Safety, patient's tolerance, and efficacy of a 2-liter vitamin C-enriched macrogol bowel preparation: a randomized, endoscopist-blinded prospective comparison with a 4-liter macrogol solution.

BACKGROUND: Optimal bowel preparation is associated with lower polyp miss rates, but patients have difficulties in complying with the usual 4-L bowel preparation. OBJECTIVE: This study aimed to compare the safety, acceptance, and efficacy of 2-L polyethylene glycol electrolyte solution enriched in vitamin C with 4-L polyethylene glycol electrolyte solution. DESIGN: This study is an endoscopist-blinded randomized controlled trial. SETTINGS: The study was conducted at a tertiary referral hospital. PATIENTS: Consecutive outpatients were randomly assigned to receive 4-L polyethylene glycol electrolyte solution or 2-L polyethylene glycol electrolyte solution enriched in vitamin C with 2 L of clear fluids in a single-dose or a split-dose regime. MAIN OUTCOME MEASURES: Safety was assessed by blood sampling before and after the preparation and by a 30-day postcolonoscopy chart and complication database review. Acceptance was investigated by questionnaires, and the adequacy of bowel preparation was assessed by the Aronchick and Ottawa scales. RESULTS: One hundred eighty-eight patients, 98 in the polyethylene glycol electrolyte solution enriched in vitamin C group and 90 in the polyethylene glycol electrolyte solution group, participated. Although changes in bicarbonate blood concentrations with polyethylene glycol electrolyte solution enriched in vitamin C were seen to such an extent that the blinded investigator correctly guessed the preparation in 75.6%, no unsafe values were observed. A 30-day chart and complication database review revealed 1 severe adverse event of a myocardial infarction in the polyethylene glycol electrolyte solution enriched in vitamin C group. Patient acceptance and compliance were significantly higher with the polyethylene glycol electrolyte solution enriched in vitamin C group. The impact on sleep, daily activities, and physical complaints were similar in both groups. Polyethylene glycol electrolyte solution enriched in vitamin C was noninferior to polyethylene glycol electrolyte solution in cleansing efficacy, but the segmental rating of excellent and good preparation in right and transverse colon was significantly better for polyethylene glycol electrolyte solution, especially when taken as a split dose. LIMITATIONS: The results cannot be extrapolated to immobile inpatients with comorbidities. Another limitation of our study was the inability to determine plasma vitamin C concentrations and to assess the quality of colonoscopy performance. CONCLUSIONS: Two-liter polyethylene glycol electrolyte solution enriched in vitamin C is a safe and patient-friendly alternative to the 4-L polyethylene glycol electrolyte solution. Endoscopists slightly preferred the 4-L polyethylene glycol electrolyte solution.

Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.

BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. RESULTS: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. CONCLUSION: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.

High cumulative risk of intussusception in patients with Peutz-Jeghers syndrome: time to update surveillance guidelines?

OBJECTIVES: Peutz-Jeghers syndrome (PJS) is characterized by gastrointestinal hamartomas. The hamartomas are located predominantly in the small intestine and may cause intussusceptions. We aimed to assess the characteristics, risk, and onset of intussusception in a large cohort of PJS patients to determine whether enteroscopy with polypectomy should be incorporated into surveillance recommendations. METHODS: All PJS patients from two academic hospitals were included in this cohort study (prospective follow-up between 1995 and July 2009). We obtained clinical data by interview and chart review. Deceased family members with PJS were included retrospectively. Cumulative intussusception risks were calculated by Kaplan­Meier analysis. RESULTS: We included 110 PJS patients (46% males) from 50 families. In all, 76 patients (69%) experienced at least one intussusception (range 1-6), at a median age of 16 (3-50) years at first occurrence. The intussusception risk was 50% at the age of 20 years (95% confidence interval 17-23 years) and the risk was independent of sex, family history, and mutation status. The intussusceptions occurred in the small intestine in 95% of events, and 80% of all intussusceptions (n=128) presented as an acute abdomen. Therapy was surgical in 92.5% of events. Based on 37 histology reports, the intussusceptions were caused by polyps with a median size of 35 mm (range 15-60 mm). CONCLUSIONS: PJS patients carry a high cumulative intussusception risk at young age. Intussusceptions are generally caused by polyps >15 mm and treatment is mostly surgical. These results support the approach of enteroscopic surveillance, with removal of small-intestinal polyps >10-15 mm to prevent intussusceptions. The effect of such an approach on the incidence of intussusception remains to be established in prospective trials.

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome.

INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable evidence concerning the magnitude of a possible excess risk is necessary to determine whether preventive measures, like screening colonoscopies, in FDRs are justified. AIMS AND METHODS: We analysed the incidence rate of CRC in FDRs and compared this with the general population through person-year analysis after adjustment for demographic characteristics. Population-based incidence data from the Eindhoven Cancer Registry during the period 1970-2006 were used to compare observed numbers of CRC cases in FDRs with expected numbers based on the incidence in the general population. RESULTS: A total of 347 FDRs (41% male) from 57 pedigrees were included, contributing 11 053 person-years of follow-up. During the study period, a total of 27 CRC cases occurred among FDRs compared to five expected CRC cases (p<0.001). The RR of CRC in FDRs compared to the general population was 5.4 (95% CI 3.7 to 7.8). Four FDRs satisfied the criteria for HPS. Based on the estimated HPS prevalence of 1:3000 in the general population the projected RR of HPS in FDRs was 39 (95% CI 13 to 121). CONCLUSIONS: FDRs of HPS patients have an increased risk for both CRC and HPS compared to the general population. Hence, as long as no genetic substrate has been identified, screening colonoscopies for FDRs seem justified but this needs to be prospectively evaluated.

High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations.

OBJECTIVES: Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with increased cancer risk. Surveillance and patient management are, however, hampered by a wide range in cancer risk estimates. We therefore performed a systematic review to assess cancer risks in PJS patients and used these data to develop a surveillance recommendation. METHODS: A systematic PubMed search was performed up to February 2009, and all original articles dealing with PJS patients with confirmed cancer diagnoses were included. Data involving cancer frequencies, mean ages at cancer diagnosis, relative risks (RRs), and cumulative risks were collected. RESULTS: Twenty-one original articles, 20 cohort studies, and one meta-analysis fulfilled the inclusion criteria. The cohort studies showed some overlap in the patient population and included a total of 1,644 patients; 349 of them developed 384 malignancies at an average age of 42 years. The most common malignancy was colorectal cancer, followed by breast, small bowel, gastric, and pancreatic cancers. The reported lifetime risk for any cancer varied between 37 and 93%, with RRs ranging from 9.9 to 18 in comparison with the general population. Age-related cumulative risks were given for any cancer and gastrointestinal, gynecological, colorectal, pancreatic, and lung cancers. CONCLUSIONS: PJS patients are markedly at risk for several malignancies, in particular gastrointestinal cancers and breast cancer. On the basis of these elevated risks, a surveillance recommendation is developed to detect malignancies in an early phase and to remove polyps that may be premalignant and may cause complications, so as to improve the outcome.

Quality of life and psychological distress in patients with Peutz-Jeghers syndrome.

Little is known about psychological distress and quality of life (QoL) in patients with Peutz-Jeghers syndrome (PJS), a rare hereditary disorder. We aimed to assess QoL and psychological distress in PJS patients compared to the general population, and to evaluate determinants of QoL and psychological distress in a cross-sectional study. PJS patients completed a questionnaire on QoL, psychological distress, and illness perceptions. The questionnaire was returned by 52 patients (85% response rate, 56% females, median age 44.5 years). PJS patients reported similar anxiety (p = 0.57) and depression (p = 0.61) scores as the general population. They reported a lower general health perception (p = 0.003), more limitations due to emotional problems (p = 0.045) and a lower mental well-being (p = 0.036). Strong beliefs in negative consequences of PJS on daily life, a relapsing course of the disease, strong emotional reactions to PJS, and female gender were major determinants for a lower QoL. PJS patients experience a similar level of psychological distress as the general population, but a poorer general health perception, more limitations due to emotional problems, and a poorer mental QoL. Illness perceptions and female gender were major predictors for this lower QoL. These results may help to recognize PJS patients who might benefit from psychological support.

High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis.

BACKGROUND AND STUDY AIM: Duodenal polyposis occurs in approximately 90 % of patients with familial adenomatous polyposis (FAP) and 5 % - 10 % develop duodenal cancer. Novel imaging techniques may improve evaluation of duodenal polyposis using the Spigelman classification. We aimed to analyze the value of high resolution endoscopy (HRE) and the additional value of chromoendoscopy in the evaluation of duodenal polyposis in FAP. PATIENTS AND METHODS: 43 FAP patients scheduled for surveillance endoscopy in two academic centers underwent gastroduodenoscopy with HRE forward- and side-viewing devices. After number and size of adenomas had been scored, indigo carmine 0.5 % was sprayed onto the mucosa, polyps were scored again and biopsies taken from the larger lesions. Subsequently, Spigelman classifications were assessed for pre- and post-staining. RESULTS: Before staining, a median of 16 adenomas per patient were detected compared with 21 adenomas after staining ( P = 0.02). Staining led to upgrading of Spigelman stage in 5/43 patients (12 %). Using the side-viewing endoscope, ampullary enlargement was detected in 22 patients (51 %) of whom 18 (42 %) had histologically confirmed ampullary adenomas. CONCLUSION: HRE has raised the quality of endoscopic imaging considerably. Consequently, re-evaluation of the original Spigelman classification system seems advisable. Chromoendoscopy further increases detection of duodenal adenomas in FAP but without considerable change in Spigelman stage. Ampullary adenomas are commonly found in FAP and are best visualized using a side-viewing endoscope. Therefore, a combination of forward-viewing HRE and chromoendoscopy with side-viewing endoscopy for the periampullary region seems useful for surveillance of duodenal adenomatosis in FAP.

The role of endoscopy in bariatric surgery.

Morbid obesity is a chronic disease of excess fat storage, characterised by premature death and obesity-associated co-morbidities. The results of the current non-surgical treatment to treat obesity are disappointing, but surgical approaches may achieve a durable and longstanding weight loss with resolution and improvement of co-morbidities. Gastrointestinal complaints and digestive complications may, however, increase and may require an actively involved gastroenterologist.

Oral aspects of obesity.

Obesity (Body Mass Index > or = 30 kg/m2) has a high prevalence of 15-30% among European and American populations. It is an incurable chronic disease with a considerable mortality and co-morbidity. The co-morbidity can be reduced substantially by a moderate weight loss of 5-15%. The main cause of obesity is an imbalance between energy intake and energy expenditure. Therefore, the treatment starts with an energy restricted diet, a reduction of sedentary lifestyle, increased physical activity, and behavioural therapy to change eating habits. When necessary, this treatment can be followed by pharmacotherapy or surgery. Obesity is related to several aspects of oral health, such as caries, periodontitis and xerostomia. In addition, obesity may have implications for the dental treatment plan.

[Surgical treatment of serious obesity: many questions on medical indications and results remain]. / Operatieve behandeling van ernstige obesitas: nog veel vragen over indicaties en resultaten.

Obesity is associated with increased mortality and a whole spectrum ofco-morbidities. Weight loss is indicated to relieve or prevent these co-morbidities and to reduce psychosocial and socio-economic consequences. The step-wise approach of obesity treatment is first the combination of energy restriction, physical activity and behavioural changes, followed by pharmacotherapy. The last step is bariatric surgery. From the results oflaparoscopic gastric banding, as published in this issue of the journal, two important aspects emerge. First, a change in the operation technique considerably reduced the long-term complication rate and second, the attrition rate decreased due to follow-ups managed by nurse practitioners. The study can also be criticised for not giving details of the selection procedures and the number of and reasons for rejection as well as for not reporting the improvements in co-morbidity and quality of life.

[Dietary supplements such as nutrient drinks have no role in the prevention of pressure sores]. / Voedingssupplementen zoals drinkvoedingen zijn niet zinvol bij de preventie van decubitus.

Pressure sores are the result of primary intrinsic factors like pressure, shear and friction forces combined with secondary extrinsic factors such as old age, malnutrition, immobility, incontinence, and poor physical and mental health. A cause-and-effect relationship between malnutrition and decubitus ulcers has never been established. There is insufficient evidence that dietary interventions can decrease the incidence of pressure sores.

[Placement of nasoenteral feeding tubes by nurses]. / Plaatsing van naso-enterale voedingssondes door verpleegkundigen.

Electromagnetic-guided placement of nasoenteral feeding tubes by nurses is an alternative to endoscopic placement by gastroenterologists. During placement, the electromagnetic signal that is emitted by the tip of the guidewire enables visualisation of the position of the tube on a portable monitor. The procedure can be performed by a trained endoscopy nurse at the bedside of the patient. This could have logistic advantages, as the patient transport is not necessary and confirmation of the position of the tube by an abdominal X-ray is not required. Other possible advantages of the new technique are no preprocedural fasting and no need for sedation. If the tube coils in the stomach, it can be repositioned without the need for a repeat procedure. A randomised multicentre trial found electromagnetic nasoenteral placement of feeding tubes to be non-inferior on comparison with endoscopic placement by gastroenterologists, and it can be considered as the preferred technique.

A prospective randomized blinded comparison of sodium phosphate and polyethylene glycol-electrolyte solution for safe bowel cleansing.

BACKGROUND: Polyethylene glycol-electrolyte solution (PEG-ELS) is routinely prescribed for bowel cleansing. Sodium phosphate (NaP) may be an effective but potentially hazardous alternative. AIM: To investigate the safety of prescription of either agent, without being informed of the patient's medical history. METHODS: One hundred consecutive patients were randomly allocated to PEG-ELS or NaP. Prior to and after the bowel cleansing, blood was sampled for renal function and electrolytes. Patients answered questionnaires about complaints and ease of intake, and endoscopists rated the quality of bowel preparation. RESULTS: Eleven patients were identified with a theoretical contraindication for NaP, of whom nine should have been discovered by taking a detailed clinical history. Actually, six of them received NaP with a doubling of serum phosphate levels or hypokalaemia in four. In subjects without a contraindication to the use of NaP, hyperphosphataemia developed in 39% and hypocalcaemia in 5%. Patients tolerated NaP better and completed the preparation more often. Endoscopists rated the quality of bowel preparation equivalent, except for a better cleansed ascending colon with PEG-ELS. CONCLUSIONS: The 11% potentially hazardous allocation to NaP and the 39% incidence of hyperphosphataemia with NaP do not justify an 'over-the-counter' prescription. Taking a detailed history and, when in doubt, using PEG-ELS will safeguard against inappropriate administration of NaP.

Incidence of refeeding syndrome in internal medicine patients.

BACKGROUND: Refeeding syndrome is a potentially fatal shift of fluids and electrolytes that may occur after reintroducing nutrition in a malnourished patient. Its incidence in internal medicine patients is not known. We aimed at determining the incidence in a heterogeneous group of patients acutely admitted to a department of internal medicine. METHODS: All patients acutely admitted to the department of internal medicine of a teaching community hospital in Amsterdam, the Netherlands, between 22 February 2011 and 29 April 2011, were included. We applied the National Institute for Health and Care Excellence (NICE) criteria for determining people at risk of refeeding syndrome and took hypophosphataemia as the main indicator for the presence of this syndrome. RESULTS: Of 178 patients included in the study, 97 (54%) were considered to be at risk of developing refeeding syndrome and 14 patients actually developed the syndrome (14% of patients at risk and 8% of study population). Patients with a malignancy or previous malignancy were at increased risk of developing refeeding syndrome (p < 0.05). Measurement of muscle strength over time was not associated with the occurrence of refeeding syndrome. The Short Nutritional Assessment Questionnaire score had a positive and negative predictive value of 13% and 95% respectively. CONCLUSION: The incidence of refeeding syndrome was relatively high in patients acutely admitted to the department of internal medicine. Oncology patients are at increased risk of developing refeeding syndrome. When taking the occurrence of hypophosphataemia as a hallmark, no other single clinical or composite parameter could be identified that accurately predicts the development of refeeding syndrome.

Long-term maintenance of weight loss with sibutramine in a GP setting following a specialist guided very-low-calorie diet: a double-blind, placebo-controlled, parallel group study.

OBJECTIVE: Very-low-calorie diets (VLCDs) are used to promote short-term weight loss in obese patients. However, long-term maintenance of weight loss is generally poor. We assessed the efficacy and safety of sibutramine in maintaining weight loss achieved in obese patients by means of a 3-month VLCD. DESIGN: A multicenter double-blind, parallel-group trial conducted over 18 months, following a 3-month open label VLCD run-in. SETTING: Eight hospital centers in The Netherlands, with subsequent follow-up in general practice. SUBJECTS: A total of 221 obese subjects, of whom 189 were randomized (mean screening BMI 36.6 kg/m(2); mean age 42.6 y). MEASUREMENTS: Patients were given a 3-month VLCD and were required to lose 10% or more of their initial weight. A total of 189 patients completed this phase (mean percentage weight loss 14.5+/-3.2%) and were randomized to sibutramine 10 mg/day (n=94) or matching placebo (n=95). All patients received a recommended diet and exercise program. The primary analysis was outcome in terms of achieving 80% weight maintenance of the VLCD period at month 18. Secondary analysis was percentage of initial weight loss maintained at months 6, 12, 18 and end point. RESULTS: At month 18, the odds ratio for achieving successful weight maintenance was 1.76 (95% CI 1.06, 2.93) in favor of sibutramine (P=0.03). In intention-to-treat analysis, more than 80% of the weight loss achieved during the VLCD phase was maintained by 70, 51 and 30% of sibutramine-treated patients at months 6, 12 and 18, respectively, compared to 48, 31 and 20% of placebo-treated patients. The differences between the treatment groups were significant (P< or =0.03) at all time points. CONCLUSION: Weight loss achieved with a VLCD is more effectively maintained with sibutramine in combination with a recommended diet and exercise program than with placebo over a follow-up period of 18 months. Sibutramine is well tolerated, with a safety profile consistent with that seen in other previous trials.

Daily enteral feeding practice on the ICU: attainment of goals and interfering factors.

BACKGROUND: The purpose of this study was to evaluate the daily feeding practice of enterally fed patients in an intensive care unit (ICU) and to study the impact of preset factors in reaching predefined optimal nutritional goals. METHODS: The feeding practice of all ICU patients receiving enteral nutrition for at least 48 hours was recorded during a 1-year period. Actual intake was expressed as the percentage of the prescribed volume of formula (a success is defined as 90% or more). Prescribed volume (optimal intake) was guided by protocol but adjusted to individual patient conditions by the intensivist. The potential barriers to the success of feeding were assessed by multivariate analysis. RESULTS: Four-hundred-and-three eligible patients had a total of 3,526 records of feeding days. The desired intake was successful in 52% (1,842 of 3,526) of feeding days. The percentage of successful feeding days increased from 39% (124 of 316) on day 1 to 51% (112 of 218) on day 5. Average ideal protein intake was 54% (95% confidence interval (CI) 52 to 55), energy intake was 66% (95% CI 65 to 68) and volume 75% (95% CI 74 to 76). Factors impeding successful nutrition were the use of the feeding tube to deliver contrast, the need for prokinetic drugs, a high Therapeutic Intervention Score System category and elective admissions. CONCLUSION: The records revealed an unsatisfactory feeding process. A better use of relative successful volume intake, namely increasing the energy and protein density, could enhance the nutritional yield. Factors such as an improper use of tubes and feeding intolerance were related to failure. Meticulous recording of intake and interfering factors helps to uncover inadequacies in ICU feeding practice.

Gastric Emptying, CCK Release, and Satiety in Weight-Stable Obese Subjects.

Scintigraphic gastric emptying studies are far from conclusive in obesity. The aim was to investigate gastric emptying and CCK release in weight-stable obese subjects on their usual diet and to study the impact of factors known to determine gastric emptying. Patients entering a weight reduction program were asked to participate in a study examining gastric emptying by scintigraphy and CCK release in response to a meal with questionnaires on feelings of satiety. Forty-five patients (9 M, 36 F) with a mean (SD) BMI of 37.0 (4.0) kg/m2 entered the study. The mean T50 (emptying of 50%) of fluids was 20.7 (10.3) min, and that of solids 141.9 (168.3) min. The percentage emptying of solids was 34.5 (19.9)%/hr. CCK values peaked within 42 min and paralleled the subjective ratings of satiety but did not correlate with gastric emptying. Five of 45 subjects (11%) had very prolonged gastric emptying of solids; they showed higher caloric intakes and higher insulin levels. They did not differ in CCK values and ratings of satiety but scored higher in being active and awake. Without these five subjects the T50 of solids was 94.3 (36.1) min, and the percentage of emptying 37.9 (18.4)%/hr. Liquid emptying was faster and solid emptying similar compared with those of normal-weight individuals. Height, fat-free mass, and waist-hip circumference were positively related to solid emptying. In weight-stable obese subjects liquid emptying was faster and solid emptying similar to those in normal-weight subjects. Higher caloric intakes and insulin levels were present in subjects with prolonged solid emptying; they also appeared more vigilant. Body size and composition were the only determinants suggesting a faster solid emptying in taller and muscular subjects or in subjects with more intraabdominal fat.

[Obesity and oral health]. / Obesitas en mondgezondheid.

Obesity has a prevalence of approximately 10% among Dutch adults. It is a chronic, incurable disease with a high mortality and co-morbidity. The co-morbidity can be reduced significantly by a sustained moderate weight loss (5-15%). The main cause of obesity is an imbalance between energy intake and energy expenditure. The primary treatment combines dietary education, behaviour modification and increased physical activity, followed by pharmacotherapy or surgery when necessary. Obesity is related to several aspects of oral health, such as caries, periodontitis and xerostomia. In addition, obesity may have implications for dental treatment.

Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity.

BACKGROUND: Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction. AIM: To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation. METHODS: Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months. RESULTS: One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat. CONCLUSIONS: One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.