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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.

Cyclic vomiting syndrome (CVS) is a chronic disorder characterized by episodic nausea and vomiting. A large proportion of patients use marijuana to control their symptoms. Several case reports implicate marijuana as a cause of intractable vomiting with compulsive hot water bathing considered pathognomonic of "cannabinoid hyperemesis." We sought to examine the relationship between marijuana use and CVS. Patients >18 years of age diagnosed by a health care provider were invited to participate in an anonymous internet-based survey. A total of 514 patients participated and 437 completed questions about marijuana use. Mean age was 34 ± 12 years with patients being predominantly female (63%), Caucasian (92%) and from the USA (82%). Nineteen percent never used marijuana and 81% did. Fifty-four percent used marijuana for health issues and 43% for recreational purposes. Users stated that it improved nausea, appetite, general well-being, stress levels and vomiting. Users were more likely to be male and have an associated anxiety disorder. Sixty-seven percent of patients reported taking hot showers/baths for symptom relief, and this was associated with marijuana use. (OR 2.54, CI 1.50-4.31, P = 0.0006). Eighty-one percent of patients with CVS who completed an internet survey reported frequent use of marijuana. With marijuana use, patients noted the greatest improvement with stress levels, appetite and nausea. Marijuana users were more likely to be male and have associated anxiety. Hot showers were not pathognomonic of marijuana use though they were more likely to be associated with its use.

Management of esophageal dysfunction must be addressed in order to optimize swallow function and, often, patient perception of function. Increased presentation of eosinophilic esophagitis (EoE) has been identified in patients across the lifespan. This article expounds upon the clinical manifestation, diagnostic indicators, and treatment management of EoE. Researchers are currently exploring treatments commonly found in the pediatric literature and finding them to possibly have positive outcomes with the adult population.

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.

SUMMARY Five cases of Sandifer syndrome are reported, and the authors suggest that frequently the diagnosis may be overlooked, especially when the patient has a milder or incomplete form of the syndrome. None of the children had hiatal hernia, so this is not an essential requirement for the syndrome. The findings in these five cases suggest that the abnormal posturing associated with this syndrome may be the result of extreme sensitivity of the esophagus to refluxed gastric acid. RESUME Le syndrome de Sandifer: une entile clinique depreciee Cinq cas de syndrome de Sandifer sont rapportes et les auteurs suggerent que le diagnostic peut etre souvent neglige, specialement quand le malade presente une forme legere ou incomplete du syndrome. Aucun des enfants n'avaient de hernie hiatale et celle-ci n'est done pas une manifestation essentielle du syndrome. Les donnees des cinq cas suggerent que les postures anormales associees au syndrome peuvent etre le resultat de l'extreme sensibilite de l'oesophage au reflux d'acide gastrique. ZUSAMMENFASSUNG Sandifer Syndrom: ein wenig beachtetes klinisches Bild Es wird uber funf Falle mit einem Sandifer Syndrom berichtet. Die Autoren sind der Ansicht, daB die Diagnose vermutlich haufig nicht gestellt wird, besonders dann, wenn der Patient eine mildere oder inkomplette Form des Syndroms aufweist. Keines der Kinder hatte eine Hiatushernie, diese ist also fur das Syndrom nicht ausschlaggebend. Die Befunde dieser fiinf Falle lassen vermuten, das die Fehlhaltung, die bei diesem Syndrom auftritt, moglicherweise mit der starken Empfindlichkeit des Oesophagus gegen die aufsteigende Magensaure zusammenhangt. RESUMEN Sindrome de Sandifer: una entidad clinica no apreciada Se aportan cinco casos de sindrome de Sandifer y los autores sugieren que con frecuencia el diagnostico puede ser pasado por alto, especialmente cuando el paciente tiene una forma menor o incompleta del sindrome. Ninguno de los nifios tenia una hernia de hiato, por lo que este no es un requisito esencial para el sindrome. Los hallazgos en los cinco casos sugieren que la anomalia postural asociada con este sindrome puede ser el resultado de un a extrema sensibilidad del esofago al reflujo acido gastrico.

The genesis of lower esophageal sphincter (LES) pressure in anesthetized opossums is a myogenic phenomenon without excitatory neural input. The mechanism responsible for generating phasic LES pressure phenomena in unanesthetized opossums, however, is not established. In this study, we evaluated the effects of potential pharmacological antagonists on LES pressure phenomena in unanesthetized opossums. We also compared LES responses to pharmacological excitatory agonists in anesthetized and unanesthetized animals. In awake animals the LES exhibited substantial tone as well as characteristic phasic activity. The tonic, or basal, LES pressure did not change during cycling of the migratory motor complex (MMC). However, atropine, 4-diphenylacetoxy-N-methylpiperidine methiodide, and hexamethonium abolished the phasic, MMC-related LES contractions while having no effect on basal pressure. Pirenzepine, prazosin, propranolol, pyrdamine, naloxone, and haloperidol did not affect either phasic or tonic LES pressure phenomena. Anesthesia substantially reduced the excitatory LES response to motilin but not to bethanechol, cholecystokinin-octapeptide, pentagastrin, or phenylephrine. The results suggest that phasic LES contractions related to the MMC cycle are mediated by postganglionic cholinergic nerves with nicotinic ganglionic transmission. Basal LES tone, however, is maintained by a myogenic phenomenon. Anesthesia reduces excitatory LES responses induced by motilin, which acts via excitatory nerves, but has no effect on excitatory responses induced by agents that act mainly or exclusively on LES smooth muscle.

To characterize gastroesophageal reflux episodes and esophageal acid clearance in patients with reflux esophagitis, we obtained 12-hour overnight esophageal pH and manometry recordings in 20 patients with macroscopic reflux esophagitis and in 15 healthy volunteers. Compared to the control subjects, the patients had less pressure in the lower esophageal sphincter (LES) and higher rates of reflux, acid clearance time, and esophageal acid exposure. However, many patients had normal values for one or more of these variables. Transient LES relaxation accounted for 96% of reflux episodes in control subjects and 60% in patients. The remaining 40% of reflux episodes in patients occurred as stress or free reflux. In the control subjects, only one reflux episode occurred during estimated sleep. Of 22 reflux episodes during estimated sleep in patients, most were associated with low basal LES pressure. During esophageal acid clearance, the major esophageal motor event was swallow-induced peristalsis rather than secondary peristalsis. We conclude that esophagitis patients have lower LES pressures, more reflux episodes, impaired esophageal acid clearance, and more esophageal exposure to acid than control subjects. Individual patients, however, exhibit heterogeneous abnormalities with respect to these variables. Transient LES relaxation is the major mechanism of gastroesophageal reflux in both patients and healthy subjects.

Previous studies of distensibility of the gastroesophageal junction (GEJ) in humans have not tried to distinguish between the effects of muscle action and passive elastic tissue properties of the GEJ. We studied 15 healthy subjects (ages 23–67 yr, 11 men/4 women) by using a catheter with a highly complaint bag positioned manometrically at the GEJ. The bag was distended with air at a rate of 20 ml/min while intrabag pressure was recorded. Distensions were performed during normal breathing, with breath held at maximum inspiration (MI) to activate the diaphragmatic crura, and with midesophageal balloon distension (BD) to relax the lower esophageal sphincter. In 10 subjects, distensions were performed after atropine injection (12 μg/kg iv). Pressure-volume curves and incremental distensibility values were calculated and compared among the different conditions. Both MI and BD significantly altered the slopes of the pressure-volume curves, whereas no effect was seen with atropine. Maximum distensibility was seen at the volume increment of 5–10 ml and was reduced with larger volumes. Distensibility measurements for the various test conditions tended to converge at the largest volume increment, suggesting that distensibility at this degree of distension was more related to the passive elastic properties of the GEJ. On the basis of these findings, we conclude that there can be significant active muscular contributions to recordings of distensibility at the GEJ, variations that must be controlled for during different study conditions.

Endoscopic treatments of gastroesophageal reflux disease (GERD) are a new and potentially useful form of therapy for reflux disorders. This type of treatment was first introduced at Digestive Disease Week (DDW) in 2000, and the most recent DDW, in 2003, included a growing number of abstracts describing further experience with endoscopic GERD treatments. The studies are still generally open-label trials involving relatively small patient groups given a variety of unique endoscopic GERD treatments, including radiofrequency, thermal ablation, plication suturing, and polymer injection and implantation techniques. Longer patient follow-up after Stretta (Curon Medical, Sunnyvale, CA) procedures, the permanency rate of EndoCinch (Bard Interventional Products, Billerica, MA) plication sutures, and new experiences with Enteryx (Boston Scientific, Natick, MA) and Gatekeeper (Medtronic, Minneapolis, MN) procedures were highlighted at DDW 2003. Despite these unique devices with significant potential for treatment of GERD, caution was expressed concerning their clinical use in anything other than appropriately designed, scientifically validated clinical trials.

The US Food and Drug Administration has approved 2 endoscopic devices for treating gastroesophageal reflux disease, and several thousand procedures have been performed to date. At least 6 other endoscopic devices designed to treat gastroesophageal reflux are in various stages of testing and may soon obtain approval for clinical use. Short-term follow-up studies uniformly report improvement in heartburn symptoms and quality-of-life scores, as well as decreases in use of antisecretory medications. However, esophageal acid reflux is not normalized after these treatments, nor is esophagitis improved. Although troubling efficacy and safety issues are currently unresolved, these techniques are becoming routine clinical procedures outside of clinical trials. Unless there is rigorous attention to scientific validation of these techniques, including comparative trials versus conventional treatments, there will remain a cloud of doubt and concern about their role and usefulness in clinical medicine. The rapid incursion of these devices into the clinical marketplace before they have undergone critical scientific scrutiny magnifies the urgency of addressing these issues.

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.

Many new and developing endoscopic techniques for treatment of gastroesophageal reflux disease (GERD) are now or will soon be available for clinical use. These new therapies are directed to the gastroesophageal junction and include three basic techniques, which are outlined in this review: thermal remodeling and neurolysis of the lower esophageal sphincter (LES) zone; bulking or reinforcing of the LES; and plicating gastric folds at the gastric cardia. Only two of these treatments, radiofrequency ablation and fundic fold plication, have been approved by the US Food and Drug Administration (FDA). Published clinical research on endoscopic treatment is reviewed, although it is mostly comprised of open-label trials and anecdotal clinical reports. Complications of endoscopic GERD treatments are described as well as real and potential pitfalls of these techniques. Problems caused by premature introduction of endoscopic GERD treatments into the marketplace are also discussed, along with the rationale for FDA approval of similar devices.

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.

Starting July 1, 2001, Medicare began to reimburse for screening colonoscopy in asymptomatic adults older than 50 yr with no risk factors for colorectal cancer. We sought to determine the short-term impact of the change in Medicare reimbursement on the demand for and yield of screening colonoscopy at our tertiary institution.Asymptomatic patients older than 50 referred for first screening colonoscopy after the change in Medicare reimbursement from July 1, 2001 to December 31, 2001 were compared with a similar cohort screened before Medicare coverage for a family history of cancer or polyps during the same months the previous year (July 1, 2000 to December 31, 2000). Patient demographics, number, size, location, and histology of polyps/cancers for these screening colonoscopies were collected.A total of 1282 colonoscopies were performed in our institution from July 1, 2001 to December 31, 2001, 257 (20%) for screening. During the same months in the previous year, 121 of 938 colonoscopies (12.9%) were for screening (p0.01). This was a 55% increase in the percentage of colonoscopies performed for screening, and a 112% increase in the number of screening colonoscopies. Patients screened after the change in Medicare reimbursement were on average 5 yr older compared with patients of the previous year (62 +/- 10 [mean +/- SD] vs 56 +/- 9 yr; p0.01). A total of 61 screening colonoscopies (24%) performed after the change in Medicare reimbursement had adenomatous lesions, compared with 25 (21%) screened for family history (p = ns). The number of adenomas 10 mm or larger or cancers did not differ significantly between the two groups (17 in 2001 vs 12 in 2000; p = ns). Age of 65 or older was associated with detection of adenomatous lesions (OR = 1.7; 95% CI = 1.01-2.9013).Since the change in Medicare reimbursement, there has been a significant increase in the number and proportion of colonoscopies performed for screening at our institution. Patients screened since this change are older, and the detection rate of neoplastic lesions is similar to those previously screened for a family history of colorectal cancer or polyps.

Background: Fundoplication is now almost exclusively a laparoscopic procedure. The aim of this study was the comparison of the diagnostic usefulness of endoscopy and barium esophagram in the detection of fundoplication abnormalities. Methods: Twenty-two patients presented with symptoms post-laparoscopic (Nissen) fundoplication that included dysphagia (14 patients), heartburn (5 patients), dyspepsia (2 patients), and chest pain (1 patient). Barium esophagram and upper endoscopy were performed in all patients and the results were compared. Key features included presence of esophagitis, resistance to endoscope passage, location of the wrap relative to the diaphragmatic hiatus, location of squamocolumnar junction greater than 1 cm proximal to the wrap zone, and the appearance of the wrap (intact, loose, disrupted, or tight). Results: The key features explained symptoms in 20 of 22 patients. Endoscopy detected twice as many key features as radiography. Disruption of the wrap or excessive proximal location of the squamocolumnar junction proximal to the wrap zone were the most incriminating endoscopic findings. Resistance to endoscope passage was rarely encountered and the esophagram was more accurate in detecting an overly tight wrap. Conclusions: Endoscopic evaluation is more accurate than barium esophagram in detecting post-fundoplication abnormalities. The appearance of the fundoplication wrap and an abnormal proximal location of the squamocolumnar junction appear to be major endoscopic clues in diagnosis of post-fundoplication problems. (Gastrointest Endosc 2001;54:351-6.)

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 use of operative therapy for GERD and hiatal hernia repair has increased substantially during the last 5 years because of the advent of “minimally invasive” laparoscopic techniques. Because of the increased use of surgery, physicians are more frequently encountering patients with symptoms and complications after operation. An extensive diagnostic evaluation is often necessary before the cause of the patient’s problem is defined and specific efforts to improve or eliminate symptoms can be undertaken. Endoscopy is a key diagnostic modality in the assessment of patients who develop symptoms after anti-reflux surgery. To maximize the information obtained by endoscopic examination, it is critical that the physician endoscopist be able to define the normal appearances for the various antireflux surgeries as well as recognize postoperative problems. The present review summarizes current knowledge and also compiles the authors’ consensus opinions based on extensive experience.

Background After patients have undergone colonoscopic polypectomy, it is uncertain whether colonoscopic examination or a barium enema is the better method of surveillance. Methods As part of the National Polyp Study, we offered colonoscopic examination and double-contrast barium enema for surveillance to patients with newly diagnosed adenomatous polyps. Although barium enema was performed first, the endoscopist did not know the results. Results A total of 973 patients underwent one or more colonoscopic examinations for surveillance. In the case of 580 of these patients, we performed 862 paired colonoscopic examinations and barium-enema examinations that met the requirements of the protocol. The findings on barium enema were positive in 222 (26 percent) of the paired examinations, including 94 of the 242 colonoscopic examinations in which one or more adenomas were detected (rate of detection of adenomas, 39 percent; 95 percent confidence interval, 33 to 45 percent). The proportion of examinations in which ...

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.

Background: The clinical significance of incomplete pancreas divisum (IPD) has not been fully described. In this study we report the clinical presentation and results of endoscopic treatment of the 32 (0.6%) patients with IPD seen at our center over a 10-year period. Methods: The study population consisted of 24 women and 8 men (mean age 42 years, range 13 to 82 years). Ten (31%) patients presented with acute recurrent pancreatitis, 5 (16%) with chronic pancreatitis, and 3 (9%) with pancreatic type pain. Detailed history, laboratory tests, US, CT, and ERCP excluded other etiologies for their symptoms. The remaining 14 (44%) presented with biliary problems. The 18 symptomatic patients with IPD were treated as follows: 8 received dorsal duct stents, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, 4 had minor papilla dilatation only, and 3 had ventral duct stents placed. Results: Patients were then followed for recurrence of pancreatitis and pancreatic-type pain. Mean follow-up was 15.5 months (range 3 to 30 months). Six (60%) of the patients with acute recurrent pancreatitis and 4 (80%) with chronic pancreatitis benefitted from the endoscopic therapy. However, only 1 (33%) of the patients with pancreatic-type pain benefitted. Conclusion: The clinical presentation and response to endoscopic therapy of patients with ICP appeared to be similar to that of patients with complete pancreas divisum. (Gastrointest Endosc 1999;49:53-7.)

Background: Chronic pancreatitis in its early stages may defy diagnosis despite existing diagnostic modalities. Endoscopic retrograde pancreatography (ERCP), secretin test, and conventional ultrasound are insensitive in detecting the early stages of chronic pancreatitis. The aim of this study was to determine whether endoscopic ultrasonography (EUS) high-resolution imaging allows for the detection of chronic pancreatitis as compared with clinical history, ERCP, and secretin test. Methods: Eighty consecutive patients with recurrent pancreatitis underwent ERCP, EUS, and secretin test. EUS evaluated parenchymal changes: echogenic foci (calcification), prominent interlobular septae (fibrosis), small cystic cavities (edema), lobulated outer gland margin (fibrosis/atrophy), and heterogeneous parenchyma; and ductal changes: dilation, irregularity, echogenic wall (fibrosis), side-branch ectasia, and echogenic foci (stones). EUS criteria for chronic pancreatitis included mild (1 to 2 features), moderate (3 to 5 features), and severe (more than 5 features). Results: Abnormal studies were EUS=63, ERCP=36, and secretin test=25. Secretin test had 100% agreement with normal and severe chronic pancreatitis by EUS criteria, but agreement was poor for mild (13%) and moderate (50%) disease. Alternatively, the agreement between ERCP- and EUS-specific criteria was excellent for normal (100%), moderate (92%), and severe (100%) chronic pancreatitis and poor for mild (17%) disease. When the 2-test modality (ERCP and secretin test) was compared with EUS alone, no enhancement in agreement was seen. Conclusion: Using the above criteria EUS may assist in the diagnosis of chronic pancreatitis not established by ERCP or secretin test. Excellent agreement can be expected between EUS and ERCP in the diagnosis of chronic pancreatitis with the exception of mild changes noted on EUS (kappa statistics=0.82: 95% CI [0.70, 0.95]). Long-term follow-up of the patients with mild EUS changes will determine the validity of EUS in diagnosing the early stages of chronic pancreatitis. (Gastrointest Endosc 1998;48:11-7.)

Perendoscopic treatments of gastroesophageal reflux have been used in clinical practice following FDA approval of the first two devices in 2000. A number of clinical trials predominantly short-term have been performed almost uniformly demonstrating patient improvement in GERD symptomatology and reduction or elimination of antacids. However, only two of these endo reflux treatment trials have included the essential elements of strict patient entry criteria, randomization, attempts at blending, and intention-to-treat analysis. Two new endoscopic antireflux trials are published in this issue of the journal. The first study compares the EndoCinch sewing device to the Enteryx copolymer injection procedure. The second report compares the EndoCinch technique to the laparoscopic fundoplication procedure. Unfortunately, both studies lack a sham-control population and have other important flaws in design. Basically, all these techniques improved GERD symptoms and well-being and decreased the patients PPI requirement during follow-up period. However, none of the endoscopic procedures reduced acid reflux impressively or improved lower esophageal sphincter tone, a consistent negative outcome with all these techniques. Morbidity was associated with all the procedures and Enteryx has been withdrawn recently from clinical use by the manufacturer because of significant complications. The efficacy durability and safety of these devices in treating GERD patients is in question. A moratorium on the continued use of the procedures in clinical practice seems appropriate at this time.

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: Glucagon is often used to inhibit duodenal motility and enhance cannulation during ERCP. Levsin is an antimuscarinic, anticholinergic agent that may be as effective as glucagon. Methods: Three hundred eight patients requiring an antimotility agent during ERCP were randomized in a double-blind prospective study to intravenous Levsin or glucagon. Parameters recorded included difficulty of procedure, predrug and postdrug motility grade, effectiveness of medication, patients requiring "crossover" drug, side effects, and cost per case. Results: One hundred fifty-three patients were randomized to glucagon and 155 to Levsin. The two groups were equally matched with regard to patient and procedure characteristics. Of statistical significance were the following: (1) 12 patients in the Levsin group required crossover compared to 1 patient in the glucagon group, (2) Levsin was slightly less effective in inhibiting motility, but this did not adversely influence procedure difficulty, (3) Levsin was associated with more minor side effects (nausea, vomiting, and pain) at 2 hours after the procedure (Levsin 36 of 143, glucagon 24 of 152, p = 0.045) but there was no difference in pancreatitis (glucagon 6, Levsin 8), (4) Levsin was associated with a significant cost advantage (Levsin $10.45/case, glucagon $29.51/case, p Conclusion: Levsin may provide a reasonable alternative antimotility agent during ERCP. Levsin does not appear to alter the rate of significant postprocedure complications. The cost benefit advantage appears to be substantial.(Gastrointest Endosc 1997;46:42)

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.

Background Cyclic Vomiting Syndrome (CVS) is a well-recognized functional gastrointestinal disorder in children but its presentation is poorly understood in adults. Genetic differences in pediatric-onset (presentation before age 18) and adult-onset CVS have been reported recently but their clinical features and possible differences in response to therapy have not been well studied. Methods This was a retrospective review of 101 CVS patients seen at the Medical College of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the diagnosis of CVS. Results Our study population comprised of 29(29%) pediatric-onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 ± 7 years) in the pediatric-onset group when compared to (5 ± 7 years) adult-onset CVS group (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group compared to adult-onset patients (0% vs. 23%, p = 0.004). Aside from these differences, the two groups were similar with regards to their clinical features and the time of onset of symptoms did not predict response to standard treatment. The majority of patients (86%) responded to treatment with tricyclic antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine. Non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of emergency department visits in the year prior to presentation, presence of disability and non-compliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response. (88% vs. 38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05). Conclusion Despite reported genetic differences, the clinical features and response to standard therapy in pediatric- and adult-onset CVS were mostly similar. Most patients (86%) responded to therapy and compliance was the only factor associated with a response.

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.

Background Cyclic vomiting syndrome (CVS), a chronic disorder characterized by recurrent episodes of vomiting, is frequently unrecognized and is associated with high utilization of emergency department (ED) services. Methods A web-based survey was posted on the Cyclic Vomiting Syndrome Association (CVSA) website to assess utilization of ED services in patients with CVS. Results Of 251 respondents, 104 (41.4%) were adult CVS patients and 147 (58.6%) were caregivers of pediatric and adult patients. In the adult group, the median number of ED visits for CVS symptoms was 15(range 1 - 200), with a median of 7 ED visits prior to a diagnosis of CVS (range 0 - 150). In the caregiver group, the median number of ED visits was 10 (range 1 - 175) and the median number of ED visits prior to a diagnosis of CVS was 5 (range 0 - 65). CVS was not diagnosed in the ED in 89/104 (93%) adults and 119/147 (93%) patients in the caregiver group. CVS was not recognized in the ED in 84/95 (88%) of adults and 97/122 (80%) of patients in the caregiver group, despite an established diagnosis of CVS. Conclusion There is a sub-group of adult and pediatric CVS patients who are high utilizers of ED services and CVS is not recognized in the ED in the majority of patients. Improved efforts to educate ED physicians are indicated to optimize treatment of patients with CVS and to decrease potential overuse of ED services.

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.