Intravenous Cholangiography: Francis
J. Scholz,
M.D.,
Carl
R. Larsen,
W
E HAVE established certain techniques and concepts in intravenous (i.v.) cholangiography which, over years of clinical use, have served us well. Periodically we have critically reexamined these concepts and our current views are presented here. Cholografin@ (meglumine iodipamide) is an organic molecule containing two iodinated benzene rings. After intravenous administration, it is removed from the blood by the hepatocyte, which excretes it directly into the biliary system. Excretion of Cholografin and visualization of the common bile duct depend on function of the hepatocytes, which can be evaluated by liver function tests. INDICATIONS
We have performed i.v. cholangiography for a wide variety of indications, including (1) nonvisualization of the gallbladder on oral cholecystography (Fig. 1); (2) evaluation of symptoms after cholecystectomy: (3) preoperative evaluation of the biliary tree in the patient with cholelithiasis; (4) evaluation of the biliary tree in the patient with pancreatitis; (5) evaluation of the gallbladder in patients with uncontrollable vomiting; and (6) abnormal liver enzyme values not satisfactorily explained on the basis of primary liver disease. Of these, the first two are the most frequent and useful indications. We perform i.v. cholangiography if no visualization is noted after the singledose oral cholecystogram, provided no explanation for the nonvisualiLation can be discovered (eg, liver disease. gastric retention, or failure to administer
Frrancis J. Scholz, M.D.: Radiologist, Lahey Clinic Foundation, and Instructor in Radiology, Harvard Medical School, Boston, Mass. Carl R. Larsen, M.D.: Radiologist, Lahey Clinic Foundation, and Instructor in Radiology, Boston University School of‘ Medicine, Boston, Mass. Robert E. Wise, M.D.: Chairman, Department of Diagnostic Radioloa, 1,ahe.v Clinic Foundation, and Clinical Prolessor of Radiolog):. Boston University School of Medicim, Boston, Mass. Reprint requests should be addressed to Francis J. Scholz, M.D., Department of Diagnostic Radiology, Lahey Clinic Foundation, 605 Commonwealth Avenue, Boston, Mass. 02215. c 19 76 by Prune & Stratton, Inc. Seminars
in Roentgenology,
Vol.
Xl,
No.
3 (July),
1976
Recurring Concepts M.D.,
and
Robert
E. Wise,
M.D.
the oral cholecystographic agent). If any degreeof definite gallbladderopacification is seen.no matter how faint, either a repeat single doseof oral contrast medium the next day or a reexamination with calcium Oragrafin@ granules on the sameday is performed, depending on the department logistics and patient availability. The last three indications in the above list are less rigid. The radiologist and clinician together should balancethe low yield againstthe likely benefit and determine whether the study is worth the risk to the patient and the cost. CONTRAINDICATIONS
The only absolute contraindication to i.v. cholangiographyis a documented hypersensitivity reaction, such as profound or persisting hypotension usually accompaniedby nausea,vomiting, and dyspnea and requiring pressor agents. steroids. and antihistamines. Patients with a history of a moderatevisceral or dermal reaction are treated with a 2-day prophylactic regimen of Benadryl@. 25 mg orally three times a day, and prednisone, 5 mg orally three times a day. In patients with coexisting impairment of renal and liver function. Cholografin should be used with caution and only when essentialclinical information cannot be obtained by other diagnostic tests. TECHNIQUE
Administratiorl of Cholografin Although the manufacturer recommendsfasting, we believe a light breakfast lessensreaction rate and severity. Numerous techniques of administration have been described.‘-3’5,6.8,9,‘~,‘7”9 but two basic choicesare (I) infusion over a period of 30-60 min or a IO-min injection, and (7) a single doseof Cholografin of 10.4 g (20 ml of 57%) or a double dose of Cholografin of 20.X g (40 ml ot 52%, or a largeramount of a more dilute solution). We prefer 20 d of 52% Cholografin injected by hand at an even rate over a IO-min period. Larger dosesare not used for we have shown that they provide no significant improvement, and evidence suggeststhat increasing quantities of Cholografin 197
SCHOLZ,
LARSEN,
AND
WISE
Fig. 1. Cystic duct calculus, normal common bile duct on i.v. cholangiography. The common bile duct angulates gently and tapers slightly. The gallbladder did not visualize during oral cholecystography or intravenous cholangiography. During filming, the oval calcification maintained a constant relationship to the common bile duct rather than to the calcified costal cartilages. With the more common rediolucent calculus impacted in the cystic duct, no abnormality will be noted on i.v. cholangiography except for nonvisualization of the gallbladder. Marked edema of the cystic duct in acute cholecystitis, even without stone impaction, may cause nonvisualization during i.v. cholangiography.
may cause hepatotoxicity.16 We do not prolong the administration of Cholografin because a decrease in biliary opacification is noted when the injection time is extended to 30 min. Hand injection is preferred to the drip-infusion method only because the injection can be stopped instantaneously if the patient begins to have an allergic reaction. We have not had a death from iv. cholangiography in more than 10,000 examinations. Filming The patient is maintained in a 15” right posterior oblique position, and films are obtained at 20-min intervals after the beginning of Cholografin administration. With a cooperative patient, progressive collimation is begun when the duct is first seen, thereby diminishing scatter and improving contrast. Tomograms with the patient in the lateral position are occasionally helpful in evaluating the terminal common bile duct and the insertion of the cystic duct. If the patient has had a previous cholecystectomy, the procedure is terminated when tomograms or conventional films delineate the normal common bile duct. If the gallbladder has not been removed and is opacified at 120 min, it is examined with supine, erect, or decubitus films. If it is not seen at 120 min, a film of the right upper
quadrant should be obtained at 4 hr. If the gallbladder is seen at this time it should be evaluated with additional films. If the gallbladder is not seen at 4 hr, a film at 24 hr may be indicated since, on occasion, a normal gallbladder has been demonstrated. REACTIONS
Reaction rates vary according to the observer and the definition of a reaction. In different series at the Lahey Clinic with the sameobservers,our reaction rates varied from 4.3% with routine antihistamine administration before intravenous cholangiogramto 1% when an antihistamine was not routinely administered.‘6 The three main classesof reactions encountered after Cholografin administration are visceral, dermal, and hypersensitivity. We believe that the visceral reaction of nausea,vomiting, and occasional tenesmusis related to the rate of administration and is not a true allergic reaction. After a few minutes’ delay, resumption of the injection of Cholografin at a slower rate will usually permit completion of the i.v. cholangiogram with satisfactory results. Dermal reactions consist of pruritus, erythema, and hives. Premeditation with an antihistamine prevents or minimizesthesereactions.r4
INTRAVENOUS
CHOLANGIOGRAPHY:
RECURRING
CONCEPTS
Hypersensitivity reactions occur in about 1% of patients (0.9% of 442 patients in our latest series). They consist of hypotension, nausea and vomiting, and dyspnea. Adrenalin (0.3 ml of a 1 : 1,000 solution injected subcutaneously), Benadryl (50 mg injected intramuscularly or intravenously), and corticosteroids (100 mg of Solu-Cortef injected intravenously) are administered. Since oxygen often moderates the symptoms. we usually administer it. If possible, medication should not be administered through the sameneedle and tubing used to administer the Cholografin, since precipitation of Cholografin occurs when it is mixed with Benadryl. These hypersensitivity reactions usually respond promptly with no harm to the patient. All reactions in our serieswere successfully treated with pressoragentsand steroids. Toxicity Toxic effects on the kidneys and liver have been Elevation noted with Cholografin.4,7,10,11,1S,16,18 of serum glutamic oxaloacetic transaminase (SCOT) levels after administration of Cholografin has been seenby severalauthors. However, in all patients the SGOT levels returned to the preinjection levels. Cholografin is probably a mild hepatotoxin. Renal failure has been reported after i.v. cholangiography but is usually seen in patients with preexisting renal and hepatic disease.In the presence of hepatic disease,a greater amount of Cholografin is excreted by the kidneys, and this increasedexcretory load may further depressan already impaired renal function. Cholografin should be used judiciously in the presenceof coexisting renal and liver disease. DIAGNOSTIC
IMPLICATIONS
The Gallbladder We firmly believe opacification of a gallbladder without calculi on i.v. cholangiographyindicates a normal gallbladdereven though the gallbladderhas failed to visualize on previous oral cholecystography. We do not believe this combination of events indicates a diagnosisof acalculouscholecystitis. A pathology report of chronic cholecystitis doesnot necessarilyestablishthe clinicopathologic entity of acalculouscholecystitis. It israre indeedwhen some slight evidence of cholecystitis cannot be found in a resectedgallbladder. When the gallbladder doesopacify during intravenous cholangiography, it must be as thoroughly
199
evaluated for calculi as the orally opacitied gallbladder with supineand decubitusor upright films. In a large seriespurporting to indicate that oral cholecystography is more reliable than intravenous cholangiography in evaluating gallbladder disease, gallstoneswere missedon i.v. cholangiography in 12 of 27 patients whose previously nonopacified gallbladder filled during i.v. cholangiography.‘* We believe this may reflect more on the technique of examining the gallbladder during i.v. cholangiography than on the procedure itself. In this same series, 152 patients with nonvisualized gallbladders after consecutive dosesof oral cholecystography were operated on. All had calculi or tumor except 13 patients who had cholecystitis. However, 193 patients were not operated on for various reasons, among them a reluctance to accept a pathologic diagnosiswhen a subsequenti.v. cholangiography showeda radiographically normal gallbladder. In more than 20 years experience we have found that clinically significant gallbladder disease,either cholelithiasisor cholecystitis, hasconsistently been diagnosedby i.v. cholangiography by the demonstration of calculi or of nonfilling of the gallbladder, indicating cystic duct obstruction. The mechanism of cystic duct obstruction may be either calculusor edemafrom cholecystitis. Nonvisualization on two consecutiveoral cholecystogramsindicates a high probability of gallbladder disease,but intravenous cholangiography adds a greater degree of certainty to the diagnosis(Fig. 1). Diameter of the Common Bile Duct If the common bile duct is 8 mm or less,common bile duct obstruction and common bile duct calculi are lesslikely to be present. If the diameter is 15 mm or greater, obstruction and the possibility of choledocholithiasismust be postulated. With a diameter between 8 and 1.5 mm, no conclusions can be drawn. Unfortunately, the majority of obstructed or partially obstructed common bile ducts as well as many normal bile ducts are within this range. Fortunately. one other finding may be of usein establishingthe diagnosisof partial obstruction of the common bile duct. In patients whosegallbladder haseither been removed or is nonvisualized becauseof cystic duct obstruction and in whom the diameter of the common bile duct suggestsobstruction, the common bile duct should be evaluated at 60 and 120 min for evidenceof increasing
SCHOLZ,
LARSEN,
AND
WISE
Fig. 2. Normal i-v. cholangiography. Savera1 anatomic relationships are demonstrated on this tomogram. The duodenal bulb and descending limb of the duodenum are seen between the gallbladder and the common bile duct. The contrast-filled duodenal bulb should not be mistaken for a reformed gallbladder, which is a nonentity, or for opacification of the previously nonopacified gallbladder. A sip of barium or ginger ale will allow identification of the bulb. The angle of the common bile duct occurs behind the duodenal bulb and is a good approximation of the point at which the common bile duct enters the tunnel in the pancreas. Narrowing distal to the angulation with proximal dilatation is evidence for pancreatitis. Between the spine and the intrapancreatic segment of the common bile duct, contrast medium is seen in the collecting system of the right kidney. Occasionally, renal excretion of Chologrefin may overlap and obscure the distal common bile duct necessitating a change in patient obliquity or tomography.
or diminishing opacification. Evaluation of density over this period of time has, on many occasions, substantiated the diagnosis of partial obstruction, whether from calculus, fibrosis, or pancreatic disease.*OY21 Patients receiving morphine or related narcotics may have retention on the basis of contraction of the sphincter of Oddi. Before invoking pathologic retention, this possibility should be investigated. Configuration
of the Common Bile Duct
The distal common bile duct is directed posteriorly and medially, courses behind the duodenal bulb, and reaches the papilla of Vater by traversing a canal in the head of the pancreas (Fig. 2). Narrowing of the distal common bile duct with a normal or dilated proximal duct is characteristic of pancreatic edema and fibrosis. A long, tapered narrowing suggests the likelihood of pancreatitis; abrupt narrowing may be the result of pancreatitis but is also seen with pancreatic or ampullary carcinoma. The duct in pancreatitis is often angulated abruptly as it enters the tunnel in the head of the pancreas. Marked angulation or displacement of the common bile duct suggests cystic pancreatic disease, either pseudocyst or cystic duct ectasia. Filling Defects in the Common Bile Duct Calculi in the common bile duct may be evident during i.v. cholangiography either on the conven-
tional or tomographic films or their presence may be suggested by a markedly and uniformly dilated duct. This indirect evidence is a hazardous basis for diagnosis, and every effort should be made to clearly show the distal end of the dilated common bile duct in the region of the ampulla where obstructing calculi usually lurk. On rare occasions, we have found the lateral view, with or without tomography, to be helpful in evaluating the distal common bile duct and the cystic duct remnant. Of course, not all radiolucent filling defects within the common bile duct are necessarily due to calculi. Rarely, polyps have been visualized on i.v. cholangiography. In patients who have had a surgical procedure on the common bile duct or who have a spontaneous or surgical fistula, air bubbles in the common bile duct may occasionally mimic calculi (Fig. 3). Air in the smaller intrahepatic radicles usually gives the clue to the proper diagnosis. Evaluation of the anastomosis or of the fistula with an upper GI series will confirm that the filling defects represent air rather than calculi. If air is seen in biliary radicles, barium cholangiography generally yields more helpful information than i.v. cholangiography. Nonvisualization
of the Biliaiy Tract
Opacification of the biliary tree depends on the functioning hepatocyte. Total serum bilirubin remains the most reliable single test for predicting
INTRAVENOUS
CHOLANGIOGRAPHY:
RECURRING
CONCEPTS
Fig. 3. Radiolucent filling defects in the common bile duct. (A) The single large and numerous small radiolucent defects on the i.v. cholangiogram were believed to be calculi. A gastrointestinal series (B) demonstrated reflux and air into the common bile duct. Sphincterotomy performed during a previous cholecystectomy had allowed air and barium.
the likelihood of visualizing the common bile duct on i.v. cholangiography. The predicted rate for successful visualization of the common bile duct with a bilirubin level of 1 mg/lOO ml or less was 92.5% in a series published in 1962. In our most recently published series, the visualization rate was 92.6T1.l~
As the bilirubin level increases,the likelihood of visualization falls. Only 9.3% of patients with a bilirubin level of 4% or more will show the com-
filling of barium reflux of
mon bile duct. However, an attempt to visualize &he common bile duct is almost always justified regardlessof the bilirubin level if the information is necessaryand cannot be obtained in any other manner. With nonvisualization of the common bile duct, impaired liver function must be assumeddespite a normal bilirubin level at the time of i.v. cholangiography. Subsequenttestsusually confirm the presenceof acute impairment of liver function.
REFERENCES 1. Allen WMC: Drip infusion cholangiography in cases of failed cholangiography. Br J Radio1 42:347-350, 1969 2. Ansell G, Faux PA: Low-dose infusion cholangiography. Clin Radio1 24:95-106, 1973 3. Cooperman LR, Rossiter SB, Reimer GW, et al: Infusion cholangiography. Thirteen years experience with 1600 cases. Am J Roentgen01 104:880-883, 1968 4. Craft IL, Swales JD: Renal failure after cholangiography. Br Med J 2:736-738,1967 5. Feldman MI, Keohane M: Slow infusion intravenous cholangiography. Radiology 87:355-356, 1966 6. Foy RE Jr: Slow-infusion compared with directinjection cholangiography: Application of zonography. Radiology 90:576-578, 1968
7. Frommhold W, Gutsche H: Quoted by Meyer-Burg (see Ref. 10) 8. Howland WJ, Rothermel WS, Topcuoglu Hlu, et al: Drip-infusion cholangiography: A second look. Radiology 107:71-73,1973 9. Margolin FR, Obata W: Drip infusion intravenous cholangiography. Radio1 Clin 37:353-356, 1968 10. Meyer-Burg J: Zur Problematik der InfusionsCholezystoCholangiographie. Dtsch Med Wochenschr 94: 2018-2023,1969 11. Meyer-Burg J, Wilhelmi U: Die Infusions-C’holezystoCholangiographie. Eine Verbesserung der rontgenologisthen Ergebnisse durch Applikation optimaler Kontrastmitteldosen. Fortschr Roentgenstr 11 I :641-649, 1969
SCHOLZ,
202
12. Mujahed Z, Evans JA, Whalen JP: The nonopacified gallbladder on oral cholecystography. Radiology 112: 1-3, 1974 13. Payne RF: Drip infusion cholangiography. Radio1 19:291-295, 1968
Clin
14. Peters GA, Hodgson JR, Donovan RJ: The effect of premeditation with chlorpheniramine on reactions to methylglucamine iodipamide. J Allerg 38:74-83, 1966 15. Russell JG: Drip infusion cholangiography. Roy Sot Med 61;262-264,1968 16. Scholz FJ, Johnston
Proc
DO, Wise RE: Intravenous
LARSEN,
AND
WISE
cholangiography: optimum dosage and methodology. Radiology 114:513-518, 1975 17. Sinclair DJ: Intravenous cholangiography-a comparative study of techniques. J Can Assoc Radio1 23: 116118, 1972 18. Stillman AE: Hepatotoxic reaction to iodipamide meglumine injection. JAMA 228:1420-1421, 1974 19. Wax RE, Crummy AB: Drip infusion cholangiography. Radiology 87:354, 1966 20. Wise RE: Intravenous Cholangiography. Springfield, Ill, Charles C Thomas, 1962 21. Wise RE: Current concepts of intravenous cholangiography. Radio1 Clin North Am 4:521-523, 1966
J. Scholz,
M.D.,
Carl
R. Larsen,
W
E HAVE established certain techniques and concepts in intravenous (i.v.) cholangiography which, over years of clinical use, have served us well. Periodically we have critically reexamined these concepts and our current views are presented here. Cholografin@ (meglumine iodipamide) is an organic molecule containing two iodinated benzene rings. After intravenous administration, it is removed from the blood by the hepatocyte, which excretes it directly into the biliary system. Excretion of Cholografin and visualization of the common bile duct depend on function of the hepatocytes, which can be evaluated by liver function tests. INDICATIONS
We have performed i.v. cholangiography for a wide variety of indications, including (1) nonvisualization of the gallbladder on oral cholecystography (Fig. 1); (2) evaluation of symptoms after cholecystectomy: (3) preoperative evaluation of the biliary tree in the patient with cholelithiasis; (4) evaluation of the biliary tree in the patient with pancreatitis; (5) evaluation of the gallbladder in patients with uncontrollable vomiting; and (6) abnormal liver enzyme values not satisfactorily explained on the basis of primary liver disease. Of these, the first two are the most frequent and useful indications. We perform i.v. cholangiography if no visualization is noted after the singledose oral cholecystogram, provided no explanation for the nonvisualiLation can be discovered (eg, liver disease. gastric retention, or failure to administer
Frrancis J. Scholz, M.D.: Radiologist, Lahey Clinic Foundation, and Instructor in Radiology, Harvard Medical School, Boston, Mass. Carl R. Larsen, M.D.: Radiologist, Lahey Clinic Foundation, and Instructor in Radiology, Boston University School of‘ Medicine, Boston, Mass. Robert E. Wise, M.D.: Chairman, Department of Diagnostic Radioloa, 1,ahe.v Clinic Foundation, and Clinical Prolessor of Radiolog):. Boston University School of Medicim, Boston, Mass. Reprint requests should be addressed to Francis J. Scholz, M.D., Department of Diagnostic Radiology, Lahey Clinic Foundation, 605 Commonwealth Avenue, Boston, Mass. 02215. c 19 76 by Prune & Stratton, Inc. Seminars
in Roentgenology,
Vol.
Xl,
No.
3 (July),
1976
Recurring Concepts M.D.,
and
Robert
E. Wise,
M.D.
the oral cholecystographic agent). If any degreeof definite gallbladderopacification is seen.no matter how faint, either a repeat single doseof oral contrast medium the next day or a reexamination with calcium Oragrafin@ granules on the sameday is performed, depending on the department logistics and patient availability. The last three indications in the above list are less rigid. The radiologist and clinician together should balancethe low yield againstthe likely benefit and determine whether the study is worth the risk to the patient and the cost. CONTRAINDICATIONS
The only absolute contraindication to i.v. cholangiographyis a documented hypersensitivity reaction, such as profound or persisting hypotension usually accompaniedby nausea,vomiting, and dyspnea and requiring pressor agents. steroids. and antihistamines. Patients with a history of a moderatevisceral or dermal reaction are treated with a 2-day prophylactic regimen of Benadryl@. 25 mg orally three times a day, and prednisone, 5 mg orally three times a day. In patients with coexisting impairment of renal and liver function. Cholografin should be used with caution and only when essentialclinical information cannot be obtained by other diagnostic tests. TECHNIQUE
Administratiorl of Cholografin Although the manufacturer recommendsfasting, we believe a light breakfast lessensreaction rate and severity. Numerous techniques of administration have been described.‘-3’5,6.8,9,‘~,‘7”9 but two basic choicesare (I) infusion over a period of 30-60 min or a IO-min injection, and (7) a single doseof Cholografin of 10.4 g (20 ml of 57%) or a double dose of Cholografin of 20.X g (40 ml ot 52%, or a largeramount of a more dilute solution). We prefer 20 d of 52% Cholografin injected by hand at an even rate over a IO-min period. Larger dosesare not used for we have shown that they provide no significant improvement, and evidence suggeststhat increasing quantities of Cholografin 197
SCHOLZ,
LARSEN,
AND
WISE
Fig. 1. Cystic duct calculus, normal common bile duct on i.v. cholangiography. The common bile duct angulates gently and tapers slightly. The gallbladder did not visualize during oral cholecystography or intravenous cholangiography. During filming, the oval calcification maintained a constant relationship to the common bile duct rather than to the calcified costal cartilages. With the more common rediolucent calculus impacted in the cystic duct, no abnormality will be noted on i.v. cholangiography except for nonvisualization of the gallbladder. Marked edema of the cystic duct in acute cholecystitis, even without stone impaction, may cause nonvisualization during i.v. cholangiography.
may cause hepatotoxicity.16 We do not prolong the administration of Cholografin because a decrease in biliary opacification is noted when the injection time is extended to 30 min. Hand injection is preferred to the drip-infusion method only because the injection can be stopped instantaneously if the patient begins to have an allergic reaction. We have not had a death from iv. cholangiography in more than 10,000 examinations. Filming The patient is maintained in a 15” right posterior oblique position, and films are obtained at 20-min intervals after the beginning of Cholografin administration. With a cooperative patient, progressive collimation is begun when the duct is first seen, thereby diminishing scatter and improving contrast. Tomograms with the patient in the lateral position are occasionally helpful in evaluating the terminal common bile duct and the insertion of the cystic duct. If the patient has had a previous cholecystectomy, the procedure is terminated when tomograms or conventional films delineate the normal common bile duct. If the gallbladder has not been removed and is opacified at 120 min, it is examined with supine, erect, or decubitus films. If it is not seen at 120 min, a film of the right upper
quadrant should be obtained at 4 hr. If the gallbladder is seen at this time it should be evaluated with additional films. If the gallbladder is not seen at 4 hr, a film at 24 hr may be indicated since, on occasion, a normal gallbladder has been demonstrated. REACTIONS
Reaction rates vary according to the observer and the definition of a reaction. In different series at the Lahey Clinic with the sameobservers,our reaction rates varied from 4.3% with routine antihistamine administration before intravenous cholangiogramto 1% when an antihistamine was not routinely administered.‘6 The three main classesof reactions encountered after Cholografin administration are visceral, dermal, and hypersensitivity. We believe that the visceral reaction of nausea,vomiting, and occasional tenesmusis related to the rate of administration and is not a true allergic reaction. After a few minutes’ delay, resumption of the injection of Cholografin at a slower rate will usually permit completion of the i.v. cholangiogram with satisfactory results. Dermal reactions consist of pruritus, erythema, and hives. Premeditation with an antihistamine prevents or minimizesthesereactions.r4
INTRAVENOUS
CHOLANGIOGRAPHY:
RECURRING
CONCEPTS
Hypersensitivity reactions occur in about 1% of patients (0.9% of 442 patients in our latest series). They consist of hypotension, nausea and vomiting, and dyspnea. Adrenalin (0.3 ml of a 1 : 1,000 solution injected subcutaneously), Benadryl (50 mg injected intramuscularly or intravenously), and corticosteroids (100 mg of Solu-Cortef injected intravenously) are administered. Since oxygen often moderates the symptoms. we usually administer it. If possible, medication should not be administered through the sameneedle and tubing used to administer the Cholografin, since precipitation of Cholografin occurs when it is mixed with Benadryl. These hypersensitivity reactions usually respond promptly with no harm to the patient. All reactions in our serieswere successfully treated with pressoragentsand steroids. Toxicity Toxic effects on the kidneys and liver have been Elevation noted with Cholografin.4,7,10,11,1S,16,18 of serum glutamic oxaloacetic transaminase (SCOT) levels after administration of Cholografin has been seenby severalauthors. However, in all patients the SGOT levels returned to the preinjection levels. Cholografin is probably a mild hepatotoxin. Renal failure has been reported after i.v. cholangiography but is usually seen in patients with preexisting renal and hepatic disease.In the presence of hepatic disease,a greater amount of Cholografin is excreted by the kidneys, and this increasedexcretory load may further depressan already impaired renal function. Cholografin should be used judiciously in the presenceof coexisting renal and liver disease. DIAGNOSTIC
IMPLICATIONS
The Gallbladder We firmly believe opacification of a gallbladder without calculi on i.v. cholangiographyindicates a normal gallbladdereven though the gallbladderhas failed to visualize on previous oral cholecystography. We do not believe this combination of events indicates a diagnosisof acalculouscholecystitis. A pathology report of chronic cholecystitis doesnot necessarilyestablishthe clinicopathologic entity of acalculouscholecystitis. It israre indeedwhen some slight evidence of cholecystitis cannot be found in a resectedgallbladder. When the gallbladder doesopacify during intravenous cholangiography, it must be as thoroughly
199
evaluated for calculi as the orally opacitied gallbladder with supineand decubitusor upright films. In a large seriespurporting to indicate that oral cholecystography is more reliable than intravenous cholangiography in evaluating gallbladder disease, gallstoneswere missedon i.v. cholangiography in 12 of 27 patients whose previously nonopacified gallbladder filled during i.v. cholangiography.‘* We believe this may reflect more on the technique of examining the gallbladder during i.v. cholangiography than on the procedure itself. In this same series, 152 patients with nonvisualized gallbladders after consecutive dosesof oral cholecystography were operated on. All had calculi or tumor except 13 patients who had cholecystitis. However, 193 patients were not operated on for various reasons, among them a reluctance to accept a pathologic diagnosiswhen a subsequenti.v. cholangiography showeda radiographically normal gallbladder. In more than 20 years experience we have found that clinically significant gallbladder disease,either cholelithiasisor cholecystitis, hasconsistently been diagnosedby i.v. cholangiography by the demonstration of calculi or of nonfilling of the gallbladder, indicating cystic duct obstruction. The mechanism of cystic duct obstruction may be either calculusor edemafrom cholecystitis. Nonvisualization on two consecutiveoral cholecystogramsindicates a high probability of gallbladder disease,but intravenous cholangiography adds a greater degree of certainty to the diagnosis(Fig. 1). Diameter of the Common Bile Duct If the common bile duct is 8 mm or less,common bile duct obstruction and common bile duct calculi are lesslikely to be present. If the diameter is 15 mm or greater, obstruction and the possibility of choledocholithiasismust be postulated. With a diameter between 8 and 1.5 mm, no conclusions can be drawn. Unfortunately, the majority of obstructed or partially obstructed common bile ducts as well as many normal bile ducts are within this range. Fortunately. one other finding may be of usein establishingthe diagnosisof partial obstruction of the common bile duct. In patients whosegallbladder haseither been removed or is nonvisualized becauseof cystic duct obstruction and in whom the diameter of the common bile duct suggestsobstruction, the common bile duct should be evaluated at 60 and 120 min for evidenceof increasing
SCHOLZ,
LARSEN,
AND
WISE
Fig. 2. Normal i-v. cholangiography. Savera1 anatomic relationships are demonstrated on this tomogram. The duodenal bulb and descending limb of the duodenum are seen between the gallbladder and the common bile duct. The contrast-filled duodenal bulb should not be mistaken for a reformed gallbladder, which is a nonentity, or for opacification of the previously nonopacified gallbladder. A sip of barium or ginger ale will allow identification of the bulb. The angle of the common bile duct occurs behind the duodenal bulb and is a good approximation of the point at which the common bile duct enters the tunnel in the pancreas. Narrowing distal to the angulation with proximal dilatation is evidence for pancreatitis. Between the spine and the intrapancreatic segment of the common bile duct, contrast medium is seen in the collecting system of the right kidney. Occasionally, renal excretion of Chologrefin may overlap and obscure the distal common bile duct necessitating a change in patient obliquity or tomography.
or diminishing opacification. Evaluation of density over this period of time has, on many occasions, substantiated the diagnosis of partial obstruction, whether from calculus, fibrosis, or pancreatic disease.*OY21 Patients receiving morphine or related narcotics may have retention on the basis of contraction of the sphincter of Oddi. Before invoking pathologic retention, this possibility should be investigated. Configuration
of the Common Bile Duct
The distal common bile duct is directed posteriorly and medially, courses behind the duodenal bulb, and reaches the papilla of Vater by traversing a canal in the head of the pancreas (Fig. 2). Narrowing of the distal common bile duct with a normal or dilated proximal duct is characteristic of pancreatic edema and fibrosis. A long, tapered narrowing suggests the likelihood of pancreatitis; abrupt narrowing may be the result of pancreatitis but is also seen with pancreatic or ampullary carcinoma. The duct in pancreatitis is often angulated abruptly as it enters the tunnel in the head of the pancreas. Marked angulation or displacement of the common bile duct suggests cystic pancreatic disease, either pseudocyst or cystic duct ectasia. Filling Defects in the Common Bile Duct Calculi in the common bile duct may be evident during i.v. cholangiography either on the conven-
tional or tomographic films or their presence may be suggested by a markedly and uniformly dilated duct. This indirect evidence is a hazardous basis for diagnosis, and every effort should be made to clearly show the distal end of the dilated common bile duct in the region of the ampulla where obstructing calculi usually lurk. On rare occasions, we have found the lateral view, with or without tomography, to be helpful in evaluating the distal common bile duct and the cystic duct remnant. Of course, not all radiolucent filling defects within the common bile duct are necessarily due to calculi. Rarely, polyps have been visualized on i.v. cholangiography. In patients who have had a surgical procedure on the common bile duct or who have a spontaneous or surgical fistula, air bubbles in the common bile duct may occasionally mimic calculi (Fig. 3). Air in the smaller intrahepatic radicles usually gives the clue to the proper diagnosis. Evaluation of the anastomosis or of the fistula with an upper GI series will confirm that the filling defects represent air rather than calculi. If air is seen in biliary radicles, barium cholangiography generally yields more helpful information than i.v. cholangiography. Nonvisualization
of the Biliaiy Tract
Opacification of the biliary tree depends on the functioning hepatocyte. Total serum bilirubin remains the most reliable single test for predicting
INTRAVENOUS
CHOLANGIOGRAPHY:
RECURRING
CONCEPTS
Fig. 3. Radiolucent filling defects in the common bile duct. (A) The single large and numerous small radiolucent defects on the i.v. cholangiogram were believed to be calculi. A gastrointestinal series (B) demonstrated reflux and air into the common bile duct. Sphincterotomy performed during a previous cholecystectomy had allowed air and barium.
the likelihood of visualizing the common bile duct on i.v. cholangiography. The predicted rate for successful visualization of the common bile duct with a bilirubin level of 1 mg/lOO ml or less was 92.5% in a series published in 1962. In our most recently published series, the visualization rate was 92.6T1.l~
As the bilirubin level increases,the likelihood of visualization falls. Only 9.3% of patients with a bilirubin level of 4% or more will show the com-
filling of barium reflux of
mon bile duct. However, an attempt to visualize &he common bile duct is almost always justified regardlessof the bilirubin level if the information is necessaryand cannot be obtained in any other manner. With nonvisualization of the common bile duct, impaired liver function must be assumeddespite a normal bilirubin level at the time of i.v. cholangiography. Subsequenttestsusually confirm the presenceof acute impairment of liver function.
REFERENCES 1. Allen WMC: Drip infusion cholangiography in cases of failed cholangiography. Br J Radio1 42:347-350, 1969 2. Ansell G, Faux PA: Low-dose infusion cholangiography. Clin Radio1 24:95-106, 1973 3. Cooperman LR, Rossiter SB, Reimer GW, et al: Infusion cholangiography. Thirteen years experience with 1600 cases. Am J Roentgen01 104:880-883, 1968 4. Craft IL, Swales JD: Renal failure after cholangiography. Br Med J 2:736-738,1967 5. Feldman MI, Keohane M: Slow infusion intravenous cholangiography. Radiology 87:355-356, 1966 6. Foy RE Jr: Slow-infusion compared with directinjection cholangiography: Application of zonography. Radiology 90:576-578, 1968
7. Frommhold W, Gutsche H: Quoted by Meyer-Burg (see Ref. 10) 8. Howland WJ, Rothermel WS, Topcuoglu Hlu, et al: Drip-infusion cholangiography: A second look. Radiology 107:71-73,1973 9. Margolin FR, Obata W: Drip infusion intravenous cholangiography. Radio1 Clin 37:353-356, 1968 10. Meyer-Burg J: Zur Problematik der InfusionsCholezystoCholangiographie. Dtsch Med Wochenschr 94: 2018-2023,1969 11. Meyer-Burg J, Wilhelmi U: Die Infusions-C’holezystoCholangiographie. Eine Verbesserung der rontgenologisthen Ergebnisse durch Applikation optimaler Kontrastmitteldosen. Fortschr Roentgenstr 11 I :641-649, 1969
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12. Mujahed Z, Evans JA, Whalen JP: The nonopacified gallbladder on oral cholecystography. Radiology 112: 1-3, 1974 13. Payne RF: Drip infusion cholangiography. Radio1 19:291-295, 1968
Clin
14. Peters GA, Hodgson JR, Donovan RJ: The effect of premeditation with chlorpheniramine on reactions to methylglucamine iodipamide. J Allerg 38:74-83, 1966 15. Russell JG: Drip infusion cholangiography. Roy Sot Med 61;262-264,1968 16. Scholz FJ, Johnston
Proc
DO, Wise RE: Intravenous
LARSEN,
AND
WISE
cholangiography: optimum dosage and methodology. Radiology 114:513-518, 1975 17. Sinclair DJ: Intravenous cholangiography-a comparative study of techniques. J Can Assoc Radio1 23: 116118, 1972 18. Stillman AE: Hepatotoxic reaction to iodipamide meglumine injection. JAMA 228:1420-1421, 1974 19. Wax RE, Crummy AB: Drip infusion cholangiography. Radiology 87:354, 1966 20. Wise RE: Intravenous Cholangiography. Springfield, Ill, Charles C Thomas, 1962 21. Wise RE: Current concepts of intravenous cholangiography. Radio1 Clin North Am 4:521-523, 1966
