Search

Summary Background Tissue-engineered extracellular matrix populated with autologous pluripotent cells can result in de-novo organogenesis, but the technique is complex, not widely available, and has not yet been used to repair large oesophageal defects in human beings. We aimed to use readily available stents and extracellular matrix to regenerate the oesophagus in vivo in a human being to re-establish swallowing function. Methods In a patient aged 24 years, we endoscopically placed a readily available, fully covered, self-expanding, metal stent (diameter 18 mm, length 120 mm) to bridge a 5 cm full-thickness oesophageal segment destroyed by a mediastinal abscess and leading to direct communication between the hypopharynx and the mediastinum. A commercially available extracellular matrix was used to cover the stent and was sprayed with autologous platelet-rich plasma adhesive gel. The sternocleidomastoid muscle was placed over the matrix. After 4 weeks, stent removal was needed due to stent migration, and was replaced with three stents telescopically aligned to improve anchoring. The stents were removed after 3·5 years and the oesophagus was assessed by endoscopy, biopsy, endoscopic ultrasonography, and high-resolution impedance manometry. Findings After stent removal we saw full-thickness regeneration of the oesophagus with stratified squamous epithelium, a normal five-layer wall, and peristaltic motility with bolus transit. 4 years after stent removal, the patient was eating a normal diet and maintaining a steady weight. Interpretation Maintenance of the structural morphology of the oesophagus with off-the-shelf non-biological scaffold and stimulation of regeneration with commercially available extracellular matrix led to de-novo structural and functional regeneration of the oesophagus. Funding None.

Pulmonary aspiration is the consequence of abnormal entry of fluid, particulate material, or endogenous secretions into the airway. The two main types of aspiration scenarios include anterograde aspiration, which occurs during swallowing, and retrograde aspiration, which can occur during gastroesophageal reflux (GER) events. The important structures that protect against aspiration include the aerodigestive apparatus: pharynx, upper esophageal sphincter, esophageal body, glottis and vocal cords, and airway. In this article we review the neuroanatomy, physiology, and pathophysiology pertinent to glottic reflexes and airway aspiration across the age spectrum from neonates to adults. We also discuss recent advances in our understanding of glottal reflexes and the relationship of these reflexes to developmental anatomy and physiology, the pathophysiology of aspiration, and aerodigestive interactions.

There is a close functional relation between the aerodigestive tract and the upper gastrointestinal tract. The pharynx and larynx are involved in respiration, speech, and deglutition. This article reviews the effects of reflexes emanating from the pharynx and larynx on the esophagus and its sphincters, as well as the effects of reflexes emanating from the esophagus on the larynx. Principally, reciprocal reflexes within these 2 regions result in protection of the airway against aspiration from above and below, either by swallowed or refluxed material. However, other reflexes appear to facilitate reflux of gastric content into the esophagus and inhibit esophageal motor function.

Functional biliary disorders encompass the conditions of SOD and gallbladder dysmotility, both of which result in clinical pain syndromes. Obtaining objective diagnostic and outcomes data for both disorders has been an ongoing challenge over the last two decades. SOD, although initially believed to be strictly a biliary disorder, has now been implicated in recurrent pancreatitis. The biliary-type classification allows a clinician to stratify patients who would benefit from SOM and endoscopic sphincterotomy. Further study into the impact of endoscopic therapy for recurrent pancreatitis is needed. By the same token, the dilemma of postcholecystectomy abdominal pain, whether classified as biliary or pancreatic type III, remains challenging. The current limitations of knowledge highlight the need for prospective randomized studies to evaluate the clinical significance of SOM abnormalities to facilitate treatment of these patients.

When deployed across the gastroesophageal junction, self-expanding metal esophageal stents can predispose to gastroesophageal reflux. Our aim was to evaluate the efficacy of a self-expanding metal esophageal stent that was modified to prevent gastroesophageal reflux.The polyurethane coating of a metal Z-stent was extended beyond its lower end to form windsock-type valve. The anti-reflux property of this stent was studied in vitro by submerging the stent under water and measuring the pressure required to invert the valve. Esophageal acid exposure time was measured in 5 dogs with a standard and the modified stent placed across the gastroesophageal junction. The modified stent was also placed in 11 patients with cancer of the gastroesophageal junction who were prospectively followed.The pressure required to invert the valve was directly proportional to the thickness of the valve membrane (48 +/- 0.4 cm water for a 0.0067-inch thick membrane). Esophageal acid exposure time was significantly less with the modified stent as compared with a standard stent (1% +/- 0.3%, 49% +/- 11%, respectively, p = 0.03). Dysphagia score in patients improved from 3.4 +/- 0.1 to 1.1 +/- 0.2 (p0.001). Daytime heartburn and regurgitation scores were less than 1 (score 10 = severe). No patient complained of nocturnal reflux symptoms. Karnofsky performance status scale did not improve significantly.The efficacy of the modified stent in relieving dysphagia is comparable with a standard stent. It also effectively prevents gastroesophageal reflux.

The upper esophageal sphincter (UES) and lower esophageal sphincter (LES) comprise the basal mechanisms against entry of gastric content into the aerodigestive tract and the airway. There are, however, other mechanisms referred to here as "response mechanisms" that become activated after certain stimulation, such as distention of the esophagus or tactile/pressure stimulation of the pharyngeal wall, and result either in fortification of the UES barriers--i.e., esophago-UES, pharyngo-UES, and laryngo-UES contractile reflexes--or closure of the glottis--i.e., esophagoglottal and pharyngoglottal closure reflexes. In addition, there are other reflexes included among the response mechanisms--such as pharyngeal swallow and secondary peristalsis induced by pharyngeal stimulation by liquid and esophageal distention by refluxate--that result in pharyngeal and esophageal volume clearance, thus reducing the chance for contact of refluxate with the tracheal, bronchial, and glottal structures.

Supraesophageal complications of GERD have become more commonly recognized or suspected by physicians. However, the direct association between these complications and GERD has often been difficult, if not impossible, to establish. Furthermore, the majority of patients with suspected supraesophageal complications of GERD do not have either the characteristic symptoms of heartburn and regurgitation or the definitive findings of esophageal inflammation, which would help reinforce the suspicion of a connection between the supraesophageal complications and GERD. Frequent acid reflux has been shown in patients with various bron-chopulmonary, laryngopharyngeal, or oral cavity disorders. GERD is one of the most common gastrointestinal complaints in the population. It is possible that the supraesophageal problems and acid reflux are mutually independent disorders that occur in the same person. The suspected mechanisms of GERD-related supraesophageal complications appear to be directed through two pathways: by a vagal reflex between the esophagus and tracheobronchial tree triggered by acid reflux or by microaspiration that causes contact damage to mucosal surfaces. The most useful diagnostic modality available to the clinician to aid in the diagnosis of supraesophageal GERD complications is the ambulatory pH recording technique. However, the sensitivity and specificity of this test for recording esophageal or pharyngeal acid reflux events has been critically challenged. Despite the many clinical studies that support the theory that GER has a role in suspected supraesophageal complications, only 1 long-term prospective controlled study of a large group of patients with asthma has shown the positive effects of the elimination of acid reflux. With the focus now on "outcomes medicine," there is a serious need for appropriately designed, controlled studies to answer the many questions surrounding a cause-and-effect association between acid reflux and supraesophageal disorders. Because of the lack of convincing proof between acid reflux and suspected supraesophageal complications, the physician must resort to an intent-to-treat strategy as both a primary therapy and a diagnostic trial. High-dose PPI therapy for prolonged periods is the recognized conservative therapy. Operative therapy (i.e., fundoplication operation) is the procedure of choice when overt regurgitation occurs or when medical therapy, although successful, is not practical for long periods. Controlled, well-designed clinical trials and more sophisticated techniques to measure and quantify acid reflux are crucial in the future to help determine which patients with suspected supraesophageal complications actually have acid reflux as a primary cause. The medical community needs to be alerted to the possibility of an association between GERD and supra-esophageal complications so that patients with a GERD-related complication will be recognized and effectively treated.

Laparoscopic fundoplication technique has become the operative modality of choice for antireflux surgery. An increasing number of patients and physicians have enthusiastically embraced this "minimally-invasive" technologic development for treatment of gastroesophageal reflux disease (GERD). However, laparoscopic fundoplication has been frequently advertised as the therapeutic solution for all GERD patients. Subsequently, the number and severity of complications resulting from laparoscopic surgery—often performed indiscriminately—has increased dramatically. This article reviews the efficacy of the laparoscopic fundoplication operation for GERD based on current, relatively short-term reports from centers specializing in this treatment modality. The majority of these reports are very positive. Unfortunately, the results of fundoplication operations performed by community surgeons are unknown. There are a number of disturbing factors relating to laparoscopic treatment for GERD that should raise a red flag of caution to the medical community, particularly primary-care physicians and their patients. The central portion of this report devotes itself to discussing the problems associated with this new minimally-invasive technique for fundoplication operations. These problems include the selectivity of current reports on outcomes of the laparascopic fundoplication operation and the lack of uniform data acquisition associated with these postoperative studies. The technical difficulties of the laparascopic fundoplication surgery are discussed, and the need for operator expertise and appreciation of esophageal physiology and anatomy are stressed. Finally, the long-term durability of the fundoplication wrap is questioned and the morbidity associated with the operation—particulary dysphagia—is addressed. In the final segment, the complications encountered after laparoscopic fundoplication operations are detailed and the techniques for evaluating the symptomatic postfundoplication patient are discussed. Laparoscopic fundoplication operation is good therapy in an appropriate clinical setting when performed by a well-trained and experienced surgeon. However, the operation should not be first-line therapy for the majority of GERD patients. An esophagus disabled by an inappropriate or dysfunctional fundoplication wrap is a terrible price to pay for control of acid reflux.

There is a growing body of clinical and research evidence to support the role of gastroesophageal reflux in the etiology of certain disorders occurring in structures located above the body of the esophagus. These supraesophageal complications have only recently been identified but substantiation of the role of gastroesophageal reflux has been difficult and sometimes impossible with the technology currently available. This introductory article to the clinical issues involved in supraesophageal complications of GERD presents several index cases and asks far more questions than it gives answers about these patients. Clinical evidence supporting the role of GERD is discussed and the results of therapy reviewed. Education of the practicing physician to the role of supraesophageal complications of GERD is urged to help recognize the likelihood of such clinical conditions. There is a real need for additional clinical use and evaluation of multi site intraesophageal and pharyngeal pH probes in patients with suspected supraesophageal complications of GERD. More importantly, development of new techniques for measuring micro reflux events and sophisticated methods for determining the duration of acid exposure in tissues above the esophagus is essential. Finally, more prospective controlled outcome studies of patients with supraesophageal complications of GERD are needed utilizing specific treatment algorithms.

Background: Possible sources of post-ERCP pancreatitis were evaluated during a prospective, randomized, controlled study comparing different contrast media. Methods: A total of 1979 patients were randomized and subdivided into groups during the study. Patients were grouped for comparison depending on the type of procedure performed during ERCP. Diagnostic patients studied with pancreatograms (Group I) were compared with other groups, specifically, those not studied with pancreatograms (Group IV). All patients had subjective and objective estimates of the difficulty in cannulation of both ducts. The incidence of postprocedural pancreatitis was compared between and within each group. Results: In Group I there was a progressively higher incidence of pancreatitis with increased numbers of pancreatic duct injections. Patients with the highest (19.5%) frequency of pancreatitis received 10 or more injections into the pancreatic duct. Group I cases with difficult common bile duct cannulations had a higher frequency of post-ERCP pancreatitis (9.5%), as compared with the entire group (5.6%). Conclusions: There was a higher incidence of pancreatitis associated with increased manipulation around the papillary orifice, especially with multiple pancreatic duct injections. There was also a slightly higher incidence of post-ERCP pancreatitis in cases with difficult common bile duct cannulation. Endoscopists are encouraged to evaluate and develop safer cannulation techniques that minimize the number of injections into the pancreatic duct and enhance selective cannulation. (Gastrointest Endosc 1997;46:217-22.)

BACKGROUND & AIMS: Nongranulomatous ulcerative enterocolitis has been reported in association with celiac sprue, lymphoma, and hypogammaglobulinemia. The objective of this study is to present evidence that this disorder exists as a primary entity. METHODS: The medical records and histological material of 9 patients (mean age, 45.7 +/- 5.9 years) who presented with severe chronic diarrhea without specific diagnosis after extensive investigations were reviewed. RESULTS: Endoscopically, the duodenum and proximal jejunum were inflamed in 6 of 7 patients, with superficial ulcerations in 5 patients. On histology, the lamina propria was infiltrated by polymorphonuclear and chronic inflammatory cells, with varying degrees of villous atrophy. There were no significant cellular abnormalities of the epithelial enterocytes. A similar inflammatory infiltrate was present in the colon in 4 or 5 patients. Eight of 9 patients responded to corticosteroids with clinical and variable histological improvement. Four patients developed bleeding from ulcerations in the small or large intestine. Three patients died: 1 patient who did not respond to treatment with corticosteroids and 2 patients with systemic infection. Four of the 6 surviving patients required maintenance low-dose corticosteroid therapy. No underlying disease was discovered during prolonged follow-up. CONCLUSIONS: Idiopathic nongranulomatous enterocolitis may present as a primary, frequently fatal disease. Corticosteroid therapy provides immediate benefit and may be required indefinitely. (Gastroenterology 1996 Sep;111(3):629-37)

The determinants of the lower esophageal sphincter relaxation response to esophageal distension have not previously been systematically examined in humans. In this study, 14 healthy subjects were tested using a manometry catheter with a sleeve device and three balloons spaced 5 cm apart. Subjects had up to five distensions with each balloon at four different diameters and two different durations of inflation. The results indicated that 1,170 separate distensions were available for analysis. Sphincter relaxation occurred more frequently (P < 0.005) with larger balloon diameters, yet occurred in only 84% of inflations at the largest diameter. Sphincter relaxation was more often observed with the proximal balloon (P < 0.005) during longer distensions (P < 0.05) and when esophageal contractions occurred above the balloon (P < 0.005). Once sphincter relaxation occurred, its magnitude was essentially independent of balloon site and diameter, distension duration, and the presence of proximal contractions. In conclusion, even large balloon distensions do not uniformly produce or maintain lower esophageal sphincter relaxation. Sphincter relaxation is more likely with proximal esophageal distension. The association of sphincter relaxation with vagally mediated proximal contractions suggests vagal modulation of this response.

We investigated the mechanisms of slow fluid infusion-induced secondary peristalsis and the effects of hydrochloric acid on this response. In 13 chronically esophagostomized opossum, acidic and neutral barium sulfate were infused into the distal esophagus at a rate of 1.1 ml/min, while recording the esophageal dimension by videofluoroscopy and esophageal intraluminal pressure concurrently. The effects of atropine, tetrodotoxin, capsaicin, and bilateral cervical vagotomy on the response to slow fluid infusion were examined. Acidic barium initiated secondary peristalsis more frequently and at shorter latency with less increase of preperistaltic intraesophageal pressure than neutral barium (P < 0.05). Atropine abolished secondary peristalsis initiated by neutral barium. For acidic barium, atropine decreased the incidence of secondary peristalsis, increased the latency for initiation of secondary peristalsis, and initiated secondary peristalsis more distally (P < 0.05). Tetrodotoxin or vagotomy and capsaicin abolished activation of secondary peristalsis. We concluded that secondary peristalsis can be stimulated in response to slow distension by minute amounts of fluid. This peristalsis is atropine and capsaicin sensitive and vagally mediated. The presence of acid significantly lowers the threshold for stimulation of secondary peristalsis induced by slow fluid distension. This effect seems to be atropine resistant.

A variety of otolaryngological abnormalities have been attributed to the contact of gastroesophageal refluxate with respective structures of the aerodigestive tract. The aim of this study was to determine and compare the pharyngoesophageal distribution of gastric acid refluxate between patients with proven laryngitis attributed clinically to gastroesophageal reflux and three control groups.An ambulatory 24-hour simultaneous three-site pharyngoesophageal pH monitoring technique was used to measure reflux parameters in the pharynx, proximal esophagus, and distal esophagus.Between-group comparison showed no significant difference in the reflux parameters in the distal esophagus between the studied groups. A significantly higher percentage of distal reflux episodes reached the proximal esophagus in the laryngitis group than in the control groups (P0.01), and the number of pharyngeal reflux episodes and time of acid exposure were significantly higher in the laryngitis group than in the control groups (P0.001).Compared with normal controls and patients with gastroesophageal reflux disease, pharyngeal reflux of gastric acid is significantly more prevalent and the ratio of proximal to distal esophageal acid reflux episodes is significantly increased in patients with posterior laryngitis. Simultaneous three-site ambulatory pharyngoesophageal pH monitoring may provide supporting evidence when the diagnosis of reflux-induced aerodigestive tract lesions is considered.

Background: Endoscopic treatment of pancreatic pseudocysts via cystenterostomy has been recognized as a successful treatment option in carefully selected patients. Pancreatic transpapillary stenting as an alternative treatment option in patients with pancreatic pseudocysts directly communicating with the main duct has received little consideration. The aim of the current study was to assess the safety and utility of transpapillary pancreatic endo-prosthesis in the treatment of communicating pseudocysts. Methods: Twenty-one patients underwent placement of 33 transpapillary endo-prostheses for the treatment of symptomatic pancreatic pseudocysts. All pseudocysts communicated with the main pancreatic duct and ranged in size from 3 to 9 cm (mean 6 cm). Eight patients had associated pancreatic duct strictures. Results: Stent placement was successful in all cases: 13 directly into the pseudocyst, 8 beyond the stricture but not into the pseudocyst. Initial resolution of pseudocysts was seen in 17 patients, with 16 patients free of pseudocyst recurrence at mean follow-up of 37 months. All patients with associated strictures were treated successfully. Factors predictive of success included presence of strictures, size of pseudocyst greater than or equal to 6 cm, location in the body of the pancreas, and duration of pseudocyst less than 6 months. Complications included one episode of mild pancreatitis. Conclusions: Endoscopic treatment of symptomatic pancreatic pseudocysts with ductal communication by transpapillary pancreatic duct stenting is a safe, effective modality and should be considered a first line therapy. (Gastrointest Endosc 1995:42:214-8.)

Benign esophageal strictures result from a variety of injuries causing local or diffuse narrowing of the lumen and compromising swallowing. Subsequently, nutritional health becomes impaired necessitating mechanical treatment (dilation) of the stricture.

We characterized and quantified a reflex from the pharyngeal mucosa to the upper esophageal sphincter (UES). Seventeen cats were decerebrated, and the pharynx was exposed by opening the cricothyroid ligament. UES motor activity was assessed by recording electromyographic (EMG) activity from the pharyngeal constrictors, i.e., the thyropharyngeus (TP) and cricopharyngeus (CP). The pharyngeal mucosa was stimulated by touch or pressure. Both stimuli activated contraction of the CP primarily when applied to the naso-, laryngo-, or hypopharynx, but pressure was more effective. The anteromedial portion of the hypopharynx was the most sensitive zone, but there was no strong stimulus-response relationship. The reflex response to a 1-s stimulus occurred at a delay of 0.46 +/- 0.06 s and lasted 4.5 +/- 0.5 s. This pharyngo-UES reflex was blocked by anesthesia of the mucosa or transection of the glossopharyngeal or pharyngoesophageal nerves but not the vagus nerves. In contrast, the esophago-UES contractile reflex was not blocked by anesthesia of the pharyngeal mucosa or transection of the glossopharyngeal nerves but was blocked by transection of either the vagus or pharyngoesophageal nerves. We concluded that the pharyngo-UES contractile reflex was activated by pharyngeal mucosal mechanoreceptors whose afferent limb was the glossopharyngeal nerve and whose efferent limb was the pharyngoesophageal branch of the vagus nerve.

Effect of aging, bolus volume, temperature, and consistency on the pharyngeal peristalsis, as well as the effect of aging on the upper esophageal sphincter (UES) resting pressure and its response to esophageal distension by air and balloon, were studied in 14 young and 12 healthy elderly volunteers. In both age groups there was no significant volume or temperature effect on amplitude, duration, or velocity of the pharyngeal peristalsis. Compared with water swallows, mashed potato swallows resulted in a significant increase in the amplitude and duration of the hypopharyngeal peristaltic pressure wave (P < 0.05). For water swallows, the amplitude and duration of the peristaltic pressure wave in the hypopharynx were significantly increased in the elderly compared with the young group (P < 0.01). UES resting pressure in the elderly measured 43 +/- 5 (SE) mmHg and was significantly less than that of the young (71 +/- 8 mmHg; P < 0.01). Magnitude of the UES pressure decrease because of esophageal distension by air, as well as magnitude of its pressure increase because of esophageal balloon distension, was similar among young and elderly. 1) Contrary to common expectations, the parameters of the pharyngeal peristaltic pressure wave do not deteriorate in the elderly in their seventh and eighth decade. 2) Compared with the young, hypopharyngeal pressure wave amplitude and duration are significantly increased in the elderly. This increase could be caused by an adaptation response to a pharyngeal outflow compromise. 3) Pharyngeal peristaltic pressure wave amplitude and duration, but not its velocity, are modulated by the bolus consistency. This modulatory mechanism is preserved in the elderly. 4) Although UES resting pressure is significantly decreased in the elderly, its pressure response to esophageal distension by air and balloon is preserved.

Despite widely available technology for removal of bile duct stones, endoscopists currently encounter approximately 3% of patients with stones that defy extraction. After sphincterotomy and unsuccessful attempts at extraction of "defiant" stones, biliary stents were placed in 22 patients. Ten patients were treated with ursodeoxycholic acid, and 12 patients treated only with stent served as control subjects. Ductal strictures preventing stone extraction were present in eight control patients and in six patients treated with ursodeoxycholic acid. The number of total calculi in the ursodeoxycholic acid group was slightly higher (4.2 per patient) than the number in the control group (3.3 per patient). Stone and bile duct dimensions were similar in each group. Nine of 10 patients in the ursodeoxycholic acid group had complete stone clearance, and 41 of 42 stones were removed during a follow-up period of 9 +/- 2 months; in contrast, no patient in the control group had complete clearance and only 6 of 40 stones were removed after a follow-up period of 31 +/- 6 months. Oral ursodeoxycholic acid facilitates extraction of defiant bile duct stones. This treatment is an effective alternative to high-tech extraction methods for large biliary stones.

With the advent of laparoscopic cholecystectomy, a number of patients with various postprocedure problems have been referred for endoscopic management. Thirty-five patients were evaluated. The group included 26 women and 9 men, ages 24 to 90 years (mean, 50 years). Twenty-five patients with retained common bile duct stones were successfully treated with endoscopic sphincterotomy and balloon or basket removal. Three patients with bile duct strictures had balloon dilation and endoprosthesis placement and were free of signs of obstruction on 9-month follow-up. Bile leaks were treated successfully with endoscopic sphincterotomy and endoprosthesis placement. Two patients with bile duct leaks and biloma formation required percutaneous or surgical drainage in addition to endoscopic treatment. Three patients had more than one complication. Two patients had strictures with retained stones above the stricture; dilation of the stricture was performed and the stones were removed. One patient with the complication of biliary leak and a long, irregular stricture was treated temporarily by sphincterotomy and stent placement while awaiting surgery. Therapeutic biliary endoscopy is a valuable, minimally invasive alternative to surgery in patients with problems arising after laparoscopic cholecystectomy.

The mechanisms of airway protection, upper esophageal sphincter (UES) opening, and their coordination during belching were studied with a concurrent videoendoscopic, videofluoroscopic, and manometric technique. Analysis of videoendoscopic recordings revealed that glottal function during gastric and esophageal belching was similar and consisted of vocal cord adduction resulting in closure of intoitus to trachea, followed by anterior-caudad movement of the glottis, followed by slitlike or triangular UES opening. When a belch episode was associated with an intragastric pressure increase, in addition to the above features, there was approximation of arytenoids to the base of the epiglottis before the UES opened. Duration of vocal cord closure during belches induced by 40 ml intraesophageal air injection was significantly longer than belches induced by 20 ml (P less than 0.01). Vocal cord closure preceded the UES opening invariably. Analysis of videofluoroscopic recordings showed that hyoid bone movement during belching had a distinctive pattern different from its movement during swallowing. UES opening started generally when the hyoid bone was pulled anteriorly. Anterior hyoid excursion of 0.78 +/- 0.1 cm during belching was significantly shorter than its excursion of 1.8 +/- 0.09 cm during swallowing (P less than 0.01). We conclude that glottal closure is an integral component of both esophageal and gastric belch reflexes that prevents aspiration of regurgitated material into the airway. Glottal closure mechanism during belching has two tiers of closure: 1) vocal cord closure and 2) aryepiglottic approximation. Glottal and UES functions are closely coordinated during belching, and finally, during belching, UES is pulled open after its relaxation.

The oesophageal acid clearance time was evaluated in 10 healthy volunteers of 'small' boluses of 0.5 and 1 ml and 'minute' boluses of 0.05 and 0.1 ml 0.1 N HCl, as well as 0.1 and 1 ml 0.01 and 0.001 N HCl. Swallow rate was normalised at q 60 seconds. For 0.1 ml 0.1 N HCl, acid clearance time was also measured for swallow intervals of q 30 and 120 seconds. Acid clearance time to restore pH to 4.0 was significantly longer (p less than 0.01) for the 0.5 and 1 ml 0.1 N HCl (210 and 273 seconds, respectively) than for the 0.05 and 0.01 ml acid boluses (83 and 94 seconds, respectively). The minimum acid clearance time was 18 seconds (0.05 ml 0.1 N HCl). Acid clearance time for 0.1 N HCl was less than one minute on only two occasions. The acid clearance times were comparable when the subjects sat upright. A longer interswallow interval--that is, 120 seconds, resulted in a significantly longer acid clearance time than shorter swallow intervals (p less than 0.05). Oesophageal acid clearance time for small acid volumes averaged more than three minutes and for minute acid volumes was generally more than one minute; and acid clearance times were comparable for the supine and upright postures, while gastrooesophageal reflux episodes causing pH drops to 3-4 may last for less than 15 seconds, substantial oesophageal pH drops to less than or equal to 1.5 that persists less than 15 seconds are difficult to be attributed to true gastrooesophageal reflux.

Background: The current standard treatment of bleeding esophageal varices is band ligation. Although endoscopic sclerotherapy has largely been supplanted by band ligation, there are still clinical situations in which injection methods are useful. Endoscopic ultrasound (EUS) may allow for a more complete evaluation of esophageal varices and perforating veins and may allow for more effective delivery of sclerosant. Our aim was to evaluate the use of color Doppler EUS-guided sclerotherapy for the obliteration of esophageal varices. Methods: Five patients with esophageal varices (Child's A = 1, B = 2, C = 2) underwent dynamic EUS-guided sclerotherapy with color flow Doppler. EUS sclerotherapy was performed using Varijet (2.5 mm catheter) injector needles and sodium morrhuate directed at the perforating vessels until flow was completely impeded (2 to 4 mL per injection site). Data collected included (1) sessions to obliteration, (2) episodes of recurrent bleeding, (3) complications, and (4) mortality. Results: Patients undergoing EUS-sclerotherapy required 2.2 sessions to achieve obliteration of varices. No patient had a recurrence of bleeding and no deaths occurred. One patient developed an esophageal stricture that responded to balloon dilation. Conclusions: Dynamic EUS-guided sclerotherapy with color flow Doppler may be safely and effectively used for the treatment of esophageal varices. It allows for effective delivery of sclerosant with favorable outcomes. Prospective, multicenter, randomized trials are warranted.

In this investigation we evaluated the effect of two new cholecystokinin (CCK) antagonists, CR 1409 and L364,718, on gallbladder emptying in the opossum. Gallbladder emptying was elicited by both exogenous and endogenous CCK. The three test challenges were 1) intravenous infusion of CCK octapeptide (OP) (10 ng.kg-1.min-1), 2) feeding, and 3) intraduodenal infusion of Isocal (0.4 ml/min), a fat-containing nutrient. During control conditions each test challenge elicited approximately 60% gallbladder emptying within 30 min and 70% emptying by 60 min. At given doses both CR 1409 and L364,718 substantially antagonized or abolished the gallbladder emptying elicited by each of the test challenges. The antagonism for postprandial gallbladder emptying was diminished between 30 and 50 min compared with that for CCK-OP infusion and intraduodenal infusion of Isocal. Unexpectedly, the gallbladder emptying induced by infusion of motilin (5 micrograms.kg-1.h-1) was antagonized by either CR 1409 or L364,718. In anesthetized animals, gallbladder contraction was induced by a variety of agonists, such as bethanechol, histamine phosphate, 5-hydroxytryptamine, and phenylephrine. In this later model CR 1409 and L364,718 functioned solely as selective antagonists. We conclude that for the opossum gallbladder 1) the CCK antagonists CR 1409 and L364,718 antagonize or abolish gallbladder emptying induced by exogenous or endogenous CCK; 2) the pattern of CCK antagonism after feeding suggests that the early phase of postprandial gallbladder emptying is mediated by a mechanism other than endogenous CCK, whereas late postprandial emptying is mediated by release of endogenous CCK; and 3) CR 1409 and L364,718 are not totally specific antagonists for gallbladder CCK receptors alone but also antagonize gallbladder contraction induced by motilin.(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic retrograde cholangiopancreatography has been shown to be a very valuable adjunct in the diagnosis of malignancy involving the biliary and/or pancreatic ductal system. However, characteristic endoscopic retrograde cholangiopancreatography radiographic findings associated with malignant strictures are frequently not specific and cytological confirmation becomes essential for the diagnosis. Unfortunately, the current overall diagnostic yield of positive cytology in such circumstances ranges from 18%-56% depending on the technique. A new brush device has been designed which is uniquely adapted to pancreaticobiliary strictures of varying anatomical configurations. This study shows results using this new cytology brush in a series of 53 patients with pancreaticobiliary malignancy. A significant improvement in the cytological yield of tumor confirmation was obtained with a diagnostic sensitivity of 70% and specificity of 100% using the new brush technique.

The goals of this study were to quantify the temporal relationship between swallow-induced glottic closure and (a) signals of swallow initiation, such as hyoid bone movement, tongue base movement, and mylohyoid electrical activity; (b) pharyngeal peristalsis; (c) laryngeal elevation; (d) vestibular closure; and (e) oropharyngeal barium bolus transit. Eight normal subjects (age 20-30 yr) were studied by concurrent transnasal video laryngoscopy, pharyngeal intraluminal manometry, and submental surface electromyography. The manometric, electromyographic, and both video recordings were synchronized with one another using a specially designed event marker. Dry, 5-ml water, and 5-ml barium swallows were recorded. Frame-by-frame analysis of the video endoscopic recordings showed that deglutitive laryngeal kinetics consisted of vocal cord adduction associated with transverse approximation of the arytenoids followed by vertical approximation of arytenoids to the base of the epiglottis followed by laryngeal ascent and epiglottic descent. Onset of swallow-induced vocal cord adduction preceded the onset of hyoid bone movement, base of the tongue movement, and submental surface myoelectric activity by 0.33 +/- 0.04 (SE) s, 0.31 +/- 0.04 s, and 0.38 +/- 0.04 s, respectively. Onset of vocal cord adduction also preceded the initiation of peristalsis in the nasopharynx and its propagation to oropharynx and upper esophageal sphincter by 0.64 +/- 0.05 s, 0.82 +/- 0.05 s, and 1.08 +/- 0.04 s, respectively. The time between the onset of vocal cord adduction and their return to full opening was 2.2 +/- 0.09 s. It was concluded that (a) among events evaluated, vocal cord adduction is the initial event during the swallowing sequence; (b) laryngeal kinetics during deglutition have distinctive features, and their close coordination with other swallowing events suggests that they are an essential feature of the swallowing program; and (c) abnormal laryngeal kinetics or lack of coordination between the glottic closure mechanism and oropharyngeal bolus transport may have an important role in swallow-induced aspiration.

Background and Study Aims: Approximately 2-7% of patients who have undergone previous removal of bile duct stones have recurrence often presenting as ascending cholangitis. The aim of this study was to identify the incidence, clinical presentation, and objective findings in this group of patients. Additionally, the effect of surveillance endoscopic retrograde cholangiopancreatography (ERCP) in preventing cholangitis, was studied. Patients and Methods: Two thousand and ninety-six patients who underwent ERCP for cholelithiasis were studied with 45 of these patients being identified as having recurrent common bile duct stones. Of the 45, 13 had two or more recurrences without having any obvious predisposing factors. The mean age of the 13 patients was 57 years. The characteristics of 13 patients were reviewed, including sphincterotomy size, liver function tests, and contrast drainage time. Results: All 13 patients with recurrent stones presented with ascending cholangitis. Stones were found to be soft, brown and accompanied by a large amount of sludge. The common bile duct in all 13 patients was noted to be dilated and had notable, widely patent sphincterotomes. There was significant delayed drainage in 77% of these patients. Yearly surveillance ERCPs were performed in the 13 patients, the incidence of acute cholangitis episodes per patient decreased from 2 to 0.6 with a four-year follow-up. Conclusion: In a subgroup of patients with multiple common bile duct stone recurrences, annual surveillance ERCP with stone removal decreases the incidence of recurrent episodes of ascending cholangitis as well as its associated morbidity and mortality.

The functional disorder of the gallbladder (GB) is a motility disorder caused initially either by metabolic abnormalities or by a primary motility alteration. The functional disorders of the sphincter of Oddi (SO) encompass motor abnormalities of either the biliary or the pancreatic SO. Dysfunction of the GB and/or biliary SO produce similar patterns of pain. The pain caused by a dysfunction of the pancreatic SO can be similar to that of acute pancreatitis. The symptom-based diagnostic criteria of motility dysfunction of the GB and biliary SO are episodes of moderate to severe steady pain located in the epigastrium and right upper abdominal quadrant that last at least 30 minutes. GB motility disorder is suspected after gallstones and other structural abnormalities have been excluded. This diagnosis should then be confirmed by a decreased GB ejection fraction induced by cholecystokinin at cholescintigraphy and after disappearance of the recurrent biliary pain after cholecystectomy. Symptoms of biliary SO dysfunction may be accompanied by features of transient biliary obstruction, and those of pancreatic SO dysfunction are associated with elevation of pancreatic enzymes and even pancreatitis. Biliary-type SO dysfunction is more frequently recognized in postcholecystectomy patients. SO manometry is valuable to select patients with sphincter dysfunction; however, because of the high incidence of complications, these patients should be referred to an expert unit for such assessment. Thus invasive tests should be performed only in the presence of compelling clinical evidence and after noninvasive testing has yielded negative findings. The committee recommends that division of the biliary or pancreatic sphincters only be considered when the patient has severe symptoms, meets the required criteria, and other diagnoses are excluded.

Background Eosinophilic esophagitis is an inflammatory condition in which there is dense eosinophilic infiltration of the surface lining of the esophagus. Reports of eosinophilic esophagitis pertain almost exclusively to pediatric populations. However, eosinophilic esophagitis is emerging as a clinical affliction of adults. This report describes the clinical and endoscopic findings of eosinophilic esophagitis in the largest cohort of adult patients reported to date. Methods Twenty-nine patients (21 men, 8 women; mean age 35 years) with documented eosinophilic esophagitis (≥15 eosinophils per high-power field in biopsy specimens) and a significant history of chronic dysphagia for solid food (24 patients) were evaluated clinically and endoscopically during a 3-year period (1999–2002). Fourteen patients (48%) had a history of asthma, environmental allergy, or atopy. In a subset of 15 patients, the diagnostic accuracy of endoscopy was compared with that of barium contrast esophagography. Results Twenty-seven patients (93%) had abnormal endoscopic findings; 25 (86%) had unique esophageal structural changes, associated with a preserved mucosal surface, that were highly atypical for acid reflux injury. Structural alterations seen in adult patients with eosinophilic esophagitis may occur in combination or as a primary characteristic, e.g., uniform small-caliber esophagus, single or multiple corrugations (rings), proximal esophageal stenosis, or 1 to 2 mm whitish vesicles scattered over the mucosal surface. Barium contrast radiography combined with swallow of a barium-coated marshmallow identified 10 (67%) of the primary features observed endoscopically in 15 patients. However, radiography failed to detect other features noted at endoscopy (e.g., only 3/6 patients with proximal stenosis, 5/9 patients with concentric rings and none of 4 patients with small caliber esophagus). Eight of the 29 patients (20%) had a history of chronic heartburn. Twelve patients had been treated with a proton pump inhibitor and only 3 reported some improvement in the severity of dysphagia. Conclusions Relatively young age, a history of chronic dysphagia for solid food, and endoscopic detection of unique structural alterations atypical for GERD in an adult patient should prompt a suspicion of EE and subsequent biopsy confirmation. Acid reflux appears to have a secondary role in eosinophilic esophagitis. In an uncontrolled comparison, endoscopy was superior to barium contrast radiography for the diagnosis of eosinophilic esophagitis. The incidence of eosinophilic esophagitis in adults appears to be increasing.

Background: Dysphagia for solids usually indicates a structural esophageal abnormality. This article is a description of a group of 5 young men referred with chronic dysphagia for solids. Esophagoscopy and barium esophagogram failed to show a cause. Our evaluation showed that these patients had eosinophilic esophagitis and a "small-caliber esophagus." This article describes the clinical features, diagnosis, and management of the small-caliber esophagus. Methods: Patients were evaluated by barium esophagogram with marshmallow challenge, esophageal manometry, Bernstein test, and EGD with biopsies. All patients underwent empiric esophageal dilation with wire-guided dilators. Observations: A diffusely narrow esophagus was appreciated in 3 of 5 patients radiographically, endoscopically, or both. However, the latter studies showed normal findings in 2 patients. Eosinophilic esophagitis was found in all 4 patients in whom biopsy specimens were obtained. Esophageal manometry was performed in 4 patients and showed normal findings in all. The feature that most confirmed the diagnosis of small-caliber esophagus in all patients was the unusually long rents (8 to 17 cm) in the esophageal wall after empiric dilation. Dilation relieved the symptoms in all cases. Conclusions: The small-caliber esophagus is a cause of dysphagia for solids in young men with eosinophilic esophagitis. It frequently defies detection by routine diagnostic studies. The clue to diagnosis lies in endoscopic reinspection after dilation and the finding of unusually long rents in the esophageal wall.

In this paper we report the case of a renal cell carcinoma (RCC) metastatic to the ampullary region. The patient presented with severe anemia due to blood loss from the ampullary tumor 11 years after nephrectomy for the primary renal cancer. The diagnosis was established by means of endoscopy and biopsy.

Background: Obstructive disorders of the pancreas, including strictures, stones, sphincter of Oddi dysfunction, and pancreas divisum, are diagnostic and therapeutic challenges. Conventional extracorporeal ultrasound with secretin stimulation has been used as a noninvasive study to detect obstruction and predict outcome of therapy. Inconsistent results have been obtained because of the inherent limitations of standard ultrasonography. The aim of this study was to evaluate the behavior of the main pancreatic duct by endoscopic ultrasonography during secretin stimulation and to diagnose obstructive disorders of the pancreas. Methods: Secretin-stimulated endoscopic ultrasound (SSEUS, 1 IU/kg secretin) was performed in 20 control subjects (no pancreatic or biliary disease), 40 patients with symptomatic chronic pancreatitis, 40 patients with symptomatic pancreas divisum, 20 patients with suspected sphincter of Oddi dysfunction, and 20 patients with suspected occlusion of pancreatic duct stents. Ductal diameter was measured by endoscopic ultrasonography at baseline and at 1-minute intervals, after administration of secretin, for 15 minutes. A result was determined to be abnormal when a 1 mm or greater dilation of the pancreatic duct was observed from baseline after secretin administration. Results: Of the 40 patients with symptomatic chronic pancreatitis, SSEUS correctly predicted obstructive pathology (stones, strictures) in 12 of 13 patients (92%). Of the 40 patients with symptomatic pancreas divisum, 22 underwent stent therapy (16 of 22 with resolution of symptoms). SSEUS accurately predicted response to stent therapy in 13 patients (81%). Seven of twenty patients with suspected sphincter of Oddi dysfunction had abnormal sphincter manometry. SSEUS accurately predicted sphincter dysfunction in only 4 of 7 patients (57%). Finally, 20 patients with suspected occlusion of pancreatic duct stents were studied. Of the 14 stent occlusions confirmed at ERCP, SSEUS correctly predicted premature occlusion in 12 patients (86%). Conclusions: SSEUS appears to be a useful diagnostic modality in the evaluation of patients with suspected obstructive disorders of the pancreas and it can predict which patients may respond to endoscopic therapy. (Gastrointest Endosc 1998;48:580-7.)

Background and study aims Although discrete ulcers are a recognized complication of Barrett's esophagus, it is not clear how common discrete ulceration is in Barrett's mucosa. Furthermore, the relationship of gastrointestinal hemorrhage to Barrett's ulceration is unknown. These issues were investigated in this paper. Methods Seventy-eight patients with histologically confirmed Barrett's esophagus were monitored by endoscopic surveillance over 1 to 11 years (mean 3.3 years). The incidence of a Barrett's ulcer was noted and its site recorded. The frequency of gastrointestinal hemorrhage at diagnosis or on follow-up was documented and the source of the bleeding was identified. Results Discrete ulcers were identified in 36 of 78 patients (46%) at some time over the period of follow-up. Eight patients had two or more ulcers. Most of ulcers were in the distal esophagus; 86% of these were within 3 cm of the anatomic gastroesophageal junction. Nineteen patients (24%) either presented with active gastrointestinal bleeding or had bleeding at follow-up. In 15 of the 19 patients with bleeding (79%) a discrete Barrett's ulcer was the source of the hemorrhage. Conclusions Ulceration is a common complication of Barrett's esophagus. These ulcers are usually located close the gastroesophageal junction and have a high incidence of bleeding.

In prior studies we found that esophageal acid exposure caused a small decrease in airway diameter, an increase in tracheobronchial mucus secretion, and a decrease in mucociliary transport rate. However, the store of mucus is not large and can easily be depleted, therefore, we hypothesized that mucus production may be under physiological control. AIM: To determine whether a physiological stimulus can affect mucus production and to investigate the mechanism of this effect. METHODS: Sixteen cats were anesthetized using alphachloralose. The esophagus was ligated 3-4 cm from the UES and the esophagus proximal and distal to the ligation was cannulated. Either the proximal (N=8) or distal (N=8) esophagus was perfused using 0.1N HCl for 30 min followed by 30 min of PBS while the opposite esophageal segment was perfused with PBS for 60 min. The trachea was excised, fixed, sliced at 5μ, and stained with Periodic Acid Schiff (PAS)-Alcian Blue (AB) at pH 1.0. The areas of neutral (PAS-positive) and acidic (AB-positive) mucosubstances in the epithelial and submucosal mucous glands of the trachea adjacent to the proximal and distal cervical segments of esophagus perfused were quantified using Image J software. RESULTS: We found that the primary type of mucous of the epithelial and submucosal mucous cells was AB-positive and PAS-positive, respectively. Acid exposure of either esophageal segment caused a greater total and PAS-positive mucous content of the submucosal cells adjacent to the HCl-administered esophagus than adjacent to the PBS-administered esophagus (Table). CONCLUSIONS: The primary types of mucosubstances of the tracheal epithelial and submucosal cells are acidic and neutral respectively. Esophageal acid exposure increases mucus production of neutral mucosubstances of the tracheal submucosa probably through the previously identified local direct neural connection between the esophagus and trachea. We hypothesize that this pathway is part of the innate tracheal defense mechanism which prepares the trachea for acid exposure due to gastric reflux. Effects of HCl and PBS on Tracheal Mucous Content

Introduction: The mechanisms involved in the development of acute cholelithiasis in humans are unclear. The pathologic changes associated with cholecystitis are similar whether or not gallstones are present. These abnormalities can be reproduced in the guinea pig model following ligation of the common bile duct for periods of 1 to 3 days. Muscle strips from this experimental model exhibit a defective contraction that has not been characterized. Functional alterations in gallbladder muscle cells were investigated by this research group.

Background:Management of supraesophageal reflux disease complications of poses a significant clinical challenge. Acid suppressive therapy does not prevent volume refluxate into the pharynx and as such in a substantial percentage of these patients outcome of medical management has been disappointing. The efficacy of a novel “UES Assist Device” in preventing of simulated pharyngeal reflux in experimental setting have been recently reported. (Shaker et al. DDW 2010) The aim of the present study was to test the efficacy of the “UES Assist Device” in management of supraesophageal symptoms of reflux disease in a clinical trial. Method: We studied 14 patients with a variety of supraesophageal symptoms most notably chronic cough, excess phlegm and throat clearing referred from GI clinic in our institution. Participants filled out a detailed symptom questionnaire at baseline and following application of the device with randomly applied therapeutic and sub-therapeutic pressure assist. Symptoms were quantified using a 5-pont Likert scale. Each therapeutic modality was tested randomly for 7 days. Result: All patients tolerated the device well and completed the study. There were no complications or complaints for the use of the device. The global symptoms severity and impact score for therapeutic and sub-therapeutic pressure assist was significantly lower than that of the baseline. In addition, therapeutic pressure assist resulted in a significantly lower symptom severity compared to sub-therapeutic pressure assist (p=0.003 ANOVA) . (Figure) Furthermore, therapeutic pressure assist significantly decreased the most bothersome symptom compared to sub-therapeutic pressure assist (p

Seventeen patients, 15 women and 2 men with upper abdominal pain categorized to biliary group I suspected sphincter of Oddi dysfunction, underwent thorough clinical evaluation including ERCP and endoscopic sphincter of Oddi manometry. All the patients were subsequently treated by endoscopic (n = 15) or surgical (n = 2) sphincterotomy. The mean age of patients studied was 62 years. They all had cholecystectomy several years previously (median, 18 years). At ERCP all patients showed a large common bile duct dilation (mean diameter, 18 mm) and delayed contrast drainage greater than 45 minutes. Sphincter of Oddi manometry, although abnormal in most patients, revealed normal sphincter of Oddi pressure in six patients (35%). Nonetheless, sphincterotomy resulted in relief of symptoms in all (mean follow-up, 28 months; range, 3 to 46 months), thus suggesting that their pain was indeed caused by the disordered sphincter of Oddi. These findings support the previous assumption that in symptomatic post-cholecystectomy patients the triad of elevated liver function tests, dilated common bile duct, and delayed contrast drainage at endoscopic retrograde cholangiopancreatography indicates a definitive sphincter of Oddi abnormality. The normal sphincter of Oddi pressures in many of these patients are probably due to a different, noncompliant type of sphincter of Oddi dysfunction. Because these patients invariably benefit from sphincterotomy, sphincter of Oddi manometry in this category is not only unnecessary, but it may also be misleading.

A symptomatic lower esophageal ring generally responds to standard bougienage therapy. However, a subset of patients with a lower esophageal ring defy dilation therapy. We have evaluated the efficacy of electrocautery incision of "defiant" lower esophageal rings, the data of which forms the basis of this report. Seven of 75 patients with a lower esophageal ring failed to respond to conventional esophageal dilation. All seven patients underwent electrocautery incision of a "defiant" lower esophageal ring with alleviation of dysphagia. One patient had recurrence of dysphagia that occurred 6 months after initial electrocautery incision. No major complication occurred, although one patient had transient chest pain. Subsequently, all patients have remained without symptoms at a mean follow-up of 36 months. Electrocautery incision of "defiant" lower esophageal ring is efficacious, safe, and results in long-term relief of dysphagia.

Previous manometric studies of esophageal fluid bolus transport in humans have generally ignored the hydrodynamic distinction between intrabolus pressure and pressure within the lumen-occluded, contracting esophageal segment. In this study we obtained concurrent esophageal videofluoroscopic and intraluminal manometric recordings in supine normal volunteers using different bolus volumes and viscosities and abdominal compression. Intrabolus pressure increased with bolus volume, viscosity, and abdominal compression. Esophageal diameter increased with larger bolus volumes, and this increase was correlated with increases in intrabolus pressure. Intrabolus pressure was highest in the bolus tail. Peak intraluminal pressures > 20 mmHg above basal intrabolus pressure almost invariably were associated with effective peristalsis, whereas values of this pressure differential < 20 mmHg frequently were associated with ineffective peristalsis and retrograde bolus escape. Intrabolus pressure can serve as an important indicator of the forces resisting peristaltic transport and the occurrence of ineffective bolus transport.

Background Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that is characterized by recurrent episodes of intense vomiting. There are several postulated mechanisms involved in its pathogenesis and one potential explanation for this disorder may be linked to autonomic dysfunction. The aim of our study was to evaluate autonomic nerve function in patients with CVS prospectively. Methods We tested the sympathetic nervous system through postural changes in heart rate (HR) and blood pressure and the thermoregulatory sweat test. The parasympathetic nervous system was tested through the HR response to deep breathing (R-R variability on EKG). Key Results A total of 20 patients who met Rome III criteria for CVS, 14 (70%) women and 6 (30%) men, and 20 controls were enrolled in the study. A total of 17 (85%) CVS subjects and 2 (10%) controls had abnormalities on thermoregulatory sweat testing (P 30 on standing. Of the subjects, 18 (90%) had either abnormal sudomotor function or postural tachycardia or both. The HR response to deep breathing was normal in 19 (95%) subjects with CVS and 18 (95%) controls. Conclusions & Inferences The results of this study suggest that the majority of subjects (90%) with CVS have impairment of the sympathetic nervous system with postural tachycardia and/or sudomotor dysfunction while parasympathetic nerve function appears to be intact. These findings of dysautonomia in CVS have implications in both the diagnosis and treatment of these patients.

Abrupt esophageal distention occurs commonly during gastroesophageal reflux, thereby generating a circumstance favorable to esophagopharyngeal regurgitation and laryngeal aspiration of gastric refluxate. The aims of the present study were to examine the glottal response to esophageal distention by air and regional esophageal distention by a balloon. Fifteen healthy volunteers (age, 25 +/- 5 years) were studied while they were in an upright position. Using concurrent videoendoscopy and manometry, glottal and upper esophageal sphincter (UES) responses to abrupt esophageal distention by air injection (10-60 mL) and balloon distention (1.5, 2.0, and 2.5 cm) were recorded simultaneously. In addition, 6 subjects were studied with concurrent synchronized videofluoroscopy. Results showed that esophageal distention by air at a threshold volume of 10-60 mL caused vocal cord closure. The UES response to this threshold volume was variable. Volumes larger than the threshold value caused complete UES relaxation and belching. In addition to vocal cord closure, belching was accompanied by anterior movement of the glottis. On videofluoroscopy, the hyoid bone moved anteriorly in association with belching, but not with vocal cord closure without belching. Proximal esophageal distention by the balloon also provoked vocal cord closure. This response was less consistent for balloon distention in the middle and distal esophagus. It is concluded that (a) esophageal distention by either air or a balloon evokes a glottal closure mechanism, thereby suggesting the existence of an esophagoglottal reflex; (b) this reflex is elicited most easily by distention of the proximal esophagus; (c) glottal and UES responses to esophageal distention are independent from each other; and (d) the esophagoglottal closure reflex may play an important role in preventing laryngeal aspiration of acid due to gastroesophageal reflux accompanied by acid regurgitation into the pharynx.

Regional differences in the esophageal distribution and clearance of refluxed gastric acid was studied in seven asymptomatic volunteers and seven patients with reflux esophagitis. Intraluminal pH was recorded for 3 postprandial hours from the distal, middle, and proximal esophagus on two separate occasions (with subjects in upright and supine positions). With the subjects in a supine position, about half of the acid reflux episodes reached the proximal esophagus in patients as well as in controls. This percentage decreased to 25% in patients and 29% in controls when they were upright. In both groups, the pH drops in the distal esophagus were significantly greater than in the proximal esophagus for both the supine and upright positions. In both patients and controls, a 4-5-fold greater acid exposure occurred in the distal esophagus, than in the proximal esophagus. In both patient and control groups, acid exposure time, as well as the number of reflux episodes in the distal esophagus, were significantly greater than that of the proximal esophagus (P less than 0.05). Spontaneous acid clearance time in the distal esophagus was significantly longer than that of the proximal esophagus in both positions (P less than 0.05) for both subject groups. In conclusion, regional differences exist in the exposure of the esophageal mucosa to refluxed gastric acid. These regional differences are more pronounced when subjects are upright than supine. Regional differences also exist in esophageal acid clearance, with clearance taking longer in the distal esophagus than in the proximal esophagus. The net effect of these phenomena is that acid exposure time in the distal esophagus is greater than that in the remainder of the esophagus.

This study shows a patient who presented with intermittent biliary tract obstruction caused by ampullary hamartoma. Endoscopic retrograde cholangiopancreatography showed a large ulcerated papilla and dilated biliary ducts. Tissue diagnosis was established by a large particle biopsy obtained with a snare. The patient underwent a successful endoscopic sphincterotomy and has remained symptom free for 4 years.

Using a minimally compliant infusion system and a triple-lumen pressure recording catheter, we obtained endoscopic manometric measurements from both the common bile duct and pancreatic duct segments of the sphincter of Oddi (SO) in 58 patients. Fifteen patients (ages 27–69) had the diagnosis of functional abdominal pain, 19 patients (ages 30–76) had partial biliary obstruction, and 24 patients (ages 15–80) had idiopathic acute recurrent pancreatitis. Resting ductal pressure was similar in the common bile duct and pancreatic duct in all patient groups. In the group with functional pain, basal SO pressure was similar, whether obtained from the common bile duct or pancreatic duct sphincteric segment. Eight of 19 patients with partial biliary obstruction had elevated basal SO pressure. Five of these eight patients had elevated basal SO pressure confined exclusively to the common bile duct segment of the sphincter, while three patients had elevated basal SO in both segments. Conversely seven of 24 patients with acute recurrent pancreatitis had an elevated basal SO pressure, with five patients having pressure elevation only in the pancreatic duct segment while two patients had abnormal basal SO pressure in both segments. We conclude that selective cannulation of the common bile duct and/or the pancreatic duct during manometric study of the SO is necessary in order to diagnose segmental SO dysfunction responsible for partial biliary obstruction or episodes of acute recurrent pancreatitis.

In conscious opossums, we evaluated the relationship between hepatic bile flow and the intestinal motor function during fasting as well as after feeding. In six opossums, bipolar electrodes were implanted from the gastric antrum to the terminal ileum. After cholecystectomy, the common duct was ligated, and a catheter was tied into the proximal common duct for collecting hepatic bile. During subsequent studies, hepatic bile flow was measured, and bile was returned to the duodenum through an externalized duodenal catheter. Cyclic increases in bile flow during fasting did not show a close correlate with the duodenal migratory motor complex (MMC) cycle. Rather, bile flow showed peak values [0.11 +/- 0.02 (SE) ml/min] when phase III MMC activity reached the midileum. Hepatic bile flow correlated closely with the amount of bile acid secreted by the liver. When the bile acid pool was depleted by diverting bile from the intestine, hepatic secretion of bile fell to uniformly low values of approximately 0.04 ml/min that did not show cyclic variation. Hepatic bile flow after feeding increased to a maximal value of 0.12 +/- 0.01 ml/min at 90 min. We conclude that increases in hepatic bile flow during fasting and after meals are determined mainly by variations in intestinal motor activity that alter small bowel transit and thereby affect the enterohepatic circulation of bile acids.

The reproduction of a patient's biliary-type pain upon initial injection of contrast material into the common bile duct during diagnostic ERCP is a dramatic experience for both patient and physician. The significance of this phenomenon is not clear, but it is touted by some to be a provocative test for sphincter of Oddi dysfunction. Sphincter of Oddi manometry was performed on 224 consecutive patients referred over a 2-year period for evaluation of post-cholecystectomy syndrome and suspected sphincter of Oddi dysfunction. All patients received only intravenous diazepam as premedication for ERCP. Delayed drainage time (greater than 45 min), bile duct dilation (greater than or equal to 12 mm), and a basal sphincter of Oddi pressure of greater than 40 mm Hg (mean +/- 3 SD) were considered elevated. We observed a reproduction of pain in 15 of 224 patients (6.7%) immediately following contrast injection. There was no correlation between pain on contrast injection and elevated basal sphincter of Oddi pressure, delayed common bile duct drainage, bile duct dilation, or abnormal liver enzymes. Therefore, we feel that reproduction of the patient's biliary-type pain associated with contrast injection of ERCP is not a provocative test for sphincter of Oddi dysfunction.

The present study evaluated the mechanism of cholecystokinin-induced gallbladder contraction in awake opossums. Each of 19 chronic animal preparations had an indwelling gallbladder cannula for monitoring changes in gallbladder volume and a jugular catheter for administration of cholecystokinin octapeptide and drugs. An intraduodenal catheter allowed intraduodenal infusion of Isocal (Mead Johnson Laboratories, Evansville, Ind.). Bipolar electrodes in the stomach, duodenum, and jejunum enabled monitoring of the duodenal migratory myoelectric complex cycle. One-hour infusions of cholecystokinin octapeptide (10 ng/kg/min), intraduodenal Isocal (0.4 ml/min), or feeding were started 20 min after cessation of phase 3 duodenal migratory myoelectric complex activity. Bolus intravenous doses of potential pharmacological antagonists were given 10 min before and 20 min after the onset of cholecystokinin octapeptide infusion, Isocal infusion, or feeding. Each test challenge induced about 60% gallbladder emptying at 30 min and 70% at 60 min. Cholecystokinin octapeptide-induced gallbladder emptying was converted to filling by hexamethonium and nearly abolished by atropine. Similar results were obtained for gallbladder emptying induced by feeding or duodenal infusion of Isocal. Phentolamine caused a modest decrease of cholecystokinin octapeptide-induced gallbladder contraction at 30 min, whereas postprandial or Isocal-induced gallbladder contraction was unaffected. Cholecystokinin octapeptide-induced gallbladder contraction was not affected by pirenzepine, 4-diphenylacetoxy-N-methylpiperidine methiodide, prazosin, pyrilamine, cimetidine, methysergide, naloxone, or propranolol. In acute studies of anesthetized animals, gallbladder contraction induced by a Dloa intravenous bolus of cholecystokinin octapeptide (800 ng/kg) was not antagonized by hexamethonium, atropine, or tetrodotoxin. It is concluded (a) that cholecystokinin-induced physiologic contraction of the opossum gallbladder occurs through neural mechanisms rather than by a direct action of cholecystokinin on gallbladder smooth muscle, and (b) that studies using pharmacologic bolus doses of cholecystokinin octapeptide and tetrodotoxin indicate that cholecystokinin receptors exist on the gallbladder smooth muscle which do not seem to have any physiological role in gallbladder emptying.