Jan Hedenbro

Endoscopic diagnosis of submucosal gastric lesions

SummaryThe accurate diagnosis of submucosal gastric lesions is difficult. In an attempt to study this problem, the endoscopic records for 8 consecutive years (July 1976–June 1984) were scanned with the help of a computer-based registration of the endoscopic findings. The examinations were identified in which the endoscopic diagnosis indicated the presence of a submucosal tumor. Fifty-four such patients were found in 15,104 routine examinations, giving an incidence of 0.36%. Six patients were lost to follow-up, so the study is based on 48 patients. The most common reason these patients underwent endoscopy was abdominal pain. Five patient groups were identified: (a) nine patients were correctly diagnosed as having gastric wall neoplasia at the initial endoscopy + biopsy; (b) in an additional 13 patients, the suspected gastric wall neoplasia was verified by further nonoperative diagnostic procedures; (c) five patients were found to have benign non-neoplastic gastric disease; (d) five patients had extragastric disease that pressed against the gastric wall; (e) in 14 patients a further work-up indicated that the initial endoscopy was false-positive. These five groups were confirmed by additional diagnostic procedures (including laparotomy)and a follow-up time of more than 5 yearsor autopsy. Two patients refused further examinations and died shortly afterward. No autopsies were performed. Based on our data, it would seem that in the vast majority of patients the suspicion of a submucosal gastric lesion at endoscopy indicates the presence of a serious condition.

Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients.

Venous thromboembolism is a significant cause of postoperative morbidity and mortality1. Risk factors include orthopaedic surgery, malignancy and obesity2. Low molecular weight heparin (LMWH) dominates for prophylaxis in general surgery3, and is usually given in a standard fixed dose; a higher dose is often suggested in high-risk situations. A study from the Mayo Clinic showed that of 32 cases of fatal pulmonary embolism after routine surgery, 16 had occurred in patients who were morbidly obese4. A survey among North American bariatric surgeons revealed that 48 per cent had personal experience of a patient with fatal thromboembolism. Fewer than 5 per cent chose not to use routine thromboprophylaxis5. The efficacy of LMWH in preventing clinically significant thromboembolic events has not been specifically studied in obese patients. Given the relative rarity of these events, such a study would require a large number of patients, and is unlikely ever to be performed. The effect of a given dose of enoxaparin can be monitored by measuring the plasma level of antifactor Xa (anti-Xa), which is thought to correlate with the antithrombotic effect, as well as with the risk of excessive bleeding6. The aim of the present study was to relate the anti-Xa activity to body-weight after injection of LMWH.

Effects of pH on Helicobacter pylori binding to human gastric mucins: identification of binding to non-MUC5AC mucins

Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.

Early Complications After Laparoscopic Gastric Bypass Surgery : Results From the Scandinavian Obesity Surgery Registry

Objective:To identify risk factors for serious and specific early complications of laparoscopic gastric bypass surgery using a large national cohort of patients. Background:Bariatric procedures are among the most common surgical procedures today. There is, however, still a need to identify preoperative and intraoperative risk factors for serious complications. Methods:From the Scandinavian Obesity Surgery Registry database, we identified 26,173 patients undergoing primary laparoscopic gastric bypass operation for morbid obesity between May 1, 2007, and September 30, 2012. Follow-up on day 30 was 95.7%. Preoperative data and data from the operation were analyzed against serious postoperative complications and specific complications. Results:The overall risk of serious postoperative complications was 3.4%. Age (adjusted P = 0.028), other additional operation [odds ratio (OR) = 1.50; confidence interval (CI): 1.04–2.18], intraoperative adverse event (OR = 2.63; 1.89–3.66), and conversion to open surgery (OR = 4.12; CI: 2.47–6.89) were all risk factors for serious postoperative complications. Annual hospital volume affected the rate of serious postoperative complications. If the hospital was in a learning curve at the time of the operation, the risk for serious postoperative complications was higher (OR = 1.45; CI: 1.22–1.71). The 90-day mortality rate was 0.04%. Conclusions:Intraoperative adverse events and conversion to open surgery are the strongest risk factors for serious complications after laparoscopic gastric bypass surgery. Annual operative volume and total institutional experience are important for the outcome. Patient related factors, in particular age, also increased the risk but to a lesser extent.

Common variants in the beta2-(Gln27Glu) and beta3-(Trp64Arg)--adrenoceptor genes are associated with elevated serum NEFA concentrations and type II diabetes

Aims/hypothesis. Higher NEFA concentrations predict Type II (non-insulin-dependent) diabetes mellitus but it is not known whether higher NEFA concentrations are genetically determined or reflect coexisting obesity. To address this question we studied whether common variants in two genes encoding for key regulators of lipolysis, the β2- and β3- adrenoceptors (B2AR and B3AR) are associated with NEFA concentrations and Type II diabetes. Methods. A total of 1054 Swedish subjects with varying degrees of glucose tolerance were genotyped for the Gln27Glu variant in the B2AR and for the Trp64Arg variant in the B3AR genes using PCR-RFLP. Results. The B2AR Gln27 allele was more frequent in 219 Type II diabetic patients than in 237 non-diabetic subjects (59.8 % vs 52.3 %; OR = 1.72, p = 0.02) while there was no significant difference in the frequency of the B3AR Arg64 allele. Subjects homozygous for the protective alleles (Glu27 and Trp64) had, however, a lower prevalence of diabetes than subjects with other genotype combinations (OR = 0.58, p = 0.03). Among sibling pairs discordant for the B2AR Gln27Glu polymorphism, siblings with an excess of the Gln27 allele had higher fasting insulin (n = 217; p = 0.02) and NEFA concentrations (107 sex-matched pairs; p = 0.01) than siblings with an excess of the Glu27 allele. Among sibling pairs discordant for the B3AR Trp64Arg variant, siblings with the Arg64 allele had higher 2 h glucose (n = 48; p = 0.01) and NEFA concentrations (16 pairs matched for sex; p < 0.04) than siblings with the Trp64Trp64 genotype. Conclusions/interpretation. Common variants in the β2- and β3- adrenoceptor genes are associated with increased fasting insulin and NEFA concentrations and could increase susceptibility to Type II diabetes. [Diabetologia (2001) 44: 629–636]

Mechanisms of gastric acid secretion after pylorus and oesophagus ligation in the rat.

1. The effect of vagotomy on gastric acid secretion was studied in chronic gastric fistula rats at various times after denervation. In these rats basal and pentagastrin‐induced acid output was permanently reduced. Thus, the magnitude of the acid response to pentagastrin in the conscious fistula rat is dependent upon an intact vagus. 2. The acid response to pylorus ligation in vagally intact rats was unaffected by drainage of the stomach and therefore not caused by distension. Bilateral vagotomy, performed simultaneously with the ligation, completely abolished acid secretion, while unilateral vagotomy reduced the acid output by half. Hence, in innervated rats, an intact vagal impulse flow appears to be essential for the acid response to pylorus ligation. When the pylorus ligation was performed 2‐8 weeks after truncal vagotomy, the acid output showed a progressive return towards pre‐denervation values. In the denervated rats the acid response to pylorus ligation was blocked by drainage of the stomach and therefore probably caused by distension, a mechanism which is independent of the vagal impulse flow. 3. The response to pylorus ligation in innervated rats was blocked by atropine and chlorisondamine but not by metiamide. In the denervated rats, the response to pylorus ligation was blocked by all three drugs. 4. Following ligation of both the pylorus and the oesophagus the acid response was poor. With drainage of the oesophagus the acid response was much enhanced, suggesting that oesophageal distension inhibits acid secretion. In the vagotomized rat the poor acid response to oesophageal + pyloric ligation could not be overcome by drainage of the oesophagus. In the innervated rat gastric distension could overcome the inhibition induced by oesophageal ligation. Also in chronically, but not in acutely vagotomized rats, gastric distension brought about a good acid response. Conceivably, gastric reflex mechanisms can activate acid secretion through vagal and/or intramural pathways. Both in innervated and denervated rats the response to gastric distension was inhibited by atropine, chlorisondamine and metiamide. 5. The results suggest that in the innervated rat vago‐vagal reflexes are important for the gastric hypersecretion following ligation of the pylorus, and for the acid response to gastric distension following ligation of the pylorus and oesophagus. In the chronically vagotomized rat local intramural reflexes elicited by gastric distension are responsible for the acid response.

Management of suspected anastomotic leak after bariatric laparoscopic Roux-en-y gastric bypass

Anastomotic leak is one of the most serious complications following bariatric laparoscopic Roux‐en‐Y gastric bypass (LRYGB), and associated with high morbidity rates and prolonged hospital stay. Timely management is of utmost importance for the clinical outcome. This study evaluated the approach to suspected leakage in a high‐volume bariatric surgery unit.

Gastric bypass improves ss-cell function and increases β-cell mass in a porcine model.

The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on β-cell function and β-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in β-cell mass, islet number, and number of extraislet β-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved β-cell function and β-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical.

Gastric acid response to pylorus ligation in rats: is gastrin or histamine involved?

1. Pylorus ligation stimulated the acid output in vagally intact rats. The serum gastrin concentration and the gastric mucosal histamine content were not affected. The gastric histidine decarboxylase activity was initially slightly elevated and then greatly reduced (12‐20 hr after ligation).

Weight Loss After Vertical Banded Gastroplasty Can Be Predicted: A Prospective Psychological Study

Background: Although treatment failure after Vertical Banded Gastroplasty (VBG) is not uncommon, the safety of the procedure makes it the most widely used form of bariatric surgery. The reasons for failure may be either technical, such as staple-line dehiscence, or psychological inability on the part of the patient to adjust to the small stomach pouch and to its consequences. Methods: We carried out prospective testing of a cohort of consecutive VBG candidates, using a battery of psychological tests consisting of the ‘Three Factor Eating Questionnaire’, ‘Hopkins Symptom Check List (HSCL)’, ‘Mood Adjective Check List (MACL)’, ‘Karolinska Scales of Personality (KSP)’, and two projective tests, the ‘Meta-Contrast Technique (MCT)’ and the ‘Perceptgenetic Object Relation Test (PORT)’. The patients had been scheduled for surgery on clinical considerations only, and the results of the psychological testing were not disclosed to the surgeons until after the follow-up. Results: Mean preoperative Body Mass Index (BMI) was 42.0 (sd 9.9). Patients were extensively tested during the 3 weeks prior to surgery. There were no operative complications. Patients were tested psychologically again after 3 years. Their mean BMI then was 32.3 (sd 5.6). Thirteen patients had lost more than 50% of their overweight (BMI mean 29.6; sd 1.1), seven patients had lost less than 50% (BMI mean 37.0; sd 1.6; p = 0.0043). These two groups were compared. The single factor that correlated consistently with an unsatisfactory weight loss was preoperative signs of depression (p = 0.04). Stepwise discriminant analysis using three preoperative factors(Hunger, Verbal aggression and Socialization) correctly classified 90% of the patients who had lost <50% of their overweight. Other variables (Impulsivity, Emotional detachment and Maladaptive psychological defence) identified patients who were later to suffer from dysphoric mood (n = 5) or disturbed eating behaviour (n = 11). These factors may compromise a sustained ability to tolerate food restriction. Despite the operations disadvantages, all patients considered it worthwhile and displayed improved psychosocial adaptation postoperatively. Conclusion: We conclude that extensive psychological testing can accurately predict the intermediate-term weight outcome following VBG and that even patients who show little weight loss benefit from the procedure.