- Email: [email protected]
Diagnostic utility of cholescintigraphy and ultrasonography in acute cholecystitis
Diagnostic Utility of Cholescintigraphy and Ultrasonography In Acute Cholecystitis
Robert K. Zeman, MD,* New Haven, Connecticut Morton I. Burrell, MD,* New Haven, Connecticut C. Elton Cahow, MD,+ New Haven, Connecticut Vicente Carlde, MD,* New Haven, Connecticut
The surgeon is faced with a myriad of radiologic tests in the investigation of acute pain in the right upper quadrant of the abdomen, including hepatobiliary scintigraphy, ultrasonography, oral cholecystography and intravenous cholangiography. These radiologic procedures, although usually highly accurate, may at times produce confusing and discordant results, leaving clinical judgment as the sole arbitrator. It is the purpose of this prospective and retrospective analysis of our experience with combined imaging of the gallbladder to clarify the indications, interpretive pitfalls and clinical implications of cholescintigraphy and cholecystosonography in patients with suspected acute cholecystitis. Although the study is not primarily directed toward an appraisal of chronic cholecystitis, acalculous cholecystitis or pancreatitis, these entities will be briefly considered in relation to differential diagnostic criteria. The technetium-99m-labelled N-substituted iminodiacetic acid derivatives were first introduced by Harvey et al [I] in 1975 (Figure 1). Technetium99m-HIDA is representative of this class of compounds and is excreted unconjugated by way of the hepatocytes. When the serum bilirubin level is less than 5 mg/lOO ml, the normal examination reveals rapid visualization of the major bile ducts and gallbladder with egress of activity into the duodenum within 1 hour of injection of the radiopharmaceutical [2,3] (Figure 2A). Related analogues of technetium99m-HIDA (such as technetium-99m-DISIDA) are currently also being evaluated and may allow demonstration of biliary structures despite serum bilirubin levels approaching 20 mg/lOO ml [4]. From the Department of Diagnostic Ftadiilogy,* the oepartment Of suge4y,+ Yale-New Haven Hospital, Yale University School of Medicine: and the Department of Nuclear Medicine,t Hospital of St. Raphael, New Haven, Connecticut. Requests for reprints should be addressed to Robert K. Zeman, MD. Da partment of Diagnostic Radiology, Yale University School of Medicine. 333 Cedar Street, New Haven, Connecticut 08510. Presented at the 61st Annual Meeting of the New EnglandSurgical Society. Portsmouth, New Hampshire, September 26-28, 1980.
446
The concept behind imaging with the iminodiacetic acid compounds is similar to the traditional iodine-131 rose bengal scan. The ability to use multimillicurie doses of technetium-99m as the radiolabel with its short half-life, pure gamma 140 keV energy peak and lower radiation exposure allows much better imaging characteristics than the maximum allowable dose of iodine-131. Technetium99m-HIDA is in phase III trials as an investigational new drug, and widespread commercial availability is anticipated in the near future. Material
and Methods
Beginning in mid-1978, 200 consecutive patients seen at the Yale-New Haven Hospital with abdominal complaints suggestive of acute cholecystitis were included in the study. Patients with jaundice were included if underlying cholelithiasis or cholecystitis was clinically implicated. This group of patients does not include all patients seen at our institution with possible acute cholecystitis as in some cases the patient or the referring physician refused participation in the study. The sample group included 76 men (mean age 51 years) and 124 women (mean age 47). Physical examination, leukocyte count, liver function tests, serum amylase and lipase and plain abdominal roentgenographic findings were recorded before imaging procedures. After obtaining the proper informed consent, imaging procedures were performed. Hepatobiliary scintigraphy with technetium-99m-HIDA and ultrasonography were performed on an emergency basis, usually within 24 hours of each other. Scintigraphic examinations were performed in the fasting state when possible. Ten millicuries (370 MBq) of technetium-99m-HIDA was prepared from a commercial kit (Merck-Frosst Laboratories, Dorval, Quebec, Canada) and injected intravenously. Utilizing a 15 inch Anger scintillation camera (Searle LFOV, Des Plaines, Illinois), scintigrams were obtained serially at 5 minute intervals in the anterior position followed by right lateral, right anterior oblique and left anterior oblique views at 1 hour. Delayed views were obtained as necessary at 2, 4, 6 and 24 hours in an effort to demonstrate gallbladder filling and egress of isotope into the small bowel.
The American Journal of Surgery
Cholescintigraphy
Cholecystokinin was not used as part of these trials. A normal study was one interpreted as showing: (1) good liver uptake with minimal renal activity and visually acceptable clearing of blood pool activity, (2) visualization of gallbladder and bile ducts within 1 hour, and (3) passage of activity into the small bowel within 1 hour. For the purposes of this study, the sole criterion for the scintigraphic diagnosis of acute cholecystitis was nonvisualization of the
COMPOUND
0
MANUFACTURER
CH2COOH NHCOCH2N CH2COOH
Q
acetanalide)-iminodiacetic acid
R
PIPIOA
N. a-(p-isopropyl-
OIETHYL-IDA N. a-(2,6-diethyl-
acetanalide)-iminodiacetic acid
INVESTIGATIONAL STATUS
Merke-Frosst Oorval.Due, Canada
Phase 111 IN0
New England Nuclear North Billerica. Mass.
Phase III IN0
Diagnostic Isotopes Bloomfield. N.J.
Phase III IN0
R
OISOFENIN OISIOA) N. a-2,6,-I diisopropyl
acetanalide)-iminodiacetic acid
in Cholecystitis
gallbladder (Figure 2B). The patients with delayed visualization represent an interesting subpopulation and will be considered further in a subsequent report. Sonographic sector scans of the gallbladder were performed while the patient was fasting when possible utilizing commercially available gray-scale ultrasound equipment (Searle Pho/Sonic or Picker 80L) with a 2.25 or 3.5 mHz transducer. Transverse, oblique, longitudinal and decub-
STRUCTURE
HIOA N, a-(2.6.-dimethylacetanalide)- imlnddiacetic acid
and Ultrasonography
mR
C2H5
0 (i
R
NA
NA
C2H5
F@re 1. finlnodkcetk acid c&npouMs and the/r commerciai availability. in the Untted States.
IN0 = tnvesttgationai new drug; NA = not -My
avaikbk
Figure 2. Technetium-Wm-HIDA scintigrams. A, normal 7 hour scan. The gallbladder (gb) has visualized. There has been signifkant washout of liver activity into the common bfie duct (singe arrowftead) and duodenum (double arrowhead). incidentally noted is bladder activity (b) from urinary excretkn. 6, abnormal I hour scan. The gallbladder has not visualized despite good liver uptake and excretkn into the common bile duct (d) and duodenum (double arrowheads). The open arrow denotes the “cold” gaiibia&krkssa.Biadderactivny(b) is a/w seen.
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Zeman et al
itus scans were performed. Echoes suggesting cholelithiasis, gallbladder size and gallbladder wall thickness were also assessed. Pain on ultrasonically guided palpation of the gallbladder and shadowing opacities that moved with gravity or high level echoes replacing the gallbladder fossa with shadowing were interpreted as consistent with cholelithiasis and diagnostic of acute cholecystitis in this group of patients with signs and symptoms of acute cholecystitis. The remainder of the sonograms were classified as normal or indeterminate. For purposes of data analysis the indeterminate examinations were counted as diagnostic failures in patients who ultimately had acute cholecystitis. Limited study of the liver and pancreas was also performed in selected patients. All imaging procedures were interpreted independently by the appropriate subspecialty services within the Diagnostic Radiology Department. For purposes of analysis, the scintigraphic studies were also retrospectively read by one author (RZ) and analyzed with regard to pitfalls of interpretation and coordination with the sonographic findings.
bladder failed to visualize on scintigraphy. Of those, 42 were proven to have acute cholecystitis and 12 chronic cholecystitis. Of these 12 patients, 7 ultimately underwent cholecystectomy with gallstones found in the cystic duct or ampullary pouch. Seven patients had false-positive technetium-99m-HIDA examinations with a surgically proven normal gallbladder in six. Forty-three patients had proven acute cholecystitis, which was predicted by cholescintigraphy in 42. Two patients in the latter group had
acute acalculous cholecystitis, both successfully predicted by the isotope study. Sonography demonstrated cholelithiasis in only 29 of the 43 patients with acute cholecystitis. On closer inspection of the false-positive scintigrams, four of seven patients with nonvisualization of the gallbladder who had normal gallbladders at surgery had evidence of pancreatic disease with marked hyperamylasemia. There was no sonographic evidence of cholelithiasis in these patients. Of the remaining three patients with false-positive findings, one had eaten just before the examination, most likely producing emptying of the gallbladder, and the other two patients had examinations with obvious interpretive errors (gallbladder activity mistaken for duodenal bulb). The normal HIDA scan was a reliable indicator of the absence of acute cholecystitis. Of 83 patients with visualization of the gallbladder, only 1 had acute cholecystitis. Sixty-one of 83 had normal sonograms, including the single patient with the false-negative HIDA examination. Twenty patients who had nonvisualization of the gallbladder had chronic chole-
Results Of 200 patients originally included in the study group, only 144 had the appropriate clinical and surgical follow-up allowing a definitive final diagnosis. Included in the sample group were 43 patients with acute cholecystitis, 32 patients with chronic cholecystitis and 69 normal subjects. Surgical intervention was carried out in 71 patients with acute and chronic cholecystitis and in 10 patients subsequently proven to have normal gallbladders. The results of the imaging procedures are presented in Tables I and II. In 61 patients the gall-
TABLE I
Flnal Diagnosis, Sclntlgraphlc and Sonographlc Flndlngs In 144 Patlents
Findings on Technetium-99mHIDA Scan Nonvisualization of gallbladder Visualization of oallbladder l
Acute Cholecystitis (43 patients) Findings on Ultrasound Normal Stones Indeterminate
Chronic Cholecystitis (32 patients) Findings on Ultrasound Normal Stones Indeterminate
5’
29
6’
5
4
3
4
0
3
1
0
0
6
13
1
54
1
7
Including one case of acute acalculous cholecystitis.
TABLE II
Flnal Diagnosis, Sclntlgraphlc and Sonographic Flndlngs in 144 Patients Based on lmaglng Procedure Results
Acute Cholecystitis Findings on ssTc-HIDA scan Nonvisualization (61 patients) Visualization (83 patients) Findings on ultrasound Stones (47 patients) Normal (75 patients) Indeterminate (22 patients) l
448
Normal (69 patients) Findings on Ultrasound Normal Stones Indeterminate
Final Diagnosis Chronic Cholecystitis
Normal
42 1
12 20
7 62
29 6’ 6’
17 11 4
1 56 10
Including one case of acute acalculous cholecystitis.
The American Journal of Surgery
Cholescintigraphy
cystitis and cholelithiasis with a patent cystic duct. Thus, while a normal HIDA scan excludes acute cholecystitis, chronic cholecystitis and cholelithiasis may still be present. Sensitivity and specificity calculations were derived from the modified Latin square data in Table I [5]. HIDA had a sensitivity of 98 percent in the detection of acute cholecystitis, but a specificity of only 81 percent for acute cholecystitis in the group with nonvisualization of the gallbladder. Sonography in all patients was only 67 percent sensitive in the detection of acute cholecystitis, but 8’2percent specific. It should be pointed out, however, that the indeterminate sonograms were counted as diagnostic errors because eight of the patients whose studies were in this group were ultimately shown to have acute cholecystitis. In addition, ultrasound was 61 percent sensitive in the detection of cholelithiasis but had 98 percent specificity. By combining criteria, that is, requiring nonvisualization of the gallbladder on HIDA scintigraphy and cholelithiasis on sonography, an overall 98 percent sensitivity in detecting acute cholecystitis is achieved, but with only a 79 percent specificity. While this specificity is somewhat low, it indicates that 79 percent of patients with nonvisualization of the gallbladder on scintigraphy and cholelithiasis on ultrasound will have acute cholecystitis. The remaining 21 percent will have chronic cholecystitis, and no patients should be normal based on our data. Comments The diagnosis of acute cholecystitis has traditionally been based on a constellation of clinical and laboratory studies. This has resulted in diagnostic error rates ranging from 16 percent [6] to 20 percent [71. The desirability of early cholecystectomy in patients with acute cholecystitis remains controversial [8,9], but at our institution early surgery has yielded favorable results. The desirability of early diagnosis to initiate appropriate therapy is supported by clinical experience and common sense, regardless of the ultimate timing of cholecystectomy. The quest for an imaging procedure that accurately and rapidly distinguishes patients with acute cholecystitis from all others dates back to 1954 [IO], when intravenous cholangiography was popularized as a sensitive and specific study for cystic duct obstruction. The procedure was plagued by indeterminate results approaching 40 percent [11,12], particularly when the serum bilirubin level exceeded 2 mg/lOO ml [13]. Significant side effects, hepatorenal toxicity and death resulting from contrast reactions occur up to 8 times more frequently than with intravenous pyelography [14]. Real-time and gray-scale ultrasonography are well established screening procedures for the presence of cholelithiasis [15-211. Results in detecting cholelithiasis using real-time ultrasonography have been comparable to those reported previously with grayVolume
141, April 1981
and Ultrasonography
in Cholecystitis
scale ultrasonography, that is, a sensitivity and specificity of approximately 90 percent [22]. The role of sonography in patients with acute cholecystitis is not as straightforward [23-291. Sonographic demonstration of gallstones is at best inferential evidence of acute cholecystitis in that 10 percent of men and 20 percent of women over 55 years of age have gallstones [30]. Ultrasonography offers no information regarding gallbladder function and cystic duct patency. While some workers propose that increased gallbladder wall thickness or a rim of echolucency is diagnostic of acute cholecystitis [26-28], others dispute this claim [31,32]. Technetium-99m-HIDA cholescintigraphy is the best single test available for the detection of acute cholecystitis. The examination is easily performed as an emergency procedure with acceptable patient radiation exposure and rapid diagnosis, usually within 4 hours. While generally consistent with previous studies in the literature [2,3,33-351, our data raise several important points. The prime importance of cholescintigraphy is in differentiating patients who are normal from those with cholecystitis. As evidenced by its 98 percent sensitivity, a normal HIDA study virtually excludes the diagnosis of acute cholecystitis. Diagnostic work-up of patients with normal findings on scintigraphy should be directed toward other possible causes of the symptoms and not the gallbladder, although incidental chronic cholelithiasis may be present. Failure of the gallbladder to visualize is clearly abnormal, but the specificity attached to this finding in previous studies [2,33-351 could not be confirmed. Four of the seven patients with intrinsically normal gallbladders and failure of visualization on HIDA scintigraphy had evidence of severe acute pancreatitis. Gallbladder distention was noted sonographitally but without evidence of cholelithiasis. Fonseca et al [36] stated previously that the gallbladder visualizes scintigraphically in 87 percent (13 of 15) of patients with acute pancreatitis. Chronic cholecystitis was present in the two cases with nonvisualization. It is difficult to explain this apparent discrepancy among reports, but the degree of bile stasis within the gallbladder in any given case may be the governing factor in determining isotope entrance into the gallbladder [37]. Delayed drainage of isotope into the duodenum may be present and indicate the underlying stasis resulting in gallbladder nonvisualization on scintigraphy [38]. Failure of the gallbladder to fill with isotope also occurred in patients with chronic cholecystitis. Seven of 12 of these patients ultimately were found to have cystic duct or ampullary pouch stones but with gross and histologic evidence of chronic rather than acute cholecystitis. It is uncertain whether this group of patients had a functional cystic duct obstruction at the time of scintigraphy or an actual anatomic obstruction from a cystic duct stone which was impacted and subsequently passed anterograde or 449
Zeman et al
retrograde. Since ending the acquisition of cases for this study we have seen two patients with known cholelithiasis who had scintigraphically nonvisualized gallbladders during acuteattacks of biliary colic with subseauent visualization on a follow-un examination soon after recovery. Our sonographic data must be assessed with caution. Studies in which “sludge” or “debris” was seen within the gallbladder without opacities meeting the criteria of cholelithiasis were called indeterminate. In calculating sensitivity data, these indeterminate studies in which the patient ultimately turned out to have stones were included as false-negative examinations, resulting in a sensitivity of 67 percent. If the indeterminate examinations were excluded, an 82 percent sensitivity would result. Most of these examinations were performed as emergency procedures in acutely ill patients in whom the duration of fasting was uncertain. Thus, the lack of sensitivity can be justified with respect to previous reports in the literature regarding detection of cholelithiasis. These data also partially refute the contention that sonography as an emergency procedure accurately distinguishes acute cholecystitis from the diseases that mimic it. In addition, ultrasound was not specific in the diagnosis of acute cholecystitis (82 percent), but highly specific in the diagnosis of cholelithiasis; that is, if stones were detected sonographically, the chances of cholelithiasis were exceedingly great (98 percent). This may reflect our institution’s requirement that strict criteria be met for the diagnosis of gallstones. Summary When faced with a patient with possible acute cholecystitis, technetium-99m-HIDA scintigraphy should be the primary diagnostic procedure performed. If scintigraphy reveals a normal gallbladder, acute cholecystitis is excluded. If the scintigram fails to visualize the gallbladder, ultrasonography is deemed advisable to exclude potential false-positive scintigrams and confirm the presence of cholelithiasis. Acknowledgment: We acknowledge the assistance of Sandra Sudac, Thomas McCarthy and Ann Curley in the preparation of this report.
References 1. Harvey E. Loberg M. Cooper M. esmTc-HIDA, a new radiopharmaceutical for hepatobiliary imaging (abstr). J Nucl Med 1975;16:533. 2. Weissman HS, Frank MS, Bernstein LH, Freeman L. Rapid and accurate diagnosis of acute cholecystitis with ss’rV~IDA cholescintigraphy. AJR 1979;132:523-8. 3. Rosenthal1 L, Shaffer EA, Lisbona R, Pare P. Diagnosis of hepatobiliary disease by eamT~-HIDA cholescintigraphy. Radiology 1978; 1261467-74. 4. Green A, Rosenberg N, Sheahan M. Multicenter triat of Tcgem Disofenin: a new hepatobiliary agent for imaging jaundiced and non-jaundiced patients (abstr). J Nucl Med 1980;21:
450
5.
18. McNeil BJ, Keeler E. Adelstein SJ. Primer on certain elements of medical decision making. N Engl J Med 1975;293:21 l* V.
6. Essenhigh DM. Management of acute cholecystitis. Br J Surg 1966;53:1032-8. 7. Halasz NA. Counterfeit cholecystitis. A common diagnostic dilemma. Am J Surg 1975;130:189-92, 8. Cole WH. Gallbladder disease. Surg Clin North Am 197858: 917-92. 9. Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by early and delayed surgery. A controlled clinical trial. Stand J Gastroenterol 1978;13:673-8. 10. Glenn F, Evans J. Hill M. McClenahan J. Intravenous cholangiography. Am J Surg 1954;140:600-14. 11. Johnson HC, McLaren JR, Weens HS. Intravenous cholangiography in the differential diagnosis of acute cholecystitis. Radiology 1960;74:790-7. 12. Harrington OB, Beall AC, Noon G, DeBakey ME. Intravenous cholangiography in acute cholecystitis. Arch Surg 1964; 88:585-g. 13. Wise RE. Intravenous cholangiography. Springfield, IL: Charles C Thomas, 1962. 14. Ansell G. Adverse reactions to contrast agents. Invest Radio1 1970;5:374-84. 15. Goldberg RB, Harris K. Brucker W. Ultrasonic and radiographic cholecystography: a comparison. Radiology 1974: 11: 405-9. 16. Leopold G, Amberg J, Gosink BB, Mittelstaedt C. Gray scale ultrasonic cholecystography:a comparison with conventional radiographic techniques. Radiology 1975;121:445-8. 17. Bartrum RJ Jr, Crow HI, Foote SR. Ultrasonic and radiographic cholecystography. N Engl J Med 1977;296:538-41. 18. Crade M, Taylor KJW, Rosenfield AT, deGraff CS, Minihan P. Swgical and pathologic correlation of cholecystosonography and cholecystography. AJR 1978;131:227-9. 19. Detweiler RP. Kim DS, Longerbeam JK. Ultrasonography and oral cholecystography. A comparison of their use in the diagnosis of gallbladder disease. Arch Surg 1980;115: 1096-8. 20. McIntosh DMF, Penney HF. Gray scale ultrasonography as a screening procedure in the detection of gallbladder disease. Radiology 1980; 136:725-7. 21. Cooperberg PL, Pon MS, Wong P, Stoller JL, Burhenne HJ. Real-time high resolution uttrasoundin the detection of biliary calculi. Radiology 1979;131:789-90. 22. Krook PM, Allen FH, Bush WH, Malmer G. MacLean MD. Comparison of real-time cholecystosonography and oral cholecystography. Radiology 1980; 135: 145-8. 23. Karp W, Herlin P, Holmin T, Owman T. Infusiontomography and ultrasonography of the gallbladder in the diagnosis of acute cholecystitis. Gastrointest Radio1 1979;4:253-61. 24. Bergman AB, Neiman HL. Kraut B. Ultrasonographic evaluation of pericholecystic abscesses. AJR 1979;132:201-3. 25. Stoller JL, Cooperberg PL, Simpson WM. Diagnostic ultrasonography in acute cholecystitis. Can J Surg 1979;22: 374-6. 26. Marchal GJF. Casaer M, Baert AL, Goddeeris PG, Kerremans R, Fevery J. Gallbladder wall sonolucency in acute cholecystitis. Radiology 1979;133:429-33. 27. Kane RA. Ultrasonographic diagnosis of gangrenous cholecystitis and empyema of the gallbladder. Radiology 1980; 134:1,91-4. 28. Ulreich S, Foster KW, Stiers SA, Rosenfield AT. Acute cholecystitis. Comparison of ultrasound and intravenous cholangiography. Arch Surg 1980; 115: 158-60. 29. Sherman M, Rails PW. Quinn M, Halls J, Keats J. Intravenous cholangiography and sonography in acute cholecystitis: - prospective evaluation. AJR 1986;135:31 l-3. _ 30. Friedman DK. Kannel WB, Dawber TR. Eoidemioloav of aallbladder disease: observations in Framingham-St&. J Chronic Dis 1966;273-92.
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31. Mindell HJ, Ring A. Gallbladder wall thickening: ultrasonic 32. 33.
34.
35.
36.
37. 38.
findings. Radioloav 1979:133:699-701. Crade My Taylor KJ$ Viscomi GN. Need for care in assessing gallbladder wall thickening. AJR 1960;135:423-4. Fonseca C, Greenberg D, Rosenthal1 L, Arzoumanian A. Assessment of the utility of gallbladder imaging with OomTcHIDA. Clin Nucl Med 1978;3:437-41. Pare P, Shaffer EA, Rosenthal1 L. Nonvisualization of the gallbladder by OOmTc-HIDA cholescintigraphy as evidence of cholecystitis. Can Med Assoc J 1978;l l&384-6. Cheng TM, Davis MA, Seltzer SE, et al. Evaluation of hepatobiliary imaging by radionuclide scintigraphy, ultrasonography, and contrast cholangiography. Radiology 1979; 133:7617. Fonseca C, Greenberg D, Rosenthal1L, Arzoumanian A, Lisbona R. ggmT~-IDA imaging in the differential diagnosis of acute cholecystitis and acute pancreatitis. Radiology 1979:130: 525-7. Rao BK, Lieberman LM. Bile layering: a cause for false-positive cholescintiscans. AJR 1980; 134: 125 l-3. Zeman RK, Segal HB, Caride V. gg”‘Tc-HIDA cholescintigraphy: the distended photon deficient gallbladder. J Nucl Med 1981;22:39-41.
Discussion Mary Keohane (West Haven, CT): Thank you for the opportunity to review this excellent paper. We have, in our institution, conducted stage III clinical trials on HIDA scanning for the last 2 years, and our findings are very similar to those in the present study. There are three points of practical value to be taken from this paper. (1) When HIDA scanning and ultrasound are used as complementary studies, their combined accuracy is significantly higher than the accuracy of either method used alone. (2) When ultrasound is positive for stones and the gallbladder is not visualized on HIDA scanning, 79 percent of patients have acute cholecystitis and 21 percent have chronic cholecystitis with stones. (3) Acute cholecystitis can virtually be excluded in any patient in whom ultrasound is negative for stones and the gallbladder visualizes on the HIDA scan. John W. Braasch (Boston, MA): At considerable risk in showing my age, I would like to make one comment about this study. I would have liked to see another column in which evaluation of a history and physical examination were done. I have always thought, maybe chauvinistically, that I was pretty good at recognizing acute cholecystitis. I wonder about the routine use of these techniques that are costly in time and money for recognition of this disease. Lester F. Williams (Boston, MA): Two comments, one of which Dr. Braasch has made. It seems to me that with acute cholecystitis the issue is the certainty of the diagnosis, that is, when the clinical diagnosis is suspected and one wants to operate, the real question is, “am I operating incorrectly?” In that clinical setting, how commonly does
Volume 141, April 1881
HIDA scan answer the question of whether one should or should not operate? That’s the only real issue. My second area of concern is biliary obstruction. We saw some partial obstructions, both anatomically and by distributibn. The implication was, at least as I heard it, that total biliary obstruction is the critical phenomenon. In fact, that is not true. Sepsis with partial biliary obstruction is an important phenomenon and I am concerned about the implication that because you see some of the isotope in the duodenum you do not have to worry; I do not think that is correct. M. A. Aliapoulios (Worcester, MA): My question is: can your scintigraphic evaluation distinguish gallstones versus metastatic carcinoma in the biliary system? Richard E. Wilson (Boston, MA): Dr. Zeman, I wonder, since pancreatitis is one of the most confusing aspects of your diagnostic technique, if you have used the computed tomographic scan in any of these patients? Our scanners say they can identify stones in the gallbladder, and they certainly should be able to see pancreatic disease as well. Robert K. Zeman (closing): Technetium-99m-HIDA is used to augment the physical examination, not replace it. Up to 20 percent of patients with conditions simulating acute cholecystitis have been subjected to cholecystectomy in various series. As our data reflect, nearly 50 percent of the patients with an initial diagnosis of acute cholecystitis ultimately were proven not to have acute cholecystitis in our series. That is not to say that all of those patients would have been operated on, but cholescintigraphy can aid in sorting our patients who are normal from those with true acute cholecystitis. Technetium-99m-HIDA is an investigational drug at the time of preparation of this manuscript. I am not certain of its ultimate cost. At present, it is planned that the examination will cost slightly more than the routine gallbladder ultrasound examination. The ultrasound and computed tomographic findings in pancreatitis have been well documented in the literature. Correlation of the physical findings, laboratory parameters and noninvasive imaging procedures is essential for proper diagnosis. As our false-positive findings suggest, caution must be exercised in making the diagnosis of acute cholecystitis in the presence of acute pancreatitis. During the initial phase of the study, intravenous cholangiography was performed in approximately the first 35 patients. It became difficult to justify doing cholangiography, as scintigraphy supplied all of the needed information with much less risk to the patient. Ongoing evaluation of the multiple diagnostic tests which are available to evaluate the patient with suspected acute cholecystitis is necessary to determine their relevance and relationships to one another.
451
Robert K. Zeman, MD,* New Haven, Connecticut Morton I. Burrell, MD,* New Haven, Connecticut C. Elton Cahow, MD,+ New Haven, Connecticut Vicente Carlde, MD,* New Haven, Connecticut
The surgeon is faced with a myriad of radiologic tests in the investigation of acute pain in the right upper quadrant of the abdomen, including hepatobiliary scintigraphy, ultrasonography, oral cholecystography and intravenous cholangiography. These radiologic procedures, although usually highly accurate, may at times produce confusing and discordant results, leaving clinical judgment as the sole arbitrator. It is the purpose of this prospective and retrospective analysis of our experience with combined imaging of the gallbladder to clarify the indications, interpretive pitfalls and clinical implications of cholescintigraphy and cholecystosonography in patients with suspected acute cholecystitis. Although the study is not primarily directed toward an appraisal of chronic cholecystitis, acalculous cholecystitis or pancreatitis, these entities will be briefly considered in relation to differential diagnostic criteria. The technetium-99m-labelled N-substituted iminodiacetic acid derivatives were first introduced by Harvey et al [I] in 1975 (Figure 1). Technetium99m-HIDA is representative of this class of compounds and is excreted unconjugated by way of the hepatocytes. When the serum bilirubin level is less than 5 mg/lOO ml, the normal examination reveals rapid visualization of the major bile ducts and gallbladder with egress of activity into the duodenum within 1 hour of injection of the radiopharmaceutical [2,3] (Figure 2A). Related analogues of technetium99m-HIDA (such as technetium-99m-DISIDA) are currently also being evaluated and may allow demonstration of biliary structures despite serum bilirubin levels approaching 20 mg/lOO ml [4]. From the Department of Diagnostic Ftadiilogy,* the oepartment Of suge4y,+ Yale-New Haven Hospital, Yale University School of Medicine: and the Department of Nuclear Medicine,t Hospital of St. Raphael, New Haven, Connecticut. Requests for reprints should be addressed to Robert K. Zeman, MD. Da partment of Diagnostic Radiology, Yale University School of Medicine. 333 Cedar Street, New Haven, Connecticut 08510. Presented at the 61st Annual Meeting of the New EnglandSurgical Society. Portsmouth, New Hampshire, September 26-28, 1980.
446
The concept behind imaging with the iminodiacetic acid compounds is similar to the traditional iodine-131 rose bengal scan. The ability to use multimillicurie doses of technetium-99m as the radiolabel with its short half-life, pure gamma 140 keV energy peak and lower radiation exposure allows much better imaging characteristics than the maximum allowable dose of iodine-131. Technetium99m-HIDA is in phase III trials as an investigational new drug, and widespread commercial availability is anticipated in the near future. Material
and Methods
Beginning in mid-1978, 200 consecutive patients seen at the Yale-New Haven Hospital with abdominal complaints suggestive of acute cholecystitis were included in the study. Patients with jaundice were included if underlying cholelithiasis or cholecystitis was clinically implicated. This group of patients does not include all patients seen at our institution with possible acute cholecystitis as in some cases the patient or the referring physician refused participation in the study. The sample group included 76 men (mean age 51 years) and 124 women (mean age 47). Physical examination, leukocyte count, liver function tests, serum amylase and lipase and plain abdominal roentgenographic findings were recorded before imaging procedures. After obtaining the proper informed consent, imaging procedures were performed. Hepatobiliary scintigraphy with technetium-99m-HIDA and ultrasonography were performed on an emergency basis, usually within 24 hours of each other. Scintigraphic examinations were performed in the fasting state when possible. Ten millicuries (370 MBq) of technetium-99m-HIDA was prepared from a commercial kit (Merck-Frosst Laboratories, Dorval, Quebec, Canada) and injected intravenously. Utilizing a 15 inch Anger scintillation camera (Searle LFOV, Des Plaines, Illinois), scintigrams were obtained serially at 5 minute intervals in the anterior position followed by right lateral, right anterior oblique and left anterior oblique views at 1 hour. Delayed views were obtained as necessary at 2, 4, 6 and 24 hours in an effort to demonstrate gallbladder filling and egress of isotope into the small bowel.
The American Journal of Surgery
Cholescintigraphy
Cholecystokinin was not used as part of these trials. A normal study was one interpreted as showing: (1) good liver uptake with minimal renal activity and visually acceptable clearing of blood pool activity, (2) visualization of gallbladder and bile ducts within 1 hour, and (3) passage of activity into the small bowel within 1 hour. For the purposes of this study, the sole criterion for the scintigraphic diagnosis of acute cholecystitis was nonvisualization of the
COMPOUND
0
MANUFACTURER
CH2COOH NHCOCH2N CH2COOH
Q
acetanalide)-iminodiacetic acid
R
PIPIOA
N. a-(p-isopropyl-
OIETHYL-IDA N. a-(2,6-diethyl-
acetanalide)-iminodiacetic acid
INVESTIGATIONAL STATUS
Merke-Frosst Oorval.Due, Canada
Phase 111 IN0
New England Nuclear North Billerica. Mass.
Phase III IN0
Diagnostic Isotopes Bloomfield. N.J.
Phase III IN0
R
OISOFENIN OISIOA) N. a-2,6,-I diisopropyl
acetanalide)-iminodiacetic acid
in Cholecystitis
gallbladder (Figure 2B). The patients with delayed visualization represent an interesting subpopulation and will be considered further in a subsequent report. Sonographic sector scans of the gallbladder were performed while the patient was fasting when possible utilizing commercially available gray-scale ultrasound equipment (Searle Pho/Sonic or Picker 80L) with a 2.25 or 3.5 mHz transducer. Transverse, oblique, longitudinal and decub-
STRUCTURE
HIOA N, a-(2.6.-dimethylacetanalide)- imlnddiacetic acid
and Ultrasonography
mR
C2H5
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NA
NA
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F@re 1. finlnodkcetk acid c&npouMs and the/r commerciai availability. in the Untted States.
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Figure 2. Technetium-Wm-HIDA scintigrams. A, normal 7 hour scan. The gallbladder (gb) has visualized. There has been signifkant washout of liver activity into the common bfie duct (singe arrowftead) and duodenum (double arrowhead). incidentally noted is bladder activity (b) from urinary excretkn. 6, abnormal I hour scan. The gallbladder has not visualized despite good liver uptake and excretkn into the common bile duct (d) and duodenum (double arrowheads). The open arrow denotes the “cold” gaiibia&krkssa.Biadderactivny(b) is a/w seen.
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Zeman et al
itus scans were performed. Echoes suggesting cholelithiasis, gallbladder size and gallbladder wall thickness were also assessed. Pain on ultrasonically guided palpation of the gallbladder and shadowing opacities that moved with gravity or high level echoes replacing the gallbladder fossa with shadowing were interpreted as consistent with cholelithiasis and diagnostic of acute cholecystitis in this group of patients with signs and symptoms of acute cholecystitis. The remainder of the sonograms were classified as normal or indeterminate. For purposes of data analysis the indeterminate examinations were counted as diagnostic failures in patients who ultimately had acute cholecystitis. Limited study of the liver and pancreas was also performed in selected patients. All imaging procedures were interpreted independently by the appropriate subspecialty services within the Diagnostic Radiology Department. For purposes of analysis, the scintigraphic studies were also retrospectively read by one author (RZ) and analyzed with regard to pitfalls of interpretation and coordination with the sonographic findings.
bladder failed to visualize on scintigraphy. Of those, 42 were proven to have acute cholecystitis and 12 chronic cholecystitis. Of these 12 patients, 7 ultimately underwent cholecystectomy with gallstones found in the cystic duct or ampullary pouch. Seven patients had false-positive technetium-99m-HIDA examinations with a surgically proven normal gallbladder in six. Forty-three patients had proven acute cholecystitis, which was predicted by cholescintigraphy in 42. Two patients in the latter group had
acute acalculous cholecystitis, both successfully predicted by the isotope study. Sonography demonstrated cholelithiasis in only 29 of the 43 patients with acute cholecystitis. On closer inspection of the false-positive scintigrams, four of seven patients with nonvisualization of the gallbladder who had normal gallbladders at surgery had evidence of pancreatic disease with marked hyperamylasemia. There was no sonographic evidence of cholelithiasis in these patients. Of the remaining three patients with false-positive findings, one had eaten just before the examination, most likely producing emptying of the gallbladder, and the other two patients had examinations with obvious interpretive errors (gallbladder activity mistaken for duodenal bulb). The normal HIDA scan was a reliable indicator of the absence of acute cholecystitis. Of 83 patients with visualization of the gallbladder, only 1 had acute cholecystitis. Sixty-one of 83 had normal sonograms, including the single patient with the false-negative HIDA examination. Twenty patients who had nonvisualization of the gallbladder had chronic chole-
Results Of 200 patients originally included in the study group, only 144 had the appropriate clinical and surgical follow-up allowing a definitive final diagnosis. Included in the sample group were 43 patients with acute cholecystitis, 32 patients with chronic cholecystitis and 69 normal subjects. Surgical intervention was carried out in 71 patients with acute and chronic cholecystitis and in 10 patients subsequently proven to have normal gallbladders. The results of the imaging procedures are presented in Tables I and II. In 61 patients the gall-
TABLE I
Flnal Diagnosis, Sclntlgraphlc and Sonographlc Flndlngs In 144 Patlents
Findings on Technetium-99mHIDA Scan Nonvisualization of gallbladder Visualization of oallbladder l
Acute Cholecystitis (43 patients) Findings on Ultrasound Normal Stones Indeterminate
Chronic Cholecystitis (32 patients) Findings on Ultrasound Normal Stones Indeterminate
5’
29
6’
5
4
3
4
0
3
1
0
0
6
13
1
54
1
7
Including one case of acute acalculous cholecystitis.
TABLE II
Flnal Diagnosis, Sclntlgraphlc and Sonographic Flndlngs in 144 Patients Based on lmaglng Procedure Results
Acute Cholecystitis Findings on ssTc-HIDA scan Nonvisualization (61 patients) Visualization (83 patients) Findings on ultrasound Stones (47 patients) Normal (75 patients) Indeterminate (22 patients) l
448
Normal (69 patients) Findings on Ultrasound Normal Stones Indeterminate
Final Diagnosis Chronic Cholecystitis
Normal
42 1
12 20
7 62
29 6’ 6’
17 11 4
1 56 10
Including one case of acute acalculous cholecystitis.
The American Journal of Surgery
Cholescintigraphy
cystitis and cholelithiasis with a patent cystic duct. Thus, while a normal HIDA scan excludes acute cholecystitis, chronic cholecystitis and cholelithiasis may still be present. Sensitivity and specificity calculations were derived from the modified Latin square data in Table I [5]. HIDA had a sensitivity of 98 percent in the detection of acute cholecystitis, but a specificity of only 81 percent for acute cholecystitis in the group with nonvisualization of the gallbladder. Sonography in all patients was only 67 percent sensitive in the detection of acute cholecystitis, but 8’2percent specific. It should be pointed out, however, that the indeterminate sonograms were counted as diagnostic errors because eight of the patients whose studies were in this group were ultimately shown to have acute cholecystitis. In addition, ultrasound was 61 percent sensitive in the detection of cholelithiasis but had 98 percent specificity. By combining criteria, that is, requiring nonvisualization of the gallbladder on HIDA scintigraphy and cholelithiasis on sonography, an overall 98 percent sensitivity in detecting acute cholecystitis is achieved, but with only a 79 percent specificity. While this specificity is somewhat low, it indicates that 79 percent of patients with nonvisualization of the gallbladder on scintigraphy and cholelithiasis on ultrasound will have acute cholecystitis. The remaining 21 percent will have chronic cholecystitis, and no patients should be normal based on our data. Comments The diagnosis of acute cholecystitis has traditionally been based on a constellation of clinical and laboratory studies. This has resulted in diagnostic error rates ranging from 16 percent [6] to 20 percent [71. The desirability of early cholecystectomy in patients with acute cholecystitis remains controversial [8,9], but at our institution early surgery has yielded favorable results. The desirability of early diagnosis to initiate appropriate therapy is supported by clinical experience and common sense, regardless of the ultimate timing of cholecystectomy. The quest for an imaging procedure that accurately and rapidly distinguishes patients with acute cholecystitis from all others dates back to 1954 [IO], when intravenous cholangiography was popularized as a sensitive and specific study for cystic duct obstruction. The procedure was plagued by indeterminate results approaching 40 percent [11,12], particularly when the serum bilirubin level exceeded 2 mg/lOO ml [13]. Significant side effects, hepatorenal toxicity and death resulting from contrast reactions occur up to 8 times more frequently than with intravenous pyelography [14]. Real-time and gray-scale ultrasonography are well established screening procedures for the presence of cholelithiasis [15-211. Results in detecting cholelithiasis using real-time ultrasonography have been comparable to those reported previously with grayVolume
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and Ultrasonography
in Cholecystitis
scale ultrasonography, that is, a sensitivity and specificity of approximately 90 percent [22]. The role of sonography in patients with acute cholecystitis is not as straightforward [23-291. Sonographic demonstration of gallstones is at best inferential evidence of acute cholecystitis in that 10 percent of men and 20 percent of women over 55 years of age have gallstones [30]. Ultrasonography offers no information regarding gallbladder function and cystic duct patency. While some workers propose that increased gallbladder wall thickness or a rim of echolucency is diagnostic of acute cholecystitis [26-28], others dispute this claim [31,32]. Technetium-99m-HIDA cholescintigraphy is the best single test available for the detection of acute cholecystitis. The examination is easily performed as an emergency procedure with acceptable patient radiation exposure and rapid diagnosis, usually within 4 hours. While generally consistent with previous studies in the literature [2,3,33-351, our data raise several important points. The prime importance of cholescintigraphy is in differentiating patients who are normal from those with cholecystitis. As evidenced by its 98 percent sensitivity, a normal HIDA study virtually excludes the diagnosis of acute cholecystitis. Diagnostic work-up of patients with normal findings on scintigraphy should be directed toward other possible causes of the symptoms and not the gallbladder, although incidental chronic cholelithiasis may be present. Failure of the gallbladder to visualize is clearly abnormal, but the specificity attached to this finding in previous studies [2,33-351 could not be confirmed. Four of the seven patients with intrinsically normal gallbladders and failure of visualization on HIDA scintigraphy had evidence of severe acute pancreatitis. Gallbladder distention was noted sonographitally but without evidence of cholelithiasis. Fonseca et al [36] stated previously that the gallbladder visualizes scintigraphically in 87 percent (13 of 15) of patients with acute pancreatitis. Chronic cholecystitis was present in the two cases with nonvisualization. It is difficult to explain this apparent discrepancy among reports, but the degree of bile stasis within the gallbladder in any given case may be the governing factor in determining isotope entrance into the gallbladder [37]. Delayed drainage of isotope into the duodenum may be present and indicate the underlying stasis resulting in gallbladder nonvisualization on scintigraphy [38]. Failure of the gallbladder to fill with isotope also occurred in patients with chronic cholecystitis. Seven of 12 of these patients ultimately were found to have cystic duct or ampullary pouch stones but with gross and histologic evidence of chronic rather than acute cholecystitis. It is uncertain whether this group of patients had a functional cystic duct obstruction at the time of scintigraphy or an actual anatomic obstruction from a cystic duct stone which was impacted and subsequently passed anterograde or 449
Zeman et al
retrograde. Since ending the acquisition of cases for this study we have seen two patients with known cholelithiasis who had scintigraphically nonvisualized gallbladders during acuteattacks of biliary colic with subseauent visualization on a follow-un examination soon after recovery. Our sonographic data must be assessed with caution. Studies in which “sludge” or “debris” was seen within the gallbladder without opacities meeting the criteria of cholelithiasis were called indeterminate. In calculating sensitivity data, these indeterminate studies in which the patient ultimately turned out to have stones were included as false-negative examinations, resulting in a sensitivity of 67 percent. If the indeterminate examinations were excluded, an 82 percent sensitivity would result. Most of these examinations were performed as emergency procedures in acutely ill patients in whom the duration of fasting was uncertain. Thus, the lack of sensitivity can be justified with respect to previous reports in the literature regarding detection of cholelithiasis. These data also partially refute the contention that sonography as an emergency procedure accurately distinguishes acute cholecystitis from the diseases that mimic it. In addition, ultrasound was not specific in the diagnosis of acute cholecystitis (82 percent), but highly specific in the diagnosis of cholelithiasis; that is, if stones were detected sonographically, the chances of cholelithiasis were exceedingly great (98 percent). This may reflect our institution’s requirement that strict criteria be met for the diagnosis of gallstones. Summary When faced with a patient with possible acute cholecystitis, technetium-99m-HIDA scintigraphy should be the primary diagnostic procedure performed. If scintigraphy reveals a normal gallbladder, acute cholecystitis is excluded. If the scintigram fails to visualize the gallbladder, ultrasonography is deemed advisable to exclude potential false-positive scintigrams and confirm the presence of cholelithiasis. Acknowledgment: We acknowledge the assistance of Sandra Sudac, Thomas McCarthy and Ann Curley in the preparation of this report.
References 1. Harvey E. Loberg M. Cooper M. esmTc-HIDA, a new radiopharmaceutical for hepatobiliary imaging (abstr). J Nucl Med 1975;16:533. 2. Weissman HS, Frank MS, Bernstein LH, Freeman L. Rapid and accurate diagnosis of acute cholecystitis with ss’rV~IDA cholescintigraphy. AJR 1979;132:523-8. 3. Rosenthal1 L, Shaffer EA, Lisbona R, Pare P. Diagnosis of hepatobiliary disease by eamT~-HIDA cholescintigraphy. Radiology 1978; 1261467-74. 4. Green A, Rosenberg N, Sheahan M. Multicenter triat of Tcgem Disofenin: a new hepatobiliary agent for imaging jaundiced and non-jaundiced patients (abstr). J Nucl Med 1980;21:
450
5.
18. McNeil BJ, Keeler E. Adelstein SJ. Primer on certain elements of medical decision making. N Engl J Med 1975;293:21 l* V.
6. Essenhigh DM. Management of acute cholecystitis. Br J Surg 1966;53:1032-8. 7. Halasz NA. Counterfeit cholecystitis. A common diagnostic dilemma. Am J Surg 1975;130:189-92, 8. Cole WH. Gallbladder disease. Surg Clin North Am 197858: 917-92. 9. Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by early and delayed surgery. A controlled clinical trial. Stand J Gastroenterol 1978;13:673-8. 10. Glenn F, Evans J. Hill M. McClenahan J. Intravenous cholangiography. Am J Surg 1954;140:600-14. 11. Johnson HC, McLaren JR, Weens HS. Intravenous cholangiography in the differential diagnosis of acute cholecystitis. Radiology 1960;74:790-7. 12. Harrington OB, Beall AC, Noon G, DeBakey ME. Intravenous cholangiography in acute cholecystitis. Arch Surg 1964; 88:585-g. 13. Wise RE. Intravenous cholangiography. Springfield, IL: Charles C Thomas, 1962. 14. Ansell G. Adverse reactions to contrast agents. Invest Radio1 1970;5:374-84. 15. Goldberg RB, Harris K. Brucker W. Ultrasonic and radiographic cholecystography: a comparison. Radiology 1974: 11: 405-9. 16. Leopold G, Amberg J, Gosink BB, Mittelstaedt C. Gray scale ultrasonic cholecystography:a comparison with conventional radiographic techniques. Radiology 1975;121:445-8. 17. Bartrum RJ Jr, Crow HI, Foote SR. Ultrasonic and radiographic cholecystography. N Engl J Med 1977;296:538-41. 18. Crade M, Taylor KJW, Rosenfield AT, deGraff CS, Minihan P. Swgical and pathologic correlation of cholecystosonography and cholecystography. AJR 1978;131:227-9. 19. Detweiler RP. Kim DS, Longerbeam JK. Ultrasonography and oral cholecystography. A comparison of their use in the diagnosis of gallbladder disease. Arch Surg 1980;115: 1096-8. 20. McIntosh DMF, Penney HF. Gray scale ultrasonography as a screening procedure in the detection of gallbladder disease. Radiology 1980; 136:725-7. 21. Cooperberg PL, Pon MS, Wong P, Stoller JL, Burhenne HJ. Real-time high resolution uttrasoundin the detection of biliary calculi. Radiology 1979;131:789-90. 22. Krook PM, Allen FH, Bush WH, Malmer G. MacLean MD. Comparison of real-time cholecystosonography and oral cholecystography. Radiology 1980; 135: 145-8. 23. Karp W, Herlin P, Holmin T, Owman T. Infusiontomography and ultrasonography of the gallbladder in the diagnosis of acute cholecystitis. Gastrointest Radio1 1979;4:253-61. 24. Bergman AB, Neiman HL. Kraut B. Ultrasonographic evaluation of pericholecystic abscesses. AJR 1979;132:201-3. 25. Stoller JL, Cooperberg PL, Simpson WM. Diagnostic ultrasonography in acute cholecystitis. Can J Surg 1979;22: 374-6. 26. Marchal GJF. Casaer M, Baert AL, Goddeeris PG, Kerremans R, Fevery J. Gallbladder wall sonolucency in acute cholecystitis. Radiology 1979;133:429-33. 27. Kane RA. Ultrasonographic diagnosis of gangrenous cholecystitis and empyema of the gallbladder. Radiology 1980; 134:1,91-4. 28. Ulreich S, Foster KW, Stiers SA, Rosenfield AT. Acute cholecystitis. Comparison of ultrasound and intravenous cholangiography. Arch Surg 1980; 115: 158-60. 29. Sherman M, Rails PW. Quinn M, Halls J, Keats J. Intravenous cholangiography and sonography in acute cholecystitis: - prospective evaluation. AJR 1986;135:31 l-3. _ 30. Friedman DK. Kannel WB, Dawber TR. Eoidemioloav of aallbladder disease: observations in Framingham-St&. J Chronic Dis 1966;273-92.
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Cholescintigraphy and Ultrasonography in Cholecystitis
31. Mindell HJ, Ring A. Gallbladder wall thickening: ultrasonic 32. 33.
34.
35.
36.
37. 38.
findings. Radioloav 1979:133:699-701. Crade My Taylor KJ$ Viscomi GN. Need for care in assessing gallbladder wall thickening. AJR 1960;135:423-4. Fonseca C, Greenberg D, Rosenthal1 L, Arzoumanian A. Assessment of the utility of gallbladder imaging with OomTcHIDA. Clin Nucl Med 1978;3:437-41. Pare P, Shaffer EA, Rosenthal1 L. Nonvisualization of the gallbladder by OOmTc-HIDA cholescintigraphy as evidence of cholecystitis. Can Med Assoc J 1978;l l&384-6. Cheng TM, Davis MA, Seltzer SE, et al. Evaluation of hepatobiliary imaging by radionuclide scintigraphy, ultrasonography, and contrast cholangiography. Radiology 1979; 133:7617. Fonseca C, Greenberg D, Rosenthal1L, Arzoumanian A, Lisbona R. ggmT~-IDA imaging in the differential diagnosis of acute cholecystitis and acute pancreatitis. Radiology 1979:130: 525-7. Rao BK, Lieberman LM. Bile layering: a cause for false-positive cholescintiscans. AJR 1980; 134: 125 l-3. Zeman RK, Segal HB, Caride V. gg”‘Tc-HIDA cholescintigraphy: the distended photon deficient gallbladder. J Nucl Med 1981;22:39-41.
Discussion Mary Keohane (West Haven, CT): Thank you for the opportunity to review this excellent paper. We have, in our institution, conducted stage III clinical trials on HIDA scanning for the last 2 years, and our findings are very similar to those in the present study. There are three points of practical value to be taken from this paper. (1) When HIDA scanning and ultrasound are used as complementary studies, their combined accuracy is significantly higher than the accuracy of either method used alone. (2) When ultrasound is positive for stones and the gallbladder is not visualized on HIDA scanning, 79 percent of patients have acute cholecystitis and 21 percent have chronic cholecystitis with stones. (3) Acute cholecystitis can virtually be excluded in any patient in whom ultrasound is negative for stones and the gallbladder visualizes on the HIDA scan. John W. Braasch (Boston, MA): At considerable risk in showing my age, I would like to make one comment about this study. I would have liked to see another column in which evaluation of a history and physical examination were done. I have always thought, maybe chauvinistically, that I was pretty good at recognizing acute cholecystitis. I wonder about the routine use of these techniques that are costly in time and money for recognition of this disease. Lester F. Williams (Boston, MA): Two comments, one of which Dr. Braasch has made. It seems to me that with acute cholecystitis the issue is the certainty of the diagnosis, that is, when the clinical diagnosis is suspected and one wants to operate, the real question is, “am I operating incorrectly?” In that clinical setting, how commonly does
Volume 141, April 1881
HIDA scan answer the question of whether one should or should not operate? That’s the only real issue. My second area of concern is biliary obstruction. We saw some partial obstructions, both anatomically and by distributibn. The implication was, at least as I heard it, that total biliary obstruction is the critical phenomenon. In fact, that is not true. Sepsis with partial biliary obstruction is an important phenomenon and I am concerned about the implication that because you see some of the isotope in the duodenum you do not have to worry; I do not think that is correct. M. A. Aliapoulios (Worcester, MA): My question is: can your scintigraphic evaluation distinguish gallstones versus metastatic carcinoma in the biliary system? Richard E. Wilson (Boston, MA): Dr. Zeman, I wonder, since pancreatitis is one of the most confusing aspects of your diagnostic technique, if you have used the computed tomographic scan in any of these patients? Our scanners say they can identify stones in the gallbladder, and they certainly should be able to see pancreatic disease as well. Robert K. Zeman (closing): Technetium-99m-HIDA is used to augment the physical examination, not replace it. Up to 20 percent of patients with conditions simulating acute cholecystitis have been subjected to cholecystectomy in various series. As our data reflect, nearly 50 percent of the patients with an initial diagnosis of acute cholecystitis ultimately were proven not to have acute cholecystitis in our series. That is not to say that all of those patients would have been operated on, but cholescintigraphy can aid in sorting our patients who are normal from those with true acute cholecystitis. Technetium-99m-HIDA is an investigational drug at the time of preparation of this manuscript. I am not certain of its ultimate cost. At present, it is planned that the examination will cost slightly more than the routine gallbladder ultrasound examination. The ultrasound and computed tomographic findings in pancreatitis have been well documented in the literature. Correlation of the physical findings, laboratory parameters and noninvasive imaging procedures is essential for proper diagnosis. As our false-positive findings suggest, caution must be exercised in making the diagnosis of acute cholecystitis in the presence of acute pancreatitis. During the initial phase of the study, intravenous cholangiography was performed in approximately the first 35 patients. It became difficult to justify doing cholangiography, as scintigraphy supplied all of the needed information with much less risk to the patient. Ongoing evaluation of the multiple diagnostic tests which are available to evaluate the patient with suspected acute cholecystitis is necessary to determine their relevance and relationships to one another.
451