Bruno Walther

Cervical or Thoracic Anastomosis After Esophageal Resection and Gastric Tube Reconstruction: A Prospective Randomized Trial Comparing Sutured Neck Anastomosis With Stapled Intrathoracic Anastomosis

Objective: The purpose of the study was to compare in prospective randomized fashion a manually sutured esophagogastric anastomosis in the neck and a stapled in the chest after esophageal resection and gastric tube reconstruction. Summary Background Data: Despite the fact that all reconstructions after esophagectomy will result in a cervical or a thoracic anastomosis, controversy still exists as to the optimal site for the anastomosis. In uncontrolled studies, both neck and chest anastomoses have been advocated. The only reported randomized study is difficult to evaluate because of varying routes of the substitute and different anastomotic techniques within the groups. The reported high failure rate of stapled anastomoses in the neck and the fact that most surgeons prefer to suture cervical anastomoses made us choose this technique for anastomosis in the neck. Our routine and the preference of most surgeons to staple high thoracic anastomoses became decisive for type of thoracic anastomoses. Methods: Between May 9, 1990 and February 5, 1996, 83 patients undergoing esophageal resection were prospectively randomized to receive an esophagogastric anastomosis in the neck (41 patients) or an esophagogastric anastomosis in the chest (42 patients). To evaluate selection bias, patients undergoing esophageal resection during the same period but not randomized (n = 29) were also followed and compared with those in the study (n = 83). Objective measurements of anastomotic level and diameter were assessed with an endoscope and balloon catheter 3, 6, and 12 months after surgery. The long-term survival rates were compared with the log-rank test. Results: Two patients (1.8%) died in hospital, and the remaining 110 patients were followed until death or for a minimum of 60 months. The genuine 5-year survival rate was 29% for chest anastomoses and 30% for neck anastomoses. The overall leakage rate was 1.8% (2 cases of 112) with no relation to mortality or anastomotic method. All patients in the randomized group had tumor-free proximal and distal resection lines, but 1 patient in the nonrandomized group had tumor infiltrates in the proximal resection margin. At 3, 6, and 12 months after operation, there was no difference in anastomotic diameter between the esophagogastric anastomosis in the neck and in the thorax (P = 0.771), and both increased with time (P = 0.004, ANOVA repeated measures). Body weight development was the same in the two groups. With similar results in randomized and nonrandomized patients, study bias was eliminated. Conclusions: When performed in a standardized way, neck and chest anastomoses after esophageal resection are equally safe. The additional esophageal resection of 5 cm in the neck group did not increase tumor removal and survival; on the other hand, it did not adversely influence morbidity, anastomotic diameter, or eating as reflected by body weight development.

Endoscopic surveillance of columnar-lined esophagus - Frequency of intestinal metaplasia detection and impact of antireflux surgery

ObjectiveTo quantify the occurrence of intestinal metaplasia in columnar-lined esophagus (CLE) during endoscopic surveillance and to evaluate the impact of antireflux surgery on the development of intestinal metaplasia. Summary Background DataThe malignant potential in segments of CLE is mainly restricted to those containing intestinal metaplasia. Patients with segments of CLE in which no intestinal metaplasia can be detected are rarely enrolled in a surveillance program but may still be at increased risk of developing esophageal adenocarcinoma because intestinal metaplasia may be missed or may develop with time. MethodsThe occurrence of intestinal metaplasia on biopsy samples was determined on repeated endoscopies in 177 patients enrolled in a surveillance program for CLE. The incidence of intestinal metaplasia in patients with no evidence of intestinal metaplasia on the two first endoscopies was evaluated on the subsequent endoscopies and compared in patients with medically and surgically treated gastroesophageal reflux disease. ResultsIntestinal metaplasia was found in 53% of the patients (94/177) on their first surveillance endoscopy and was more prevalent in long segments of CLE. The prevalence of intestinal metaplasia increased markedly with increasing number of surveillance endoscopies. Intestinal metaplasia tended to be detected early in patients with long segments of CLE; in patients with shorter segments, intestinal metaplasia was also detected late in the course of endoscopic surveillance. Patients with surgically treated reflux disease were 10.3 times less likely to develop intestinal metaplasia compared with a group receiving standard medical therapy. ConclusionBiopsy samples from a single endoscopy, despite an adequate biopsy protocol, are insufficient to rule out the presence of intestinal metaplasia. Patients in whom biopsy specimens from a segment of CLE show no intestinal metaplasia have a significant risk of having undetected intestinal metaplasia or of developing intestinal metaplasia with time. Sampling error is probably the reason for the absence of intestinal metaplasia in segments of CLE longer than 4 cm, whereas development of intestinal metaplasia is common in patients with shorter segments of CLE. Antireflux surgery protects against the development of intestinal metaplasia, possibly by better control of reflux of gastric contents.

Metaplastic columnar mucosa in the cervical esophagus after esophagectomy

ObjectiveTo evaluate the pathogenesis of metaplastic processes within the esophagus using a human model in which the exact duration of reflux was known. Summary Background DataThe pathogenesis of Barrett’s esophagus (BE) is incompletely understood. Patients undergoing esophagectomy and gastric tube reconstruction represent a good model for studying the pathophysiology of columnar cell metaplasia of the human esophagus because the cervical esophagus is rarely or never exposed to gastric contents before the surgical procedure. MethodsThirty-two patients underwent manometry, simultaneous 24-hour pH and bilirubin monitoring, and endoscopy with biopsy 3 to 10.4 years after esophagectomy. The presence of columnar mucosa in the cervical esophagus was confirmed on histologic examination. The findings on endoscopy and histology were related to clinical data and the results of pH and bilirubin monitoring 1 cm proximal to the esophagogastrostomy. ResultsFifteen (46.9%) of the 32 patients had metaplastic columnar mucosa within their cervical esophagus. Metaplasia was significantly more common in patients with a preoperative diagnosis of BE. The length of metaplastic mucosa correlated significantly with the degree of esophageal acid exposure, but the presence of abnormal bilirubin exposure was unrelated to the presence of metaplasia. The prevalence of metaplasia did not change with increasing time. Intestinal metaplasia was found within the columnar-lined segment in three patients 8.5, 9.5, and 10.4 years after esophagectomy. All patients with intestinal metaplasia had abnormal exposure of both acid and bilirubin, but the presence of combined reflux was not significantly higher in these patients compared with patients with nonintestinalized segments of columnar mucosa. ConclusionsEsophageal columnar metaplasia is a common complication after gastric pull-up esophagectomy. Metaplasia is more likely to develop in patients with previous BE than other patients. Metaplasia develops in response to squamous epithelial injury in predisposed individuals.

Barrett Esophagus: Risk Factors for Progression to Dysplasia and Adenocarcinoma

Objective:To evaluate risk factors for dysplasia and adenocarcinoma development in nondysplastic Barrett mucosa. Summary Background Data:The risk for patients with Barrett esophagus to develop esophageal adenocarcinoma is low, and most patients undergoing surveillance will not develop malignancy. Identification of risk factors may allow for more rational surveillance programs in which patients are stratified according to their individual risk of progressing to dysplasia and invasive adenocarcinoma. Methods:The development of dysplasia and esophageal adenocarcinoma was studied during long-term endoscopic and histologic surveillance in 140 patients with Barrett esophagus free from dysplasia. Risk factors for progression to dysplasia and adenocarcinoma were evaluated. Results:Median follow-up was 5.8 years. Forty-four patients (31.4%) developed low-grade dysplasia and 7 patients (5%) developed high-grade dysplasia or esophageal adenocarcinoma. Dysplasia development was significantly less common after antireflux surgery compared with conventional medical therapy. Low-grade dysplasia (relative risk = 5.5; 95% confidence interval, 1.1–28.6) and long duration of reflux symptoms (relative risk = 1.3; 95% confidence interval, 1.2–1.7) were independently associated with an increased risk of developing high-grade dysplasia or esophageal adenocarcinoma. Conclusions:Successful antireflux surgery protects the Barrett mucosa from developing high-grade dysplasia and esophageal adenocarcinoma, possibly by better control of reflux of gastric contents. Low-grade dysplasia is the only clinically useful risk factor that permits stratification of the surveillance intervals according to the risk of the individual patient.

Heller's esophagomyotomy with or without a 360 degrees floppy Nissen fundoplication for achalasia. Long-term results from a prospective randomized study.

Hellers esophagomyotomy relieves dysphagia but does not restore esophageal peristalsis. The myotomy may induce reflux and the addition of a 360 degrees fundoplication may be hazardous with regard to the remaining aperistaltic esophagus. The aim of this prospectively randomized clinical trial was to compare the outcome for patients with uncomplicated achalasia who underwent an anterior Hellers esophagomyotomy (H group) with or without an additional floppy Nissen fundoplication (H + N group). Between 1984 and 1995, 20 patients were prospectively randomized to one or other of the performed operations, 10 patients per group. Esophagitis including Barretts esophagus (n = 2) was seen under medical treatment, in 6 of 9 in the H group but none in the H + N group. No patient in the H + N group required postoperative continuous acid-reducing drugs. Twenty-four-hour esophageal pH-studies in median 3.4 years after surgery showed pathological reflux expressed as a percentage of time below pH 4 of 13.1% in the H group compared to 0.15% (P < 0.001) in H + N group. One patient with recurrent dysphagia in the H + N group later had an esophagectomy. The remaining patients reported significant improvement of dysphagia without symptoms of reflux at 8.0 years follow-up. Hellers esophagomyotomy eliminates dysphagia, but can induce advanced reflux that requires medical treatment. The addition of a 360 degrees fundoplication eliminates reflux without adding dysphagia in the majority of patients and can be recommended for most patients with uncomplicated achalasia.

Detection of adenocarcinoma in Barrett's oesophagus by means of laser induced fluorescence.

PATIENTS: Seven patients with Barretts metaplastic epithelium and oesophageal adenocarcinoma were investigated by means of laser induced fluorescence after low dose intravenous injection (0.35 mg/kg bw) of Photofrin (QLT, Vancouver, Canada). Laser induced fluorescence measurements were performed immediately after resection of the oesophagus. METHODS: Laser induced fluorescence spectra were recorded from 15-30 locations in each surgical specimen from normal mucosa, Barretts epithelium, and tumour tissue. Histological examination was performed on each location to correlate the fluorescence spectral characteristics with histological status of the epithelium (normal, metaplastic or malignant). Measurements were also performed during endoscopy in five patients to test the applicability of the method in a clinical setting. Fluorescence spectra were recorded and evaluated at characteristic wavelengths, and biopsy specimens were collected. Fluorescence ratios were calculated as the quotient of Photofrin fluorescence divided by autofluorescence. RESULTS: The mean (SD) fluorescence ratio values were 0.10 (0.058) for normal oesophageal mucosa, 0.16 (0.073) for normal gastric mucosa, 0.205 (0.17) for Barretts epithelium with moderate dysplasia, 0.79 (0.54) for severe dysplasia, and 0.78 (0.56) for adenocarcinoma. The highest fluorescence ratios were obtained for adenocarcinoma tissue, which could generally be distinguished from all nonmalignant tissue. Metaplastic Barretts epithelium also yielded higher fluorescence ratios than did normal mucosa. CONCLUSIONS: The results suggest that the technique can be used during endoscopy for real time tissue characterisation in the oesophagus, as an aid in detecting malignant transformation not macroscopically apparent at endoscopy.

The healing process of anastomoses of the colon

In spite of modern suture materials and different techniques in colonic anastomoses after resection, leakage is still the most feared complication in colonic surgery. In female pigs of Swedish land breed, standardized 5-cm long colonic resection was performed 10 cm above the peritoneal deflection, usign either a single layer of Gambee-stitches (n=6, Vicryl® 4-0), two-layer interrupted stitches (n=6, Vicryl® 4-0) or the intraluminal stapling device (n=6, ILS Ethicon®). After one week, the animals were sacrificed and an anastomotic index was calculated usingin vitro x-ray. Also, anastomotic circulation (calculated by the microsphere technique), breaking strength, and histologic evaluation were performed. All animals survived and no leakage was observed. The time to perform, the anastomosis was significantly shorter (P<0.05) for the stapling device compared with the manual techniques used. The anastomotic index was lower (P<0.05) for two rows (0.24) compared with Gambee-stitches (0.38) or stapler anastomoses (0.37). There were no differences in blood flow among the three groups and no differences in breaking strength. Macroscopic investigation revealed mucosal defects in two of the stapled anastomoses and histologic investigation showed small areas of necrosis. The stapling device did not induce any inflammatory reaction. On the other hand, a severe inflammatory reaction was seen when using conventional suture materials. In conclusion, this study shows that a single row of Gambee-stitches is equal to the ILS stapling device when performing colonic anastomoses and these two methods seem to be superior to the two-layer technique.

Impact of Proton Pump Inhibitors on Benign Anastomotic Stricture Formations After Esophagectomy and Gastric Tube Reconstruction: Results From a Randomized Clinical Trial.

Objective:The primary aim of this study was to evaluate if the use of proton pump inhibitors (PPIs) reduced the prevalence of benign anastomotic strictures after uncomplicated esophagectomies with gastric tube reconstruction and circular stapled anastomoses. Summary Background Data:Benign anastomotic strictures are associated with anastomotic leaks or conduit ischemia. Also patients without those complications develop benign anastomotic strictures. We hypothesize that patients without postoperative anastomotic complications may develop benign anastomotic strictures due to exposure of acid gastric tube contents to the anastomotic area, and that the formation of such strictures may be reduced by prophylactic use of PPIs. Methods:Eighty patients without preoperative chemo- or radiotherapy, without clinical or radiological signs of anastomotic leaks were included in this clinical trial. The patients were randomized to b.i.d. PPIs or no treatment for 1 year. Benign anastomotic strictures were defined as anastomotic narrowing not allowing a standard diagnostic endoscope to pass without dilatation. The study was registered in the EudraCT database (2009-009997-28) for clinical trials. Results:Seventy-nine patients were evaluated. Benign anastomotic strictures developed in 5/39 (13%) patients in the PPI group and in 18/40 (45%) in the control group (RR 5.6, 95% CI: 2.0–15.9, P = 0.001). The use of a narrower 25 mm cartridge as compared to a wider 28 or 31 mm cartridge significantly increased stricture formations (RR 2.9, 95% CI: 1.1–7.6, P = 0.025). Conclusions:Prophylactic PPI treatment reduced the prevalence of benign anastomotic strictures following esophagectomy with gastric tube reconstruction and circular stapled anastomoses. Larger sized circular staple cartridges additionally reduced the stricture prevalence.

Anastomotic diameters and strictures following esophagectomy and total gastrectomy in 256 patients.

The prevalence of anastomotic strictures in esophageal anastomoses provides us with limited information about the anastomotic healing process. This prospective study evaluates the exact esophageal anastomotic diameters in 256 patients who underwent esophagectomy and esophagogastrostomy without pyloroplasty (n= 107) or total gastrectomy and Roux reconstruction (n= 149). No perioperative chemoradiotherapy was given. Anastomotic strictures and diameters were assessed during endoscopy by a separately inserted (inflated to the anastomotic width) balloon catheter. The anastomotic diameters increased significantly during the first postoperative year in the esophagectomy (p= 0.001) and gastrectomy (p < 0.001) groups. The anastomoses in the gastrectomy group were significantly wider than those in the esophagectomy group 3 (25.7 versus 19.9 mm), 6 (28.5 versus 22.0 mm), and 12 (30.5 versus 23.3 mm) months after surgery (p < 0.001). Neither the anastomotic site (neck or chest) in the esophagectomy group (p= 0.176) nor that in the gastrectomy group (abdomen or chest) (p= 0.577) influenced the anastomotic diameter. Benign anastomotic strictures were most frequently found after 3 months and after esophagectomy. Esophagojejunostomies performed with 2 linear stapling devices or cartridge size 28 mm showed the widest anastomoses with only 1 stricture. Esophagogastric anastomoses following esophagectomy are narrower and develop more strictures than esophagojejunal anastomoses after total gastrectomy, but both dilate during the first year.

Pharyngeal reflux after gastric pull-up esophagectomy with neck and chest anastomoses

OBJECTIVE Pharyngeal reflux after a gastric pull-up esophagectomy may cause aspiration. This study evaluates acid exposure to the esophageal remnant and to the pharynx after gastric pull-up esophagectomy and evaluates the impact of additional dissection of the esophagus that is necessary for neck anastomoses versus no neck exploration and proximal chest anastomoses. METHODS Forty-seven patients had circular stapled anastomoses in the apex of the right chest (n = 27 patients) or manually sutured neck anastomoses (n = 20 patients). A 24-hour double-pH study with the probes placed 3 cm cranial and 3 cm distal to the cricopharyngeal muscle was performed. The percent time pH less than 4 was registered 3, 6, and 12 months after the operation. RESULTS Mean acid exposure to the proximal pH probe ranged between 0.2% and 0.96% and between 1.45% and 6.5% to the distal pH probe during the 3 measurements. Acid exposure was always lower to the proximal than to the distal probe (P =.001). Patients with neck anastomoses had increasing acid exposure to the distal (P =.023) and proximal (P =.002) pH probes during the study year, whereas patients with chest anastomoses had similar acid exposure. CONCLUSIONS Acid exposure to the esophageal remnant and to the pharynx increased during the first postoperative year in patients with neck anastomoses but not in patients with proximal chest anastomoses. The results suggest a less favorable acid clearance in patients with the neck approach.