The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease

OBJECTIVE: Crohn's disease (CD) is associated with a high prevalence of gallstone disease but the relative risk has not been completely established. Ileal disease or resection have been considered as contributing factors to the increased risk. The aim of this study was to evaluate the prevalence of gallstone disease in a defined cohort of CD patients, to evaluate possible risk factors, and to evaluate the relative risk compared with the general population. METHODS: All inhabitants in Stockholm County born in 1933-1935 or 1953-1955, with CD diagnosed between 1955-1989 and not having had a previous cholecystectomy, were invited for an ultrasonography of the gallbladder. The prevalence of gallstone disease was related to disease extent, previous intestinal resections, age, and gender. The relative risk of developing gallstones was calculated using a recent study of gallstone disease in general, with similar age groups as controls. RESULTS: We found that 26.4% had gallstone disease (relative risk [RR] = 1.8; 95% confidence interval [CI], 1.2-2.7). The number of previous intestinal resections was the only significant risk factor. There was no significant difference in gallstone disease between gender (28.2% vs 24.1%) or age (34% vs 21.8%). CONCLUSIONS: Patients with Crohn's disease, regardless of gender and age, have almost a doubled risk of developing gallstone disease compared with the general population. Circumstances related to laparotomy may contribute to the increased risk. The lack of association between the disease extent and the site of previous intestinal resection, together with a previous finding of normal cholesterol saturation of the bile in patients with CD, indicate that these patients may develop pigment stones rather than cholesterol stones.     

Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn''s disease.

Biliary lipid composition, cholesterol saturation, and bile acid pattern were determined in fasting duodenal bile of 10 patients (four men and six women, mean age 41 years) with Crohn's disease and a history of ileal resection (mean 64 cm). The data were compared with corresponding values in a group of healthy subjects. None of the patients with Crohn's disease had supersaturated bile. Cholesterol saturation was significantly lower in the patients with Crohn's disease than in the healthy subjects. The molar percentage of cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile acids were normal. Bile acid composition in the patients with ileal resection was characterised by a significant decrease in the deoxycholic acid fraction and a pronounced increase in the ursodeoxycholic acid fraction compared with the healthy subjects. The surprisingly high percentage of ursodeoxycholic acid may contribute to the low degree of cholesterol saturation in bile. Based on these results patients with Crohn's disease should not have an increased risk of cholesterol gall stone formation.     

Postcholecystectomy symptoms. A prospective study of gall stone patients before and two years after surgery.

The results of cholecystectomy in terms of symptomatic improvement were prospectively evaluated in 124 unselected gall stone patients interviewed before and two years after elective surgery. Indications for cholecystectomy were biliary pain (n = 65), previous complications of gall stone disease (n = 52), and flatulent dyspepsia (n = 7). At two years 93 patients could be re-evaluated, of whom only 49 (53%) were completely symptom free. Postcholecystectomy symptoms occurring in the remaining 44 patients were mainly flatulent dyspepsia (which had relapsed in 22 of 46 patients who suffered it preoperatively), dull abdominal pain or diarrhoea. Incisional hernia was present in five patients and one had recurrence of pain because of retained common bile duct stones. Symptomatic cures after cholecystectomy decreased with the duration of the preoperative history. The results reconfirm that cholecystectomy eradicates specific symptoms and complications of gall stone disease, but they also show that nearly one half of operated patients are dissatisfied with the procedure because of mild but distressing 'postcholecystectomy' symptoms. These are probably caused by previously undiagnosed functional gut disease associated with, but unrelated to, gall stones. A systemic approach to multisymptomatic patients with gall stones is recommended.     

Gallstones in Crohn's disease

The prevalence of gallstones in 52 patients operated on for Crohn's disease at the University Central Hospital of Tampere over a 17-year period (1972-1988) was 21%, as compared with 23% in an age- and sex-matched control population. The gallstone prevalence rate among patients with Crohn's ileitis was significantly higher than in patients with ileocolitis (p less than 0.05) or patients with Crohn's colitis (p less than 0.005). The prevalence of gallstones in 33 patients with ileal resection was 24%. In patients with an ileal resection of more than 50 cm in length the frequency of gallstones was 33% as against 17% in patients with a minor resection (p less than 0.001). Patients with gallstones had no significantly longer duration of Crohn's disease prior to the diagnosis of gallstones than patients with no gallstones during the median observation period of 12 years.     

Effect of intestinal surgery on the risk of urinary stone formation.

The prevalence of urinary stone disease in 426 patients who had undergone bowel surgery at the General Infirmary at Leeds from 1958 to 1978 was found by postal questionnaire to be 9.4%. The risk of urinary stone formation was determined from the composition of 24 hour urines from 61 unselected patients, in whom intestinal resections had been performed. There were 27 patients with an ileostomy, 17 patients with an ileostomy and a small bowel resection, and 17 patients with a small bowel resection, or bypass, and an intact colon. Of this group of 61 patients, 9.8% gave a history of urinary stones after surgery. Compared with normal control subjects ileostomy patients had significantly lower urinary pH and volume, higher concentrations of calcium, oxalate, and uric acid, and increased risk of forming uric acid and calcium stones: a small bowel resection combined with an ileostomy increased the ileostomy output, lowered the urinary volume further, and reduced urinary calcium excretion. The concentration of urinary oxalate increased and the risk of both uric acid and calcium stones was high. Patients with small bowel resection and intact colon had hyperoxaluria and an increased risk of calcium stones despite a low urinary calcium. There was no increased risk of uric acid stones in this sub-group. It is concluded that the risk of forming urinary stones after this type of surgery is considerable. The follow-up of patients with ileostomies and with small bowel resections should include an assessment of faecal losses and urinary composition to identify the patients who have a high risk of forming urinary stones.     

Prevalence of biliary tract disease in India: a sonographic study in adult population in Kashmir.

Sonography was used to investigate the prevalence of symptomatic and silent biliary tract disease, in free living urban population in Kashmir. A randomly drawn sample of 1695 subjects aged 15 years or above was interviewed by a questionnaire. Twenty six had previous cholecystectomies, all for gall stones. Ultrasonography was carried out on 1104 (65.1%). The responder rates for ultrasonography in men (64.3%) and in women (66.0%) were similar (p greater than 0.2). Gall stones were detected in 49 adults. Three of these had previous biliary symptoms. The prevalence of gall stones in adult population was 6.12% (men 3.07% and women 9.6%). The prevalence of gall stones rose with age in both sexes to a peak in the sixth decade prevalence of gall stones was significantly higher in age adjusted parous women than in nullipara. There was no correlation with obesity, diet, or socioeconomic status. Five subjects had sonographic appearances of the worm Ascaris lumbricodis in the bile ducts: and had previous biliary symptoms.     

Surgical resections in parous patients with distal ileal and colonic Crohn's disease.

The surgical resection rates among parous women with distal ileal and colonic Crohn's disease have been compared with resection rates among distal ileal (n = 197) and colonic (n = 332) Crohn's disease patients. Thirty of 44 parous women with distal ileal Crohn's disease and 28 of 44 with colonic Crohn's disease had achieved their first pregnancy on average 8 years and 6.2 years respectively before the diagnosis of Crohn's disease was established. Resections for each patient were negatively correlated with parity in both groups. (Distal ileal disease (p = 0.034, rs = 0.3207), colonic disease (p = 0.051, rs = -0.2960)). Patients with distal ileal Crohn's disease and a history of pregnancy at diagnosis (n = 30, mean follow up = 15 years) had fewer resections/patient when compared with the published resection group: mean (SD); 1.17 (0.65) v 1.57 (1.05), p = 0.006. Patients with colonic Crohn's disease and a history of pregnancy at diagnosis (n = 28, mean follow up = 16.5 years) had fewer resections/patient when compared with the published resection group: mean (SD); 0.68 (0.77) v 1.05 (0.77), p = 0.019. In summary, patients with distal ileal and colonic Crohn's disease, who had been pregnant in the past subsequently need fewer surgical resections. Pregnancy could influence the natural history of Crohn's disease either by decreasing immune responsiveness or by retarding fibrous stricture formation, which is the commonest indication for surgical intervention.     

Increased phospholipase A2 activity of Ileal mucosa in Crohn's disease

The activity of phospholipase A2 (EC 3.1.1.4) in endoscopic biopsy specimens of intestinal mucosa was compared in patients with Crohn's disease and controls without inflammatory bowel disease. In postresection Crohn patients there was significantly enhanced phospholipase A2 activity proximal to the anastomosis in the neoterminal ileum, whether or not the mucosa was inflamed at the time of biopsy. Highly elevated ileal phospholipase A2 activity had a predictive value for symptomatic relapse within 1 year after resection. Patients with concomitant Crohn's colitis, in whom the risk of ileal recurrence is particularly high, had greater ileal phospholipase A2 activity than noncolitis Crohn patients. Association thus was demonstrated between activity of phospholipase A2 in ileal mucosa and proneness to ileal inflammation in Crohn's disease.     

Decreased absorption of ingested unconjugated chenodeoxycholic acid in patients with Crohn's disease

The intestinal absorption of unconjugated chenodeoxycholic acid (CDA) was studied in 27 healthy individuals and 28 patients with Crohn's disease who had undergone ileal resection. After they had taken 1 g CDA orally serum levels of bile acids were significantly lower in the patients than in the healthy individuals; the difference was apparent already 30 min after ingestion. There was no correlation between CDA absorption and recurrent disease, length of ileal resection, or number of defecations. These findings indicate that the intestinal absorption of ingested CDA in patients with Crohn's disease is decreased. Since CDA is absorbed mainly in proximal areas of the gut, these observations may indicate that proximal areas are involved in ileocolic Crohn's disease.     

Gall stones in a Danish population: fertility period, pregnancies, and exogenous female sex hormones.

From a cross sectional study of gall stone disease ascertained by ultrasonography, the prevalence in relation to age at menarche, use of oral contraceptives, childbirths, breastfeeding, abortions, age at menopause, and menopausal hormone therapy was assessed. The random sample comprised 2301 women of Danish origin aged 30, 40, 50, and 60 years, of whom 1765 (77%) attended the investigation. Gall stone disease was significantly associated with young age at menarche, abortions, and multiple childbirth. Use of oral contraceptives was significantly associated with gall stone disease in univariate analysis, but not in multivariate analysis. Breastfeeding, age at menopause and menopausal hormone therapy were not associated with gall stones. These determining variables seemed sufficient to explain the higher prevalence of gall stone disease in women than in men.     

Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study.

Fasting insulin, lipids and lipoproteins were measured in 22 middle aged female non-insulin dependent diabetics with gall stone disease (cases) and in 22 non-insulin dependent diabetics without gall stone disease (controls). The groups were matched for sex, age, obesity, and fasting glucose concentrations. No differences were observed between the cases and controls in duration of diabetes, glycated haemoglobin A1, alcohol intake, smoking, use of cardiovascular drugs or a history of myocardial infarction. Diabetics with gall stone disease had higher fasting insulin concentrations (p less than 0.5), lower total (p less than 0.01) and low density lipoprotein cholesterol (p less than 0.01) and high density lipoprotein cholesterol (not statistically significant) concentrations than diabetics without gall stone disease. These changes in insulin, lipids and lipoproteins are similar to reported changes in non-diabetic subjects with gall stone disease. Therefore, they are characteristic for gall stone disease and not as such explanatory to an increased risk of gall stones in patients with non-insulin dependent diabetes.     

Prospective study of malabsorption induced risk of gall stone formation in relation to fall in plasma cholesterol.

The relationship between cholesterol in plasma and risk of gall stone formation was investigated in 210 obese patients who underwent jejunoileal bypass surgery and were free of gall stone disease at the time. Among 185, successfully reexamined on average 19 months after surgery, 26 (14%) developed gall stones. The fall in plasma cholesterol after surgery exhibited a U-shaped relation to risk of gall stone formation with a minimum risk around the average fall (2.6 mmol/l). This was confirmed by multivariate logistic regression analysis (p less than 0.01) taking into account other possible determinants. The relation was not significantly dependent on weight loss or ratio between jejunum and ileum left in function. The study suggests that malabsorption induced fall in plasma cholesterol is related to risk of gall stone formation by two oppositely working mechanisms, one enhancing and one reducing the risk.     

Prior appendectomy and the phenotype and course of Crohn＇s disease

AIM: To determine whether prior appendectomy modifies the phenotype and severity of Crohn's disease. METHODS: Appendectomy status and smoking habits were specified by direct interview in 2838 patients consecutively seen between 1995 and 2004. Occurrence of complications and therapeutic needs were reviewed retrospectively. Additionally, annual disease activity was assessed prospectively between 1995 and 2004 in patients who had not had ileocecal resection and of a matched control group. RESULTS: Compared to 1770 non-appendectomized patients, appendectomized patients more than 5 years before Crohn's disease diagnosis (n=716) were more often females, smokers, with ileal disease. Cox regression showed that prior appendectomy was positively related to the risk of intestinal stricture (adjusted hazard ratio, 1.24; 95% confidence interval, 1.13 to 1.36; P=0.02) and inversely related to the risk of perianal fistulization (adjusted hazard ratio, 0.75; 95% confidence interval, 0.68 to 0.83; P=0.002). No difference was observed between the two groups regarding the therapeutic needs, except for an increased risk of surgery in appendectomized patients, attributable to the increased prevalence of ileal disease. Between 1995 and 2004, Crohn's disease was active during 50% of years in appendectomized patients (1318 out of 2637 patient-years) and 51% in non-appendectomized patients (1454 out of 2841 patient-years; NS). CONCLUSION: Prior appendectomy is associated with a more proximal disease and has an increased risk of stricture and a lesser risk of anal fistulization. However, the severity of the disease is unaffected.     

Meckel's diverticulum in Crohn's disease.

Meckel's diverticulum is a congenital abnormality of the distal ileum associated with failed vitelline duct closure. Detailed pathological studies have estimated its frequency to be about 2% of the general population, and it has been anecdotally recorded in patients with Crohn's disease. Most patients with Crohn's disease have imaging studies of the small intestine during the course of their disease, and often, an intestinal resection. Thus, it seems possible to estimate the prevalence of Meckel's diverticula in Crohn's disease. In addition, patient characteristics may be important, especially if management of Crohn's disease is altered. Of 877 patients with Crohn's disease, 10 (about 1%) had a Meckel's diverticulum diagnosed, including six men and four women. All were diagnosed with Crohn's disease before age 50 years and seven were diagnosed before age 30 years. There were five with ileocolonic disease, two with colon-only disease and three with ileum-only disease. The clinical behaviour of five patients could be classified as penetrating and two as stricturing. A total of 311 patients had an ileocolonic resection, including eight (about 2%) with a Meckel's diverticulum. In contrast to some case reports, no heterotopic mucosa was detected and the Meckel's diverticulum was incidental and, apparently, an unexpected finding. In each case, the diverticulum was not involved with Crohn's disease but was included in the ileal resection. These results suggest that the overall prevalence of a Meckel's diverticulum is not increased in Crohn's disease but may result in resection of additional small intestine.     

Gall stone disease without gall stones--bile acid and bile lipid metabolism after complete gall stone dissolution.

Although bile acid and bile lipid metabolism have been studied in established cholelithiasis, little is known about them in patients destined to develop gall stones, but in whom the stones have not yet appeared (prestone gall stone disease). After confirmed complete gall stone dissolution and withdrawal of treatment, gall stones recur frequently. Before the stones reappear, these patients have 'poststone gall stone disease'. In 13 such patients we confirmed complete gall stone dissolution with two normal cholecystograms and in 11 of the 13 by normal ultrasonography, measured bile acid and bile lipid composition in fasting duodenal bile, bile acid synthesis from marker corrected three day faecal bile acid excretion, bile acid pool size using an abbreviated isotope dilution technique, 'steady-state' bile lipid secretion using a duodenal amino acid perfusion system and then calculated the enterohepatic cycling frequency of the bile acid pool and the relationship between pool size and body weight. The results confirm that after withdrawal of treatment the biliary cholesterol saturation index reverts to levels (1.6 +/- SEM 0.4) comparable with those before dissolution therapy first began (1.6 +/- 0.2; NS). The mean bile acid pool size in the 13 patients of 4.4 +/- 0.5 mmol was comparable with that in untreated gall stone patients. Pool size was significantly smaller in the nine non-obese patients (3.5 +/- 0.3), than in the four obese (6.0 +/- 0.8; p less than 0.05). It also correlated significantly with body weight (r = 0.72) and with %IBW (r = 0.79). The coefficients of variation for biliary bile acid, phospholipid and cholesterol secretion were high, but the mean hourly secretion rates were of the same order as those seen in untreated gall stone patients studied with the amino acid duodenal perfusion stimulus. These results provide a baseline for assessing the response to postdissolution treatment and may indicate metabolic events leading to gall stone formation.     

Detection of gall stones after acute pancreatitis.

Four methods of gall stone diagnosis after an attack of acute pancreatitis are analysed. Of 128 consecutive patients with acute pancreatitis, 99 patients were discharged from hospital without a definite aetiology. These patients had biochemical tests performed on admission and ultrasonography and oral cholecystography performed six weeks later. The sensitivity for ultrasonography was 87% and the specificity was 93%; the respective figures for oral cholecystography were 83% and 90%. The predictive value of positive ultrasonography was 100% and of negative ultrasonography 75%; the respective values for oral cholecystography were 95% and 68%. A combination of ultrasonography and oral cholecystography failed to detect nine of 70 patients with gall stones (13%). Of 35 patients with normal ultrasonography and oral cholecystography, 33 patients had an endoscopic retrograde cholangiogram (ERCP) which showed gall stones in a further seven patients. All three methods failed to reveal gall stones in two patients, confirmed by laparotomy. The sensitivity of admission biochemical analysis was 73% and the specificity was 94%; the predictive value of a positive result was 97% and of a negative result was 57%. Biochemical analysis predicted gall stones in six of the seven patients shown by ERCP. Only 9% of patients were finally considered to be idiopathic. In conclusion ultrasonography is the investigation of choice and ERCP should be undertaken in all patients who have normal ultrasonography and/or oral cholecystography but have biochemical criteria indicative of gall stones.     

Increased frequency of ultrasonographic findings suggestive of renal stones in patients with ankylosing spondylitis

OBJECTIVE: To determine the frequency of hypercalciuria and renal stones in ankylosing spondylitis (AS) sufferers. METHODS: This study involved 83 consecutive AS patients (21 female, 62 male; mean age 36.7 yr), 72 consecutive Behcet's disease (BD) patients (29 female, 43 male; mean age 37.7 yr) as disease control and 92 healthy control (HC) (26 female, 66 male; mean age 32.9 yr.) Twenty-four hour urine analyses for urinary calcium and uric acid levels were performed in each patient. Likewise, blood samples for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), parathyroid hormone (PTH), calcium and uric acid evaluation were taken. Renal ultrasonography to evaluate the presence of renal stone was performed in patients with AS, as well as in the BD patients and HC individuals after a fasting period of 12 hours. RESULTS: 20 of the 80 (25%) patients with AS were diagnosed with renal stones. Only 4/72 (5.5%) BD patients, and 3/98 (3.3%) HC individuals had renal stones by ultrasonography. AS patients had a significantly higher frequency of renal stones compared with BD (p < 0.001) and HC (p < 0.0001). AS patients with renal stones were much older and their disease duration was much longer in comparison with AS patients without renal stones. Ultrasonographic and laboratory findings did not correlate. The number of AS patients with hypercalciuria who had renal stones was higher than that of AS patients who did not have renal stones (p < 0.01). There was a negative correlation between acute phase response and spinal mobility. CONCLUSION: Renal stone prevalence was found to increase in AS patients. The likelihood of renal stone formation was also found to increase with the extension of the disease duration of AS sufferers.     

Gallbladder bile composition in patients with Crohn＇s disease

AIM:To further elucidate the pathogenesis andmechanisms of the high risk of gallstone formation inCrohn's disease.METHODS:Gallbladder bile was obtained from patientswith Crohn's disease who were admitted for electivesurgery (17 with ileal/ileocolonic disease and 7 withCrohn's colitis).Fourteen gallstone patients servedas controls.Duodenal bile was obtained from tenhealthy subjects before and after the treatment withursodeoxycholic acid.Bile was analyzed for biliary lipids,bile acids,bilirubin,crystals,and crystal detection time(CDT).Cholesterol saturation index was calculated.RESULTS:The biliary concentration of bilirubin wasabout 50% higher in patients with Crohn's disease thanin patients with cholesterol gallstones.Ten of the patientswith Crohn's disease involving ileum and three of thosewith Crohn's colitis had cholesterol saturated bile.Fourpatients with ileal disease and one of those with colonicdisease displayed cholesterol crystals in their bile.About1/3 of the patients with Crohn's disease had a shortCDT.Treatment of healthy subjects with ursodeoxycholicacid did not increase the concentration of bilirubin induodenal bile.Several patients with Crohn's disease,with or without ileal resection/disease had gallbladderbile supersaturated with cholesterol and short CDT andcontained cholesterol crystals.The biliary concentrationof bilirubin was also increased in patients with Crohn'scolitis probably not due to bile acid malabsorption.CONCLUSION:Several factors may be of importance forthe high risk of developing gallstones of both cholesteroland pigment types in patients with Crohn's disease.     

Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly.

Octreotide therapy in acromegaly is associated with an increased prevalence of gall stones, which may be the result of an inhibition of gall bladder motility. Gall stone prevalence in untreated acromegalic patients relative to the general population is unknown, however, and the presence of gall stones and gall bladder motility in these patients and in acromegalic patients receiving octreotide was therefore examined. Thirty four percent of 39 patients who had taken octreotide for a mean of 20 months had gall stones compared with 16% of 38 patients who had not been treated with octreotide (p < 0.005). In a subgroup of 21 patients studied prospectively over 4 to 18 months, two patients developed stones. No patient had symptoms referrable to their gall stones. In 31 untreated acromegalic patients, the mean fasting gall bladder volume was similar to that in normal subjects. Maximal percentage emptying, however, was impaired (34 v 64%, p < 0.001) and the mean postprandial residual gall bladder volume increased (21.7 v 9.0 ml, p < 0.001). Treatment with octreotide increased the mean postprandial residual volume further to 36.8 ml (p < 0.001). Gall bladder emptying in untreated acromegalic subjects is impaired. Octreotide further increases postprandial residual gall bladder volume and this may be a factor in the increased gall stone prevalence seen in these patients.     

Symptomatic and silent gall stones in the community.

The prevalence of gall stone disease in a stratified random sample of 1896 British adults (72.2% of those approached) was established using real time ultrasound. The prevalence rose with age, except in women of 40-49 years, so that at 60-69 years, 22.4% of women and 11.5% of men had gall stones or had undergone cholecystectomy. The cholecystectomy rate of people with gall stone disease was higher in women than in men (43.5% v 24%, p less than 0.05). Very few subjects with gall stones had convincing biliary symptoms. In women, 10.4% had symptoms according to a questionnaire definition of biliary pain and 6.3% according to conventional history taking, while no men at all admitted to biliary pain. Nevertheless, cholecystectomy in men had nearly always been preceded by convincing biliary symptoms. The age at cholecystectomy was, on average, nine years less than the age at detection of silent gall stones in both sexes. It is concluded that either gall stones are especially prone to cause symptoms in younger people or that there are two kinds of cholelithiasis - symptomatic and silent. The lack of symptomatic gall stones in cross sectional surveys is probably due to their rapid diagnosis and treatment.