analysis in all animals and located as follows [mean (range)]: submucosa 61.5% (37.5–91%), muscularis propria 21.5% (0–58%), mucosa 11% (0–25%), and subserosa 6% (0–17%). Neither esophageal perforation nor death was observed. A significant increase in GYV (1,404 versus 905xa0ml; pxa0=xa00.02) and a borderline increase in GYP (8.1 versus 6.5xa0mmHg; pxa0=xa00.057) were detected 6xa0months later.ConclusionsEndoscopic augmentation of the esophagogastric junction with PMMA was durable and had no complications after 6xa0months. However, the occurrence of implants in the subserosa requires technical refinement before use in clinical trials.