technetium-tc-99m-disofenin and Cholestasis--Intrahepatic

Ursodeoxycholic acid (UDCA) has been shown to improve pruritus, alanine aminotransferase (ALT), and cholesterol levels in children with intrahepatic cholestatic liver disease. However, the effect of UDCA on quantitative tests of hepatic function in children is uncertain.. A 2.5-year, open label, crossover study, was designed to determine the effect of UDCA (15-20 mg/kg per day for 12 months, off for 6 months, and on again for 12 months) on clinical symptoms, biochemical test results, galactose and caffeine elimination half-lives (t1/2), and quantitative hepatic scintigraphy in 13 subjects aged 13.1 +/- 2.1 years (10 of whom completed the entire study), with intrahepatic cholestasis.. Pruritus improved with UDCA in the 6 patients with pruritus on entry into the study. At 12 months, there was a significant decline in ALT, gamma-glutamyl transpeptidase, and plasma levels of copper and manganese, with no further decline in these levels at 24 months. There were no changes in bilirubin or cholylglycine levels. After therapy was discontinued at 12 months, UDCA was restarted within 1 month in 9 of 12 patients in response to a doubling of ALT (n = 6) or worsening pruritus (n = 3). Galactose t1/2 increased after 12 months, with no further increases after 24 months of UDCA therapy, whereas caffeine t1/2 did not change. There were no significant changes in hepatic scintigraphy throughout the study.. These data suggest that although UDCA therapy improves pruritus and results in a reduction in ALT and gamma-glutamyl transpeptidase, UDCA therapy did not improve quantitative measures of hepatic function in children with intrahepatic cholestasis.

Topics: Adolescent; Adult; Alanine Transaminase; Caffeine; Child; Child, Preschool; Cholestasis, Intrahepatic; Copper; Cross-Over Studies; Galactose; gamma-Glutamyltransferase; Half-Life; Humans; Liver; Manganese; Radiography; Technetium Tc 99m Disofenin; Ursodeoxycholic Acid

99mTc-disofenin, a derivative of iminodiacetic acid, was used for cholescintigraphy in 6 volunteers (in addition to assessment of blood and urine clearance) and in 82 patients referred for evaluation of hepatobiliary tract disease. This radionuclide was cleared rapidly from the blood by the hepatocytes, which permitted satisfactory to excellent images of the hepatobiliary system; interference by renal activity was seen in only 9/82 patients (11%). Acute cholecystitis was correctly diagnosed in 20 patients, although 9 (45%) had jaundice; bilirubin levels ranged from 1.2 to 7.6 mg/dl. The biliary tract was normal in 16 of the 27 patients with jaundice (60%).

Topics: Bile Ducts; Cholangiography; Cholecystitis; Cholelithiasis; Cholestasis, Intrahepatic; Clinical Trials as Topic; Humans; Imino Acids; Liver; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin

Topics: Acute Disease; Adult; Biliary Tract; Cholestasis, Intrahepatic; Hepatitis; Humans; Liver; Male; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Disofenin

Topics: Aged; Cholestasis, Intrahepatic; Humans; Liver Abscess; Male; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Disofenin

Byler's syndrome is a rare form of autosomal recessive intrahepatic cholestasis that is fatal in children. A 10-year-old girl diagnosed with Byler's syndrome underwent reduced-size liver transplantation using lateral segments of her living mother's liver. The donor's and the recipient's liver functions after transplantation were evaluated using Tc-99m disofenin and Tc-99m SC to investigate morphology, liver perfusion, and hepatobiliary function.

Topics: Child; Cholestasis, Intrahepatic; Female; Genes, Recessive; Hepatectomy; Humans; Imino Acids; Liver Transplantation; Organotechnetium Compounds; Radionuclide Imaging; Syndrome; Technetium Tc 99m Disofenin; Technetium Tc 99m Sulfur Colloid; Tissue Donors

Topics: Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Female; Humans; Imino Acids; Indium Radioisotopes; Leukocytes; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Technetium Tc 99m Disofenin

We compared 76 99mTc-DISIDA hepatobiliary studies with corresponding liver biopsies in 36 liver transplant patients to determine the histopathologic abnormalities that corresponded to scintigraphic abnormalities in uptake and excretion. Uptake was judged normal if the cardiac blood pool was barely visible or invisible on the ten minute image. Excretion was judged normal if images subsequent to the 15-min image showed a subjectively normal rate of decreasing parenchymal intensity. Biopsies were graded subjectively for hepatocyte damage and for findings of cholestasis. Uptake criteria were successful in differentiating high from low hepatocyte damage scores (p less than 0.0001), and excretion criteria were successful in differentiating high from low cholestasis scores (p = 0.002), while uptake criteria were not capable of differentiating high from low cholestasis scores, nor were excretion criteria capable of differentiating high from low hepatocyte damage scores (p's greater than 0.05). These results suggest that scintigraphy can distinguish intrahepatic cholestasis from pure hepatocyte damage.

Topics: Biopsy, Needle; Cholestasis, Intrahepatic; Humans; Imino Acids; Liver; Liver Transplantation; Organotechnetium Compounds; Radionuclide Imaging; Technetium Tc 99m Disofenin

Previous results from tests on a limited number of patients suggested that the combination of relatively normal hepatocyte clearance, prolonged parenchymal transit time, and eventual passage of radiotracer into the intestine or gallbladder without evidence of biliary tract dilatation were relatively specific for intrahepatic cholestasis. We reevaluated the specificity of cholescintigraphy for the diagnosis of intrahepatic cholestasis in an unselected group of patients from a general hospital. Sixteen patients had the cholescintigraphic findings of intrahepatic cholestasis and an established diagnosis of biliary tract dilatation or nondilatation by ultrasound, ERCP, or intraoperative cholangiography. Using 6 mm as the upper limits of normal for the diameter of the common hepatic duct by ultrasonography resulted in a specificity of 63% (10 correct out of 16); using 6 mm plus 1 mm for for every decade over 60 years of age gave a specificity of 75% (12 correct out of 16); and using the more liberal criterion of 8 mm as the upper limits of normal increased the specificity to 81% (13 out of 16). The data suggest that cholescintigraphy alone is unreliable in differentiating intrahepatic cholestasis from extrahepatic obstruction, even when the obstruction is partial and radiotracer eventually passes through the extrahepatic biliary tract.

Topics: Aniline Compounds; Bile Ducts; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Evaluation Studies as Topic; Female; Gallbladder; Glycine; Humans; Imino Acids; Liver; Male; Middle Aged; Organotechnetium Compounds; Premedication; Radionuclide Imaging; Sensitivity and Specificity; Sincalide; Technetium Tc 99m Disofenin

We evaluated [99mTc]diisopropylphenyl-carbamoylmethylimidodiacetic acid ([99mTc]DISIDA) cholescintigraphy with measurement of duodenal fluid radioactivity collected by the string test in patients with neonatal cholestasis. Twenty-six infants with prolonged jaundice and acholic stools were studied prospectively. Twelve patients had neonatal hepatitis, 12 biliary atresia, and one each Alagille syndrome and alpha 1-antitrypsin deficiency liver disease. All infants except the biliary atresia patients and four of the neonatal hepatitis patients revealed bowel activity on scan 6 h after tracer administration. At 24 h, three of these latter patients with neonatal hepatitis and two of the patients with biliary atresia revealed bowel activity. String radioactive counts for neonatal hepatitis ranged from 99,574 to 967,205 cpm (374,504 +/- 232,210 cpm; mean +/- SD) and for biliary atresia from 8,342 to 370,346 cpm (117,149 +/- 98,698 cpm; mean +/- SD). While neither test alone was capable of correctly differentiating among all patients, those patients with biliary atresia had either a negative hepatobiliary scan at 24 h or string radioactive count below 197,007 cpm. Disparity between the hepatobiliary scan and the string radioactive counts mandates further diagnostic investigation. These data suggest that simultaneous administration of the string test with hepatobiliary scintigraphy is advantageous in the evaluation of infants with cholestatic jaundice.

Topics: Acute Disease; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Diagnosis, Differential; Duodenum; Female; Humans; Imino Acids; Infant; Infant, Newborn; Intestinal Secretions; Jaundice, Neonatal; Male; Organometallic Compounds; Radionuclide Imaging; Specimen Handling; Technetium Tc 99m Disofenin

In 43 patients with various hepatobiliary disorders, we compared retrospectively the sensitivity and specificity of hepatobiliary scintigraphy and ultrasonography in diagnosing extrahepatic biliary obstruction. Hepatic uptake of radioactivity from the circulation was assessed by early scintiscan at 2 min, and the clearance ratio was combined with transit time in the interpretation of hepatobiliary scintiscans. The transit time was defined as the time taken by detectable radioactivity to appear in the extrahepatic biliary tree or small intestine, whichever occurred sooner. The sensitivity and specificity were 92% and 97%, respectively. However, the specificity dropped to 74% when biliary-bowel transit time, i.e., time taken for detectable radioactivity to appear in small intestine only, was used instead of transit time in the interpretation of the scintiscans. The sensitivity and specificity of ultrasonography were 55% and 94%, respectively. We conclude that hepatobiliary scintiscan is more sensitive than ultrasonography and is reliable for diagnosing extrahepatic biliary obstruction when it is done and interpreted by the method described here.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Diagnosis, Differential; Evaluation Studies as Topic; Female; Gastrointestinal Transit; Humans; Imino Acids; Male; Middle Aged; Organometallic Compounds; Predictive Value of Tests; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Disofenin; Time Factors; Ultrasonography

Hepatobiliary scintigraphy has proven to be of great utility in distinguishing biliary atresia from other causes of neonatal cholestasis. Arteriohepatic dysplasia (Alagille's syndrome) is an uncommon entity characterized by typical facial features, pulmonary artery stenosis, and a liver disorder which presents during the neonatal period as progressive jaundice. Two neonates, who were later shown to have Alagille's syndrome, underwent hepatobiliary scintigraphy to rule out biliary atresia. Findings on the hepatobiliary scans from the two patients were similar to those usually associated with biliary atresia and both finally required surgical exploration to rule out biliary atresia. The findings on hepatobiliary scans in these patients with Alagille's syndrome are discussed and compared with those associated with other forms of neonatal cholestasis.

Topics: Bile Ducts, Intrahepatic; Biliary Atresia; Biliary Tract; Child; Cholestasis, Intrahepatic; Constriction, Pathologic; Diagnosis, Differential; Female; Humans; Imino Acids; Infant; Male; Organometallic Compounds; Organotechnetium Compounds; Pulmonary Artery; Radionuclide Imaging; Syndrome; Technetium Tc 99m Disofenin

During the intestinal phase of hepatobiliary imaging studies in four patients, unusual small intestinal abnormalities were noted. These findings were correlated with surgery in three patients. Recognition of these patterns gives additional clinical information of significant diagnostic value. Further attention to small intestinal pattern and/or radionuclide evaluation of small intestine is a promising method of noninvasive evaluation of clinically suspected small intestinal infarction and obstruction.

Topics: Adult; Aged; Cholecystitis; Cholelithiasis; Cholestasis, Intrahepatic; Diagnosis, Differential; Female; Humans; Imino Acids; Infarction; Intestinal Diseases; Intestinal Obstruction; Intestinal Perforation; Intestine, Small; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Organometallic Compounds; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin; Thrombosis

We retrospectively evaluated the utility of hepatobiliary scintigraphy and various clinical factors in differentiating intrahepatic cholestasis from biliary atresia in 28 consecutive infants with neonatal cholestasis. One millicurie of technetium-labeled diisopropyliminodiacetic acid (DISIDA) was administered intravenously, and images were obtained for up to 24 hours or until gastrointestinal excretion was noted. Nine separate studies in seven infants with biliary atresia were correctly interpreted as showing no gastrointestinal excretion of radionuclide. Of the 21 patients with intrahepatic cholestasis, only nine had gastrointestinal excretion on the first study; in eight without excretion, a second study was done, and five of these showed gut excretion. All infants with either neonatal hepatitis (six) or inspissated bile syndrome (three) had demonstrable gastrointestinal excretion either on the first or second DISIDA study. However, five of six infants with paucity of intrahepatic bile ducts, two of six infants with cholestasis secondary to total parenteral nutrition, and one infant with cholangiolitis did not show evidence of gastrointestinal excretion. The mean birth weight, mean gestational age, and mean weight at study were significantly greater (P less than 0.005) for infants with biliary atresia without excretion than for infants with intrahepatic cholestasis without excretion. The mean direct bilirubin concentration was 6.0 mg/dL for both infants with biliary atresia and infants with intrahepatic cholestasis without excretion; however, infants with excretion had a significantly lower (P less than 0.02) mean direct bilirubin value of 3.4 mg/dL. Excretion was noted in four infants with total bilirubin values greater than 10.0 mg/dL. The absence of gut excretion on the first DISIDA study was 100% sensitive but only 43% specific for biliary atresia. In infants without gut excretion of DISIDA, birth weight greater than 2200 g was 100% sensitive and 92% specific for biliary atresia. We conclude that DISIDA scanning, together with clinical data, is useful in differentiating extrahepatic from intrahepatic cholestasis. The absence of gut excretion on the first DISIDA study does not necessarily indicate extrahepatic obstruction; the study should be repeated if the diagnosis is not clear.

Topics: Bile Ducts, Intrahepatic; Biliary Atresia; Biliary Tract; Bilirubin; Cholangitis; Cholestasis, Intrahepatic; Diagnosis, Differential; Hepatitis; Humans; Imino Acids; Infant, Newborn; Jaundice, Neonatal; Liver; Methods; Organometallic Compounds; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Disofenin; Time Factors

Biliary scintigraphy and ultrasound imaging were performed in 52 patients with suspected biliary tract pathology. Results were correlated with the findings of direct cholangiography. Several new innovations in scintigraphic technique were used. The combination of ultrasound imaging and scintigraphy correctly identified biliary tract obstruction in 17 of 19 patients, 12 of whom had dilated bile ducts on ultrasonography. Intrahepatic cholestasis was correctly diagnosed in 11 of 13 patients. Accurate discrimination between intrahepatic and extrahepatic cholestasis was achieved in 28 of 32 patients (88%) with the combined studies. Scintigraphy also provided a correct diagnosis of acute cholecystitis in all 9 patients with surgically confirmed disease. Eleven additional patients with gallbladder or pancreatic disease had normal bile ducts at scintigraphy, which was confirmed with cholangiography. When combined with ultrasound imaging, modern biliary scintigraphy can (a) provide excellent discrimination between intrahepatic and extrahepatic cholestasis and (b) help determine the need for subsequent invasive diagnostic studies in selected patients.

Topics: Adult; Aged; Biliary Tract; Cholangiography; Cholecystitis; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Common Bile Duct Diseases; Female; Gallbladder Diseases; Humans; Imino Acids; Male; Middle Aged; Pancreatic Diseases; Prospective Studies; Radionuclide Imaging; Sincalide; Technetium; Technetium Tc 99m Disofenin; Ultrasonography

This case is another example of the usefulness of hepatobiliary scan for the evaluation of biliary-enteric anastomoses and stresses the point that performing late scan could help reveal pathologic process in an obvious way.

Topics: Cholestasis, Intrahepatic; Female; Humans; Imino Acids; Liver; Middle Aged; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin

The records of all patients undergoing hepatobiliary imaging at our hospital from January 1980 to March 1983 were reviewed and 29 scans met the criteria for a pattern consistent with complete biliary tract obstruction. Biliary tract obstruction (due to choledocholithiasis, primary or secondary carcinoma involving the common bile duct, and pancreatitis) was documented in 24 of these patients. However, the remaining five patients had a patent common bile duct, and the etiologic factor was intrahepatic cholestasis secondary to sepsis in four and peritonitis in one. A classification of altered biliary dynamics in hepatobiliary imaging, which is based on the classification of jaundice, is proposed.

Topics: Animals; Bile Ducts; Cholestasis; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Dogs; Humans; Imino Acids; Jaundice; Kidney; Liver; Radionuclide Imaging; Rats; Technetium; Technetium Tc 99m Disofenin

Topics: Adult; Cholestasis; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Common Bile Duct Neoplasms; Diagnosis, Differential; Humans; Imino Acids; Infant, Newborn; Jaundice, Neonatal; Postoperative Complications; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin

Tc-99m disofenin, a derivative of iminodiacetic acid, was used to evaluate the biliary tract of 28 children who had a total of 33 examinations. This radiopharmaceutical was rapidly cleared from the blood by the hepatocytes and yielded excellent images of the biliary system. Renal activity did not present difficulty in image interpretation. It provided clinically useful information in a bilirubin range of 0.3 to 14.1 mg/dl. The major categories of acquired and congenital biliary tract abnormalities in children presented no diagnostic difficulty with Tc-99m disofenin.

Topics: Biliary Tract; Child; Cholelithiasis; Cholestasis, Intrahepatic; Hepatitis; Humans; Imino Acids; Infant, Newborn; Infant, Newborn, Diseases; Jaundice; Liver; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin

Topics: Bile Ducts; Biliary Tract Diseases; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Humans; Imino Acids; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin

Tc-99m-diisopropyl-IDA (DISIDA) and Tc-99m-p-butyl-IDA (BIDA) were compared in each of 33 patients who had serum bilirubins ranging from normal to 23.5 mg/dl. DISIDA exhibited quantitatively a higher liver uptake and faster rate of washout at all levels of bilirubinemia. There was a tendency for BIDA to have a slower blood clearance, particularly in hyperbilirubinemias exceeding 5 mg/dl. On visual comparison of the images, BIDA failed to identify the gallbladder in three icteric patients and dilated biliary tracts in two others.

Topics: Adult; Aged; Biliary Tract; Bilirubin; Cholestasis, Intrahepatic; Female; Gallbladder; Humans; Imino Acids; Kinetics; Liver; Liver Cirrhosis; Male; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin