Gregory S. Sayuk

Parameters on Esophageal pH-Impedance Monitoring That Predict Outcomes of Patients With Gastroesophageal Reflux Disease

BACKGROUND & AIMS pH-impedance monitoring detects acid and nonacid reflux events, but little is known about which parameters predict outcomes of different management strategies. We evaluated a cohort of medically and surgically managed patients after pH-impedance monitoring to identify factors that predict symptom improvement after therapy. METHODS In a prospective study, we followed up 187 subjects undergoing pH-impedance testing from January 2005 through August 2010 at Washington University in St. Louis, Missouri (mean age, 53.8 ± 0.9 y; 70.6% female). Symptom questionnaires assessed dominant symptom intensity (DSI) and global symptom severity (GSS) at baseline and at follow-up evaluation. Data collected from pH impedance studies included acid exposure time (AET), reflux exposure time (RET) (duration of impedance decrease 5 cm above lower esophageal sphincter, reported as the percentage of time similar to AET), symptom reflux correlation (symptom index and symptom association probability [SAP]), and the total number of reflux events. Univariate and multivariate analyses were performed to determine factors associated with changes in DSI and GSS after therapy. RESULTS Of the study subjects, 49.7% were tested on proton pump inhibitor (PPI) therapy and 68.4% were managed medically. After 39.9 ± 1.3 months of follow-up, DSI and GSS scores decreased significantly (P < .05). On univariate analysis, an abnormal AET predicted decreased DSI and GSS scores (P ≤ .049 for each comparison); RET and SAP from impedance-detected reflux events (P ≤ .03) also were predictive. On multivariate analysis, abnormal AET consistently predicted symptomatic outcome; other predictors included impedance-detected SAP, older age, and testing performed off PPI therapy. Abnormal RET, acid symptom index, or SAP, and numbers of reflux events did not independently predict a decrease in DSI or GSS scores. CONCLUSIONS Performing pH-impedance monitoring off PPI therapy best predicts response to antireflux therapy. Key parameters with predictive value include increased AET, and correlation between symptoms and reflux events detected by impedance.

Learners favour high resolution oesophageal manometry with better diagnostic accuracy over conventional line tracings

Background High resolution manometry (HRM) provides a colourful representation of oesophageal motility. Novice and intermediate learners were tested to compare HRM Clouse plots and conventional manometry for accuracy, ease of interpretation and knowledge retention. Methods 36 learners evaluated 60 randomised motility sequences (30 HRM Clouse plots with corresponding line tracings) 4 months apart, following a tutorial. Learners rated prior knowledge of oesophageal pathophysiology and manometry and scored ease and speed of interpretation on 10 cm visual analogue scales (VAS). Results Understanding of oesophageal pathophysiology was low in all cohorts (2.9±0.4 on VAS) and knowledge of HRM and conventional motility studies was even lower (1.9±0.4 and 1.8±0.3, respectively, p=NS). After the tutorial, diagnostic accuracy was significantly higher with HRM Clouse plots than with line tracings (p<0.001). HRM gains in diagnostic accuracy were evident over line tracings (43.1%), particularly with aperistalsis (36.1%), oesophageal body hypomotility (25.8%) and relaxation of the lower oesophageal sphincter (21.0%) (p<0.001 for each comparison); these were maintained at the second evaluation. Gains were independent of academic level (F=0.56, p=0.5) and did not correlate with prior experience of learners (r=−0.18, p=0.29). Learners favoured HRM Clouse plots (80.6%) over line tracings and reported faster interpretation (94.4%). Conclusions HRM Clouse plots provide ease of interpretation that translates into higher diagnostic accuracy and better knowledge retention in novice and intermediate learners of oesophageal manometry. These results implicate the value of pattern recognition in HRM interpretation, irrespective of academic level and prior understanding of oesophageal motor function.

Measuring symptoms in the irritable bowel syndrome: development of a framework for clinical trials

Aliment Pharmacol Ther 2010; 32: 1275–1291

Impact of Retroflexion Vs. Second Forward View Examination of the Right Colon on Adenoma Detection: A Comparison Study

OBJECTIVES:Although screening colonoscopy is effective in preventing distal colon cancers, effectiveness in preventing right-sided colon cancers is less clear. Previous studies have reported that retroflexion in the right colon improves adenoma detection. We aimed to determine whether a second withdrawal from the right colon in retroflexion vs. forward view alone leads to the detection of additional adenomas.METHODS:Patients undergoing screening or surveillance colonoscopy were invited to participate in a parallel, randomized, controlled trial at two centers. After cecal intubation, the colonoscope was withdrawn to the hepatic flexure, all visualized polyps removed, and endoscopist confidence recorded on a 5-point Likert scale. Patients were randomized to a second exam of the proximal colon in forward (FV) or retroflexion view (RV), and adenoma detection rates (ADRs) compared. Logistic regression analysis was used to evaluate predictors of identifying adenomas on the second withdrawal from the proximal colon.RESULTS:A total of 850 patients (mean age 59.1±8.3 years, 59% female) were randomly assigned to FV (N=400) or RV (N=450). Retroflexion was successful in 93.5%. The ADR (46% FV and 47% RV) and numbers of adenomas per patient (0.9±1.4 FV and 1.1±2.1 RV) were similar (P=0.75 for both). At least one additional adenoma was detected on second withdrawal in similar proportions (10.5% FV and 7.5% RV, P=0.13). Predictors of identifying adenomas on the second withdrawal included older age (odds ratio (OR)=1.04, 95% confidence interval (CI)=1.01–1.08), adenomas seen on initial withdrawal (OR=2.8, 95% CI=1.7–4.7), and low endoscopist confidence in quality of first examination of the right colon (OR=4.8, 95% CI=1.9–12.1). There were no adverse events.CONCLUSIONS:Retroflexion in the right colon can be safely achieved in the majority of patients undergoing colonoscopy for colorectal cancer screening. Reexamination of the right colon in either retroflexed or forward view yielded similar, incremental ADRs. A second exam of the right colon should be strongly considered in patients who have adenomas discovered in the right colon, particularly when endoscopist confidence in the quality of initial examination is low.

Abnormal GERD parameters on ambulatory pH monitoring predict therapeutic success in noncardiac chest pain.

OBJECTIVES:The value of gastroesophageal reflux disease (GERD) indicators (acid exposure time (AET), symptom association probability (SAP), and symptom index (SI)) in predicting therapeutic success in noncardiac chest pain (NCCP) has not been systematically evaluated in outcome studies.METHODS:We retrospectively identified 98 subjects with NCCP (age 51.8±1.2 years, 75 women, mean duration of symptoms 7.3±0.4 years) who underwent pH monitoring off antireflux therapy. Distal esophageal AET (abnormal if ≥4.0%), SAP (measured as Ghillibert probability estimate, abnormal if P<0.05), and SI (abnormal if ≥50%) were calculated; symptom severity and change after therapy were assessed on a 10-point Likert scale. Subjects were interviewed 2.8±0.9 years after the pH study to determine the degree of symptom change (high-degree response (HDR), with definite, sustained symptom improvement) after antireflux therapy. Regression analysis was used to determine the independent predictors of HDR.RESULTS:GERD indicators were present in 61 subjects (62.2%); 52 subjects (53.1%) had abnormal AET, 26 (26.5%) had positive SAP, and 25 (25.5%) had positive SI. With therapy, mean symptom scores improved from 6.3±0.3 at the time of the pH study to 2.9±0.3 at the time of interview (P<0.001). A total of 58 subjects (59.2%) achieved HDR, and another 29.6% had moderate symptom improvement. On univariate analysis, HDR was associated with positive SAP (P=0.003) and elevated AET (P=0.015) but not with demographics, SI, or esophageal motor pattern. In regression analysis containing demographics, GERD indicators, psychiatric comorbidity, and esophageal motor pattern, positive SAP was retained as a significant predictor of HDR (P=0.003); elevated AET trended toward significance (P=0.055). Frequency of HDR was highest when subjects had all three GERD parameters abnormal (93.3% HDR) or both elevated AET and positive SAP (88.2% HDR, P<0.001 compared with only one or no GERD parameter abnormal).CONCLUSIONS:Positive statistical tests of symptom association predict the therapeutic success of GERD management in NCCP. When used hierarchically, response to antireflux therapy is best predicted when GERD parameters are all abnormal and poorest when parameters are normal. These results support the importance of GERD, the relevance of symptom association testing during ambulatory pH monitoring, and the value of intensive antireflux therapy in NCCP.

Diagnosis of esophageal motility disorders: Esophageal pressure topography vs. conventional line tracing

OBJECTIVES:Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT.METHODS:Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder.RESULTS:The total group agreement was moderate (κ=0.57; 95% CI: 0.56–0.59) for EPT and fair (κ=0.32; 0.30–0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65–0.71) for EPT and moderate (κ=0.46; 0.43–0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45–0.50) for EPT and poor to fair (κ=0.20; 0.17–0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4–4.5; P<0.0001), and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT (OR: 3.4; 2.4–5.0; P<0.0001).CONCLUSIONS:Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses were demonstrated with analysis using EPT over CLT among our selected raters. On the basis of these findings, EPT may be the preferred assessment modality of esophageal motility.

Acid-based parameters on pH-impedance testing predict symptom improvement with medical management better than impedance parameters.

OBJECTIVES:pH-impedance testing detects reflux events irrespective of pH, but its value in predicting treatment outcome is unclear. We prospectively evaluated subjects treated medically after pH-impedance testing to determine predictors of symptom improvement.METHODS:Subjects referred for pH-impedance testing completed questionnaires in which dominant symptoms and global symptom severity (GSS) were recorded. Acid-reflux parameters (acid-exposure time, AET; symptom association by Ghillebert probability estimate, GPE; symptom index, SI) and impedance reflux parameters (reflux-exposure time, RET; number of reflux events; GPE and SI with impedance data) were extracted. Symptoms and GSS were prospectively reevaluated after medical therapy. Univariate and multivariate analyses determined predictors of GSS improvement following medical management.RESULTS:Over 5 years, 128 subjects (mean 53.3±1.3 years, 66.4% female; typical symptoms 57.0%, 53.9% tested on therapy) underwent pH-impedance testing and subsequent medical therapy for reflux symptoms, and completed required questionnaires. On follow-up 3.35±0.14 years later, mean GSS declined by 45.0%, with 42.2% patients reporting ≥50% GSS improvement. On univariate analysis, total AET, AET≥4.0%, and GPE for all reflux events predicted both linear and ≥50% GSS improvement, but RET and number of reflux events did not. On multivariate analysis, controlling for testing on or off therapy, only AET (P=0.003) and GPE for all reflux events (P=0.029) predicted GSS improvement.CONCLUSIONS:Acid-based reflux parameters offer greater value over impedance-based nonacid-reflux parameters in predicting symptomatic responses to proton pump inhibitor (PPI) therapy. Our findings support conducting pH-impedance studies off PPI therapy to maximize clinical utility in predicting outcome.

Polysymptomatic, polysyndromic presentation of patients with urological chronic pelvic pain syndrome.

PURPOSE Somatization disorder has been described in several comorbid functional syndromes of urological chronic pelvic pain syndrome, such as irritable bowel syndrome. We investigated whether a subset of patients with urological chronic pelvic pain syndrome may have the polysymptomatic, polysyndromic presentation pattern that is common in somatization disorder. MATERIALS AND METHODS A total of 70 male and female patients with urological chronic pelvic pain syndrome and 35 age matched controls without the syndrome completed a 59-item symptom checklist to assess the classic polysymptomatic, polysyndromic symptom pattern. The 2 operational tools used were the Perley-Guze derived symptom checklist and the somatic symptom algorithm used for Diagnostic and Statistical Manual, 4th Edition, Text Revision somatization disorder criteria. RESULTS Female patients with urological chronic pelvic pain syndrome (interstitial cystitis/bladder pain syndrome) reported significantly more nonpain symptoms and pain symptoms outside the pelvis than control female urology patients (p=0.0016 and 0.0018, respectively). Female patients with urological chronic pelvic pain syndrome were more likely to endorse a polysymptomatic, polysyndromic symptom pattern than female controls (27% vs 0%, p=0.0071). In contrast, male patients with urological chronic pelvic pain syndrome (interstitial cystitis/bladder pain syndrome and/or chronic prostatitis/chronic pelvic pain syndrome) did not report more extrapelvic pain than male controls (p=0.89). Male patients with urological chronic pelvic pain syndrome were not more likely than male controls to have a polysymptomatic, polysyndromic symptom pattern. CONCLUSIONS A subset of female patients with urological chronic pelvic pain syndrome endorses numerous extrapelvic symptoms across multiple organ systems. The checklist may be valuable to assess patients for this polysymptomatic, polysyndromic symptom pattern, which is common in somatization disorder. Recognizing this polysymptomatic, polysyndromic presentation will prompt clinicians to investigate further to determine whether somatization disorder may be an underlying diagnosis in a small subset of patients with urological chronic pelvic pain syndrome who complain of numerous extrapelvic symptoms.

MULTIPLE RAPID SWALLOW RESPONSES SEGREGATE ACHALASIA SUBTYPES ON HIGH RESOLUTION MANOMETRY

Background  Multiple rapid swallows (MRS) inhibit esophageal peristalsis and lower esophageal sphincter (LES) tone; a rebound excitatory response then results in an exaggerated peristaltic sequence. Multiple rapid swallows responses are dependent on intact inhibitory and excitatory neural function and could vary by subtype in achalasia spectrum disorders.

The impact of psychiatric and extraintestinal comorbidity on quality of life and bowel symptom burden in functional GI disorders

Functional gastrointestinal disorders (FGID) patients report poor health‐related quality of life (HRQOL) and experience high rates of psychiatric and extraintestinal functional disorder (EIFD) comorbidity. The independent influence of these comorbidities on HRQOL and symptom burden remains unknown. We sought to determine whether FGID with mood or EIFD comorbidity have poorer HRQOL and greater GI symptom burdens; to determine the influence of comorbidities on HRQOL in FGID independent of bowel symptoms.