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Endoscopic retrograde cholangiography in the detection of small stones in the gallbladder.

Multiple small (2-5 mm in size) gallstones were demonstrated only by endoscopic retrograde cholangiopancreatography in eight patients who had recurrent upper abdominal pain and vomiting. Three patients had mild, rapidly resolving abnormalities of liver biochemistry and serum amylase. In the other five, both serum amylase and liver biochemistry were repeatedly normal. We conclude that endoscopic retrograde cholangiography may be useful in the detection of small gallstones in patients with symptoms suggestive of biliary tract disease, even in the presence of normal oral cholecystography, ultrasonography, serum amylase, and liver biochemistry.

Amylases↗

A combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.

Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.

Bile↗

Agenesis of the gallbladder--an inherited defect?

Agenesis of the gallbladder is a rare anomaly believed to be an organogenetic failure. This is the third instance of familial agenesis of the gallbladder reported in the literature. The diagnosis of agenesis of the gallbladder can only be made during exploratory celiotomy and must be confirmed by an intraoperative needle cholecystogram. This congenital anomaly should be suspected when oral cholecystography shows a nonvisualizing gallbladder in relatives of any patient with proven agenesis of the gallbladder.

Adult↗

High incidence of early cholelithiasis detected by ultrasonography in children and young adults with hereditary spherocytosis.

OBJECTIVES: Retrospective cholecystography studies in adults with hereditary spherocytosis (HS) suggested detectable gallstones in 37% to 43% of patients. Since longitudinal studies using biliary ultrasonography are unavailable, the aim of the present study was to determine the incidence of gallstone disease, as detected by biliary ultrasonography, in children and young adults with HS. As individuals with HS who co-inherit Gilbert syndrome have a greater risk of developing gallstones, uridine diphosphate-glucuronyl transferase (UGT-1A) gene polymorphism was also determined. PATIENTS AND METHODS: The authors retrospectively evaluated 44 patients aged 1.4 to 22 years with HS, 12 (27%) of whom underwent splenectomy. Ultrasonography was performed annually starting at the age of 4 years or at the time of diagnosis, if later. RESULTS: Of the 44 patients, 18 (41%) developed cholelithiasis as demonstrated by gallbladder ultrasonography. In most patients (94%) the test first proved positive at age 4 to 13 years. Patients with HS and Gilbert syndrome tended to be younger at the time of cholelithiasis. CONCLUSIONS: Early cholelithiasis was detected in children and young adults with HS. To identify this complication, the authors recommend early annual biliary ultrasonography in HS children, starting at about 4 years of age. In patients with Gilbert syndrome, closer follow-up may be indicated.

Adolescent↗

Carcinoid tumours of the biliary tract.

Data on 13 patients, including two not previously reported, with carcinoid tumours of the biliary tract are reported. In ten of them the primary tumour was located in the gallbladder and in three in the biliary duct. No specific symptoms were recorded, and the carcinoid syndrome has not been reported in carcinoid tumours of the biliary tract. In five patients the tumour was first found at autopsy. Metastases were found in three patients at operation or autopsy. Cholecystography can show either a functioning or a non-functioning gallbladder. Some patients had concretions in the gallbladder. The prognosis appears to be good, and one of the patients reported survived 20 years with metastases.

Aged↗

Dublin-Johnson syndrome with some unusual features in a Chinese family.

Three cases of chronic nonhaemolytic jaundice with conjugated bilirubin in the serum are described in a Chinese family. Bromsulphthalein excretion tests gave results typical of the Dubin-Johnson syndrome. Liver histology in the proband showed cytoplasmic pigment of the lipofuscinmelanin variety, and intravenous cholecystography failed to show visualisation of the gallbladder. Unusual findings included onset during the neonatal period in the proband and the presence of some iron pigment in the hepatic cells with a little canalicular cholestasis. It is suggested that the infant may have had a concomitant nonspecific hepatitis. These cases are regarded as belonging to a disease group in which the Dubin-Johnson syndrome is at one end of a spectrum. The mode of inheritance is discussed.

Adult↗

Postprandial gall-bladder emptying in patients with gall stones.

Gall-bladder emptying in response to a standard meal was assessed in 34 patients with radiolucent gall stones and 34 matched controls. Percentage gall-bladder emptying, derived from volume measurements made on standardised oral cholecystography, was significantly higher at 15 minutes in the patients than the controls (mean +/- SE of mean 38.0 +/- 3.7% v 28.0 +/- 3.8%). This difference was maintained at 30 and 60 minutes. It is concluded that postprandial gall-bladder emptying is increased in patients with cholesterol gall stones, and that this may be the cause of the small bile-acid pool found in these patients.

Cholelithiasis↗

Pilot study of combination treatment for gall stones with medium dose chenodeoxycholic acid and a terpene preparation.

Thirty patients with radiolucent stones in a radiologically functioning gall bladder were treated for up to two years with a combination of Rowachol (one capsule twice daily), a mixture of cyclic monoterpenes, and chenodeoxycholic acid (7.0-10.5 mg/kg/day). The patients were not selected for body weight or size of stones. All complete dissolutions diagnosed by oral cholecystography were confirmed or refuted by ultrasound examination. Control of symptoms was excellent, only one patient withdrawing from the study because of persistent biliary pain. No evidence of hepatotoxicity was detected biochemically, and diarrhoea due to chenodeoxycholic acid was minimal at this dose. Stones disappeared completely in 11 patients (37%) within one year and in 15 (50%) within two years. These results compared favourably with those obtained with similar doses of chenodeoxycholic acid alone, in particular those of the National Co-operative Gallstone Study (complete dissolution in 13.5% of patients at two years). Treatment with a combination of medium dose chenodeoxycholic acid with Rowachol for radiolucent gall stones is economical, effective, and likely to minimise persistent symptoms and adverse effects of treatment.

Adult↗

The use of cholecystokinin to test gall bladder function in man.

In 100 subjects the cholecystokinin test has been used in conjunction with the secretin test of gall bladder function. The response of the normal gall bladder to a standard dose of pancreozymin has been studied and the results in patients following cholecystectomy and in the presence of biliary tract disease have been recorded and contrasted with the results obtained by the secretin test and oral cholecystography. These are sufficiently characteristic to warrant the conclusion that used in this way the cholecystokinin test provides a new and valuable semi-quantitative estimate of gall bladder function.

Biological Assay↗

Occurrence of cholesterol crystals in human bile.

The occurrence of cholesterol crystals was studied in 20 consecutive gallstone patients with functioning gallbladders. The frequency with which crystals were found rose sharply with the number of stones. Gallbladder bile was found more often to contain cholesterol crystals than hepatic bile of the same individual. Such crystals were absent in T tube drain bile from 10 consecutive choledochostomy patients, studied after the reestablishment of the enterohepatic circulation for at least five days. In gallstone patients in whom the gallbladder was visualized at cholecystography the hepatic bile contained cholesterol crystals more often than in patients with gallbladders not so visualized. In the latter patients the crystals tended to disappear after prolonged fasting. Bile analysis showed hepatic bile of patients with non-functioning gallbladders to be less lithogenic than bile in cases with functioning gallbladders. In the former group bile contained relatively more chenodeoxycholic acid than in the latter. The composition of bile with cholesterol crystals did not differ significantly from that of bile without crystals. In the final analysis it is important to identify possible factors responsible for the precipitation of cholesterol from supersaturated bile.

Bile↗

Cholelithiasis in subjects with hypercalcaemia and primary hyperparathyroidism detected in a health screening.

The frequency of gallstone disease was studied in a group of 82 subjects (69 females and 13 males; mean ages 55-0 and 52-3 years, respectively) with verified hypercalcaemia (VHC) detected in a health screening in the Stockholm area. All non-cholecystectomised subjects were examined with a peroral cholecystography. Causes of hypercalcaemia other than primary hyperparathyroidism (PHPT) had been excluded as far as possible. Sixty-two patients had been operated upon and all but two males were found to have parathyroid adenomas. The patients were compared with a series of 82 normocalcaemic age- and sex-matched subjects, selected from the health screening register. The patients with VHC and/or PHPT had about the same frequency of gallstone disease as the controls. The results are at variance with those of other investigators who have reported that PHPT is associated with an abnormally high frequency of gallstone disease. Possible explanations of the discrepancy in results is discussed.

Cholelithiasis↗

Optimum bile acid treatment for rapid gall stone dissolution.

To determine the optimum bile acid regimen for rapid gall stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealtime ursodeoxycholic acid (UDCA, 12 mg/kg/day). An additional 10 patients treated with a combination of CDCA plus UDCA (each 6 mg/kg/day) at bedtime were matched with the 10 patients on bedtime CDCA and the 10 on bedtime UDCA. The gall stone dissolution rates at six and 12 months were determined by standardised oral cholecystography and expressed as the percentage reduction in the gall stone volume after treatment. The gall stone dissolution rate at six months was higher for UDCA than CDCA treatment (median 78% v 48%, p less than 0.01), and for bedtime than mealtime administration (69% v 39%, p less than 0.02). Both differences were greater for stones less than 8 mm diameter. The dissolution rate was faster for combination therapy than for CDCA alone at both six (82% v 36%, p less than 0.05) and 12 months (100% v 54%, p less than 0.05), but was not different from UDCA alone. We conclude that bile acid treatment should be confined to patients with small gall stones and that bedtime administration of combined UDCA and CDCA is likely to provide the most effective and safe combination.

Chenodeoxycholic Acid↗

Cholelithiasis and biliary tract disease in sickle-cell disease in Nigerians.

The incidence of biliary tract disease was investigated by oral cholecystography and/or intravenous cholangiography in 77 unselected Nigerians with homozygous sickle-cell disease (SCD). They included 32 males and 45 females with ages ranging from 8 to 31 years. The prevalence of cholelithiasis was 9% with equal sex incidence. The stones were always multiple and 71.4% of them were radio opaque. Visualization and contractility of all gall bladders examined were normal. The only patient with symptoms and signs which suggested biliary tract disease had no radiographic evidence of cholelithiasis and it was impossible to predict the presence of cholelithiasis from the incidence of abdominal crises in the patients. The prevalence of cholelithiasis is significantly less than that reported in American patients with SCD (35%) and different dietary habits are probably responsible for this.

Adolescent↗

Medical imaging.

There is now a wide choice of medical imaging to show both focal and diffuse pathologies in various organs. Conventional radiology with plain films, fluoroscopy and contrast medium have many advantages, being readily available with low-cost apparatus and a familiarity that almost leads to contempt. The use of plain films in chest disease and in trauma does not need emphasizing, yet there are still too many occasions when the answer obtainable from a plain radiograph has not been available. The film may have been mislaid, or the examination was not requested, or the radiograph had been misinterpreted. The converse is also quite common. Examinations are performed that add nothing to patient management, such as skull films when CT will in any case be requested or views of the internal auditory meatus and heal pad thickness in acromegaly, to quote some examples. Other issues are more complicated. Should the patient who clinically has gall-bladder disease have more than a plain film that shows gall-stones? If the answer is yes, then why request a plain film if sonography will in any case be required to 'exclude' other pathologies especially of the liver or pancreas? But then should cholecystography, CT or scintigraphy be added for confirmation? Quite clearly there will be individual circumstances to indicate further imaging after sonography but in the vast majority of patients little or no extra information will be added. Statistics on accuracy and specificity will, in the case of gall-bladder pathology, vary widely if adenomyomatosis is considered by some to be a cause of symptoms or if sonographic examinations 'after fatty meals' are performed. The arguments for or against routine contrast urography rather than sonography are similar but the possibility of contrast reactions and the need to limit ionizing radiation must be borne in mind. These diagnostic strategies are also being influenced by their cost and availability; purely pragmatic considerations are not infrequently the overriding factor. Non-invasive methods will be preferred, particularly sonography as it is far more acceptable by not being claustrophobic and totally free of any known untoward effects. There is another quite different but unrelated aspect. The imaging methods, apart from limited exceptions, cannot characterize tissues as benign or malignant, granulomatous or neoplastic; cytology or histology usually provides the answer. Sonography is most commonly used to locate the needle tip correctly for percutaneous sampling of tissues. Frequently sonography with fine needle aspiration cytology or biopsy is the least expensive, safest and most direct route to a definitive diagnosis. Abscesses can be similarly diagnosed but with needles or catheters through which the pus can be drained. The versatility and mobility of sonography has spawned other uses, particularly for the very ill and immobile, for the intensive therapy units and for the operating theatre, as well in endosonography. The appointment of more skilled sonographers to the National Health Service could make a substantial contribution to cost-effective management of hospital services. Just when contrast agents and angiography have become safe and are performed rapidly, they are being supplanted by scanning methods. They are now mainly used for interventional procedures or of pre-operative 'road maps' and may be required even less in the future as MRI angiography and Doppler techniques progress. MRI will almost certainly extent its role beyond the central nervous system (CNS) should the equipment become more freely available, especially to orthopaedics. Until then plain films, sonography or CT will have to suffice. Even in the CNS there are conditions where CT is more diagnostic, as in showing calculations in cerebral cysticercosis. Then, too, in most cases CT produces results comparable to MRI apart from areas close to bone, structures at the base of the brain, in the posterior fossa and in the spinal cord. Scintigraphy for pulmonary infarcts and bone metastases and in renal disease in children plays a prominent role and its scope has increased with new equipment and radionuclides. Radio-immunoscintigraphy in particular is likely to expand greatly not only in tumour diagnosis but also in metabolic and infective conditions. Whether the therapeutic implications will be realized is more problematic. The value of MRS and NM for metabolic studies in clinical practice is equally problematical, although the data from cerebral activity are extremely interesting. While scanning has replaced many radiographic examinations, endoscopy has had a similar effect on barium meals and to a lesser extent on barium enemas. The combined visual/sonographic endoscope is likely to accelerate this process. There is no doubt that over the last 2 decades medical imaging has changed the diagnostic process, but its influence on the outcome of disease other than infections is less certain and probably indefinable. Data concerning the comparative efficacy in terms of patient outcome for each of the imaging techniques would be of considerable interest and a great help in determining diagnostic strategies.

Angiography, Digital Subtraction↗

Choledochal cysts: roentgenographic techniques.

Twenty-four cases of choledochal cysts were reviewed. Only 7 cases were definitely diagnosed preoperatively: 3 by 131I rose bengal scanning, 2 by intravenous cholangiography, 1 by oral cholecystography, and 1 by 99mTc sulfur colloid scanning followed by angiography. The highest percentage of definitive positive examinations was found in the 131I rose bengal scan (3 of 4), but the study most helpful in suggesting the diagnosis in a general way was the upper gastrointestinal series. The more frequent use of 131I rose bengal scanning and ultrasound should increase diagnostic accuracy.

Adolescent↗

Visualization of the bile ducts using focused ultrasound.

The feasibility of using focused ultrasound for studying structures as small as biliary ducts and correlative radiological and ultrasonic studies of the common and larger hepatic ducts are presented. Patients whose bile ducts were visualized on intravenous or T-tube cholangiography or oral cholecystography underwent radiography with a metallic skin marker along the right anterior lower costal margin. The marker was then correlated with ultrasonic observations of multiple oblique scans parallel to the lower costal margin. The common duct could be identified in 15 of 21 patients. Ultrasonic visualization circumvents the problems of elevated serum bilirubin, iodine contrast media sensitivity, and pregnancy.

Bile Ducts↗

Technetium-99m pyridoxylideneglutamate (P.G.) cholescintigraphy.

Technetium-99m P.G. cholescintigraphy was performed in 27 human volunteers and 81 patients referred for hepatobiliary tract disease. The gallbladder, biliary system, and gastrointestinal tract were well visualized in the normal patients and volunteers. The gallbladder was not visualized in 22 patients with histologically proved cholecystitis with cystic duct obstruction. Nine patients with complet extrahepatic obstruction of the common bile duct were correctly diagnosed. Hepatocellular disease and incomplete obstruction, with and without jaundice, were diagnosed with this technique. Oral cholecystography is superior to this method for the detection of cholelithiasis in nonjaundiced patients.

Biliary Tract Diseases↗

Gallbladder stones: imaging and intervention.

Imaging of the gallbladder for cholelithiasis and its complications has changed dramatically in recent decades along with expansion of interventional techniques related to the disease. Ultrasonography (US) is the method of choice for detection of gallstones. The characteristic US findings of gallstones are a highly reflective echo from the anterior surface of the gallstone, mobility of the gallstone on repositioning the patient, and marked posterior acoustic shadowing. Oral cholecystography remains an excellent method of gallstone detection, but its role has been limited due to the advantages of US. Most people with cholelithiasis will not experience symptoms or complications related to gallstones. When biliary colic does occur, it is typically caused by transient obstruction of the cystic duct by a stone. The primary imaging modality in suspected acute calculous cholecystitis is usually US or cholescintigraphy. Detection of gallstones alone does not permit a diagnosis of acute cholecystitis; however, secondary US findings provide more specific information. In detection of choledocholithiasis, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography are superior to US. In certain clinical settings, interventional radiologic procedures have become an important alternative to surgery in the treatment of gallstones and their complications; techniques include percutaneous cholecystostomy and gallstone removal.

Acute Disease↗