Gerold J. Wetscher

Laparoscopic Nissen fundoplication is an effective treatment for gastroesophageal reflux disease.

ObjectveThe open Nissen fundoplication is effective therapy for gastroesophageal reflux disease. In this study, the outcomes in 198 patients treated with the laparoscopic Nissen fundoplication was evaluated for up to 32 months after surgery to ascertain whether similar positive results could be obtained. Summary Background DataTo ensure surgical success, patients were required to have mechanically defective sphincters on manometry and increased esophageal acid exposure on 24-hour pH monitoring. The patients either had severe complications of gastroesophageal reflux disease or had failed medical therapy. These requirements have been found to be necessary to ensure a successful surgical outcome. MethodsThe disease was complicated by ulceration (46), stricture (25) and Barretts esophagus (33). Patients underwent standard Nissen fundoplications identical in every detail to open procedures except that the procedures were carried out by the laparoscopic route. ResultsPerioperative complications included gastric or esophageal perforation (3), pneumothorax (2), bleeding (2), breakdown of crural repair (2) and periesophageal abscess (1). The only mortality occurred from a duodenal perforation. Six patients required conversion to the open procedure. The median hospital stay was 3 days. One hundred patients were observed for follow-up for 6 to 32 months (median 12 months), with outcomes similar to the open Nissen fundoplication. Further surgery was required for two patients who had recurrent gastroesophageal reflux and one who developed an esophageal stricture. Ninety-seven percent are satisfied with their decision to have the operation. ConclusionsThe laparoscopic Nissen fundoplication can be carried out safely and effectively with similar positive results to the open procedure and with all of the advantages of the minimally invasive approach.

Free radical production in nicotine treated pancreatic tissue

The ability of nicotine to induce oxidative stress in the pancreatic tissue of rats was investigated. Homogenized pancreatic tissue of Sprague-Dawley rats was incubated with nicotine in a dose of 200 ng/mg protein/ml for 15, 30, 45, and 60 min or was incubated for 30 min with nicotine in a dose of 50, 100, 200, 400, and 800 ng/mg protein/ml. Pancreatic tissue was also incubated with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD+catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a positive correlation between the duration of nicotine incubation and chemiluminescence (r = 0.6) or lipid peroxidation (r = 0.71) and also between the nicotine dose and chemiluminescence (r = 0.54) or lipid peroxidation (r = 0.66). Thirty minutes incubation of pancreatic tissue with nicotine in a dose of 200 ng/mg protein/ml increased chemiluminescence 5 fold and lipid peroxidation 2.5 fold. This response was dampened by SOD or catalase and abolished by SOD+catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the pancreatic tissue of rats.

Reflux esophagitis in humans is mediated by oxygen-derived free radicals☆

BACKGROUND Oxidative stress in reflux esophagitis was investigated before and after antireflux surgery. PATIENTS AND METHODS Oxidative stress was studied in the distal and proximal esophagus of control patients (without esophagitis, but with other gastrointestinal disorders), of patients with various grades of esophagitis (including Barretts esophagus), and in patients who had a Nissen fundoplication. Oxidative stress was assessed by chemiluminescence, lipid peroxidation (LP), and by measuring superoxide dismutase (SOD). RESULTS Chemiluminescence and LP increased with the degree of esophagitis and was highest in patients with Barretts esophagus; SOD decreased with damage, except in cases of Barretts esophagus associated with mild esophagitis. Chemiluminescence and LP in reflux patients were higher in the distal than in the proximal esophagus, and SOD was lower, whereas no such difference was found in controls. Findings after Nissen fundoplication were similar to those of controls. CONCLUSIONS Reflux esophagitis is mediated by free radicals depleting SOD. Barretts esophagus is a severe form of oxidative damage; in some patients, high SOD levels may prevent severe esophagitis. Antireflux surgery prevents oxidative damage.

Esophagitis in sprague-dawley rats is mediated by free radicals

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.

Free radical scavengers prevent reflux esophagitis in rats.

Free radical damage in reflux esophagitis of rats induced by 24-hr duodenojejunal ligation was studied. Oxygen free radicals were selectively blocked. Groups were: sham operation, reflux, reflux+superoxide dismutase (SOD), catalse, dimethylthiourea, allopurinol, and inactivated SOD or inactivated catalase alone or in the combination SOD+catalase or SOD+catalase+dimethylthiourea+allopurinol. Macroscopic esophagitis was inhibited only by SOD, alone or in combination with other agents. Esophageal mucosal lipid peroxidation was 10-fold increased in the reflux group compared to the sham group (P<0.05). This response was damped by SOD>catalase (P<0.05) but not by the inactivated enzymes, dimethylthiourea or allopurinol. SOD+catalase showed no significant improvement on SOD alone. Total inhibition of lipid peroxidation was achieved by combining all scavengers. Total glutathione (GSH) in the esophageal mucosa was stimulated by reflux. This response was inhibited by scavengers equivalent to their efficacy in preventing lipid peroxidation. It is concluded that reflux esophagitis is associated with free radical release with O2− being the main source. Free radicals appear to stimulate GSH production in this prolonged oxidative stress.

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.

Efficacy of medical therapy and antireflux surgery to prevent Barrett's metaplasia in patients with gastroesophageal reflux disease.

ObjectiveTo investigate whether Barrett’s metaplasia may develop despite effective medical therapy. Summary Background DataGastroesophageal reflux disease has a multifactorial etiology. Therefore, medical treatment may not prevent complications of reflux disease. MethodsEighty-three patients with reflux disease and mild esophagitis were prospectively studied for the development of Barrett’s metaplasia while receiving long-term therapy with proton pump inhibitors and cisapride. Only patients who had effective control of reflux symptoms and esophagitis were included. The surveillance time was 2 years. The outcome of these 83 patients was compared with that of 42 patients in whom antireflux surgery was performed with a median follow-up of 3.5 years. ResultsTwelve (14.5%) patients developed Barrett’s while receiving medical therapy; this was not seen after surgery. Patients developing Barrett’s had a weaker lower esophageal sphincter and peristalsis before treatment than patients with uncomplicated disease. ConclusionsAntireflux surgery is superior to medical therapy in the prevention of Barrett’s metaplasia. Therefore, patients with reflux disease who have a weak lower esophageal sphincter and poor esophageal peristalsis should undergo antireflux surgery, even if they have only mild esophagitis.

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

Duodenogastric reflux (DGR) in rats causesgrowth stimulation of the foregut mucosa that ispotentiated by gastric acid blockade. It was the aim ofthis study to investigate if DGR with gastric acidblockade has a higher incidence of carcinomas of theforegut than DGR alone. DGR was induced in 40Sprague-Dawley rats using a split gastroenterostomy. Acardiomyotomy was performed across the gastroesophagealjunction, inducing reflux into the esophagus. Twenty ofthese rats received omeprazole postoperatively. Afterone year 18 rats (90%) with DGR + omeprazole treatmentand 7 rats (35%) with DGR alone developed adenocarcinoma of the stomach (P < 0.05). None of the ratsdeveloped esophageal cancer, but esophageal mucosalhyperplasia was more pronounced in rats receivingomeprazole. Control rats, treated with omeprazole, did not develop carcinomas of the foregut. Inconclusion, gastric acid blockade enhanced DGR-inducedcarcinogenesis of the stomach and promotes growthstimulation of the esophageal mucosa.

In Vitro free radical production in rat esophageal mucosa induced by nicotine

Oxidative stress induced by nicotine was investigated in the esophageal mucosa of rats. The homogenized mucosa was incubated for 30 min with 50, 100, 200, 400, and 800 ng/mg protein/ml nicotine or with 200 ng/mg protein/ml nicotine for 15, 30, 45, and 60 min. Esophageal mucosa was also incubated for 30 min with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD + catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a strong correlation between chemiluminescence and the nicotine dose (r=0.75) or the nicotine incubation time (r=0.77). Thirty-minute incubation of the esophageal mucosa with 200 ng/mg protein/ml nicotine increased chemiluminescence 5.5-fold and lipid peroxidation 3.3-fold. This response was dampened by SOD or catalase and abolished by SOD + catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the esophageal mucosa.

Dieulafoy's disease of the large and small bowel.

The Dieulafoy lesion is a rare cause of severe gastrointestinal hemorrhage. The lesion is usually located in the stomach, although it may occur anywhere in the gastrointestinal tract. We describe four patients with extragastric Dieulafoys disease, in the duodenum (one), the proximal jejunum (two), and the left hemicolon (one). Diagnosis was made by endoscopy in all four and confirmed by histology in three. The pathology of the Dieulafoy lesion is essentially the same throughout the gastrointestinal tract. Endoscopic treatment by sclerotherapy combined with electrocoagulation was successful in the duodenal and colonic Dieulafoy lesions, but not in the jejunal lesions.