Christer Staël von Holstein

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.

Surgical approach and prognostic factors after peptic ulcer perforation

OBJECTIVE To find out which prognostic factors were important in predicting postoperative mortality and length of hospital stay in patients with perforated peptic ulcers. DESIGN Retrospective study. SETTING Teaching hospital, Lund, Sweden. SUBJECTS 246 patients with perforated peptic ulcer who presented between January 1974 and December 1992. INTERVENTION Cox proportional hazards analysis. MAIN OUTCOME MEASURES Influence of age, sex, coexisting disease, duration of symptoms, site of perforation and operative technique on mortality and length of hospital stay. RESULTS Age over 75 years (p = 0.002), coexisting cardiac or pulmonary disease (p = 0.02), perforation of the cardia or body of the stomach (p = 0.02), lapse of more than 12 hours between start of symptoms and operation (p = 0.006) and type of operation (p < 0.0001) had a significant influence on hospital mortality. Age over 75 years (p < 0.0001) and lapse of more than 12 hours between start of symptoms and operation (p = 0.03) significant influenced the likelihood of a prolonged stay in hospital. CONCLUSION Patients with perforated peptic ulcers should be operated on as soon as possible. Simple closure is simple and safe with relatively low mortality and short stay in hospital.

Hemospray Application in Nonvariceal Upper Gastrointestinal Bleeding: Results of the Survey to Evaluate the Application of Hemospray in the Luminal Tract.

Background: Hemospray TM (TC-325) is a novel hemostatic agent licensed for use in nonvariceal upper gastrointestinal bleeding (NVUGIB) in Europe. Goals: We present the operating characteristics and performance of TC-325 in the largest registry to date of patients presenting with NVUGIB in everyday clinical practice. Methods: Prospective anonymized data of device performance and clinical outcomes were collected from 10 European centers using the multicentre SEAL survey (Survey to Evaluate the Application of Hemospray in the Luminal tract). TC-325 was used as a monotherapy or as second-line therapy in combination with other hemostatic modalities at the endoscopists’ discretion. Results: Sixty-three patients (44 men, 19 women), median age 69 (range, 21 to 98) years with NVUGIB requiring endoscopic hemostasis were treated with TC-325. There were 30 patients with bleeding ulcers and 33 with other NVUGIB pathology. Fifty-five (87%) were treated with TC-325 as monotherapy; 47 [85%; 95% confidence interval (CI), 76%-94%] of them achieved primary hemostasis, and rebleeding rate at 7 days was 15% (95% CI, 5%-25%). Primary hemostasis rate for TC-325 in patients with ulcer bleeds was 76% (95% CI, 59%-93%). Eight patients, who otherwise may have required either surgery or interventional radiology, were treated with TC-325 as second-line therapy after failure of other endoscopic treatments, all of whom achieved hemostasis following the adjunct of TC-325. Conclusions: This multicentre registry identifies potentially useful characteristics of Hemospray (TC-325) when used either as monotherapy or as a rescue therapy in a wide variety of ulcer and nonulcer NVUGIB.

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.

Impact of aspirin, NSAIDs, warfarin, corticosteroids and SSRIs on the site and outcome of non-variceal upper and lower gastrointestinal bleeding

Abstract Objective. To assess the impact of increased use of low-dose aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, corticosteroids and selective serotonin re-uptake inhibitors (SSRIs) on the site and outcome of non-variceal gastrointestinal (GI) bleeds. Methods. Retrospective review of 731 patients with peptic ulcer bleeds (PUBs), non-ulcer, non-variceal upper (NUUPGIBs) and lower GI bleeds (LGIBs) in 1984, 1994 and 2004 at Lund University Hospital, Sweden. Incidence and mortality rates, risk factors for fatal outcome and associations with different sites of GI bleeds were evaluated. Results. Between 1984 and 2004, incidence of PUBs decreased from 62.0 to 32.1 per 100,000 inhabitants (p < 0.001). Incidence of NUUPGIBs (29.0–30.4 per 100,000) and LGIBs (45.5–43.2 per 100,000) was stable. The case-fatality rate ranged from 4–6% (p = 0.65) for upper GI bleed to 1–8% (p = 0.033) for LGIB. No drug impacted on fatal outcome. Aspirin, warfarin and SSRI users tended to suffer more severe GI bleeds than non-users of these drugs. When comparing non-ulcer GI bleeds with PUBs, aspirin (OR 0.56, 95% CI 0.38–0.82) was more strongly associated with PUBs, whereas SSRIs (OR 3.71, 95% CI 1.39–12.9) and corticosteroids (OR 2.8, 95% CI 1.28–6.82) were more associated with non-ulcer GI bleeds after adjusting for age, gender and co-morbidity. Conclusion. Increased use of drugs that promote bleeding has not impacted on incidence and fatal outcome of non-variceal GI bleeds, although the severity of bleeding has increased. Aspirin is more strongly associated with PUBs, while corticosteroids and SSRIs are associated with non-ulcer, non-variceal GI bleeds.

Mucosal changes in the gastric remnant: long-term effects of bile reflux diversion and Helicobacter pylori infection.

Objective Bile reflux is thought to be responsible for reflux gastritis and stump carcinoma occurring after partial gastrectomy for peptic ulcer. Gastritis and gastric carcinoma are also correlated with Helicobacter pylori. The aim of this study was to investigate whether diversion of enteric reflux and the presence of H. pylori infection alter long-term histological developments in the gastric remnant. Methods Twenty-nine patients partially gastrectomized for peptic ulcer were reoperated on with re-resection and a Roux-en-Y reconstruction because of reflux gastritis (12 patients) or severe dysplasia/early gastric cancer (17 patients). The resected specimens and subsequent biopsies from the new anastomotic region taken at endoscopies 5–17 years after reoperation were evaluated regarding the presence of H. pylori, the grade of active and non-active chronic gastritis, and the premalignant changes – atrophy, intestinal metaplasia and dysplasia. Results A progression of active chronic gastritis, atrophy, intestinal metaplasia and dysplasia was seen after re-resection and Roux-en-Y reconstruction. Non-active chronic gastritis remained unchanged. The development was, in general, independent of H. pylori infection. Conclusions Enteric reflux may perhaps induce a histological transformation of the gastric mucosa that cannot be reversed, even if the reflux is diverted. In our study, H. pylori infection had no impact on the histological development. Factors other than enteric reflux and H. pylori infection might also be of importance.

Long-term Prognosis after Partial Gastrectomy for Gastroduodenal Ulcer

The decline in duodenal ulcer disease and the established relation of peptic ulcer to Helicobacter pylori have virtually abolished the need for elective ulcer surgery. However, a substantial proportion of the population around retirement age has previously been subjected to partial gastric resection due to peptic ulcer, and the long-term outcome of these patients is of continuing relevance. Patients subjected to elective surgery could represent a selected group of healthy subjects with a lower overall morbidity, but reports indicate that patients operated on for peptic ulcer have more advanced disease associated with excess smoking and a different pattern of social behavior. The surgical procedure induces enterogastric reflux, leading to profound changes in the remnant mucosa and the formation of carcinogens in the gastric juice. In addition, metabolic abnormalities are common, especially fat malabsorption. Evaluation of the impact of these factors on morbidity and mortality is difficult. Increased mortality in gastrointestinal tumors (especially gastric stump carcinoma), respiratory diseases and other smoking-related malignancies, and suicide are found in the long-term follow-up after partial gastric resection due to peptic ulcer. However, these hazards to life are offset by a decreased mortality in cardiovascular disease. Preventive measures against suicide and especially tobacco smoking are recommended to improve the outcome for this cohort.The decline in duodenal ulcer disease and the established relation of peptic ulcer to Helicobacter pylori have virtually abolished the need for elective ulcer surgery. However, a substantial proportion of the population around retirement age has previously been subjected to partial gastric resection due to peptic ulcer, and the long-term outcome of these patients is of continuing relevance. Patients subjected to elective surgery could represent a selected group of healthy subjects with a lower overall morbidity, but reports indicate that patients operated on for peptic ulcer have more advanced disease associated with excess smoking and a different pattern of social behavior. The surgical procedure induces enterogastric reflux, leading to profound changes in the remnant mucosa and the formation of carcinogens in the gastric juice. In addition, metabolic abnormalities are common, especially fat malabsorption. Evaluation of the impact of these factors on morbidity and mortality is difficult. Increased mortality in gastrointestinal tumors (especially gastric stump carcinoma), respiratory diseases and other smoking-related malignancies, and suicide are found in the long-term follow-up after partial gastric resection due to peptic ulcer. However, these hazards to life are offset by a decreased mortality in cardiovascular disease. Preventive measures against suicide and especially tobacco smoking are recommended to improve the outcome for this cohort.

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.

The significance of ulcer disease on late mortality after partial gastric resection.

Objective: To study the causes of long‐term mortality after peptic ulcer surgery with special attention to the impact of underlying ulcer disease. Design: Retrospective cohort investigation. Patients: A cohort of 1305 patients who had surgery for gastric and duodenal ulcer disease 29 to 59 years ago. At the end of follow‐up 80% of gastric ulcer patients, and 64% of duodenal ulcer patients were dead. Results: Overall mortality was significantly higher among gastric ulcer patients: standardized mortality ratio (SMR) 1.17 (95% confidence interval (CI) 1.05‐1.29); duodenal ulcer patients had an overall mortality comparable to the reference population: SMR 1.06 (CI 0.97‐1.15). Excess mortality among gastric ulcer patients was found to be due to neoplasms in gastrointestinal organs (SMR 1.54 (CI 1.11‐2.11)) which developed more than 20 years postoperatively, and to respiratory diseases and suicide unrelated to time since surgery. An increased mortality due to malignant tumours, respiratory diseases and suicide was also found among duodenal ulcer patients but this increased mortality was offset due to a significantly decreased mortality in diseases of the heart and vascular system (SMR 0.86 (CI 0.75‐0.97)), evident mainly after 20 years postoperatively. Excess mortality due to gastrointestinal cancers outnumbered excess mortality from carcinomas in the respiratory organs, and was due to cancers in the stomach, colon and pancreas. Conclusion: An increased mortality due to gastrointestinal carcinoma, especially gastric and pancreatic carcinoma, is apparent regardless of underlying ulcer disease. As preventive measures against these tumours have yielded little benefit in prospective trials, and as smoking‐related diseases and tumours together with suicide constitute 75% of the excess mortality, measures to combat smoking and suicide might be more worthwhile to reduce mortality in this cohort.