Biomedical subjects
Publications and source records attributed to Donald O Castell.
These epidemiologic studies suggest that gastroesophageal reflux and incompetence of the LES are the most important factors in development of this condition. An unexplained genetic factor must be present, however, to explain the predominance of BE in white middle-aged men.
Gastroesophageal reflux disease (GERD) is a chronic condition that affects a large proportion of the adult population. Persistent untreated GERD can lead to esophageal strictures, premalignant Barrett's esophagus, and an increased risk of adenocarcinoma of the esophagus. Currently, the most effective medical treatment targets gastric acid suppression, allowing healing of erosive/peptic lesions and controlling symptoms. Most patients take over-the-counter medication or are successfully treated by their primary care physician. Gastroenterologists and gastrointestinal surgeons see patients with complications, refractory symptoms despite acid-suppressive therapy, or atypical symptoms. For the medical management of GERD, proton pump inhibitors are potent acid suppressants with favorable side-effect profiles and long-term efficacy and safety. Medical therapy can heal 80% to 100% of patients with erosive esophagitis with 30% to 60% of patients reporting sustained resolution of heartburn. Surgery may be offered to patients with GERD as an alternative to long-term antireflux medication. Careful selection of appropriate surgical candidates is important, and the risk of developing new or recurrent symptoms requiring medication should be disclosed to patients contemplating the surgical alternative.
Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of the distal esophagus yet, the term "diffuse" persists in the medical literature to identify DES. The aim of our study was to assess the diffuse or limited nature of this entity by evaluating the prevalence of simultaneous contractions in both proximal and distal esophagus in patients with DES. We reviewed esophageal motility tracings of 53 consecutive patients (32 F, 21 M) with DES and compared them with 53 age-matched patients with manometric normal studies. In the distal esophagus we found 195 simultaneous contractions (37% of swallows) with a median of 3 and range of 2-7 per patient. Of the 53 patients with DES a total of 13 simultaneous contractions (2% of swallows) occurred in the proximal esophagus with only 3 (5.6%) of the 53 patients having 2 or more simultaneous contractions in 10 swallows. None of the patients with normal manometry showed more than one simultaneous contraction in either proximal or distal esophagus. In conclusion, these findings suggest that the term diffuse esophageal spasm is a misnomer and the DES is more appropriately described as "distal" esophageal spasm.
BACKGROUND & AIMS: Combined multichannel intraluminal impedance and manometry (MII-EM) assesses esophageal function by simultaneous measurement of both pressure and bolus transit. Normative data for this method have not been published. The aim of this study was to establish normative data for combined MII-EM and to correlate liquid and viscous bolus transit by impedance with esophageal contractions by manometry. METHODS: Forty-three normal volunteers recruited from 4 centers (15 women, 28 men; age range, 21-72 years) underwent combined MII-EM with a catheter containing 4 impedance-measuring segments and 4 solid-state pressure transducers. Each center recruited and analyzed subjects independently, according to pre-established criteria. Each subject received 20 x 5 mL swallows, 10 liquid and 10 viscous material. Tracings were analyzed manually for bolus presence time, bolus head advance time, segmental transit times, total bolus transit time, contraction amplitude, duration, and onset velocity. RESULTS: Ninety-seven and four-tenths percent of manometrically normal liquid and 96.1% of manometrically normal viscous swallows had complete bolus transit by impedance. Almost half (47.2%) of manometrically ineffective liquid and 34.7% of ineffective viscous swallows had complete bolus transit, whereas 91.7% of manometric simultaneous liquid swallows and 54.5% of simultaneous viscous swallows had complete bolus transit. More than 93% of normal individuals had at least 80% complete liquid or at least 70% complete viscous bolus transit. CONCLUSIONS: This study establishes normative data for combined MII-EM. Combined MII-EM may be a more sensitive tool in assessing esophageal function compared to standard manometry because impedance can distinguish different bolus transit patterns. Studies in patients with manometrically defined esophageal motility abnormalities should help clarify the functional importance of manometric ineffective and simultaneous swallows.
Gastroesophageal reflux disease (GERD) is a chronic condition requiring long-term treatment. Simple lifestyle modifications are the first methods employed by patients and, because of their low cost and simplicity, should be continued even when more potent therapies are initiated. Potent acid-suppressive therapy is currently the most important and successful medical therapy. Whereas healing of the esophageal mucosa is achieved with a single dose of any proton pump inhibitor (PPI) in more than 80% of cases, symptoms are more difficult to control. Patients with persistent symptoms on therapy should be tested (preferably with combined multichannel intraluminal impedance and pH) for association of symptoms with acid, nonacid, or no GER. Long-term follow-up studies indicate that PPIs are efficacious, tolerable, and safe medication. So far, promotility agents have shown limited efficacy, and their side-effect profile outweighs their benefits. Antireflux surgery in carefully selected patients (ie, young, typical GERD symptoms, abnormal pH study, and good response to PPI) is as effective as PPI therapy and should be offered to these patients as an alternative to medication. Still, patients should be informed about the risks of antireflux surgery (ie, risk of postoperative dysphagia; decreased ability to belch, possibly leading to bloating; increased flatulence). Endoscopic antireflux procedures are recommended only in selected patients and given the relative short experience with these techniques, patients treated with endoscopic procedures should be enrolled in a rigorous follow-up program.
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Multichannel intraluminal impedance (MII) is a new technique for evaluating esophageal function and gastroesophageal reflux. This technique depends on changes in resistance to alternating current between two metal electrodes produced by the presence of bolus inside the esophageal lumen. Combined MII and manometry (MII-EM) provides simultaneous information on intraluminal pressure changes and bolus movement, whereas combined MII and pH (MII-pH) allows detection of pH episodes irrespective of their pH values (ie, acid and non-acid reflux). Combined MII-EM studies are performed very similarly to standard manometry. Based on studies in healthy volunteers and patients, combined MII-EM challenges current existing criteria that define the effectiveness of esophageal body function. Combined MII-pH testing brings a shift in gastroesophageal reflux testing paradigm. In MII-pH studies, reflux events are no longer detected by pH. Refluxate presence, distribution, and clearing are primarily detected by MII and simply characterized as acid versus non-acid based on pH change and as liquid, gas, or mixed based on MII. MII determines refluxate clearance time, whereas pH measures acid clearance time. MII-pH shows promise to become an important clinical tool, particularly to assess gastroesophageal reflux in the postprandial period and in patients with persistent symptoms on therapy and with atypical symptoms.
OBJECTIVE: To define normal values for laryngopharyngeal reflux using an improved catheter design with adjustable electrode placement for pH monitoring. STUDY DESIGN: Cohort study of normal volunteers. METHODS: The setting was an institutional-based gastroenterology practice. Subjects included 20 healthy volunteers with no history of laryngeal, pharyngeal, or reflux symptoms. These included 10 men and 10 women (mean age, 33 y; age range, 26-49 y). Ambulatory 24-hour triple-electrode monitoring of pH in distal esophagus, proximal esophagus, and pharynx using new bifurcated probe was performed. The distal electrode was placed 5 cm above the lower esophageal sphincter, with the proximal two electrodes straddling the upper sphincter. The main outcome measure was the number of true pharyngeal reflux episodes. RESULTS: Sixteen of 20 subjects had no episodes, and 2 subjects had only one episode of pharyngeal reflux. The two subjects exceeding this value (8 and 15 episodes, respectively) had abnormal distal and proximal esophageal reflux. Artifacts for pharyngeal reflux due to acidic meals or "pseudoreflux" were excluded. Subject tolerance of this new probe was excellent. CONCLUSION: The triple-electrode bifurcated adjustable pH probe provides a well-tolerated technique to identify true hypopharyngeal acid reflux episodes. When artifacts produced by meals and pseudoreflux are excluded, 90% of normal subjects show no episodes or a single episode over a 24-hour period.
OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in which the average distal esophageal amplitude is greater than 180 mm Hg. The underlying mechanism responsible for these abnormalities is not known. The aim of this study was to test the hypothesis that NE might be caused by a defect in the inhibitory pathway controlling esophageal peristalsis. METHODS: Eight patients with NE (seven women, 1 man, mean age 50 yr) and eight age- and sex-matched normal volunteers (seven women, 1 man, mean age 48 yr) underwent a special protocol using three-channel (3, 8, and 16 cm above the lower esophageal sphincter) solid state esophageal manometry to evaluate deglutitive inhibition. Ten pairs of 5 ml of wet swallows were given at each of five different time intervals (30, 20, 15, 10, and 5 s). Pairs of swallows were spaced by 30 s, and different time intervals were spaced by 1 min. Tracings were recorded using a computer program and blindly automatically analyzed for both amplitude and duration of the contraction separately for the first and second swallow of each pair. Presence of deglutitive inhibition or muscle refractoriness was assessed according to interactions between the first and second swallow of the pair. Results were found abnormal when larger than the mean percent variation of the second and first swallow calculated for the 30-s interval, considered as baseline for each participant. Statistics included paired and nonpaired nonparametrical comparisons as appropriate. RESULTS: The median amplitude for the NE was 202 mm Hg (range 186-376) and for the controls was 118 mm Hg (range 64-167) (p = 0.0002). The median duration in the NE group was 5.1 s (range 4-9.3) versus 4.1 (range 3.3-5.0) for the controls (p = 0.02). The percent variation in duration (p = 0.31), amplitude (p = 0.42), and propagation velocity of the peristaltic waves (p = 0.69) did not differ between the control and NE groups. Peristalsis frequency dropped at the 5-s interval for both studied groups (p = 0.84). CONCLUSION: Central and local inhibitory mechanisms induced by closely timed swallows are preserved in the NE and do not explain the mechanism of the high amplitude and long duration contractions.
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OBJECTIVE: Although a large body of information exists about the prevalence of gastroesophageal reflux disease (GERD) in general, available data specifically addressing nocturnal reflux are limited. Because nocturnal acid reflux is reported to be associated with more severe injuries such as esophagitis and stricture, as well as adenocarcinoma of the esophagus, a better understanding of the prevalence and impact of nighttime heartburn as a sign of nocturnal acid reflux events can have significant potential management implications. The aims of this study were to determine the prevalence of nighttime heartburn and reflux-attributed supraesophageal symptoms among patients with GERD; and the impact of nighttime heartburn on sleep and several activities of daily living that could affect quality of life. METHODS: A nationwide telephone survey of 1000 adults experiencing heartburn at least once a week was conducted by the Gallup Organization on behalf of the American Gastroenterological Association. RESULTS: Altogether, 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, but only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines, and 49% of these rated this approach extremely effective. CONCLUSIONS: Nighttime heartburn occurs in a large majority of adults with GERD, resulting in sleeping difficulties and impaired next-day function. The expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients.
BACKGROUND: This multicenter prospective study investigated the longer-term (12 month) safety and efficacy of radiofrequency energy delivery for the treatment of GERD. METHODS: A prospective study was conducted of 118 patients with chronic heartburn and/or regurgitation who required antisecretory medication daily and had demonstrated pathologic esophageal acid exposure, a sliding hiatal hernia (<or=2 cm), and esophagitis (<or= grade 2). RF energy was delivered with the Stretta catheter and thermocouple-controlled generator to create thermal lesions below the mucosa at the gastroesophageal junction. GERD symptom scores, quality of life (SF-36), and medication use were assessed at 0, 1, 4, 6, and 12 months; esophageal acid exposure, motility, and endoscopy were assessed at 0 and 6 months. RESULTS: Seventy-two men and 46 women were treated. At 12 months, 94 patients were available for follow-up. There were improvements after 12 months in the median heartburn score (4 to 1, p = 0.0001), GERD score (27 to 9, p = 0.0001), satisfaction (1 to 4, p = 0.0001), mental SF-36 (46.3 to 55.4, p < 0.0001), and physical SF-36 (40.9 to 53.1, p = 0.0001); proton pump inhibitor requirement fell from 88.1% to 30% of patients. Esophageal acid exposure improved significantly (10.2% to 6.4%, p = 0.0001). There were 10 (8.6%) complications, none of which required therapeutic intervention. CONCLUSION: The Stretta procedure significantly improves GERD symptoms, quality of life, and esophageal acid exposure and eliminates the need for antisecretory medication in the majority of patients at 12 months.
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The lower esophageal mucosal ring, or Schatzki's ring, was first described by Templeton. Anatomically, it represents the lower end of the esophagus. Patients classically present with intermittent dysphagia to solids. Diagnosis is made by endoscopy or a barium esophagram. Gastroesophageal reflux disease has been suggested as an etiology. It can usually be treated by passing a large dilator. Further controlled studies are needed to study its cause.
OBJECTIVES: Esomeprazole, the S isomer of omeprazole, has been shown to have higher healing rates of erosive esophagitis than omeprazole. This study compared esomeprazole with lansoprazole for the healing of erosive esophagitis and resolution of heartburn. METHODS: This United States multicenter, randomized, double blind, parallel group trial was performed in 5241 adult patients (intent-to-treat population) with endoscopically documented erosive esophagitis, which was graded by severity at baseline (Los Angeles classification). Patients received 40 mg of esomeprazole (n = 2624) or 30 mg of lansoprazole (n = 2617) once daily before breakfast for up to 8 wk. The primary efficacy endpoint was healing of erosive esophagitis at week 8. Secondary assessments included proportion of patients healed at week 4, resolution of investigator-recorded heartburn, time to first and time to sustained resolution of patient diary-recorded heartburn, and proportion of heartburn-free days and nights. RESULTS: Esomeprazole (40 mg) demonstrated significantly higher healing rates (92.6%, 95% CI = 91.5-93.6%) than lansoprazole (30 mg) (88.8%, 95% CI = 87.5-90.0%) at week 8 (p = 0.0001, life-table estimates, intent-to-treat analysis). A significant difference in healing rates favoring esomeprazole was also observed at week 4. The difference in healing rates between esomeprazole and lansoprazole increased as baseline severity of erosive esophagitis increased. Sustained resolution of heartburn occurred faster and in more patients treated with esomeprazole. Sustained resolution of nocturnal heartburn also occurred faster with esomeprazole. Both treatments were well tolerated. CONCLUSIONS: Esomeprazole (40 mg) is more effective than lansoprazole (30 mg) in healing erosive esophagitis and resolving heartburn. Healing rates are consistently high with esomeprazole, irrespective of baseline disease severity.