Endoscopic valvuloplasty for GERD.

BACKGROUND: The transoral, endoscopic route has been suggested as a possible approach for the correction of severe gastroesophageal reflux. Such a procedure would involve no mobilization of the cardia or other structures. The optimal placement, number, and configuration of sutures remains undefined. METHODS: With the use of a previously developed endoscopic sewing machine, this study was undertaken in baboons with two suture arrangements immediately below the lower esophageal sphincter. A linear arrangement (group I) and a circular arrangement (group II) were compared. During the 6 months after the procedure, the animals were evaluated using manometry, fluoroscopic barium swallow, upper gastrointestinal endoscopy, and a pressure volume test. RESULTS: A significant increase in lower esophageal sphincter length was demonstrated only in group II (p = 0. 010). A significant increase in lower esophageal sphincter pressure was demonstrated only in group I animals (p = 0.008). The abdominal length increased in group I (p = 0.004) and group II (p = 0.004). The yield pressure and yield volume did not differ significantly from those measured previously in control animals. No evidence of reflux, stricture formation, esophagitis, or other pathology was noted. CONCLUSIONS: Some manometric parameters associated with gastroesophageal reflux are altered by the endoscopic placement of sutures below the gastroesophageal junction, with no associated serious complications.

Gastric acid blockade with omeprazole promotes gastric carcinogenesis induced by duodenogastric reflux.

Duodenogastric reflux (DGR) in rats causes growth stimulation of the foregut mucosa that is potentiated by gastric acid blockade. It was the aim of this study to investigate if DGR with gastric acid blockade has a higher incidence of carcinomas of the foregut than DGR alone. DGR was induced in 40 Sprague-Dawley rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroesophageal junction, inducing reflux into the esophagus. Twenty of these rats received omeprazole postoperatively. After one year 18 rats (90%) with DGR + omeprazole treatment and 7 rats (35%) with DGR alone developed adenocarcinoma of the stomach (P < 0.05). None of the rats developed esophageal cancer, but esophageal mucosal hyperplasia was more pronounced in rats receiving omeprazole. Control rats, treated with omeprazole, did not develop carcinomas of the foregut. In conclusion, gastric acid blockade enhanced DGR-induced carcinogenesis of the stomach and promotes growth stimulation of the esophageal mucosa.

Indications, technical modalities and results of the duodenal switch operation for pathologic duodenogastric reflux.

BACKGROUND/AIMS: Reflux gastritis is caused by the excessive reflux of alkaline duodenal content into the stomach and can lead to intractable symptoms. The main cause of pathologic duodenogastric reflux (DGR) is previous gastric surgery in which the pylorus is removed or rendered dysfunctional. The entity of abnormal DGR without previous gastric surgery is called "primary duodenogastric reflux". The main symptoms in these patients are severe upper abdominal pain, nausea and bilious vomiting. DGR remains very difficult to diagnose and treat. Investigations include endoscopy with histological examination, intragastric pH-monitoring, radionuclide scanning, gastric aspiration, antroduodenal manometry, and bile detection with special probes. Medical therapy is generally not helpful. Acid-blocking medications, sucralfate, prostaglandin E2 and cholestyramine used as an ion-exchange resin to bind bile salts do not usually improve symptoms. There is some evidence that ursodeoxycholate favorably affects symptoms but experience is limited. METHODOLOGY: Surgical therapy was initially performed on selected patients with intractable symptoms. A variety of operative procedures have been used to treat pathologic DGR but cause significant side effects through changes in the normal physiology of the foregut. DeMeester et al proposed a suprapapillary duodenojejunostomy succinctly called the duodenal switch procedure. It has been reported to maintain the integrity of the antro-pyloro-duodenal mechanism with great patient satisfaction. Between 1984 and 1995, 32 patients (9 men and 23 women), mean age 50 years (range: 30-77), required pancreaticobiliary diversion using the switch procedure for symptomatic gastritis related to abnormal primary DGR. Symptoms were evaluated with a symptom score using a detailed questionnaire. RESULTS: After a mean follow-up of 4 years (n = 32, range: 0.5-8.2), 94% of the patients had a good clinical outcome as defined by a significant reduction in pre-operative symptoms. There was no mortality. CONCLUSIONS: Suprapapillary Roux-en-Y duodenojejunostomy (duodenal switch procedure) is an effective surgical therapy in patients with pathologic primary DGR.

Management of patients with giant paraesophageal hernia.

Paraesophageal herniation can cause massive bleeding, strangulation or perforation. This study reviews the experience with 24 patients (74.6 years, range 63-89 years, 20 males, 4 females) with a total or near-total intrathoracic stomach, managed at the Royal Lancaster Infirmary. All patients were symptomatic with 3/24 patients presenting as emergencies. Twenty-three of 24 patients underwent surgery: gastropexy alone-5, gastropexy and hiatal repair-17, gastropexy, hiatal repair and fundoplication 1. One of the emergency patients died prior to surgery. Median operative time was 50 min (range 35-65 min) and median hospital stay was 7 days (range 5 days-3 weeks). A splenectomy was necessary in 1/23 (4.4%) patients. Postoperative morbidity included: recurrent hernia requiring surgery-1, pleural effusion requiring chest tube-1, empyema-1, dysphagia requiring dilatation-1, reflux with stricturing-1. Elderly patients with a total or a near-total intrathoracic stomach can be managed by gastropexy and hiatal repair, with acceptable morbidity.

Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

Respiratory symptoms in patients with gastroesophageal reflux disease following medical therapy and following antireflux surgery.

BACKGROUND: It is not known whether antireflux surgery is more effective than medical therapy to control respiratory symptoms (RS) in gastroesophageal reflux disease (GERD). METHODS: In 21 GERD patients with RS, reflux was assessed by endoscopy, manometry, and pH monitoring. Patients had proton pump inhibitor therapy and cisapride for 6 months. After GERD relapsed following withdrawal of medical therapy, 7 patients with normal esophageal peristalsis had a laparoscopic Nissen fundoplication and 14 with impaired peristalsis a Toupet fundoplication. Respiratory symptoms were scored prior to treatment, at 6 months following medical therapy, and at 6 months after surgery. RESULTS: Heartburn and esophagitis were effectively treated by medical and surgical therapy. Only surgery improved regurgitation. Respiratory symptoms improved in 18 patients (85.7%) following surgery and in only 3 patients (14.3%) following medical therapy (P <0.05). Esophageal peristalsis improved following the Toupet fundoplication. CONCLUSION: Medical therapy fails to control reflux since it does not inhibit regurgitation. Surgery controls reflux and improves esophageal peristalsis, which contributes to its superiority over medical therapy in the treatment of RS associated with GERD.

Management of the failed antireflux operation.

A further operation is required in a small proportion of patients who have had prior antireflux surgery. This has a surprisingly good chance for success in appropriately evaluated patients. The surgeon must make very specific decisions regarding the surgical approach. The use of laparoscopy for redo surgery is being defined.

Laparoscopic Toupet fundoplication for gastroesophageal reflux disease with poor esophageal body motility.

Impaired esophageal body motility is a complication of chronic gastroesophageal reflux disease (GERD). In patients with this disease, a 360-degree fundoplication may result in severe postoperative dysphagia. Forty-six patients with GERD who had a weak lower esophageal sphincter pressure and a positive acid reflux score associated with impaired esophageal body peristalsis in the distal esophagus (amplitude <30 mm Hg and >10% simultaneous or interrupted waves) were selected to undergo laparoscopic Toupet fundoplication. They were compared with 16 similar patients with poor esophageal body function who underwent Nissen fundoplication. The patients who underwent Toupet fundoplication had less dysphagia than those who had the Nissen procedure (9% vs.44%; P=0.0041). Twenty-four-hour ambulatory pH monitoring and esophageal manometry were repeated in 31 Toupet patients 6 months after surgery. Percentage of time of esophageal exposure to pH <4.0, DeMeester reflux score, lower esophageal pressure, intra-abdominal length, vector volume, and distal esophageal amplitude all improved significantly after surgery. Ninety-one percent of patients were free of reflux symptoms. The laparoscopic Toupet fundoplication provides an effective antireflux barrier according to manometric, pH, and symptom criteria. It avoids potential postoperative dysphagia in patients with weak esophageal peristalsis and results in improved esophageal body function 6 months after surgery.

Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus.

OBJECTIVE: To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequence. DESIGN: Archival tissue samples of 85 lesions in 58 cases were used. The lesions represented 7 groups: normal esophagus (n = 10), reflux esophagitis (n = 12), Barrett metaplasia (n = 21), Barrett low-grade dysplasia (n = 17), Barrett high-grade dysplasia (n = 5), well- or moderately differentiated adenocarcinoma (n = 10), and poorly differentiated adenocarcinoma (n = 10). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) method. Monoclonal antibodies against bcl-2 protein were applied using the avidin-biotin complex immunoperoxidase method. RESULTS: The esophagitis group showed many apoptotic cells on the epithelial surface; in the other groups, few apoptotic cells were seen. Weak bcl-2 expression was seen in the basal cells in normal subjects and those with esophagitis. There was overexpression of bcl-2 in 72% of Barrett metaplasia, 100% of Barrett low-grade dysplasia, 25% of Barrett high-grade dysplasia, 40% of well- or moderately differentiated adenocarcinoma, and 20% of poorly differentiated adenocarcinoma. CONCLUSIONS: Increased apoptosis in reflux esophagitis may be a protective mechanism counteracting increased proliferation. Inhibition of apoptosis by overexpression of bcl-2 protein occurs early in the dysplasia-carcinoma sequence of Barrett esophagus. The resulting prolongation of cell survival may promote neoplastic progression. Despite the absence of apoptosis, bcl-2 was not widely overexpressed in Barrett high-grade dysplasia and adenocarcinoma, suggesting that cells acquire other ways of avoiding apoptosis as malignancy appears.

Laparoscopic paraesophageal hernia repair.

BACKGROUND: Paraesophageal hernias require surgery to avoid potentially serious complications. OBJECTIVE: To evaluate paraesophageal hernia repair using the laparoscopic approach. DESIGN: Case series. SETTING: University hospital and foregut testing laboratory. SUBJECTS: Sixty-five consecutive patients (mean age, 63.6 years; range, 26-90 years). Preoperative evaluation included barium esophagogram, endoscopy, esophageal manometry, and 24-hour pH monitoring. OUTCOME MEASURES: Operative complications, postoperative morbidity, follow-up symptoms (53 patients; mean, 18 months; range, 2-54 months) and barium esophagogram (46 patients). RESULTS: Fifty-six patients (86%) had a type III hernia and 9 (14%) had a type II hernia. Twenty (65%) of 31 patients who underwent pH monitoring had a positive 24-hour pH score, and 24 (56%) of 43 patients who underwent manometry had an incompetent lower esophageal sphincter. Four patients had a gastric volvulus and 21 patients had more than 50% of their stomach in the chest. All patients underwent hernia reduction, crural repair, and fundoplication (64 Nissen procedures and 1 Toupet procedure). The average duration of surgery was 2 hours. There were 2 conversions: gastric perforation and a difficult dissection because of a large fibrotic sac. Other complications, all managed intraoperatively, were 2 gastric perforations and bleeding in 6 patients. Average length of hospital stay was 2 days (range, 1-23 days). Early re-operation was required in 3 patients: slipped Nissen; small-bowel obstruction due to trocar-site hernia; and organo-axial rotation with gastroduodenal obstruction. Four patients required esophageal dilatation after surgery. Forty-nine of 53 patients available for long-term follow-up were satisfied with the results of surgery. Time to full recovery was 3 weeks (range, 1 week to 2 months). Seven of 46 patients experienced small type I hernias observed on routine follow-up esophagograms. CONCLUSIONS: Most paraesophageal hernias are type III. A concomitant antireflux procedure is recommended. Paraesophageal hernias can be managed successfully by the laparoscopic route with good outcome.

Interrelationship between cellular calcium homeostasis and free radical generation in myocardial reperfusion injury.

This review describes the interrelationship between two important biological factors, intracellular calcium overloading and oxygen-derived free radicals, which play a crucial role in the pathogenesis of myocardial ischemic reperfusion injury. Free radicals are generated during the reperfusion of ischemic myocardium, and polyunsaturated fatty acids in the membrane phospholipids are the likely targets of the free radical attack. On the other hand, activation of phospholipases can provoke the breakdown of membrane phospholipids which results in the activation of arachidonate cascade leading to the generation of prostaglandins, and oxygen free radicals can be produced during the interconversion of the prostaglandins. In conclusion, it has been emphasized that the two seemingly different causative factors of reperfusion injury, intracellular calcium overloading and free radical generation are, in fact, highly interrelated.

Heller myotomy is superior to dilatation for the treatment of early achalasia.

OBJECTIVES: To study the pretreatment characteristics that predispose a patient to rupture and to compare the outcome after dilatation with the outcome after surgical myotomy. DESIGN: A survey of all patients treated for achalasia at the Creighton University Medical Center, Omaha, Neb, during a 16-year period. Clinical examination and testing of consenting patients at 12 months and longer after treatment. SETTING: Tertiary referral center. PATIENTS: Of the 61 patients, 55 were treated with dilatation. Esophageal rupture developed in 8 patients (14.5%) with achalasia after pneumatic dilatation; these patients underwent surgery for the rupture. Dilatation failed in 8 other patients; these patients underwent a surgical myotomy. Six patients underwent a primary surgical myotomy. MAIN OUTCOME MEASURES: Duration of symptoms, weight loss, lower esophageal sphincter resting pressure and relaxation, amplitude and quality of distal esophageal contractions (assessed by manometry), 24-hour esophageal pH, and maximal esophageal diameter (assessed by barium swallow examination). RESULTS: Surgical myotomy at a mean (+/-SEM) of 44.9 +/- 18.6 months alleviated dysphagia in 13 (93%) of the 14 patients compared with only 12 (39%) of the 31 patients after dilatation at a mean (+/-SEM) of 55.0 +/- 11.7 months (P < .001). Of the 14 patients who underwent surgical myotomy, 13 (93%) were able to return to a normal diet compared with only 2 (7%) of the 31 patients who underwent dilatation (P < .001). Compared with patients without perforations, patients with perforations after pneumatic dilatation had pretreatment characteristics consistent with "early" disease: shorter symptom duration (20.1 +/- 5.4 vs 68.9 +/- 4.9 months, P < .001), less weight loss (4.7 +/- 1.2 vs 10.3 +/- 0.8 kg, P < .001), a less dilated esophagus (24.0 +/- 1.8 vs 45.6 +/- 3.0 mm, P < .005), lower lower esophageal sphincter resting pressures (19.3 +/- 2.6 vs 34.2 +/- 1.3 mm Hg, P < .001), a greater percentage of lower esophageal sphincter relaxation (47.6% +/- 4.9% vs 20.7% +/- 2.1%, P < .001), and a lower percentage of synchronous contractions in the distal esophageal body (66.2% +/- 4.9% vs 85.3% +/- 2.3%, P < .005). (All data given as the mean [+/-SEM].) All patients with pneumatic perforations were successfully treated by thoracotomy and surgical repair. CONCLUSIONS: Surgical myotomy provides a better long-term outcome. The early disease stage is associated with perforation after pneumatic dilatation. Surgical myotomy rather than balloon dilatation should be considered in patients with early achalasia.

Laparoscopic Nissen fundoplication: where do we stand?

Laparoscopic Nissen fundoplication was first performed in 1991. With the increasing number of these procedures being performed it is appropriate to review the published short-term results. A retrospective review of reports on this subject was performed. There were a total of 2453 patients available for review. Twenty-five of 2453 (1.0%) patients had an esophageal or gastric perforation and 28 of 2453 (1.1%) patients required transfusion for bleeding. Forty-nine of 2453 (2%) patients developed a pneumothorax. Two of 2453 (0.1%) patients required a splenectomy. Conversion to the open procedure was necessary in 5.8% (143 of 2453) of patients. The laparoscopic approach is associated with minimal postoperative morbidity. Four of 2453 (0.2%) needed further early surgery for persistent bleeding, 11 of 2453 (0.4%) for a missed perforation, 22 of 2453 (0.9%) for crural disruption, paraesophageal herniation, or gastric volvulus. Four of 2453 (0.2%) patients died of either a missed duodenal perforation, a missed esophageal perforation, ischemic bowel with mesenteric thrombosis, or myocardial infarction. Early postoperative dysphagia occurred in 500 of 2453 (20.3%) patients. Late postoperative dysphagia occurred in 114 of 2068 (5.5%), with the need for dilatation in 72 of 2068 (3.5%). Endoscopy was required for food impaction in 11 of 2068 (0.5%) and re-operation for dysphagia occurred in 18 of 2068 (0.9%). Fifty-seven of 1658 (3.4%) patients developed reflux symptoms and 11 of 1658 (0.7%) required revisional surgery. Satisfaction rates ranged from 87 to 100%. In the short term, laparoscopic fundoplication can be performed with less morbidity and mortality than the open procedure. It is superior to medical therapy. Long-term follow-up is awaited.

Medical treatment of gastroesophageal reflux disease does not prevent the development of Barrett's metaplasia and poor esophageal body motility.

OBJECTIVE: Duodenal contents refluxing into the esophagus may be involved in the pathophysiology of gastroesophageal reflux disease (GERD). This study was performed to investigate whether medical treatment of GERD aimed at suppression of gastric acid production can prevent the development of complications, such as Barrett's metaplasia or poor esophageal body motility. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: 138 GERD patients were analyzed regarding the development of Barrett's metaplasia or poor esophageal body motility, despite intermittent or continuous treatment with H2 blockers or omeprazole. MAIN OUTCOME MEASURES: The rate of patients with Barrett's metaplasia or poor esophageal body motility with or without effective medical treatment. RESULTS: Barrett's metaplasia was found in 33.8% of patients receiving medical treatment, although it was not present when treatment was induced. This rate was 21.9% among patients who were not receiving therapy (not significant). In all, 41.9% of patients with medication had impaired esophageal body motility compared with 59.3% of patients not receiving treatment (P < 0.05), but these patients had a significantly shorter history of GERD. CONCLUSIONS: Medical treatment with H2 blockers or omeprazole does not prevent the development of Barrett's metaplasia or poor esophageal body motility.

Reflux esophagitis in humans is a free radical event.

UNLABELLED: In this study, we investigated the implication of oxygen-derived free radicals in reflux esophagitis of humans. For this purpose we assessed oxidative stress in distal esophageal biopsies of controls, patients with various grades of esophagitis, Barrett's esophagus with and without severe associated esophagitis and patients following Nissen fundoplication. The total amount of oxygen-derived free radicals was measured by chemiluminescence. Membrane damage caused by free radicals was assessed by analysis of lipid peroxidation. In addition, we measured esophageal mucosal tissue levels of the free radical scavenger superoxide dismutase. RESULTS: Chemiluminescence and lipid peroxidation increased with the grade of esophagitis and were highest in patients with Barrett's esophagus. Findings following Nissen fundoplication were similar to controls. Superoxide dismutase decreased as the grade of esophagitis increased being lowest in Barrett's patients with severe associated esophagitis. High superoxide dismutase levels were found in Barrett's mucosa with mild associated esophagitis. CONCLUSIONS: Reflux esophagitis is mediated by free radicals. Barrett's is a severe form of oxidative damage. Antireflux surgery prevents oxidative damage of the esophageal mucosa. Superoxide dismutase is consumed by esophageal damage. In some patients with Barrett's, high superoxide dismutase levels of the esophageal mucosa may prevent severe esophagitis.

The surgical option for gastroesophageal reflux disease.

Gastroesophageal reflux disease is a common condition. Most patients can be managed with medications, but patients with refractory disease, particularly those with an incompetent lower esophageal sphincter, should be referred for surgery. The open Nissen fundoplication cures >90% of patients of their symptoms. The laparoscopic approach was first applied for patients with gastroesophageal reflux disease in 1991, and since then numerous reports evaluating the early experience with this technique have been published with results similar to the open procedure. Over the last 5 years, 595 laparoscopic antireflux procedures have been performed by us. There was 1 mortality due to an unrecognized duodenal perforation. Splenic injury did not occur compared to an incidence of up to 8.5% for the open procedure. A total of 9 patients required conversion to the open procedure for perforation, bleeding, or dissection difficulties. However, in the last 350 cases no conversions have been necessary. Most patients are now being discharged from hospital on the day after surgery with some patients being discharged on the same day as surgery. The overall reoperation rate, both for early postoperative morbidity and for late poor outcome, was 3.9% with follow-up ranging from 2 months to 5 years. The laparoscopic Nissen fundoplication achieves the same short-term outcome as the open procedure with significantly less postoperative morbidity and a shorter hospital stay.

Three-dimensional imaging of the lower esophageal sphincter in healthy subjects and gastroesophageal reflux.

The resting pressure and intraabdominal length are the most important factors which determine competence of the lower esophageal sphincter (LES). The intraabdominal sphincter vector volume (ISVV) is a single value which takes into account both of these measurements. Normal values of ISVV and of the total sphincter vector volume (TSVV) were established in 20 normal subjects. The sensitivity and the specificity of ISVV and TSVV were then evaluated in 81 patients with gastroesophageal reflux disease (GERD) and in 19 normal subjects and were compared with the usual stepwise pullback manometry (SPM) measuring the resting pressure of the LES at the respiratory inversion point. The motorized pullthrough technique was used to perform the vector volume procedure. Normal values of ISVV were 1870-10740 mm Hg2 x mm, and of TSVV 2200-13110 mm Hg2 x mm. The sensitivity of ISVV was 93.8% (p < 0.05), of TSVV 80.2%, and of SPM 81.5%. The specificity of ISVV and TSVV was 89.5% and of SPM 78.9% (not significant). Analysis of the intraabdominal sphincter vector volume is more sensitive than the total sphincter vector volume or standard stationary manometry in establishing a defective LES in patients with GERD. Intraabdominal sphincter vector volume analysis will allow surgeons better to identify patients with a defective LES who may be suitable for antireflux surgery.