Myenteric plexus abnormalities associated with epiphrenic diverticula.

OBJECTIVE: To (1) categorize histologic esophageal myenteric plexus abnormalities in patients undergoing surgical treatment for epiphrenic diverticulum, and (2) correlate histologic changes with associated esophageal motility disorders and hiatal hernia. METHODS: From January 1987 to May 2008, 40 patients had surgery for epiphrenic diverticulum. Esophageal manometry was abnormal in 29 (73%); 23 (58%) had hiatal hernia. Esophageal muscle specimens were evaluated for ganglion cell number, myenteric inflammations and myenteric fibrosis. RESULTS: Myenteric plexus abnormalities were present in 31 (78%). Ganglion cells were reduced in 8 (20%) and absent in 13 (33%). Myenteric inflammation was present in 21 (53%) and myenteric fibrosis in 9 (23%). Abnormalities were seen in 10 (83%) with motility disorders only, 5 (83%) with hiatal hernia only, 13 (76%) with both, and 3 (60%) with neither. Abnormalities in diffuse esophageal spasm (n=3) were similar to those of achalasia (n=14). Ineffective esophageal motility (n=6) was strongly associated with hiatal hernia, and abnormalities were similar to those of hiatal hernia without motility disorders (n=6). All patients with nutcracker esophagus (n=3) had hiatal hernia and histologic abnormalities, and two patients with hypertensive lower esophageal sphincter (n=3, hiatal hernia in 2) had myenteric inflammation. CONCLUSIONS: Myenteric plexus abnormalities predominate in epiphrenic diverticulum. Disease-specific patterns exist, but are incomplete. These associations and patterns point to causes of distal obstruction, with some commonality. In the absence of associated disorders, myenteric plexus abnormalities may be the sole finding. Isolated epiphrenic diverticulum is uncommon and may reflect an inability to detect abnormalities by current investigative techniques.

Does diffuse esophageal spasm progress to achalasia? A prospective cohort study.

Diffuse esophageal spasm (DES) and achalasia share both clinical and manometric characteristics. Some reports support the notion of progression of DES to achalasia. However, there are currently no prospective data in support of this theory. To assess prospectively the rate of manometric progression of DES to achalasia. Manometry tracings of DES patients diagnosed between 1992 and 2003 were independently reviewed blindly and agreed on by two esophageal experts. Patients with DES who agreed to undergo repeat esophageal manometry constituted the study cohort. Follow-up manometry tracings were evaluated blindly and independently by the same two interpreters to determine the rate of manometric progression to achalasia. Predictors of manometric progression were assessed. A total of 32 patients were diagnosed with DES between 1992-2003. Twelve patients (9M/3F; median age 62 years) agreed to participate and underwent second manometry (mean +/- SD follow-up of 4.8 +/- 3.4 years). Achalasia was diagnosed on follow-up manometry in one patient (8%), seven (58%) patients continued to have DES, three (25%) had normal motility, and one (8%) had nutcracker esophagus. There were no predictors of progression to achalasia based on the initial manometry parameters. A subgroup of DES patients with initial low esophageal body amplitude developed increase in esophageal simultaneous contractions on follow-up similar to the patient who evolved to achalasia. Following were the results. 1) Progression from DES to achalasia is uncommon. 2) DES patients with low esophageal body amplitude may develop increased simultaneous contractions over time. 3) DES remains an elusive diagnosis clinically and manometrically.

Esophageal manometry: assessment of interpreter consistency.

BACKGROUND AND AIMS: Manometry is used widely in the evaluation of esophageal disorders. Our aim was to assess the intra- and interobserver reliability of esophageal manometry and identify potential causes for diagnostic variability. METHODS: Seventy-two esophageal manometry tracings were selected randomly from archives. Eight interpreters randomly and blindly evaluated tracings. Interpreters were divided into 3 groups: highly experienced (N = 3), moderately experienced (N = 3), and inexperienced (N = 2). Each tracing was examined for abnormalities involving the lower-esophageal sphincter (LES) and esophageal body. Interpreters rendered a single diagnosis from a list of 7 manometric diagnoses: normal, nutcracker, hypertensive LES, hypotensive LES, diffuse esophageal spasm (DES), nonspecific/ineffective esophageal motility (IEM), and achalasia. Intra- and interobserver agreements were determined and reasons for varied diagnoses were investigated. RESULTS: Overall intraobserver agreement was good (kappa = .63, P < .0001). There was no difference ( P = .9) between the highly and midexperienced interpreters (kappa = .61 and .65, respectively). Interobserver agreement for the diagnosis of achalasia and normal motility was good (kappa = .65 and .56, respectively). However, other manometric diagnoses yielded only fair interobserver agreement (kappa = .27). DES, nonspecific/ineffective esophageal motility (IEM), and hypo- and hypertensive LES diagnoses showed the least agreement. Poor adherence to established manometric criteria, misinterpretation of intrabolus pressure, and technical inadequacy were the most common sources of inconsistency in interpretations. CONCLUSIONS: Manometric diagnoses of conditions other than normal or achalasia are variable and have poor interobserver variability. Given their uncertain clinical implications, we must either redefine them or eliminate them from practice.

Multichannel intraluminal impedance accurately detects fasting, recumbent reflux events and their clearing.

Multichannel intraluminal impedance (MII) is a new diagnostic test for gastroesophageal reflux disease (GERD). The objective of this report is to determine the accuracy of MII in detecting individual reflux events (REs) identified by pH probe and manometry, as well as their clearing in patients with severe GERD compared with normal volunteers. Ten severe GERD patients and 10 normal volunteers underwent simultaneous manometry [7 sites: gastric, lower esophageal sphincter, esophagus (4), pharynx], pH, and MII (6 sites in esophagus) for 15 min in the left and right recumbent posture while fasting. We found that patients had 30-fold more REs than normal volunteers (41 +/- 11 vs. 1.3 +/- 0.4), and 95% of all REs were detected by MII. An average 15-fold fall in impedance with liquid and fivefold rise with gas made REs and their composition easy to detect with MII. In the right recumbent posture, nearly all REs detected by MII were liquid (98%, 98/100). In contrast, all 283 REs detected by MII in the left recumbent posture were gas. Nearly all REs detected by MII were cleared (98%, 368/374). Mean acid clearing time was threefold longer (47 s) than clearing time by either manometry (15 s) or MII (13 s), primarily due to acid rereflux, i.e., additional acid REs during acid clearing. We conclude that MII is accurate in detecting REs identified by manometry and/or pH probe, their composition, and their clearing.

Acid rereflux: a review, emphasizing detection by impedance, manometry, and scintigraphy, and the impact on acid clearing pathophysiology as well as interpreting the pH record.

Acid clearing, the interval while intraesophageal pH is < 4 after a traditional acid reflux event (RE), is a potential "blind spot" during pH monitoring, when reflux of acidified gastric contents may occur undetected by the pH probe. This is termed "acid rereflux." Acid rereflux comprised 61% (169/262) of acid REs in recumbent postprandial patients with severe GERD in two reports using simultaneous pH monitoring and manometry as well as multichannel intraluminal impedance (MII) in one, and scintigraphy in the other. Acid rereflux events often recurred with short intervals between them. The pH probe alone was insufficient to detect most acid rereflux REs, since expanding pH criteria for an acid RE (> 1 unit fall while pH < 4) detected only 35% of acid rereflux REs. When a variety of patients and study conditions was examined, simultaneous manometry-pH monitoring found more frequent acid rereflux in the following situations: (1) patients with vs those without esophagitis; (2) recumbent vs upright posture, and (3) postprandial vs preprandial. Of pathophysiologic importance, acid rereflux in the blind spot is the most common cause of prolonged daytime acid REs in GERD patients. Of clinical importance, the 24-hr pH parameter "% acid exposure" should be relied upon most in interpreting the 24-hr pH record, because those parameters that relate to RE frequency may be inaccurate due to acid rereflux REs that are not counted. Furthermore, identifying as many REs as possible gives a more reliable indication of the severity of antireflux barrier incompetence, as well as more REs to correlate with patients symptoms that should improve sensitivity of the symptom index. Ambulatory simultaneous pH monitoring and MII will allow these and other roles for acid rereflux to be assessed during the patients normal day.

Multichannel intraluminal impedance in esophageal function testing and gastroesophageal reflux monitoring.

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.

Automated graphic assessment of respiratory activity is superior to pulse oximetry and visual assessment for the detection of early respiratory depression during therapeutic upper endoscopy.

BACKGROUND: Recommendations from the American Society of Anesthesiologists suggest that monitoring for apnea using the detection of exhaled carbon dioxide (capnography) is a useful adjunct in the assessment of ventilatory status of patients undergoing sedation and analgesia. There are no data on the utility of capnography in GI endoscopy, nor is the frequency of abnormal ventilatory activity during endoscopy known. The aims of this study were to determine the following: (1) the frequency of abnormal ventilatory activity during therapeutic upper endoscopy, (2) the sensitivity of observation and pulse oximetry in the detection of apnea or disordered respiration, and (3) whether capnography provides an improvement over accepted monitoring techniques. METHODS: Forty-nine patients undergoing therapeutic upper endoscopy were monitored with standard methods including pulse oximetry, automated blood pressure measurement, and visual assessment. In addition, graphic assessment of respiratory activity with sidestream capnography was performed in all patients. Endoscopy personnel were blinded to capnography data. Episodes of apnea or disordered respiration detected by capnography were documented and compared with the occurrence of hypoxemia, hypercapnea, hypotension, and the recognition of abnormal respiratory activity by endoscopy personnel. RESULTS: Comparison of simultaneous respiratory rate measurements obtained by capnography and by auscultation with a pretracheal stethoscope verified that capnography was an excellent indicator of respiratory rate when compared with the reference standard (auscultation) (r = 0.967, p < 0.001). Fifty-four episodes of apnea or disordered respiration occurred in 28 patients (mean duration 70.8 seconds). Only 50% of apnea or disordered respiration episodes were eventually detected by pulse oximetry. None were detected by visual assessment (p < 0.0010). CONCLUSIONS: Apnea/disordered respiration occurs commonly during therapeutic upper endoscopy and frequently precedes the development of hypoxemia. Potentially important abnormalities in respiratory activity are undetected with pulse oximetry and visual assessment.

Esophageal function testing with combined multichannel intraluminal impedance and manometry: multicenter study in healthy volunteers.

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.

Cholecystokinin-stimulated peak lipase concentration in duodenal drainage fluid: a new pancreatic function test.

OBJECTIVE: Hormonal stimulation with secretin or cholecystokinin (CCK) is the most sensitive means of assessing pancreatic function. Secretin is not available, and current CCK tests are cumbersome, requiring dual tube intubation and marker perfusion techniques. The aim of this study was to test the efficacy of a new CCK-stimulated pancreatic function test measuring peak lipase concentration. METHODS: A Dreiling gastroduodenal tube was inserted to the ligament of Treitz, and fluid was collected on ice for 80 min in four 20-min aliquots. CCK was infused i.v. at a constant rate of 40 ng/kg/h. Gastric aspirations were discarded. Duodenal aspirates were analyzed for volume and enzyme concentration with a clinical laboratory autoanalyzer. RESULTS: Nineteen healthy volunteers and 18 chronic pancreatitis patients were studied. Lipase concentration and secretory volume showed a peak response by 40 min of stimulation, whereas amylase response was variable. The mean peak lipase concentrations (+/-SEM) for normal volunteers and mild, moderate, and advanced chronic pancreatitis patients were 16.9+/-1.9, 7.9+/-1.7, 3.7+/-1.2, and 2.1+/-0.6 x 10 5 IU/L, respectively. Lower peak lipase concentrations were significantly associated with more advanced chronic pancreatitis (p < 0.001). The receiver operating characteristic curve area for all chronic pancreatitis patients was 0.944 (95% CI = 0.825-0.985). A peak lipase concentration of 780,000 IU/L provided a sensitivity and specificity of 0.833 and 0.867, respectively. This CCK test was well tolerated and without complications. CONCLUSIONS: Lipase concentration in duodenal fluid increases nearly 3-fold from baseline after CCK stimulation in healthy volunteers but is markedly reduced in patients with chronic pancreatic disease. Peak lipase concentration is a significant predictor of chronic pancreatitis and correlates with severity of pancreatic disease. Aspiration of duodenal drainage fluid with a Dreiling tube and analysis with a laboratory autoanalyzer are less cumbersome than marker perfusion and back titration techniques. Measurement of enzyme concentration instead of output could lead to the development of an endoscopic or through-the-scope screening method for assessing patients with suspected chronic pancreatitis or chronic abdominal pain.