Yolande C. A. Keulemans

Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial

BACKGROUND Patients who undergo endoscopic sphincterotomy for common bile-duct stones, who have residual gallbladder stones, are referred for laparoscopic cholecystectomy. However, only 10% of patients who do not have this operation are reported to develop recurrent biliary symptoms. We aimed to assess whether a wait-and-see policy is justified. METHODS We did a prospective, randomised, multicentre trial in 120 patients (age 18-80 years) who underwent endoscopic sphincterotomy and stone extraction, with proven gallbladder stones. Patients were randomly allocated to wait and see (n=64) or laparoscopic cholecystectomy (56). Primary outcome was recurrence of at least one biliary event during 2-year follow-up, and secondary outcomes were complications of cholecystectomy and quality of life. Analysis was by intention to treat. FINDINGS 12 patients were lost to follow-up immediately. Of 59 patients allocated to wait and see, 27 (47%) had recurrent biliary symptoms compared with one (2%) of 49 patients after laparoscopic cholecystectomy (relative risk 22.42, 95% CI 3.16-159.14, p<0.0001). 22 (81%) of 27 patients underwent cholecystectomy, mainly for biliary pain (n=13) or acute cholecystitis (7). Conversion rate to open surgery was 55% in patients allocated to wait and see who underwent cholecystectomy compared with 23% in those who were allocated laparoscopic cholecystectomy (p=0.0104). Morbidity was 32% versus 14% (p=0.1048), and median hospital stay was 9 versus 7 days. Quality of life returned to normal within 3 months after either treatment policy. INTERPRETATION A wait-and-see policy after endoscopic sphincterotomy in combined cholecystodocholithiasis cannot be recommended as standard treatment, since 47% of expectantly managed patients developed at least one recurrent biliary event and 37% needed cholecystectomy. No major biliary complications arose, but conversion rate was high.

Impaired Quality of Life 5 Years After Bile Duct Injury During Laparoscopic Cholecystectomy: A Prospective Analysis

ObjectiveTo assess the impact of bile duct injury (BDI) sustained during laparoscopic cholecystectomy on physical and mental quality of life (QOL). Summary Background DataThe incidence of BDI during laparoscopic cholecystectomy has decreased but remains as high as 1.4%. Data on the long-term outcome of treatment in these patients are scarce, and QOL after BDI is unknown. MethodsOne hundred six consecutive patients (75 women, median age 44 ± 14 years) were referred between 1990 and 1996 for treatment of BDI sustained during laparoscopic cholecystectomy. Outcome was evaluated according to the type of treatment used (endoscopic or surgical) and the type of injury. Objective outcome (interventions, hospital admissions, laboratory data) was evaluated, a questionnaire was filled out, and a QOL survey was performed (using the SF-36). Risk factors for a worse outcome were calculated. ResultsMedian follow-up time was 70 months (range 37–110). The objective outcome of endoscopic treatment (n = 69) was excellent (94%). The result of surgical treatment (n = 31) depended on the timing of reconstruction (overall success 84%; in case of delayed hepaticojejunostomy 94%). Five patients underwent interventional radiology with a good outcome. Despite this excellent objective outcome, QOL appeared to be both physically and mentally reduced compared with controls (P < .05) and was not dependent on the type of treatment used or the severity of the injury. The duration of the treatment was independently prognostic for a worse mental QOL. ConclusionsDespite the excellent functional outcome after repair, the occurrence of a BDI has a great impact on the patient’s physical and mental QOL, even at long-term follow-up.

Laparoscopic cholecystectomy: day-care versus clinical observation.

OBJECTIVE To determine the feasibility and desirability of laparoscopic cholecystectomy (LC) in day-care versus LC with clinical observation. SUMMARY BACKGROUND DATA Laparoscopic cholecystectomy has been performed regularly as outpatient surgery in patients with uncomplicated gallstone disease in the United States, but this has not been generally accepted in Europe. The main objections are the risk of early severe complications (bleeding) or other reasons for readmission, and the argument that patients might feel safer when observed for one night. Quality-of-life differences hitherto have not been investigated. METHODS Eighty patients (American Society of Anesthesiology [ASA] I/II) with symptomatic gallstones were randomized to receive LC either in day-care or with clinical observation. Complications, (re)admissions, consultations of general practitioners or the day-care center within 4 days after surgery, use of pain medication, quality of life, convalescence period, time off from professional activities, and treatment preference were assessed. The respective costs of day-care and clinical observation were determined. RESULTS Of the 37 patients assigned to the day-care group who underwent elective surgery, 92% were discharged successfully after an observation period of 5.7+/-0.2 hours. The remainder of the patients in this group were admitted to the hospital and clinically observed for 24 hours. For the 37 patients in the clinical observation group who underwent elective surgery, the observation time after surgery was 31+/-3 hours. Three patients in the day-care group and one patient in the clinical observation group had complications after surgery. None of the patients in either group consulted a general practitioner or the hospital during the first week after surgery. Use of pain medication was comparable in both groups over the first 48 hours after surgery. There were no differences in pain and other quality-of-life indicators between the groups during the 6 weeks of follow-up. Of the patients in the day-care group, 92% preferred day-care to clinical observation. The same percentage of patients in the clinical observation group preferred at least 24 hours of observation to day-care. Costs for the day-care patients were substantially lower (approximately

Enterohepatic cycling of bilirubin: A putative mechanism for pigment gallstone formation in ileal Crohn's disease

750/patient) than for the clinical observation patients. CONCLUSION Effectiveness was equal in both patient groups, and both groups appeared to be satisfied with their treatment. Because no differences were found with respect to the other outcomes, day-care is the preferred treatment in most ASA I and II patients because it is less expensive.

Effects of regular physical activity on defecation pattern in middle-aged patients complaining of chronic constipation

BACKGROUND & AIMS Patients with ileal disease, bypass, or resection are at increased risk for developing gallstones. In ileectomized rats, bilirubin secretion rates into bile are elevated, most likely caused by increased colonic bile salt levels, which solubilize unconjugated bilirubin, prevent calcium complexing, and promote its absorption and enterohepatic cycling. The hypothesis that ileal disease or resection engenders the same pathophysiology in humans was tested. METHODS Sterile gallbladder bile samples were obtained intraoperatively from 29 patients with Crohns disease and 19 patients with ulcerative colitis. Bilirubin, total calcium, biliary lipids, beta-glucuronidase activities, and cholesterol saturation indices in bile were measured, and markers of hemolysis and ineffective erythropoiesis in blood were assessed. RESULTS Bilirubin conjugates, unconjugated bilirubin, and total calcium levels were increased 3-10-fold in bile of patients with ileal disease and/or resection compared with patients with Crohns colitis or ulcerative colitis. Biliary bilirubin concentrations correlated positively with the anatomic length and duration of ileal disease. Endogenous biliary beta-glucuronidase activities were comparable in all groups, and both the hemogram and serum vitamin B12 levels were normal. CONCLUSIONS This study establishes that increased bilirubin levels in bile of patients with Crohns disease are caused by lack of functional ileum, supporting the hypothesis that enterohepatic cycling of bilirubin occurs.

New strategies for the treatment of gallstone disease.

Objective . It is not well known whether physical activity (PA) is useful in the management of patients complaining of constipation. The aim of this study was to test the influence of regular PA on colonic transit time and defecation in middle-aged inactive patients suffering from chronic idiopathic constipation. Material and methods . Forty-three subjects (>45 years) were randomly divided into group A (n=18, 16 F, 2 M) and group B (n=25, 20 F, 5 M). Group A subjects maintained their normal lifestyle during 12 weeks, followed by a 12-week PA programme. Group B performed a 12-week PA programme after randomization. PA comprised 30 min of brisk walking and a daily 11-min home-based programme. Both groups received dietary advice. Colonic transit time was measured using a radiographic multiple marker single film technique. Results . Despite dietary advice, mean fibre and fluid intake did not change. In group B a significant reduction in 3 out of 4 of the Rome I criteria for constipation was observed, i.e. percentage of incomplete defecations, percentage of defecations requiring straining and percentage of hard stools (p<0.05). As a consequence, the number of fulfilled Rome criteria for constipation decreased (2.7 to 1.7; p<0.05). Furthermore, the rectosigmoid and total colonic transit time decreased (17.5 to 9.6 h and 79.2 to 58.4 h, respectively; p<0.05). After PA the number of fulfilled Rome criteria also decreased in group A (2.6 to 1.7; p<0.05). Conclusions . In middle-aged inactive subjects with symptoms of chronic constipation, it is advisable to promote regular physical activity since it improves both the defecation pattern and rectosigmoid or total colonic transit time.

The role of the Concanavalin A-binding fraction in cholesterol crystallization in native human bile

Background : Symptomatic gallstones are generally accepted as being the indication for cholecystectomy. Generally, severe abdominal pain in epigastrium and in the right upper abdominal quadrant, and lasting for more than 15 min, is thought to be caused by gallstones. However, many patients with other abdominal complaints undergo cholecystectomy and are satisfied with the outcome of surgery. Possible ways to improve the results of cholecystectomy are discussed. Methods : Review of previous work by the authors. Results : The introduction of laparoscopic cholecystectomy has even led to an increase in cholecystectomies; in a higher complication rate; and in increased costs of the treatment of gallstone disease. Because of faster recovery, 70% of symptomatic gallstone patients are able and willing to undergo laparoscopic cholecystectomy in day care. Cholecystectomy after sphincterotomy and stone extraction in patients who have stones in the gallbladder was demonstrated to prevent gallstone-related symptoms in at least 40% of patients. If the gallbladder had to be removed later for symptomatic disease, however, this did not result in a higher rate of conversions and complications. Because of shortage in operation capacity in The Netherlands, there is a considerable delay between the diagnosis of symptomatic stones and cholecystectomy. Better selection of patients for cholecystectomy will not only improve the results of cholecystectomy, it will also reduce the number of cholecystectomies and patients on waiting lists. Delay of cholecystectomy is associated with more complications, longer operative times, higher conversion rates to open cholecystectomy and prolonged hospitalization. The efficacy of the bile salt ursodeoxycholic acid in preventing gallstone-related pain attacks and complications in patients with contraindications for operation or waiting to undergo cholecystectomy should be investigated further, since two retrospective studies have demonstrated favourable outcomes for this strategy. Conclusion : The results of cholecystectomy are likely to be improved by better selection of patients, prevention of delay of the procedure and possibly treatment with ursodeoxycholic acid.

Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis

BACKGROUND/AIMS Many Concanavalin A-binding glycoproteins have been proposed to influence cholesterol crystallization in human bile. This has been studied mainly by addition of the Concanavalin A-binding fraction to model bile. The physiological relevance of the proteins in native bile is not yet known. The aim of this study was to establish the role of the Concanavalin A-binding fraction in cholesterol crystallization in native human gallbladder bile. METHODS To determine the effects of the removal of Concanavalin A-binding fraction, fresh human gallbladder bile was incubated with either Concanavalin A-Sepharose or Sepharose alone. Beads were sedimented and crystallization was studied in the supernatant. RESULTS Extraction of Concanavalin A-binding fraction decreased crystallization in fast-nucleating biles (Crystal Detection Time < or =4 days). Slow-nucleating biles were not affected. The effect could not be related to the content of known pronucleating proteins (IgA, IgM, haptoglobin, aminopeptidase N and alpha1-acid glycoprotein), since the slow-nucleating biles contained similar amounts of these proteins. CONCLUSIONS Although Concanavalin A-binding fraction always accelerated crystallization when added to model bile, removal of the same fraction from native bile often had no effect. We conclude that slow-nucleating biles in particular contain undetermined factors which regulate the activity of pronucleators.

Improvement in the management of bile duct injuries

BACKGROUND/AIMS Crohns disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohns disease and ulcerative colitis patients. METHODS Gallbladder bile was obtained by aspiration during bowel resections (26 Crohns disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. RESULTS Cholesterol crystals were present in seven of the 26 bile samples of Crohns disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohns disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohns disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. CONCLUSIONS Compared to ulcerative colitis patients, gallbladder bile of Crohns disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.