Michal M. Szczesniak

Predictors of Outcome in an Open Label, Therapeutic Trial of High-Dose Omeprazole in Laryngitis

BACKGROUND:Gastroesophageal reflux is implicated in some cases of laryngitis. There are no established predictors of response to acid suppression therapy in suspected reflux laryngitis.AIM:In a population with laryngitis, the aim is to determine whether (a) omeprazole 20 mg tds (3 months) improves symptoms and laryngitis, and (b) the outcome in response to potent acid suppression can be predicted by esophageal and/or pharyngeal parameters during ambulatory pH monitoring or by other pretreatment variables.METHODS:From the 70 consecutive patients with laryngitis screened, 20 patients met the inclusion criteria (dysphonia >3 months; laryngoscopically demonstrated laryngitis); and 50 patients were excluded because of one or more criteria indicating alternative causes for laryngeal injury. The primary outcome measure was improvement of at least one level in a 4-point laryngitis grading at 3 months. Twenty-four-hour dual, pharyngo-esophageal pH monitoring was performed at baseline. Secondary outcomes (symptom questionnaire; computerized voice analysis) were measured at baseline, and at 6 and 12 wk.RESULTS:Response rates at 6 and 12 wk were 47% and 63%, respectively. GERD symptoms (heartburn (p= 0.03) and regurgitation (p= 0.0001)) improved. However, neither baseline GERD symptoms nor endoscopic findings predicted laryngoscopic or symptomatic response. Neither baseline laryngitis grade (p= 0.46) nor esophageal acid exposure on pH testing (p= 0.3) predicted outcome. Four of 20 patients demonstrated pharyngeal regurgitation on pH testing, all four of whom responded to potent acid suppression (p= 0.2). Computerized voice measures were not predictive of outcome, although fundamental frequency (Fo) was inversely related to baseline laryngoscopic grade.CONCLUSION:In a carefully defined population of patients with laryngitis (a) 63% have a laryngoscopic response to 3 months of potent acid suppression without significant improvement in laryngeal symptoms; (b) neither voice measures, esophageal acid exposure time, symptoms nor severity of laryngitis predict outcome; and (c) although numbers were small, all patients with a positive pharyngeal pH study responded to therapy and pharyngeal pH-metry may prove useful; (4) available evidence supports an empiric trial of high-dose proton pump inhibitors (PPI), for at least 12 wk, as the initial diagnostic step for suspected reflux laryngitis.

Design of a high-sensor count fibre optic manometry catheter for in-vivo colonic diagnostics

The design of a fibre Bragg grating based manometry catheter for in-vivo diagnostics in the human colon is presented. The design is based on a device initially developed for use in the oesophagus, but in this instance, longer sensing lengths and increased flexibility were required to facilitate colonoscopic placement of the device and to allow access to the convoluted regions of this complex organ. The catheter design adopted allows the number of sensing regions to be increased to cover extended lengths of the colon whilst maintaining high flexibility and the close axial spacing necessary to accurately record pertinent features of peristalsis. Catheters with 72 sensing regions with an axial spacing of 1 cm have been assembled and used in-vivo to record peristaltic contractions in the human colon over a 24hr period. The close axial spacing of the pressure sensors has, for the first time, identified the complex nature of propagating sequences in both antegrade (towards the anus) and retrograde (away from the anus) directions in the colon. The potential to miss propagating sequences at wider sensor spacings is discussed and the resultant need for close axial spacing of sensors is proposed.

Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow‐transit constipation

Sacral nerve stimulation (SNS) is emerging as a potential treatment for patients with constipation. Although SNS can elicit an increase in colonic propagating sequences (PSs), the optimal stimulus parameters for this response remain unknown. This study evaluated the colonic motor response to subsensory and suprasensory SNS in patients with slow‐transit constipation.

Pancolonic spatiotemporal mapping reveals regional deficiencies in, and disorganization of colonic propagating pressure waves in severe constipation

Background  The morphology, motor responses and spatiotemporal organization among colonic propagating sequences (PS) have never been defined throughout the entire colon of patients with slow transit constipation (STC). Utilizing the technique of spatiotemporal mapping, we aimed to demonstrate ‘manometric signatures’ that may serve as biomarkers of the disorder.

In-vivo demonstration of a high resolution optical fiber manometry catheter for diagnosis of gastrointestinal motility disorders

Fiber optic catheters for the diagnosis of gastrointestinal motility disorders are demonstrated in-vitro and in-vivo. Single element catheters have been verified against existing solid state catheters and a multi-element catheter has been demonstrated for localized and full esophageal monitoring. The multi-element catheter consists of a series of closely spaced pressure sensors that pick up the peristaltic wave traveling along the gastrointestinal (GI) tract. The sensors are spaced on a 10 mm pitch allowing a full interpolated image of intraluminal pressure to be generated. Details are given of in-vivo trials of a 32-element catheter in the human oesophagus and the suitability of similar catheters for clinical evaluation in other regions of the human digestive tract is discussed. The fiber optic catheter is significantly smaller and more flexible than similar commercially available devices making intubation easier and improving patient tolerance during diagnostic procedures.

Proximal colonic propagating pressure waves sequences and their relationship with movements of content in the proximal human colon

Abstract  Abnormal colonic motor patterns have been implicated in the pathogenesis of severe constipation. Yet in health, the mechanical link between movement of colonic content and regional pressures have only been partially defined. This is largely due to current methodological limitations. Utilizing a combination of simultaneous colonic manometry, high‐resolution scintigraphy and a quantitative technique for detecting discrete episodic flow, our aim was to examine the propulsive properties of colonic propagating sequences (PS) in the healthy colon. In six healthy volunteers a nasocolonic manometry catheter was positioned to record colonic pressures at 7.5 cm intervals from terminal ileum to the splenic flexure. With subjects positioned under a gamma camera, 30 MBq of 99mTc sulfur colloid was instilled into the terminal ileum, 22.5 cm proximal to the ileocolonic junction. Isotopic images were recorded (10 s/frame) and synchronized with the manometric trace. In the proximal colon we identified 137 antegrade PSs, of which 93% were deemed to be associated temporally with movements of luminal content. Low amplitude PSs, with component pressure waves between 2 mmHg and 5 mmHg, were as likely to be associated with colonic movements as higher amplitude PSs. As such there was no correlation between the amplitude of the PS and the temporal relationship with colonic movements. Within the proximal colon, 24 retrograde PSs were identified, 23 of which were associated with retrograde movements of colonic content. We conclude that proximal colonic PSs are highly propulsive and are a major determinant of proximal colonic flow.

Treatment Efficacy of Sacral Nerve Stimulation in Slow Transit Constipation: A Two-Phase, Double-Blind Randomized Controlled Crossover Study

Objectives:Sacral nerve stimulation (SNS) is a potential treatment for constipation refractory to standard therapies. However, there have been no randomized controlled studies examining its efficacy. In patients with slow transit constipation, we evaluated the efficacy of suprasensory and subsensory SNS compared with sham, in a prospective, 18-week randomized, double-blind, placebo-controlled, two-phase crossover study. The primary outcome measure was the proportion of patients who, on more than 2 days/week for at least 2 of 3 weeks, reported a bowel movement associated with a feeling of complete evacuation.Methods:After 3 weeks of temporary peripheral nerve evaluation (PNE), all patients had permanent implantation and were randomized to subsensory/sham (3 weeks each) and then re-randomized to suprasensory/sham (3 weeks each) with a 2-week washout period between each arm. Daily stool dairies were kept, and quality of life (QoL; SF36) was measured at the end of each arm.Results:Between November 2006 and March 2012, 234 constipated patients were assessed, of whom 59 were willing and deemed eligible to participate (4 male; median age 42 years). Of the 59 patients, 16 (28%) responded to PNE. Fifty-five patients went on to permanent SNS implantation. The proportion of patients satisfying the primary outcome measure did not differ between suprasensory (30%) and sham (21%) stimulations, nor between subsensory (25%) and sham (25%) stimulations. There were no significant changes in QoL scores.Conclusions:In patients with refractory slow transit constipation, SNS did not improve the frequency of complete bowel movements over the 3-week active period.

Twenty‐four hour spatiotemporal mapping of colonic propagating sequences provides pathophysiological insight into constipation

Abstract  Colonic propagating sequences (PS)s are a major determinant of luminal propulsion. A global appreciation of spatiotemporal patterning of PSs requires evaluation of 24 h pan‐colonic recordings, a difficult task given that PSs are relatively infrequent events that are not uniformly distributed throughout the colon. Here we developed a means of space‐time‐pressure ‘mapping’ in a condensed format, 24 h of colonic recording in such a manner that readily permits an overall view of colonic antegrade and retrograde colonic PSs within a single figure. Such graphical representation readily permits appreciation and identification of aberrant patterns in severe constipation and may be an important clinical and research tool in the assessment of colonic motor disorders.

Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation

BACKGROUND AND AIMS the neural mechanisms of distension-induced esophagoupper esophageal sphincter (UES) reflexes have not been explored in humans. We investigated the modulation of these reflexes by mucosal anesthesia, acid exposure, and GABA(B) receptor activation. In 55 healthy human subjects, UES responses to rapid esophageal air insufflation and slow balloon distension were examined before and after pretreatment with 15 ml of topical esophageal lidocaine, esophageal HCl infusion, and baclofen 40 mg given orally. In response to rapid esophageal distension, UES can variably relax or contract. Following a mucosal blockade by topical lidocaine, the likelihood of a UES relaxation response was reduced by 11% (P < 0.01) and the likelihood of a UES contractile response was increased by 14% (P < 0.001) without alteration in the overall UES response rate. The UES contractile response to rapid esophageal air insufflation was also increased by 8% (P < 0.05) following sensitization by prior mucosal acid exposure. The UES contractile response, elicited by balloon distension, was regionally dependent (P < 0.05) (more frequent and of higher amplitude with proximal esophageal distension), and the response was attenuated by topical lidocaine (P < 0.05). Baclofen (40 mg po) had no effect on these UES reflexes. Abrupt gaseous esophageal distension activates simultaneously both excitatory and inhibitory pathways to the UES. Partial blockade of the mucosal mechanosensitive receptors permits an enhanced UES contractile response mediated by deeper esophageal mechanoreceptors. Activation of acid-sensitive esophageal mucosal chemoreceptors upregulates the UES contractile response, suggestive of a protective mechanism.

Optimal criteria for detecting bolus passage across the pharyngo-oesophageal segment during the normal swallow using intraluminal impedance recording

Abstract  The impedance criteria for the detection of the arrival of bolus head and clearance of bolus tail in the pharynx have not been defined, and may differ from accepted criteria used in the oesophagus. Our aim was to define the optimal impedance criteria that most accurately defined passage of the swallowed bolus moving through the pharyngo‐oesophageal segment. In eight healthy volunteers, an assembly incorporating seven impedance‐measuring segments was positioned across the pharyngo‐oesophageal segment, and subjects swallowed liquid and semisolid radio‐opaque boluses (2–20 mL) while impedance was simultaneously recorded with videofluoroscopic images. To derive the optimal criteria, in an iterative process we correlated impedance defined bolus presence with fluoroscopy (Cohen’s Kappa) for a range of impedance cut‐off values from 100% to 0% for both the initial fall, and recovery of impedance. Bolus presence in the pharynx, as determined by the ‘standard’ criteria (50% drop and recovery to 50% of baseline), correlated very modestly with videofluoroscopy (κ≈0.35). The criteria that most accurately defined bolus passage varied between pharyngeal regions. Threshold (% of baseline) for bolus head entry into the region ranged from 71% to 80%. Threshold for bolus tail clearance varied from nadir to 19%. Correlation of impedance with videofluoroscopy improved to κ≈0.6 with the above criteria. The impedance criteria defining bolus presence across the pharyngo‐oesophageal segment differ from those adopted in the oesophagus. Pharyngeal impedance provides an accurate, non‐radiological indicator of bolus transit through the pharynx.