Can multichannel intraluminal pH‐impedance monitoring be limited to 3 hours? Comparison between ambulatory 24‐hour and post‐prandial 3‐hour recording

Esophageal multichannel intraluminal pH‐impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post‐prandial 3‐hour recording could predict the results obtained in ambulatory 24‐hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post‐prandial 3‐hour MII was recorded after a test meal, then followed by ambulatory 21‐hour MII. Correlation between the total number of liquid reflux events in the 3‐hour and 24‐hour recordings was elevated (R = 0.71; P < 0.001), with better correlation for acid (R = 0.80; P < 0.001) and weak acid reflux (R = 0.56; P < 0.001) than non‐acid reflux (R = 0.44;P < 0.01). Sensitivity and specificity of 3‐hour recording in detecting elevated liquid reflux over 24 hours (id>75reflux/24h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3‐hour post‐prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24‐hour MII recording.     

Evaluation and management of patients with symptoms after anti‐reflux surgery

Over the past two decades, there has been an increase in the number of anti‐reflux operations being performed. This is mostly due to the use of laparoscopic techniques, the increasing prevalence of gastroesophageal reflux disease (GERD) in the population, and the increasing unwillingness of patients to take acid suppressive medications for life. Laparoscopic fundoplication is now widely available in both academic and community hospitals, has a limited length of stay and postoperative recovery time, and is associated with excellent outcomes in carefully selected patients. Although the operation has low mortality and postoperative morbidity, it is associated with late postoperative complications, such as gas bloat syndrome, dysphagia, diarrhea, and recurrent GERD symptoms. This review summarizes the diagnostic evaluation and appropriate management of such postoperative complications. If a reoperation is needed, it should be performed by experienced foregut surgeons.     

Non‐erosive reflux disease,functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation

Non‐erosive reflux disease (NERD) has emerged as a real entity in the spectrum of gastroesophageal reflux disease (GERD) and may, indeed, represent the most common manifestation of reflux disease. Recent information indicates NERD can be further subclassified based on the results of pH studies and suggests that functional heartburn needs to be differentiated as that subgroup of patients in which there appears to be no relationship between symptoms, however ‘typical’ of GERD, and acid exposure. Other aspects of NERD need to be appreciated, including overlap with functional dyspepsia and the potential variations in response to such therapeutic interventions as acid‐suppressive therapy and fundoplication. It seems quite possible that our failure to separate functional heartburn from NERD, in general, has contributed, in large measure, to diagnostic difficulties and therapeutic disappointment in GERD. An appreciation of the range of entities, of different etiology and pathology, within NERD will foster the development of effective approaches to the assessment and therapy of this challenging disorder.     

The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower‐esophagus of GERD patients

The study aims to determine whether light microscopy can be used to accurately measure the diameters of intercellular spaces between squamous epithelial cells in the lower esophagus, and whether changes in this outcome measure can be used as a diagnostic marker for gastroesophageal reflux disease (GERD). The study has two parts. Part 1 involves 42 asymptomatic controls and 119 patients with typical symptoms of GERD, including 58 with erosive esophagitis (EE), and 61 patients with nonerosive gastroesophageal reflux disease (NERD). All biopsies were taken from the lower esophagus. All samples were observed using an immersion objective, after which diameters were measured by computer‐assisted morphometry. Part 2 involves 61 individuals who were randomly selected from part 1, including 19 controls, 13 with NERD and 29 with EE. Diameter measurements using both light microscopy and transmission electron microscopy (TEM) were performed for samples of 61 individuals. Samples from a total of 61 individuals (31 male, 30 female, mean age 44.3 ± 16.0 years) were observed using both light microscopy and TEM. Both methods showed significant differences between control and disease groups; the outcomes from the two methods had a certain correlation (r = 0.605, P = 0.000). Morphometric analysis of all 161 individuals (83 males, 78 females, mean age 41.4 ± 15.7) showed mean diameters from light microscopy to be 0.58 ± 0.16 µm for controls, 1.07 ± 0.30 µm for NERD, and 1.29 ± 0.20 µm for EE; differences between control and disease groups were significant (P < 0.05). The optimal cut‐off value from receiver operator characteristic analysis was 0.85 µm. Diagnoses were validated using the combination of symptoms of GERD, endoscopy, and 24 h ambulatory pH monitoring as the gold standard. At the optimal cutoff, sensitivity was 93.3% and specificity was 100%. The diameters of the intercellular spaces in squamous epithelium of lower esophagus from controls and in patients with GERD can be quantitatively measured using light microscopy. Dilated diameters can serve as a sensitive, specific, and objective indicator for diagnosis of GERD.     

Association between coffee intake and gastroesophageal reflux disease: a meta‐analysis

Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting patients worldwide, but its risk factors and causes are not clearly known. The aim of this study was to investigate the effect of coffee intake on GERD by a meta‐analysis. We searched online published research databases such as PubMed, EMBASE, and Cochrane Library for studies that were published up to December 2012. These publications were reviewed by two independent authors, and studies that fulfilled the criteria were selected. Whenever there was a disagreement between the authors, a consensus was reached by discussion. Fifteen case–control studies were included in the final analysis. A meta‐analysis showed that there was no significant association between coffee intake and GERD. The odds ratio was 1.06 (95% confidence interval, 0.94–1.19). In subgroup analyses in which the groups were subdivided based on the definition of GERD (diagnosed by endoscopy or by symptoms alone), only the endoscopy group showed a significantly higher odds ratio. In subgroup analyses in which the groups were subdivided based on the amount of coffee intake, quality of study, and assessment of exposure, there was no significant association between coffee intake and GERD.     

High‐resolution manometry findings in symptomatic post‐Nissen fundoplication patients with normal endoscopic configuration

The aim of this study was to investigate high‐resolution manometry (HRM) findings in symptomatic post‐fundoplication patients with normal endoscopic configuration. A retrospective review of a prospectively maintained database was conducted to identify patients who underwent evaluation with HRM and endoscopy for symptom evaluation after previous fundoplication. Study period extends from September 2008 to December 2012. Only patients with complete 360° fundoplication (Nissen) were included, and patients with partial fundoplication were excluded. Patients with endoscopic abnormality or patients who underwent Collis procedure were also excluded. Additionally, contrast study and 24‐hour pH study if done were reviewed. Symptoms were graded using a standard questionnaire with symptoms graded on a scale of 0–3. Symptom grade 2 or 3 was considered a significant symptom. One hundred seventy‐nine symptomatic patients with previous Nissen fundoplication underwent HRM and endoscopy during the study period. Of these, 136 patients were excluded (51 had recurrent hiatal hernia, 2 had disrupted fundoplication, 68 had slipped fundoplication, 10 had twisted fundoplication, 2 had esophageal stricture, and 3 had Collis procedure). Remaining forty‐three patients met inclusion criteria (mean age of 56.0 ± 14.8, 32 females).The most common symptom was dysphagia (67%). Patients with dysphagia had a significantly longer length of distal esophageal high pressure zone (HPZ) and a higher integrated relaxation pressure (IRP) than patients without dysphagia (P = 0.020, 0.049). Especially, patients who had shorter HPZ (≤2 cm) were less likely to have significant dysphagia. Twenty‐three patients (53%) had heartburn. There was no significant difference in HRM findings between patients with and without heartburn. Only 4 of 28 patients with concomitant pH study showed abnormal DeMeester score (>14.7), and there was no correlation between results of pH study and lower esophageal sphincter pressure/length and IRP. Longer HPZ complex length and higher IRP as measured with HRM is associated with post‐Nissen fundoplication dysphagia in patients with normal endoscopic configuration. No HRM parameters are associated with reported heartburn or a positive pH score.     

How to differentiate non‐erosive reflux disease from functional heartburn

Heartburn is a common symptom in gastroesophageal reflux disease. Endoscopic examination can differentiate between reflux esophagitis and non‐erosive reflux disease (NERD), but not between NERD and functional heartburn. With the development of new techniques, more NERD patients could be identified among those previously diagnosed with functional heartburn. Most patients with NERD, however, could be identified based on their clinical characteristics and response to proton pump inhibitors and/or integrated anti‐gastroesophageal reflux therapy.     

MAGNIFYING ENDOSCOPIC FINDINGS OF NON‐EROSIVE REFLUX DISEASE

Magnifying endoscopies have been remarkably developed to visualize the microstructure of gastrointestinal surface mucosa and mucosal vascularity. Close examination is necessary not only for colorectal tumors but also for upper gastrointestinal disease. Magnifying endoscopic observations for a change of capillary vessels in the esophageal epithelium was helpful to diagnose the invasive depth of squamous cell carcinoma. Magnifying endoscopic observations using narrow‐band imaging of capillary vessels in esophageal epithelium is useful for the diagnosis of non‐erosive reflux disease, which cannot be visualized by conventional endoscopy.     

New diagnostic criteria for nutcracker esophagus using conventional water‐perfused manometry: A comparison between nutcracker esophagus with and without gastroesophageal reflux disease

Background and Aim: Controversy continues as to whether nutcracker esophagus (NE) is a ‘real’ manometric disease due to its poor correlation with clinical symptoms such as chest pain or dysphagia. While new NE criteria were proposed in a recent study, that study included NE patients both with and without gastroesophageal reflux disease (GERD). We aimed to analyze both general NE (with or without GERD) and pure NE (without GERD) patients in terms of distal esophageal amplitude (DEA) and its correlation with symptoms. Methods: Using previously known normal DEA values (mean and SD), patients were stratified into three different groups: group A (DEA 180 to 220 mmHg, 2 to 3 SD), B (DEA 220 to 260 mmHg, 3 to 4 SD), and C (DEA > 260 mmHg, > 4 SD). Results: A total of 72 patients who simultaneously underwent esophageal manometry and 24‐h pH monitoring were diagnosed with NE. They were separated into groups A (n = 43), B (n = 18), and C (n = 11). Although the proportion of general NE patients with symptoms appeared to be greater in group A (65.6%) than in group C (90.9%), statistical analysis showed that this was not a significant correlation (P = 0.07). Pure NE patients were defined as those returning negative findings after 24‐h pH monitoring. These patients were separated into three groups based on the same DEA criteria as above: group A‐1 (n = 33), B‐1 (n = 11), C‐1 (n = 8). The proportion of patients with symptoms increased from 54.5% in group A‐1 to 87.5% in group C‐1, and this correlation was found to be significant (P < 0.05). Conclusions: There exists in the general NE population a subset with pure NE. DEA values correlated with symptoms in this subset.     

Exclusion of meal periods from ambulatory 24-hour pH monitoring May improve diagnosis of esophageal acid reflux

Distal esophageal pH less than 4 is frequently seen during meal ingestion in 24-hr ambulatory pH monitoring for the diagnosis of gastroesophageal reflux disease (GERD). The characteristics of this meal-related apparent reflux without diet restriction was evaluated. Data from normal volunteers (N=21) and consecutive patients (N=66) referred with heartburn and/or chest pain were studied with ambulatory pH monitoring. The median percent times pH<4 in the distal esophagus were significantly greater in symptomatic patients than controls for total 24-hr, upright, and supine periods, and postprandial periods of 30, 60, 90, 120, and 150 min (P values of 0.007–0.03). However, the median percent time pH<4 during the meal periods was the same for patients (4.4%) and for controls (6.6%) withP=0.23. Excluding the meal periods from analysis resulted in greater separation between controls and patients with abnormal acid exposure when compared to the conventional method. Patients should maintain their usual routine without diet restriction during 24-hr ambulatory pH studies in the clinical setting. Furthermore, exclusion of meal periods can eliminate meal-time pH variabilities without affecting postprandial acid exposure and improve the diagnosis of GERD.     

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

Objective. A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. Material and methods. Twelve patients (7 M, age range 24–65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25–54 years). Results. In the patients’ group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)±6 (SEM) versus 86±6 and 232 min±16 versus 160±7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): ?22 min (mean); ?10 to ?34 (95% CI) and ?48 min; ?10 to ?85, respectively, decreased both percentage of time at pH?p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R²<0.005). Conclusion. The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.     

Wireless ‘mini’ multichannel intraluminal impedance‐pH: what is the optimal design of a miniature wireless device?

Catheter‐based methods for multichannel intraluminal impedance‐pH monitoring are invasive and uncomfortable. The current alternative is a wireless system that clips to the esophageal mucosa, but which only measures pH. A shorter two‐site wireless sensor that detects impedance and pH, and can be clipped to the esophagus, would be desirable. This study compares sensor positions and separations to determine the optimal configuration of a two‐site wireless sensor. Records of 20 patients (10 on and 10 off proton pump inhibitor) who had ambulatory reflux testing with a multichannel intraluminal impedance‐pH system (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with six impedance and two pH sensors were reviewed. An investigator was blinded to four combinations of impedance channels plus pH. He read a 3‐hour postprandial section from each of the combinations (total of 80 studies) and marked reflux episodes. Results were compared with his own interpretation of the full tracing. Two hundred and two total reflux episodes were analyzed, 113 acid (pH < 4) and 89 nonacid (pH > 4). Mean and median numbers of total reflux episodes were calculated. In the full study, the interpreter detected a mean of 10 reflux episodes per study. In the 5 cm and 7 cm, 3 cm and 7 cm, and 3 cm and 5 cm studies, the interpreter found a mean of 8.1, 11.1, and 9.8 reflux episodes per study, respectively. One‐way analysis of variance yielded a P‐value of 0.43. The trend of these preliminary findings suggests that the 3 cm and 5 cm site is the most sensitive and the 5 cm and 7 cm is the least, with the 3 cm and 7 cm site perhaps as the preferred location. The lack of a significant difference, at the very least, suggests that any of the ‘mini’ locations could be used. The small number of observations could have resulted in a Type II statistical error.     

Stratification and symptom characteristics of non-erosive reflux disease based on acid and duodenogastroesophageal reflux

Background and Aim: The subgroups and symptom characteristics of non‐erosive reflux disease (NERD) based on acid and duodenogastroesophageal reflux may be different in Chinese patients to Western patients. This study aimed to explore the stratification and symptom characteristics of patients with NERD. Methods: Patients with typical heartburn and/or acid regurgitation symptoms were enrolled. Each patient filled out a questionnaire. An upper gastrointestingal endoscopy was performed for each patient followed by simultaneous ambulatory 24‐h esophageal pH and Bilitec (bilirubin) monitoring. A symptom index (SI) of ≥50% was considered to be positive. Results: Eighty‐two consecutive NERD patients were evaluated. Abnormal (NERD pH+) and normal (NERD pH–) 24‐h pH tests were found in 24 (29.3%) and 58 (70.7%) patients, respectively. Among 42 NERD pH– patients who reported heartburn symptoms during monitoring, SI was positive in 19 (45.2%) patients (NE‐SI+) and negative in 23 (54.8%) patients (NE‐SI–). Pathological duodenogastroesophageal reflux (DGER) was found in 43 (52.4%) patients. No significant differences were noted regarding the prevalence of other upper gastrointestinal symptoms, except for acid regurgitation in NERD pH+ and NERD pH– groups. Additionally, no significant differences were seen in the prevalence of other symptoms, except for chest pain, in groups with pathological and normal DGER. Conclusion: The proportion of NERD patients with pathological acid reflux was somewhat lower than that reported in Western countries. The role of DGER in NERD may be important. It is difficult to differentiate whether NERD patients have pathological acid or bile reflux according to symptoms.