Karl Glaser

Role of octreotide in the prevention of postoperative complications following pancreatic resection

Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

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.

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 teria. It avoids potential postoperative dysphagia in patients with weak esophageal peristalsis and results in improved esophageal body function 6 months after, surgery.

Tailored Antireflux Surgery for Gastroesophageal Reflux Disease: Effectiveness and Risk of Postoperative Dysphagia

Abstract The Nissen fundoplication is not the proper antireflux procedure for patients with poor esophageal peristalsis as it does not strengthen impaired esophageal peristalsis. The aim of this study was to investigate if tailoring of antireflux surgery according to esophageal contractility is an effective treatment of gastroesophageal reflux disease (GERD) with a low incidence of postoperative dysphagia. The Toupet fundoplication was laparoscopically performed on 32 patients with poor esophageal peristalsis and the Nissen fundoplication on 17 patients with normal peristalsis. After a median follow-up of 15 months, only 1 of the 49 patients (2.04%) complained of heartburn. Acute esophagitis was found in none of them on endoscopy. Of 40 patients tested postoperatively, 2 (5%) underwent pathologic esophageal pH monitoring. Postoperative dysphagia was found in two patients (4.1%) compared with 25 (51%) preoperatively ( p < 0.05). There was a significant reduction of dysphagia following the Toupet fundoplication. Both procedures increased the resting pressure of the lower esophageal sphincter (LES) significantly, which was more pronounced following the Nissen fundoplication. Relaxation of the LES was significantly better following the Toupet than after the Nissen fundoplication. There was significant improvement of esophageal peristalsis following the Toupet fundoplication. Tailored antireflux surgery is an effective strategy for treatment of GERD. The incidence of postoperative dysphagia is low owing to improvement of impaired esophageal peristalsis following the Toupet fundoplication. It may be due to the fact that the Toupet fundoplication causes less esophageal outflow resistance than the Nissen fundoplication.

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.

The effect of medical therapy and antireflux surgery on dysphagia in patients with gastroesophageal reflux disease without esophageal stricture.

BACKGROUND Poor esophageal body motility and trapping of the hernial sac by the hiatal crura are the major pathomechanisms of gastroesophageal reflux disease (GERD)-induced dysphagia. There is only little knowledge of the effect of medical therapy or antireflux surgery in reflux-induced dysphagia. METHODS Fifty-nine consecutive GERD patients with dysphagia were studied by means of a symptom questionnaire, endoscopy, barium swallow, esophageal manometry, and 24-hour pH monitoring of the esophagus. Patients had proton pump inhibitor therapy and cisapride for 6 months. After GERD relapsed following withdrawal of medical therapy, 41 patients decided to have antireflux surgery performed. The laparoscopic Nissen fundoplication was chosen in 12 patients with normal esophageal body motility and the laparoscopic Toupet fundoplication in 29 patients with impaired peristalsis. Dysphagia was assessed prior to treatment, at 6 months of medical therapy, and at 6 months after surgery. RESULTS Heartburn and esophagitis were effectively treated by medical and surgical therapy. Only surgery improved regurgitation. Dysphagia improved in all patients following surgery but only in 16 patients (27.1%) following medical therapy. Esophageal peristalsis was strengthened following antireflux surgery. CONCLUSIONS Medical therapy fails to control gastroesophageal reflux as it does not inhibit regurgitation. Thus, it has little effect on reflux-induced dysphagia. Surgery controls reflux and improves esophageal peristalsis. This may contribute to its superiority over medical therapy in the treatment of GERD-induced dysphagia.

Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium.

BACKGROUND Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barretts mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barretts mucosa. RESULTS Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barretts epithelium. Squamous epithelium adjacent to Barretts mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barretts epithelium. CONCLUSIONS Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barretts may promote carcinogenesis. This may not change following surgery.

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

ZusammenfassungZie: Duodenalinhaltsstoffe, die aufgrund eines Reflux in den ösophagus gelangen, sind möglicherweise in die Pathophysiologie der gastroösophagealen Refluxkrankheit (GERD) involviert. Ziel dieser Studie war, zu untersuchenk ob die medikamentöse Behandlung von GERD mit dem Ziel die Magensäureproduktion zu unterdrücken, das Auftreten von Komplikationen, wie z.B. Barrett-Metaplasie oder schwache Ösophagusmotilität, verhindern kann. Studiendesign: Retrospektive Untersuchung,. Ort: Universitätsklinik. Patienten: 138 GERD-Patienten wurden bezüglich des Auftretens von Barrett-Metaplasie oder beeinträchtigter Ösophagusmotilität bei intermittierender oder ständiger Behandlung mit H2-Blockern oder Omeprazol untersucht. Hauptuntersuchungspunkte: Rate der Patienten mit Barrett-Metaplasie oder beeinträchtigter Ösophagusmotilität mit und ohne effektive medikamentöse Behandlung. Ergebnisse: Eine Barrett-Metaplasie, die bei Beginn der Behandlung nicht nachweisbar war, wurde bei 33,8% der Patienten mit medikamentöser Behandlung bzw. bei 21,9% ohne Therapie gefunden (nicht signifikant). 41,9% der Patienten mit Medikation hatten eine beeinträchtigte Ösophagusmotilität im Vergleich zu 59,3% der Patienten ohne Behandlung (p<0,05), aber diese Patienten wiesen eine signifikant kürzere Verlaufszeit von GERD auf. Schlußfolgerungen: Die medikamentöse Behandlung mit H2-Blockern oder Omeprazol verhindert nicht das Auftreten einer Barrett-Metaplasie oder beeinträchtigten Ösophagusmotilität.AbstractObjective: 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 Barretts metaplasia or poor esophageal body motility.Design: Retrospective study.Setting: University hospital.Patients: 138 GERD patients were analyzed regarding the development of Barretts metaplasia or poor esophageal body motility, despite intermittent or continuous treatment with H2 blockers or omeprazole.Main outcome measures: The rate of patients with Barretts metaplasia or poor esophageal body motility with or without effective medical treatment.Results: Barretts 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 Barretts metaplasia or poor esophageal body motility.

The laparoscopic fundoplications: Nissen and partial posterior (Toupet) fundoplication

ZusammenfassungGRUNDLAGEN: Die gastroösophageale Refluxkrankheit ist weit verbreitet und kann mit einer laparoskopischen Fundoplikation kausal behandelt werden. Die Nissen-Fundoplikation und die partielle posteriore Fundoplikation (nach Toupet) sind die gängigsten Operationen. METHODIK: Detaillierte Beschreibung der Operationstechnik und der Ergebnisse mit Übersicht über die Literatur. ERGEBNISSE: Die Nissen- und die partielle posteriore Fundoplikation können GERD-Symptome heilen und die Lebensqualität verbessern, sie können eine Ösophagitis zur Abheilung bringen und der Karzinogenese entgegenwirken. SCHLUSSFOLGERUNGEN: Die laparoskopische Nissen-Fundoplikation stellt quasi den Goldstandard in der operativen Behandlung von GERD dar, obwohl sie in einigen Publikationen von der partiellen posterioren Fundoplikation ernsthaft konkurriert wird.SummaryBACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease and can successfully be treated by laparoscopic fundoplication. The Nissen and the partial posterior fundoplication (Toupet) are the most widespread documented techniques. METHODS: Detailed description of the operative techniques and results including review of the literature. RESULTS: The Nissen- and partial posterior fundoplication (Toupet) can cure GERD symptoms and improve quality of life, they can cure esophagitis and are able to prevent carcinogenesis. CONCLUSIONS: The laparoscopic Nissen fundoplication represents the gold standard in antireflux surgery, although in some publications, it is challenged by the partial posterior fundoplication (Toupet) regarding postoperative side effects.

Survival and local recurrence after anterior resection and abdominoperineal excision for rectal cancer

The aim of this retrospective study is to compare the outcome of abdominoperineal excision (APE) and anterior resection (AR) for rectal cancer in 136 patients. Local recurrence rates and 5-year survival probabilities were estimated for the AR and APE group. Further comparisons were carried out between hand-sewn and stapled anastomoses after AR, and between patients after AR and APE for tumours 2 to 6 cm from the dentate line. Local recurrence after AR occurred in 14% and after APE in 10% of these cases. Five-year survival probabilities and local recurrence frequencies showed no statistically significant difference (P > 0.05). Local recurrence rates were 13.5% after hand-sewn anastomoses and 15% after the stapled procedure. No statistically significant difference was observed in the 5-year survival and recurrence rate (P > 0.05). Seventy-four of 136 patients had tumours located 2 to 6 cm from the dentata line. Local recurrence occurred in 21% after AR and 5% after APE, showing a statistically significant difference in frequency (P < 0.05). No significant difference was found in cumulative 5-year survival probabilities. APE for advanced low rectal cancer showed a significant reduction in local recurrences compared to AR.