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Biomedical subjects

Peter J Kahrilas

Publications and source records attributed to Peter J Kahrilas.

At least 19 recordsLinked to original sources
PubMed2006

Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry.

BACKGROUND & AIMS: The aim of this study was to perform a detailed analysis of the mechanics leading to esophagogastric junction (EGJ) opening during transient lower esophageal sphincter relaxations (tLESRs) using high-resolution manometry coupled with simultaneous fluoroscopy. METHODS: Six subjects without hiatus hernia had endoclips placed at the squamocolumnar junction and 10 cm proximal. A 36-channel solid-state manometric assembly was placed spanning from stomach to pharynx, and subjects were studied for 2 hours after a high-fat meal. An esophageal pH electrode also was placed and fluoroscopy was initiated at the onset of a tLESR. Axial clip movement was measured during replay of the videotaped fluoroscopy and was correlated with manometric data. RESULTS: Ninety-three tLESRs were recorded, 62 tLESRs of which had good fluoroscopic visualization. Seventy-eight tLESRs had manometric evidence of flow and the majority had evidence of a common cavity (88%), but few were detected by the pH electrode. Esophageal shortening and crural diaphragm inhibition always preceded EGJ opening and common cavity. A positive pressure gradient between the stomach and the EGJ lumen of 7.1 mm Hg (interquartile range, 4.1-9.1 mm Hg) preceded the EGJ opening. CONCLUSIONS: Key events leading to the EGJ opening during tLESRs were LES relaxation, crural diaphragm inhibition, esophageal shortening, and a positive pressure gradient between the stomach and the EGJ lumen. The manometric signature of opening was pressure equalization within the EGJ, but this only occasionally was associated with pH evidence of reflux. Future investigations will need to analyze how this delicately balanced anatomic-physiologic system is perturbed in subjects with reflux disease.

Adult↗
PubMed2006

Deglutitive upper esophageal sphincter relaxation: a study of 75 volunteer subjects using solid-state high-resolution manometry.

This study aimed to use a novel high-resolution manometry (HRM) system to establish normative values for deglutitive upper esophageal sphincter (UES) relaxation. Seventy-five asymptomatic controls were studied. A solid-state HRM assembly with 36 circumferential sensors spaced 1 cm apart was positioned to record from the hypopharynx to the stomach. Subjects performed ten 5-ml water swallows and one each of 1-, 10-, and 20-ml volume swallows. Pressure profiles across the UES were analyzed using customized computational algorithms that measured 1) the relaxation interval (RI), 2) the median intrabolus pressure (mIBP) during the RI, and 3) the deglutitive sphincter resistance (DSR) defined as mIBP/RI. The automated analysis succeeded in confirming bolus volume modulation of both the RI and the mIBP with the mean RI ranging from 0.32 to 0.50 s and mIBP ranging from 5.93 to 13.80 mmHg for 1- and 20-ml swallows, respectively. DSR was relatively independent of bolus volume. Peak pharyngeal contraction during the return to the resting state postswallow was almost 300 mmHg, again independent of bolus volume. We performed a detailed analysis of deglutitive UES relaxation with a novel HRM system and customized software. The enhanced spatial resolution of HRM allows for the accurate, automated assessment of UES relaxation and intrabolus pressure characteristics, in both cases confirming the volume-dependent effects and absolute values of these parameters previously demonstrated by detailed analysis of concurrent manometry/fluoroscopy data. Normative values were established to aid in future clinical and investigative studies.

Adult↗
PubMed2006

Quantifying EGJ morphology and relaxation with high-resolution manometry: a study of 75 asymptomatic volunteers.

Our aim was to define normal esophagogastric junction (EGJ) morphology and relaxation characteristics using high-resolution manometry (HRM). To this end, 75 asymptomatic controls underwent HRM with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals positioned to record from the hypopharynx to the stomach. Ten 5-ml water swallows were obtained. EGJ relaxation was quantified by 1) nadir pressure, 2) the lowest 3-s mean residual pressure after swallow (E-sleeve), and 3) the transsphincteric gradient 2-6 s after swallowing measured from 2 cm above to 2 cm below the EGJ. A new parameter, integrated relaxation resistance (IRR), was also calculated. The IRR calculation accounted for both the duration of EGJ relaxation and instantaneous E-sleeve-type relaxation pressures during the entire interval of relaxation. The means and ranges (5-95th percentile) for nadir lower esophageal sphincter relaxation pressure (mean: 3.9 mmHg, range: 0-10.1 mmHg) and E-sleeve relaxation pressure (mean: 8.1 mmHg, range: 4.1-15.1 mmHg) were consistent with previously reported values. The mean relaxation interval was 7.95 +/- 0.2 s (mean +/- SE), whereas the median relaxation pressure during that interval was 10.7 +/- 0.5 mmHg (mean +/- SE). Mean IRR was 1.3 mmHg/s (95th percentile: 3.0 mmHg/s). Mean EGJ length was 3.7 cm. In conclusion, HRM provides a seamless dynamic representation of pressure within and across the EGJ. In addition to providing conventional EGJ relaxation parameters, this technology also creates opportunities to quantify more precise measures of EGJ relaxation and morphology.

Adult↗
PubMed2006

Quantifying esophageal peristalsis with high-resolution manometry: a study of 75 asymptomatic volunteers.

The vastly enhanced spatial resolution of high-resolution manometry (HRM) makes it possible to simultaneous monitor contractile activity over the entire length of the esophagus. The aim of this investigation was to define the essential features of esophageal peristalsis in novel HRM paradigms and establish their normative values. Ten 5-ml water swallows were recorded in each of 75 asymptomatic controls with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals positioned to record from the hypopharynx to the stomach. The data set was then subjected to intensive computational analysis to distill out the essential characteristics of normal peristalsis. Esophageal peristalsis was conceptualized in terms of a proximal contraction, a distal contraction, and a transition zone separating the two. Each contractile segment was quantified in length and then normalized among subjects to summarize focal fluctuation of contractile amplitude and propagation velocity. Furthermore, the temporal and spatial characteristics of the transition zone separating the proximal and distal contraction were quantified. For each paradigm, graphics were developed, establishing median values along with the 5th to 95th percentile range of observed variation. In addition, the synchronization between peristalsis and esophagogastric junction relaxation was analyzed using a novel concept of the outflow permissive pressure gradient. We performed a detailed analysis of esophageal peristalsis aimed at quantifying its essential features and, in so doing, devised new paradigms for the quantification of peristaltic function that will hopefully optimize the utility of HRM in clinical and investigative studies.

Adult↗
PubMed2006

Endoscopic measurement of cardia circumference as an indicator of GERD.

BACKGROUND: It is theorized that repeated gastric distention leads to dilatation of the cardia and the development of GERD. We hypothesize that cardia circumference correlates with the presence and the severity of GERD, and we developed software to measure cardia circumference from static endoscopic images. Our aims were to validate the software and to quantify cardia circumference along the spectrum of GERD. METHODS: Software-based measurements were compared with actual measurements in animal and mechanical models. A retrospective review of an endoscopic database and patient charts produced 273 subjects, grouped as follows: controls, GERD, < or = 3-cm Barrett's esophagus, or > 3-cm Barrett's esophagus. A blinded abstractor measured cardia circumference by using images from the database. RESULTS: Software and actual measurements correlated closely and were reproducible among observers. Median cardia circumference for each group was the following: control, 31.8 mm; GERD, 37.8 mm; < or = 3-cm Barrett's esophagus, 38.4 mm; and > 3-cm Barrett's esophagus, 45.0 mm (p < 0.001). By using 34.3 mm as a cutoff, cardia circumference was 85.3% sensitive and 89.6% specific for the diagnosis of GERD. CONCLUSIONS: There was a direct relationship between cardia circumference and the presence of GERD. This finding augments our understanding of the anatomic contributions of the esophagogastric junction in the pathogenesis of GERD. Cardia measurement may prove to be a useful diagnostic tool.

Animals↗
PubMed2006

EUS characteristics of Nissen fundoplication: normal appearance and mechanisms of failure.

BACKGROUND: In patients who develop symptoms after Nissen fundoplication, the precise mechanism of failure can be difficult to determine. Current testing modalities do not demonstrate sufficient anatomic detail to definitively determine the mechanism. This observational study establishes that EUS can determine fundoplication integrity and hiatal anatomic relationships after Nissen fundoplication. METHODS: EUS was performed on the native esophagogastric junction and after Nissen fundoplication in two swine. The EUS characteristics of a properly performed fundoplication were determined. Subsequently, complications of Nissen fundoplication were created, and EUS was performed on each. The EUS criteria of each mechanism of failure were defined. RESULTS: EUS provided sufficient axial resolution to distinguish the esophagus, the fundoplication, and the surrounding hiatal structures within a single image. US of the native esophagogastric junction discerned the length of intra-abdominal esophagus, esophagogastric junction, crura, and anterior hiatus, and, thus, the point of entry into the abdominal cavity. EUS of Nissen fundoplication revealed a 5-layered pattern in a 360 degree configuration. These layers represent the following: (1) the esophageal wall, (2) the space between the esophagus and the fundoplication, (3) the inner gastric wall of the fundoplication, (4) the gastric lumen, and (5) the outer gastric wall of the fundoplication. A slipped repair was identified by the presence of an echogenic gastric serosa within the fundoplication. A tight fundoplication results in attenuation of the gastric walls, thickening of the esophageal wall, and loss of the 5-layer pattern secondary to obliteration of the potential spaces of the gastric lumen. Dehiscence of the fundoplication was evidenced by a less than 360 degree 5-layer pattern. CONCLUSIONS: EUS of hiatal anatomic relationships is feasible and provides detailed information regarding the integrity and the position of a Nissen fundoplication. EUS may enable a precise determination of the anatomic causes of failure after antireflux surgery.

Animals↗
PubMed2006

Functional esophageal disorders.

Functional esophageal disorders represent processes accompanied by typical esophageal symptoms (heartburn, chest pain, dysphagia, globus) that are not explained by structural disorders, histopathology-based motor disturbances, or gastroesophageal reflux disease. Gastroesophageal reflux disease is the preferred diagnosis when reflux esophagitis or excessive esophageal acid exposure is present or when symptoms are closely related to acid reflux events or respond to antireflux therapy. A singular, well-defined pathogenetic mechanism is unavailable for any of these disorders; combinations of sensory and motor abnormalities involving both central and peripheral neural dysfunction have been invoked for some. Treatments remain empirical, although the efficacy of several interventions has been established in the case of functional chest pain. Management approaches that modulate central symptom perception or amplification often are required once local provoking factors (eg, noxious esophageal stimuli) have been eliminated. Future research directions include further determination of fundamental mechanisms responsible for symptoms, development of novel management strategies, and definition of the most cost-effective diagnostic and treatment approaches.

Animals↗
PubMed2006

Obesity: a challenge to esophagogastric junction integrity.

BACKGROUND & AIMS: The aim of the current study was to analyze the relationship between obesity and the morphology of the esophagogastric junction (EGJ) pressure segment using high-resolution manometry. METHODS: Two hundred eighty-five patients (108 men, aged 18-87) were studied. A solid-state manometric assembly with 36 circumferential sensors spaced 1 cm apart was placed transnasally, and simultaneous intra-esophageal and intragastric pressures were measured over 6-8 respiratory cycles. Separation of the lower esophageal sphincter (LES) and crural diaphragm was quantified by measuring the distance between the two EGJ elements during inspiration. The association between anthropometric variables and pressure values were examined using univariate and multivariate analysis. RESULTS: There was a significant correlation of body mass index (BMI) and waist circumference (WC) with intragastric pressure (inspiration, BMI [r = 0.57], WC [r = 0.62] P < .0001; expiration, BMI [r = 0.58], WC [r = 0.64], P < .0001) and gastroesophageal pressure gradient (GEPG) (inspiration, BMI [r = 0.37], WC [r = 0.43], P < .0001; expiration, BMI [r = 0.24], WC [r = 0.26], P < .0001). Multivariate analysis adjusting for age, gender, and patient type did not alter the direction or magnitude of this relationship. In addition, obesity was associated with separation of the EGJ pressure components (BMI, r = 0.17, P < .005; WC, r = 0.21, P < .001). CONCLUSIONS: Obese subjects are more likely to have EGJ disruption (leading to hiatal hernia) and an augmented GEPG providing a perfect scenario for reflux to occur. Whether or not weight loss can reverse these abnormalities is unknown.

Adolescent↗
PubMed2005

The mechanical basis of impaired esophageal emptying postfundoplication.

Fundoplication (FP) efficacy is a trade-off between protection against reflux and postoperative dysphagia from the surgically altered mechanical balance within the esophagogastric segment. The purpose of the study was to contrast quantitatively the mechanical balance between normal and post-FP esophageal emptying. Physiological data were combined with mathematical models based on the laws of mechanics. Seven normal controls (NC) and seven post-FP patients underwent concurrent manometry and fluoroscopy. Temporal changes in geometry of the distal bolus cavity and hiatal canal, and cavity-driving pressure were quantified during emptying. Mathematical models were developed to couple cavity pressure to hiatal geometry and esophageal emptying and to determine cavity muscle tone. We found that the average length of the hiatal canal post-FP was twice that of NC; reduction of hiatal radius was not significant. All esophageal emptying events post-FP were incomplete (51% retention); there was no significant difference in the period of emptying between NC and post-FP, and average emptying rates were 40% lower post-FP. The model predicted three distinct phases during esophageal emptying: hiatal opening (phase I), a quasi-steady period (phase II), and final emptying (phase III). A rapid increase in muscle tone and driving pressure forced normal hiatal opening. Post-FP there was a severe impairment of cavity muscle tone causing deficient hiatal opening and flow and bolus retention. We conclude that impaired esophageal emptying post-FP follows from the inability of distal esophageal muscle to generate necessary tone rapidly. Immobilization of the intrinsic sphincter by the surgical procedure may contribute to this deficiency, impaired emptying, and possibly, dysphagia.

Adult↗
PubMed2005

Efficacy of rabeprazole in the treatment of symptomatic gastroesophageal reflux disease.

The purpose of this study was to assess the rapidity of symptom relief and 4-week efficacy of rabeprazole 20 mg in patients with moderately severe nonerosive gastroesophageal reflux disease. Data were analyzed from 2 similarly designed, double-blind, placebo-controlled, multicenter, U.S. trials. After a 2-week placebo run-in period, patients (N = 261) were randomized to 4 weeks of rabeprazole 20 mg once daily or placebo. Patients kept symptom diaries and scored symptom severity. Median time to first 24-hour heartburn-free interval was 3.5 days for the rabeprazole group compared with 19.5 days for the placebo group (P < or = .0002). Complete heartburn relief at week 4 was 32% with rabeprazole and 3.8% with placebo (P < or = .001). Rabeprazole also significantly improved other GERD-associated symptoms (e.g., regurgitation, belching, early satiety) by week 4 compared with placebo (P < or = .05). Rabeprazole provides fast and potent relief from heartburn and other symptoms of nonerosive gastroesophageal reflux disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Endoluminal therapy for gastroesophageal reflux disease: is the evidence for efficacy any stronger?

Gastroesophageal reflux disease is a common disorder often requiring chronic treatment. Joining the conventional options of antisecretory medications and fundoplication, endoluminal therapies have emerged in recent years. These techniques have entered US and European markets, claiming effectiveness comparable with antireflux surgery. Nevertheless, a paucity of data is available to support that efficacy, even as more devices are coming onto the market. This review examines published reports of endoluminal reflux therapies from January 2004 to January 2005. After another year, there are still no compelling data supporting the efficacy of any of the available endoluminal treatments.

Esophagoscopy↗
PubMed2005

Prolonged pH monitoring: Bravo capsule.

The Bravo pH monitoring system is a safe and well-tolerated reliable method for measuring esophageal acid exposure. Key potential advantages of this system are related to its ability to be unobtrusive, comfortable, and provide study periods of longer duration. These advantages make it an excellent option for subjects who are unwilling or unable to tolerate conventional catheter pH monitoring. Whether the Bravo capsule improves diagnostic accuracy is still unclear; however, initial results are promising and further validation studies are expected. Whether this method is preferred over conventional monitoring for diagnostic evaluation depends on multiple considerations ranging from cost to possible contraindications for both systems. Further refinements in methodology and recording protocol are likely to be made, which will improve diagnostic accuracy and lower cost.

Catheterization↗
PubMed2005

Pathophysiology of gastroesophageal reflux disease.

From a pathophysiologic viewpoint, GERD results from the excessive reflux of gastric contents into the distal esophagus. Under normal conditions, this is prevented as a function of the antireflux barrier at the EGJ, the integrity of which is dependent on the delicate interplay of a host of anatomic and physiologic factors, including the integrity of the LES, TLESR, and anatomic degradation of the EGJ inclusive of but not limited to hiatus hernia. Considerable investigative focus is aimed at describing the subtle aberrations of the EGJ that may contribute to the root causes of GERD. The net result is an increased number of reflux events, an increasing diversity of potential mechanisms of reflux, and a diminished ability of the stomach to selectively vent gas, as opposed to gas and gastric juice, during TLESR. Once reflux occurs, the duration of resultant esophageal acid exposure is determined by the effectiveness of esophageal acid clearance, the dominant determinants of which are peristalsis, salivation, and, again, the anatomic integrity of the EGJ. Approximately half of patients who have GERD have abnormal acid clearance and the major contributor to this is hiatus hernia. Abnormalities of acid clearance probably are the major determining factor influencing which patients who have GERD are most prone to developing esophagitis as opposed to symptomatic GERD. In summary, GERD is a multifactorial process involving physiologic and anatomic abnormalities. These abnormalities exhibit a complicated interplay that degrades the ability of the EGJ to contain gastric juice within the stomach and to clear the esophagus of gastric juice effectively once reflux has occurred.

Disease Progression↗
PubMed2005

Effectiveness of esophageal dilation for symptomatic cricopharyngeal bar.

BACKGROUND: The cricopharyngeal (CP) bar is an uncommon but important cause of oropharyngeal dysphagia (OPD). Treatment options include CP myotomy, which can be problematic, because CP bars primarily occur in elderly patients who are at higher risk for perioperative complications. The effectiveness of esophageal dilation for patients with symptoms caused by a CP bar is not well studied. METHODS: A review of medical records (1999 to 2002) identified 32 patients with CP bar. Six of these patients who had OPD that could only be attributed to a CP bar underwent EGD and dilation with either over-the-guidewire polyvinyl dilators (5) or a balloon (1). OBSERVATIONS: All 6 patients experienced immediate relief of dysphagia. Five had continued improvement at short-term follow-up (1 to 4 weeks). Three patients still had complete resolution of dysphagia at long-term follow-up (range 8 to 27 months). CONCLUSIONS: CP bar is an important cause of dysphagia in elderly patients. Esophageal dilation of a CP bar can produce long-term relief of dysphagia.

Aged↗
PubMed2005

Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study.

BACKGROUND & AIMS: This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings and determined impact on disability days in a nationally representative US sample. METHODS: A telephone survey of 21,128 adults was conducted including questions about the presence of upper GI symptoms during the past 3 months. Respondents were categorized as symptomatic (ie, reported GI symptoms once per month) or asymptomatic. The survey included questions about missed work, leisure activity, or household activity days. Symptom groupings were identified by using factor analysis, and cluster analysis was used to assign respondents into distinct groups on the basis of these symptom groupings. RESULTS: The prevalence of an average of 1 or more upper GI symptoms during the past 3 months was 44.9%. The most common symptoms experienced during the past 3 months were early satiety, heartburn, and postprandial fullness. Factor analysis identified 4 symptom groupings: (1) heartburn/regurgitation; (2) nausea/vomiting; (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five respondent clusters were identified; the largest clusters were primarily early satiety/fullness (44%) and gastroesophageal reflux disease-like symptoms (28%). Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom profile (4%). Symptomatic respondents reported significantly more missed work, leisure, and household activity days than asymptomatic respondents (all P < .0001). CONCLUSIONS: Factor analysis separated GI symptoms into groupings reflecting gastroesophageal reflux disease and dyspepsia: early satiety, postprandial fullness, and loss of appetite; bloating and abdominal pain/discomfort; and nausea and vomiting. These upper GI symptoms were associated with significant loss of work and activity days.

Adolescent↗
PubMed2005

Four-day Bravo pH capsule monitoring with and without proton pump inhibitor therapy.

BACKGROUND & AIMS: Ambulatory pH testing often is used to guide the management of reflux symptoms that do not respond to proton pump inhibitor (PPI) therapy and to evaluate the contribution of acid reflux to atypical symptoms. Controversy exists as to whether such clinical studies are performed optimally off or on PPI therapy. The aim of the present study was to determine the feasibility of 4-day pH recordings using a pH system that would encompass time periods both before and during PPI therapy. METHODS: Eighteen patients underwent 4-day ambulatory pH testing using 2 separate receivers calibrated to a single Bravo pH capsule. Rabeprazole was administered on days 2-4 of the study (20 mg orally twice a day). RESULTS: Indications for pH testing were refractory heartburn, chest pain, or chronic cough. pH recordings showed that 9 patients (53%) had esophageal acid exposure values that exceeded 4% on day 1 and 7 patients (41%) had values that exceeded 5.3%. Patients showed significant and progressive reductions in acid exposure on days 2-4 of the recording period. Of the 7 patients with quantitatively abnormal levels of acid exposure on day 1, 86% had normalization by day 3. CONCLUSIONS: Prolonged, esophageal pH recordings using the Bravo pH system are feasible and allow for combined testing both off and on a therapeutic trial of PPI. Such studies may allow for the acquisition of complementary information in a single test that may be useful in the management of patients with suspected gastroesophageal reflux disease symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗