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Relationships of timed barium esophagram (TBE) findings to achalasia types defined by high-resolution manometry (HRM) have not been elucidated. Therefore, we correlated preoperative TBE and HRM measurements in achalasia types and related these to patient symptoms and prior treatments. From 2006 to 2013, 248 achalasia patients underwent TBE and HRM before Heller myotomy. TBE height and width were recorded at 1 and 5 minutes; HRM measured lower esophageal sphincter mean basal pressure, integrated relaxation pressure (IRP), and mean esophageal body contraction amplitude. Achalasia was classified into types I (25%), II (65%), and III (9.7%). TBE height at 5 minutes was higher for I (median 8 cm; interquartile range 6-12) and II (8 cm; 8-11) than for III (1 cm; 0-7). TBE width at 5 minutes was widest (3 cm; 2-4), narrower in II (2 cm; 2-3), and narrowest in I (1 cm; 0-2), P < 0.001. Volume remaining at 1 and 5 minutes was lower in III (1 m(2) ; 0-16) than I (42 m(2) ; 17-106) and II (39 m(2) ; 15-60), highlighting poorer emptying of I and II. Increasing TBE width correlated with deteriorating morphology and function from III to II to I. Symptoms poorly correlated with TBE and HRM. Prior treatment was associated with less regurgitation, faster emptying, and lower IRP. Although TBE and HRM are correlated in many respects, the wide range of their measurements observed in this study reveals a spectrum of morphology and dysfunction in achalasia that is best characterized by the combination of these studies.

Summary We examined the value of impedance monitoring in measuring bolus volume compared with videoesophagram. Eighty consecutive subjects were studied with simultaneous impedance-manometry-videoesophagram. A catheter with both an impedance electrode pair and a pressure transducer at four sites (5, 10, 15, 20 cm above lower esophageal sphincter) was passed per nares. Six 10-cc boluses of 45% barium mixed with 0.9% NaCl were swallowed at 20- to 30-second intervals. When impedance fell to below 1000 ohms, other than that occurring during administered swallows, the videofluoroscopic image corresponding to the time of impedance nadir was reviewed. If barium was present at the impedance site, barium area was calculated. The video was reviewed for the cause of abnormal barium transit causing barium presence. We found 38/80 subjects had a total of 169 impedance falls to below 1000 ohms. Ninety-seven percent (164/169) of impedance falls had barium present at the impedance site, and there was good correlation (r = 0.83, P 1000 ohms to a low nadir value from all forms of abnormal esophageal bolus transit imply a large bolus amount.

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%). Ganglioncells were reducedin 8 (20%) and absent in 13 (33%). Myentericinflammation 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, and3 (60%)with neither. Abnormalities in diffuseesophageal spasm(n = 3) weresimilarto thoseof 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. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

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.

Impedance monitoring (Imp) measures bolus transit. Combining Imp with manometry (EM) allows the effect of contractile patterns on transit to be assessed. The objective of this study is to identify bolus transit patterns in normal subjects, correlate Imp findings with the gold standard barium esophagram (Ba), and compare bolus transit with concomitant EM findings. Simultaneous Ba-Imp-EM was performed for 2 min in 15 normal volunteers (women, 11; age, 43 yr). Combined impedance-pressure sites were 5, 10, 15, 20 cm above the lower esophageal sphincter (LES). Boluses (10 ml) of 45% barium mixed with 0.9% NaCl were swallowed at ≥20-s intervals (5–6 swallows/subject). Imp and Ba showed three bolus transit patterns, and the two methods were in agreement on the pattern type in 97% (83/86) of swallows. Normal bolus transit was found in 73% (61/83), and each had normal peristalsis and contraction amplitude. Stasis in the proximal esophagus occurred in 7 of 83 swallows despite normal manometric parameters in 4 of 7 swallows. Retrograde escape of a residue of incompletely cleared bolus from just above the LES to the site 5 cm above occurred in 14 of 83 swallows. Retrograde escape was triggered by the next swallow, occurred despite normal manometric parameters, and did not occur if the swallow interval was >30 s. In 55% (47/86) of swallows, air accumulated in the distal esophagus and persisted there for a mean of 3.6 s until cleared into the stomach. We conclude that impedance monitoring is a valid transit test and describe bolus transit patterns in normal subjects for comparison with patients with esophageal motility disorders.

Acid clearing, the interval while intraesophageal pH is 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.

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.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.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, p0.001). 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 (p0.0010).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.

OBJECTIVES: Inflammatory cytokines are released during acute pancreatitis. Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine with immunosuppressive and anti-inflammatory activities. IL-10 has been shown to attenuate pancreatitis in an animal model. A double blind, placebo-controlled pilot study was conducted to evaluate the safety and efficacy of low dose IL-10 for the prevention of ERCP-induced pancreatitis. METHODS: Patients were randomized to receive a single i.v. dose of recombinant human IL-10 (8 μg/kg) or a placebo i.v. bolus injection 15 min before the procedure. Pancreatitis was defined as abdominal pain radiating to the back associated with elevated amylase or lipase two or more times the upper limit of normal requiring hospitalization for ≥2 days. Severity of pancreatitis was based on days of hospitalization. RESULTS: Two hundred patients were enrolled (101 IL-10, 99 placebo). No difference in age, gender, degree of pancreatic duct filling, therapeutic intervention, or complication was detected between the two groups. Eleven patients in the IL-10 group and nine patients in the placebo group had pancreatitis ( p = 0.65). The median length of hospitalization was 4 days in the IL-10 group and 3 days in the placebo group ( p = 0.75). CONCLUSIONS: IL-10 at the 8-μg/kg i.v. dose was not effective in reducing the incidence or severity of ERCP-induced pancreatitis. Further investigations are necessary to determine if manipulation of the cytokine pathway can prevent ERCP-induced pancreatitis.

Practice guidelines call for the careful titration of sedatives and analgesics during endoscopy, with time taken between incremental doses to assess effect. This approach is time-consuming and has never been validated in a prospective trial. The aim of this study was to compare the safety and efficacy of titration, as outlined in practice guidelines, with a single, rapid bolus of sedatives before colonoscopy.Consecutive colonoscopy outpatients were randomized to a single, rapid bolus of meperidine and midazolam or to a titration of doses every 3 min until predefined levels of somnolence were achieved. The colonoscopist was not present during sedation and remained blinded as to which technique was used. Supplemental O2 was given for SaO290% on three or more occasions. Total physician time was calculated from the first injection of sedatives to the removal of the colonoscope. Patient assessments of pain and tolerance were obtained at the time of discharge using visual analog scales of 100 mm (0 = excellent and 100 = unbearable).A total of 101 patients were randomized (49 bolus, 52 titration). Demographic features were similar for both groups. Titration required more physician time than did bolus (32.2 min vs 20.1 min, p0.001) and was associated with an increased need for supplemental O2 (44% vs 14%, p = 0.002). Mean tolerance scores were similar (titration 16.3 vs bolus 15.3, p = 0.72).Rapid bolus sedation for colonoscopy saves significant endoscopist time, is associated with less O2 desaturation, and provides equivalent levels of patient comfort. A revision of the guidelines for sedation and analgesia during endoscopy should be considered.

Background: Traditional methods of sedation and analgesia for advanced endoscopic procedures can be inadequate and frequently prolong recovery room observation. Propofol is a rapidly acting agent that produces an excellent hypnotic state, but its use is typically limited to anesthesiologist-assisted cases because of the inadequacy of current monitoring standards to reliably detect early stages of respiratory depression. Methods: Ten patients undergoing advanced upper endoscopic procedures (endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, esophageal stent placement) received a propofol infusion under the control of a second qualified gastroenterologist with advanced cardiac life support skills. Graphic assessment of respiratory activity was made by using a sidestream carbon dioxide detecting cannula. Patient satisfaction was measured with a 100 mm visual analog scale. Recovery scores were measured by standardized scoring of discharge criteria. Results: Monitoring with graphic assessment of respiratory activity detected early phases of respiratory depression, resulting in a timely decrease in the propofol infusion without significant hypoxemia, hypercapnia, hypotension, or arrhythmias. Satisfaction scores were extremely high (median score 92 of 100) and 9 of 10 patients met discharge criteria at 15 minutes after discontinuation of the propofol infusion. Conclusions: With the use of monitoring by graphic assessment of respiratory activity, propofol infusion by a second qualified gastroenterologist for prolonged upper endoscopic procedures is safe and results in high levels of patient satisfaction with rapid recovery times.

Disorders from increased intraabdominal pressure (IAP) result from filling the abdominal cavity beyond its capacity. The aims of this study were 1) to examine pressure:volume curves as fluid is infused into the intraabdominal cavity, and 2) to ascertain the best UGI site for indirect IAP measurements.Chronic ambulatory peritoneal dialysis patients were studied (n = 4) supine. On day 1, manometry catheters measured IAP indirectly (intragastric and intrarectal) and intraesophageal (three sites) pressure. On day 2, antral-duodenal-jejunal manometry was performed to compare indirectly measured IAP at multiple sites. On both days, dialysate was infused at 200 ml/min until IAP wasor = 15 mm Hg or patient experienced severe discomfort.Filling had three phases: 1) an initial small increase in IAP as infusion began; 2) minimal further increase in IAP during infusion to about 3 L concurrent with a progressive increase in abdominal girth and mild abdominal discomfort; and 3) a linear increase in IAP with infusion3 L concurrent with intense abdominal discomfort and little increase in abdominal girth. During study day 2, intragastric, intraduodenal, and intrajejunal pressures were usually similar.The compliance curve of the abdomen with filling is similar to that of the bladder and large veins. Compliance curves with provocative meals may be useful in evaluating postprandial abdominal pain, dyspepsia, and bloating.

Decreased swallow frequency and low-amplitude ornonconducted primary peristaltic contractions arereported to prolong acid clearing in gastroesophagealreflux disease (GERD) patients. The aim of this study is to investigate which of these, or otherfactors, have a dominant role in long-duration pH refluxevents (pHRE). Simultaneous manometry and pH monitoringwas performed for 40 min before and after (beginning 40 min postprandial) a test meal. Wearbitrarily chose 180 sec to divide pHREs into long orshort pHREs. Twenty GERD patients with and withoutesophagitis were studied. Esophagitis patients hadthreefold more long pHREs than patients withoutesophagitis. In most (56%) long pHREs, additional refluxevents during acid clearing was the only finding. Only11% of long pHREs had either a decreased swallow rate (3%) or decreased peristaltic contractionamplitude (8%), as the only finding contributing to pooracid clearing. However, 18% of long pHREs had one ofthese peristaltic dysfunctions in combination with additional reflux events prolonging acidclearing. Only 15% of long pHREs had no apparent reasonfor poor acid clearing. In interpreting 24-hr pHmonitoring, one should not assume prolonged acidclearing is due to peristaltic dysfunction; instead, itis often due to additional reflux events.

Impedance monitoring was first proposed as a method for gastrointestinal motility 10 yr ago. It detects changes in resistance to current flow when a bolus traverses an electrode pair, and can distinguish liquid (low-impedance) from gas (high-impedance) boluses (1). Electrode pairs placed at multiple sites on a standard solid-state esophageal manometry catheter can track antegrade bolus transit through the esophagus to correlate with manometry findings. In contrast, the electrode pairs placed at multiple sites on a standard pH probe can track retrograde bolus transit from the stomach to the esophagus to correlate with pH. This issue of The American Journal of Gastroenterology contains reports that relate to each of these two distinct applications of impedance monitoring.

A Balancing View: Impedance–pH Testing in GERD—Limited Role for Now, Perhaps More Helpful in the Future

This article discusses a wide spectrum of intrinsic benign structural lesions of the esophagus. Additionally discussed are extrinsic benign structural lesions that may cause esophageal symptoms. Because any congenital anomaly or disease of a structure that normally impinges on the esophagus, or is adjacent to it, may distort the esophagus, we review disorders from several different organ systems.

To compare reflux events detected by intraesophageal pH monitoring with that of scintigraphy, we simultaneously performed both techniques along with esophageal manometry in nine patients with severe reflux esophagitis. Two hundred eighteen reflux events were detected in the recumbent posture after a meal during a 40-min interval. Both techniques simultaneously detected only 23% of all reflux events. Scintigraphy alone detected 61% of all reflux events as opposed to 16% for pH monitoring. Of those reflux events diagnosed only by scintigraphy, more occurred while the intraesophageal pH was less than 4 (ie, during an acid-clearing interval) than while the intraesophageal pH was greater than 4 (ie, when intragastric contents were neutralized by the meal). Most reflux events occurred during periods of stable, but low LES pressure. While reflux events diagnosed by scintigraphy significantly decreased during the second of two 20-min postprandial intervals, those by pH monitoring tended to increase. That simultaneous scintigraphy and pH monitoring agreed on less than 1/3 of all reflux events not only underscores the fact that both techniques measured different physical components of the esophageal refluxate (ie, volume vs acid concentration, respectively), but also were influenced by different physiologic events such as the ingestion of a meal, gastric emptying, and esophageal acid clearance.

Background and aims: Empiric proton pump inhibitor (PPI) trials have become increasingly popular leading to gastroenterologists frequently evaluating gastro-oesophageal reflux disease (GORD) patients only after they have “failed” PPI therapy. Combined multichannel intraluminal impedance and pH (MII-pH) monitoring has the ability to detect gastro-oesophageal reflux (GOR) episodes independent of their pH and evaluate the relationship between symptoms and all types of GOR. Using this technique, we aimed to characterise the frequency of acid and non-acid reflux (NAR) and their relationship to typical and atypical GOR symptoms in patients on PPI therapy. Methods: Patients with persistent GORD symptoms referred to three centres underwent 24 hour combined MII-pH monitoring while taking PPIs at least twice daily. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15, and 17 cm above the lower oesophageal sphincter (LOS) and classified into acid or non-acid based on pH data from 5 cm above the LOS. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes. Results: A total of 168 patients (103 (61%) females and 65 (39%) males; mean age 53 (range 18–85) years) underwent combined MII-pH monitoring while taking PPIs at least twice daily. One hundred and forty four (86%) patients recorded symptoms during the study day and 24 (15%) patients had no symptoms during testing. Sixty nine (48%) symptomatic patients had a positive SI for at least one symptom (16 (11%) with acid reflux and 53 (37%) with NAR) and 75 (52%) had a negative SI. A total of 171 (57%) typical GORD symptoms were recorded, 19 (11%) had a positive SI for acid reflux, 52 (31%) for NAR, and 100 (58%) had a negative SI. One hundred and thirty one (43%) atypical symptoms were recorded, four (3%) had a positive SI for acid reflux, 25 (19%) had a positive SI for NAR, and 102 (78%) had a negative SI. Conclusion: Combined MII-pH identifies the relation of reflux of all types to persistent symptoms and the importance of NAR in patients taking PPIs.

Background & 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 (κ = .63, P P = .9) between the highly and midexperienced interpreters (κ = .61 and .65, respectively). Interobserver agreement for the diagnosis of achalasia and normal motility was good (κ = .65 and .56, respectively). However, other manometric diagnoses yielded only fair interobserver agreement (κ = .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.

Impedance monitoring is a new diagnostic method for gastroesophageal reflux disease (GERD) where multiple impedance electrode pairs are placed on a standard pH catheter. It detects reflux of a liquid and/or gas bolus into the esophagus, as well as its distribution, composition, and clearing. The aim of this collaborative study is to define normal values for 24-h ambulatory simultaneous impedance and pH monitoring (24-h Imp-pH), and compare bolus parameters by impedance monitoring to changes in [H(+)] measured by pH monitoring.Sixty normal volunteers without GER symptoms underwent 24-h Imp-pH with impedance measured at six sites (centered at 3, 5, 7, 9, 15, and 17 cm above lower esophageal sphincter) and pH 5 cm above the LES. Reflux detected by impedance was characterized by the pH probe as either acid, weakly acidic, nonacid, or superimposed acid reflux. Proximal reflux was defined as reflux that reached the impedance site 15 cm above the LES.Reflux frequency was common upright (median-27, 25th and 75th quartile-16, 42), but rare recumbent (median-1; 0, 4). A median of 34% (14%, 49%) of upright reflux reached the proximal esophagus. There was a similar number of mixed composition (liquid + gas; 49%) and liquid-only reflux (51%). Acid reflux was two-fold more common than weakly acidic reflux (p0.001). Superimposed acid reflux and nonacid reflux were rare. Acid neutralization to pH 4 took twice as long as volume clearance measured by impedance.Combining impedance and pH monitoring improves the detection and characterization of GER. This study characterizes the frequency, duration, and extent of reflux in health and provides normal values for 24-h Imp-pH for future comparison with GERD patients.

Combining GERD tests allows strengths and weaknesses of each method to be identified in detecting and characterizing reflux (RE). Aim of this study was to compare two methods that measure bolus volume of a refluxant (impedance monitoring (Imp) and manometry (common cavity)) to pH monitoring which measures changes in acid concentration of a refluxant. Nineteen symptomatic GERD patients and 10 normal volunteers were studied before and after a meal. All had 2-hr simultaneous manometry, pH, and Imp (six sites: 3, 5, 7, 9, 15, 17 cm above LES). Reflux by pH was a fall in pH from above to below 4. There were 973 RE's in all subjects, but only 19% were detected simultaneously by all three methods. Imp detected more RE's (96%) than manometry (76%) or pH probe (28%). Imp was the only method to detect 15% (144/973) of RE's, while detection only by pH probe (2%) or manometry (2%) was rare. Most RE's detected by Imp were detected simultaneously by manometry (75%,720/937). Those not detected by manometry were usually in blind spots either in the vulnerable period 2-3 sec after a swallow, during a posture change, or during a Valsalva. Most RE's detected by Imp were not detected by the pH probe. Though most liquid RE's fasting were detected by pH, most liquid postprandial RE's were not, due primarily to weakly acidic rather than superimposed acid RE's. Bolus clearing time by Imp and manometry was nearly identical, while acid clearing was threefold longer than bolus clearing by Imp or manometry. In conclusion, impedance monitoring is better than manometry and pH monitoring in RE detection before and after a meal, and manometry in determining RE composition as liquid or gas. The pH probe measures RE acidity and acid clearing. Simultaneous impedance and pH combines the two methods strengths, and is a powerful tool for reflux detection and characterization.

Acid clearing, the interval while intraesophageal pH is4 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 pH4) 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.

INTRODUCTION AND AIMS Hormonal stimulatory agents are used to assess pancreatic function. Biologically derived secretin, the most widely used pancreatic secretagogue, is no longer available in the United States. Existing secretory tests using cholecystokinin alone are cumbersome, requiring a unique dual tube (gastric and duodenal) collection system and constant perfusion of a nonabsorbable marker to calculate enzyme output (in international units [IU]). A simpler, quantitative cholecystokinin stimulation test that measures enzyme concentrations (in international units per liter [IU/L]) instead of total output would obviate need for marker perfusion/collection. The aim of our experiment was to study the secretory patterns of pancreatic enzyme concentration in duodenal fluid after cholecystokinin stimulation in healthy volunteers. METHODOLOGY Healthy subjects had a Dreiling tube inserted endoscopically into the ligament of Treitz. Gastric and duodenal aspiration ports were connected to low intermittent suction. A 20-minute baseline was obtained to clear the gastric and duodenal lumina of residual fluid. Cholecystokinin was infused at a constant rate of 40 ng/kg per hour. Duodenal fluid was collected on ice for 80 minutes in four 20-minute aliquots. Aspirated fluid was analyzed for enzyme concentration with an automated chemistry analyzer in the hospital biochemistry laboratory. RESULTS Nineteen healthy volunteers were studied. The mean volume (+/-SEM) of duodenal fluid collected was 85 +/- 4.4 mL (range, 48 to 118 mL). Fluid analysis revealed a significant rise in mean lipase concentration (+/-SEM) from a baseline of 595,680 +/- 11,930 IU/L to a peak of 1,778,847 +/- 171,204 IU/L (mean difference = 1,183,167 IU/L; 95% CI= 664,459 IU/L to 1,701,875 IU/L; < 0.001, Student test). Increases in amylase concentrations were markedly less pronounced and did not reach statistical significance. Mean peak lipase concentration occurred within 50 minutes of acinar cell stimulation. All patients tolerated tube placement, and there were no episodes of acute pancreatitis or abdominal pain. CONCLUSIONS Pancreatic lipase concentrations in duodenal fluid increase nearly threefold after cholecystokinin stimulation in healthy volunteers. This magnitude of enzyme secretory response may be a marker of pancreatic function and could potentially lead to a more clinically useful and simpler pancreatic function test. This physiologic study serves as the basis for our further investigations of cholecystokinin-stimulated lipase concentrations as a new test in the assessment of pancreatic insufficiency.

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.

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.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.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 (p0.001). 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.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.

Esophageal manometry assesses lower esophageal sphincter (LES) pressure and its relaxation. In addition, it detects the ability of the esophageal body to initiate a peristaltic contraction and the contraction's amplitude in response to a water bolus. The study is indicated in patients with symptoms suggestive of an esophageal motor disorder and to assist in the diagnosis of some miscellaneous disorders. The most common disorders diagnosed by esophageal manometry are the primary motility disorders, such as achalasia. Manometry is indicated in the subset of patients with gastroesophageal reflux disease (GERD) who are being considered for antireflux surgery or have symptoms after antireflux surgery.

New techniques in esophageal monitoring are allowing for better differentiation in the role of different gastric refluxates in esophageal mucosal damage and patient symptoms. The Bilitec 2007 (Synectics, Stockholm, Sweden) is a portable spectrophotometer that measures bilirubin as a surrogate marker for bile reflux and multichannel intraluminal impedance (MII) (Sandhill Scientific Inc, Highlands Ranch, CO) is a new technique allowing measurement of esophageal volume refluxate. Both techniques assess the role of nonacidic esophageal reflux. Despite their novel approach in assessing nonacid reflux, both methods have limitations. Future studies in this area, however, will prove beneficial in identifying their role in diagnosis and management of patients with suspected nonacid reflux disease.

Chronic pancreatic pain is difficult to treat. Surgical and medical therapies directed at reducing pain have met with little long-term success. In addition, there are no reliable predictors of response including pancreatic duct diameter. A differential neuroaxial blockade allows characterization of chronic abdominal pain into visceral and nonvisceral pain origins and may be useful as a guide to the treatment. Pain from an inflamed, and scarred pancreas should be visceral in origin. The purpose of our study was to determine the frequency with which patients with chronic pancreatitis have visceral pain and whether our modified differential neuroaxial blockade technique using thoracic epidural analgesia can accurately predict which patients will respond to medical or surgical therapy.We retrospectively reviewed the medical records of patients with a firmly established diagnosis of chronic pancreatitis (Cambridge classification, calcifications) who had undergone a differential neuroaxial block for their chronic abdominal pain evaluation. Patient demographics and medical or surgical treatment for pancreatic pain was recorded. Response to therapy was defined by a 50% reduction in pain by verbal response score.A total of 23 patients were identified. Alcohol was the most common etiology for chronic pancreatitis (15 of 23, 55%). Surprisingly, the majority of chronic pancreatitis patients had nonvisceral pain (18 of 23, 78%) and only 22% (5 of 23) had visceral pain by differential neuroaxial block. Four of five patients (80%) with visceral pain responded to therapy, whereas only 5 of 17 (29%) of patients with nonvisceral pain responded.Surprisingly, patients with chronic pancreatitis commonly have nonvisceral pain. Differential neuroaxial blockade can predict which patients will respond to therapy.

Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP). Uncontrolled data suggest a lower incidence of pancreatitis in patients with a history of iodine sensitivity when given pretreatment with corticosteroids. We conducted a clinical trial to assess the efficacy of a commonly prescribed corticosteroid, methylprednisolone, to prevent ERCP-induced pancreatitis.Patients were entered into a randomized, multicenter, double-blind, placebo-controlled study of intravenous methylprednisolone (125 mg) versus a saline placebo immediately before the ERCP. All patients were evaluated for early and late complications.Two hundred eighty-six patients were randomized. Thirty-one randomized patients were excluded for technical reasons at the time of ERCP. Overall, the incidence of pancreatitis was 16 of 129 (12.4%, 95% CI: 6.7-18.1%) in the methylprednisolone group and 11 of 126 (8.7%, 95% CI: 4.4-15.1%) in the placebo group, which was not significantly different (p = 0.34). Although there was a higher rate of sphincterotomy performed in the methylprednisolone group compared to the control group (31.8% vs 16.8%, p = 0.005), the incidence of pancreatitis was not different when patients undergoing sphincterotomy were analyzed separately (13.6% in the methylprednisolone group and 9.6% in the placebo group,p = 0.50). There was no significant difference between the two groups for those with ERCP-induced pancreatitis in hospital length of stay (p = 0.22), days of parenteral analgesia (p = 0.09), or days of parenteral nutrition (p = 0.15).Intravenous methylprednisolone is not beneficial in preventing ERCP-induced pancreatitis.

In summary, we evaluated a 39-year-old man two years after partial esophagectomy and gastroesophageal anastomosis. He had developed recurrent Barrett's esophagus and atypical reflux symptoms. We found free reflux and no antireflux barrier at the hiatus or the esophagogastric anastomosis. Three different reflux techniques performed simultaneously demonstrated that the composition of refluxant varied with posture, explaining the atypical nature of the symptoms. In the left recumbent posture, the refluxate was comprised of acidified liquid and gaseous gastric contents with the patient complaining of heartburn and chest pain. In the right recumbent posture the refluxate was composed of only nonacidic gas, and the patient complained of chest pain without heartburn. We propose that multiple reflux tests performed simultaneously in the setting where a patient experiences his atypical symptoms may help clarify their origin. Furthermore, this case illustrates how posture may dramatically influence refluxant composition.

The purpose of this study is to determine if frequent reflux events from an incompetent LES or poor clearance from decreased peristalsis is the predominant abnormality in PSS patients with severe reflux esophagitis. Seven patients with both classic manometric findings of PSS and endoscopic findings of esophageal ulcerations and/or Barrett's esophagus were compared to nine patients with similar endoscopic findings but with no evidence of a connective tissue disorder. All patients underwent simultaneous intraesophageal pH monitoring and scintigraphy for a total of 40 min after a radiolabeled meal. Four of the PSS patients and all the non-PSS patients had simultaneous manometry. We found that PSS patients had significantly fewer reflux events (P less than 0.01), but the reflux events had significantly longer duration (P less than 0.01) compared to patients with similar severity of esophagitis and no connective tissue disease. We conclude that decreased smooth muscle peristalsis appears to be the primary contributor to acid exposure and esophageal injury in PSS.

Eighteen years after having a duodenal leiomyosarcoma resected, a patient presented with weight loss, pruritus, and abdominal pain. ERCP was consistent with a cholangiocarcinoma with proximal hepatic duct stricture and nonfilling of the cystic duct. CAT scan revealed no extrinsic masses compressing the gallbladder or biliary tract. At surgical exploration, the patient was found to have a suture granuloma with surrounding fibrosis within the common bile duct. There was no evidence of malignancy.

Plasma cholecystokinin (CCK) levels increase immediately following ERCP and predict the degree of hyperamylasemia