Gokulakrishnan Balasubramanian

Prevalence and Predictors of Columnar Lined Esophagus in Gastroesophageal Reflux Disease (GERD) Patients undergoing upper endoscopy

OBJECTIVES:Chronic gastroesophageal reflux disease (GERD) is a risk factor for Barretts esophagus (BE), the most important surrogate marker for the development of esophageal adenocarcinoma (EAC). The need to document the presence of intestinal metaplasia in esophageal biopsies from a columnar lined esophagus (CLE) to diagnose BE is debated. The objective of this study was to prospectively evaluate the prevalence and risk factors of CLE in a large cohort of GERD patients undergoing upper endoscopy.METHODS:Consecutive patients presenting to the endoscopy unit at a tertiary referral center for their index upper endoscopy for evaluation of GERD symptoms were enrolled in this prospective cohort study. Patients were asked to complete a validated GERD questionnaire that documents the onset of GERD symptoms (heartburn and acid regurgitation) and grades the frequency and severity of symptoms experienced over the past year. Demographic information, body mass index, and use of aspirin/nonsteroidal antiinflammatory drugs were recorded. Endoscopic details including length of CLE, presence and size of hiatal hernia were noted. Patients with CLE (cases) were compared with those without CLE (controls) using Fischers exact test and t-test. All factors that were statistically significant (P<0.05) were then entered into stepwise logistic regression to evaluate for independent predictors of CLE.RESULTS:A total of 1058 patients with GERD symptoms were prospectively enrolled. On index endoscopy, the prevalence of CLE was 23.3%, whereas of CLE with documented intestinal metaplasia was 14.1%. On univariate analysis, male gender, Caucasian race, heartburn duration of >5 years, presence and size of hiatal hernia were significantly associated with the presence of CLE compared with controls (P<0.05). On multivariate analysis, heartburn duration >5 years (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.07–2.09, P=0.01), Caucasian race (OR: 2.40, 95% CI: 1.42–4.03, P=0.001), and hiatal hernia (OR: 2.07, 95% CI: 1.50–2.87, P<0.01) were found to be independent predictors for CLE. CLE length was significantly associated with the presence of intestinal metaplasia (P<0.001).CONCLUSIONS:If BE is defined by the presence of CLE alone on upper endoscopy, up to 25% of GERD patients are diagnosed with this lesion. Enrolling all these patients in surveillance programs would have significant ramifications on health-care resources.

Clinical utility and interobserver agreement of autofluorescence imaging and magnification narrow-band imaging for the evaluation of Barrett's esophagus: a prospective tandem study

BACKGROUND New endoscopic imaging techniques, such as autofluorescence imaging (AFI) and narrow-band imaging (NBI), have been developed to improve the detection of neoplastic lesions in Barretts esophagus (BE). OBJECTIVE To evaluate the clinical utility of AFI and magnification NBI to detect high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) and the interobserver agreement. DESIGN Prospective tandem study of eligible patients. SETTING Single, academic tertiary care center. PATIENTS Forty-two patients with a history of confirmed BE were prospectively enrolled. INTERVENTIONS The BE segment was examined under high-definition white-light endoscopy, and the presence of visible lesions was recorded. Subsequently, AFI and magnification NBI were performed in tandem on areas of the BE segment away from visible lesions; images obtained by these 2 systems were graded according to the color of reflected light and surface patterns, respectively. Biopsy specimens were obtained at the end of the procedure. MAIN OUTCOME MEASUREMENTS The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the AFI and NBI patterns for the detection of HGD/EAC and interobserver agreement. RESULTS Of the 42 patients enrolled, 14 (33%) had HGD/EAC. On patient-based analysis, AFI alone had a sensitivity, specificity, and NPV of 50%, 61%, and 71%, respectively, and the overall accuracy for the detection of HGD/EAC patients was 57%. By using magnification NBI in tandem fashion, the sensitivity and NPV improved to 71% and 76%, respectively, with a decrease in specificity to 46% and in overall accuracy to 55%. The 2 techniques had moderate interobserver agreement for both the patterns and prediction of histology. LIMITATIONS Uncontrolled study performed at an academic center by expert endoscopists in a high-risk population. CONCLUSIONS By using a multimodality endoscope, both AFI and magnification NBI had limited clinical accuracy and moderate overall interobserver agreement. AFI does not appear to be useful as a broad-based technique for the detection of neoplasia in patients with BE.

Cigarette smoking is a modifiable risk factor for Barrett's oesophagus.

Background Cigarette smoking has been associated with an increased risk of oesophageal adenocarcinoma (OAC). However, the impact of smoking and more importantly smoking cessation on Barrett’s oesophagus (BO) is unclear. Objective The aim of the study is to evaluate the association between cigarette smoking and presence of BO in a large prospective cohort of patients with gastro-oesophageal reflux disease (GORD). Methods Patients presenting to the endoscopy unit for upper endoscopy completed a validated GORD questionnaire and information on demographics (age, gender, and ethnicity), cigarette smoking [status (current/past), amount (pack years) and duration of smoking cessation], clinical data [medication history, body mass index (BMI), and family history] and endoscopic findings [BO and hiatal hernia] were recorded. Cigarette smokers (current and past) and nonsmokers were compared using Fisher’s Exact test for categorical variables and Mann–Whitney test for continuous variables. Effects of cigarette smoking and smoking cessation on BO risk was assessed by stepwise logistic regression analysis. Results A total of 1056 patients were included in the analysis [mean age: 57.2 ± 12.7years, Caucasian 880 (83.3%), male 985 (93.3%), and mean BMI 29.6 (SD: ± 5.6)]. 827 (78.3%) were smokers and 229 (21.6%) were nonsmokers. 474 subjects (44.9%) had a previous history of smoking. Anytime smokers were more likely to have BO (adjusted OR: 3.3; 95 CI: 1.7–6.3; p < 0.01). Higher smoking burden (pack years) was associated with higher risk of BO in this GORD cohort (p for trend < 0.01). Duration of smoking cessation was inversely associated with risk of BO (p for trend: 0.01). Conclusion This study shows that smokers with reflux symptoms have about threefold higher risk of BO compared with nonsmokers, whereas discontinuing smoking is associated with a significant reduced risk. Smoking cessation appears to be a viable option to reduce BO risk in patients with reflux disease.

Characterization of pharyngeal peristaltic pressure variability during volitional swallowing in healthy individuals

Recent technological advances incorporated in high resolution manometry have justifiably heightened interest in manometric evaluation of the pharynx. Despite this interest, from both physiologic and clinical perspective there remain a number of unanswered questions regarding the magnitude of variability of pharyngeal pressure phenomena. Therefore, the aim of the present study was to characterize in healthy individuals the inter‐subject and recording‐site specific variability of pharyngeal peristaltic pressure phenomena.

Tu1117 Recurrence of Disease After Endoscopic Eradication Therapy (Eet) for Barrett's Esophagus (BE) With High Grade Dysplasia (HGD) and Early Cancer (EC)

G A A b st ra ct s high-risk, post-treated high-risk and post-treated low-risk patients (Fig. 1). For post-treated patients, a logistic regression model was developed using the most sensitive parameter of intra-nuclear uniformity, andwewere able to detect the high-risk patients with 88% sensitivity and 50% specificity. Conclusion: The optical analysis of gastric cardia can discriminate high-risk patients with esophageal dysplasia from low-risk patients after endoscopic therapy. It may serve as a novel biomarker for risk assessment or predicting the response to endoscopic therapy through examination of uninvolved gastric cardia. Given the decreased mucosal disruption with such sampling, this technique may also prove useful as a way to collect diagnostic information during the same endoscopy as an ablative session, thus decreasing the need for interval surveillance procedures. While these results are encouraging, future experiments using brushings from the GE junction may yield improved performance.

Pharyngeal Peristaltic Pressure Variability, Operational Range and functional Reserve

The present understanding of pharyngeal motor function remains incomplete. Among the remaining gaps of knowledge in this regard is the magnitude of variability of pharyngeal peristaltic pressure amplitude. Although variability can pose difficulty in interpretation of manometric findings, its magnitude can inform the operational range and reserve of the pharyngeal contractile function. We aimed to define the intra- and intersubject and intersession variability of select pharyngeal manometric parameters and, using this information, determine the number of swallow repetitions for acquiring reliable pharyngeal manometric data. We recorded pharyngeal peristalsis in 10 healthy subjects (age: 50 ± 25 yr, 5 women) by high-resolution manometry during two separate sessions of 20 sequences of 0.5-ml water swallows. Two-way ANOVA showed significant variation in the mean peak peristaltic pressure value across sites (P < 0.0001) as well as within the data at each site (P < 0.0001). Similarly, the pharyngeal contractile integral exhibited significant inter- (P = 0.003) and intrasubject (P < 0.001) variability. The Shapiro-Wilk normality test showed mixed results, in that some sites showed normally distributed data, whereas others did not. A robust Monte Carlo simulation showed that the nominal sample size was different for various tested metrics. For a power of 0.8, commonly accepted as an adequate threshold for acceptable statistical power, the optimal sample size for various peristaltic parameters ranged between 3 and 15. There is significant intra- and intersubject variability in site-specific and integrated parameters of pharyngeal peristalsis. The observed variance indicates a significant operational range and reserve in pharyngeal contractile function while necessitating parameter-specific sample size for reliable results.NEW & NOTEWORTHY Intra- and intersubject variability are significant and different at various sites within the contractile pharynx. In addition, significant swallow-to-swallow and subject-to-subject variability exists in pharyngeal contractile integral. The range of intrasubject variability indicates the existence of broad operational range and reserve. Lastly, our variability studies informed Monte Carlo and power analyses, yielding estimates of sample size that would ensure accurate representation of pressure metric variability.

841 Variability of Pharyngeal Peristaltic Pressure Parameters Measured by High Resolution Manometry (HRM); A Study of Over 900 Pressure Signatures

Introduction: With the many alluring features of HRM including superior spatial resolution and rapid recording frequency, interest in manometric evaluation of the pharynx during swallowing has been renewed. However, crucial information about the physiologic variability of pharyngeal peristaltic pressure wave parameters is scarce. These data are vital for developing normative data and correct interpretation of pharyngeal manometry results. The aims of the present study were to determine: 1) the variability of pharyngeal peristaltic pressure wave amplitude and duration between swallows at various distances from the upper esophageal sphincter (UES) and 2) Pharyngeal Contractile Integral(PCI),hypo-pharyngeal intra-bolus pressure(IBP) and nadir UES pressure(N-UESP) for a range of swallowed volumes. Methods: We studied seven healthy individuals (age:51±25 years, 6F) in upright head neutral position using a high resolution manometry catheter with 36 recording sites positioned trans-nasally such that pressure was recorded from the entire pharynx, UES and proximal esophagus. In each subject, we tested three repetitions each of dry and room temperature 0.5,5 and 10ml water at 20-30second intervals. Statistical analysis included ANOVA, Kruskal-Wallis Testing, Bartletts Test of variance, Conovers Squared Rank Test of Variance and the coefficient of variation. Results: Spatial variation of the peak peristaltic pressure wave amplitude showed significant difference in variance across locations 2, 3, 4, 5, 6, 7 and 8cm above the upper margin of the UES high pressure zone (umUESHPZ) for dry(p=0.043), 0.5 (p=0.006) and 5ml (p=0.049)swallows (table). There was significant variability in the peak amplitude between swallows at all sites as seen by the standard deviation bars in the figure (representative example for 5ml swallows). The smallest degree of variability across sites was seen at p6 (6 cm above the umUESHPZ) shown in the figure as circles representing the coefficients of variation. Variance due to volume effects also showed significant differences; however, these difference in variance were confined only to sites 3 (p=0.015), 4 (p=0.020) and 6 (p=0.022) cm above the umUESHPZ. In contrast, PCI and IBP showed similar variability for the tested swallow volumes. Conclusions: 1) Parameters of pharyngeal peristaltic pressure wave vary significantly from one swallow to the other for dry and water swallows,2) this variability is significantly different for different locations across the pharynx. 3) these findings should be taken into account for defining normative data and using pharyngeal manometry for clinical purposes. Supported in part by R01DK025731 and P01DK068051.

Case Report: Functional paraganglioma

Paraganglioma are tumours arising from neural crest cells of the sympathetic and parasympathetic paraganglia. Functional paraganglioma presents with symptoms of catecholamine excess that includes hypertension, flushing, diaphoresis, etc. Non-functional paraganglioma are usually found incidentally during imaging studies. Early diagnoses of functional paraganglioma are important because their removal is often curative. We present the case of a young man who presented with hypertensive crisis and severe headache, who was later found to have functional paraganglioma.

Defining pharyngeal contractile integral during high-resolution manometry in neonates: a neuromotor marker of pharyngeal vigor

BackgroundPharyngeal contractility is critical for safe bolus propulsion. Pharyngeal contractile vigor can be measured by Pharyngeal Contractile Integral (PhCI): product of mean pharyngeal contractile amplitude, length, and duration. We characterized PhCI in neonates and examined the hypothesis that PhCI differs with mode of stimulation.MethodsNineteen neonates born at 38.6 (34–41) weeks gestation were evaluated at 42.9 (40.4–44.0) weeks postmenstrual age using high-resolution manometry (HRM). PhCI was calculated using: (a) Conventional and (b) Automated Swallow Detection algorithm (ASDA) methods. Contractility metrics of all pharyngeal regions were examined using mixed statistical models during spontaneous and adaptive state (pharyngeal and oral stimulus) swallowing.ResultsPhCI of oral stimuli swallows were distinct from pharyngeal stimuli and spontaneous swallows (P < 0.05). Correlation between conventional and ASDA methods was high (P < 0.001). PhCI increased with swallows for pharyngeal stimulation (P < 0.05) but remained stable for swallows with oral stimulation. PhCI differed between proximal and distal pharynx (P < 0.001).ConclusionsPhCI is a novel reliable metric capable of distinguishing (1) proximal and distal pharyngeal activity, (2) effects of oral and pharyngeal stimulation, and (3) effects of prolonged stimulation. Changes in pharyngeal contractility with maturation, disease, and therapies can be examined with PhCI.

Swallow strength training exercise for elderly: A health maintenance need

Recent studies have shown high prevalence of oropharyngeal dysphagia associated with frailty‐ and age‐related muscle weakness. Strength training exercises have been advocated for locomotive health maintenance in the elderly and have shown positive outcomes. As muscles involved in oropharyngeal phase of swallowing are also comprised of striated muscles, the aim of this study was to determine biomechanical effect of a novel resistance exercise program, Swallowing Against Laryngeal Restriction (SALR), on pharyngeal phase swallowing in the healthy elderly.