Utility and Accuracy of Ultrasonically Measured Gallbladder Wall as a Diagnostic Criteria in Biliary Tract Disease EDWIN A. DEITCH, M.D.

Biliary tract sonography has achieved wide acceptance as a screening test for chronic calculous disease. However, the clinical usefullness of biliary sonography is limited by the inability of this test to identify patients with acalculous cholecystitis or to separate patients with calculous cholecystitis from those with asymptomatic calculi. A prospective blinded study of 106 patients undergoing cholecystectomy was performed to determine if, cholecystosonography could visualize the gallbladder wall accurately and to evaluate gallbladder wall thickening as a predictor of disease. Of these patients, 88 had a sonographically visible gallbladder wall and in 95% o f the patients the ultrasonic and direct surgical measurements o f the gallbladder wall agreed within I mm. To determine the sonographic size range o f gallbladder wall thickness in the normal population, the width of the gallbladder wall in the fasting state was measured in 100 patients without biliary tract disease. One percent of the normal population had thickened gallbladder walls, in contrast to 96% o f the patients with acute calculous or acalculous cholecystitis. Gallbladder wall thickness appears to be an accurate noninvasive technique for diagnosing patients with acute calculous and acalculous cholecystitis in the absence o f other entities which thicken the gallbladder wall such as ascites and hypoproteinemic states.

Over the past 20 years the role of ultrasound has evolved from a largely research technique into a basic clinical diagnostic tool. Cholecystosonography, using modern gray scale equipment and the expanded diagnostic criteria of Crow et al (1) for calculous disease, has an overall diagnostic accuracy of 95% and compares favorably with oral cholecystography as a diagnostic test (2). However, in spite of these advancements, biliary tract sonography still has some major limitations, specifically the inability to diagnose noncalculous disease, as

Manuscript received November 24, 1980; revised manuscript received February 2, 1981; accepted February 10, 1981. From the Louisiana State University Medical Center, Shreveport, Louisiana. Address for reprint requests: Dr. Edwin A. Deitch, Department of Surgery, L.S.U. Medical Center, P.O. Box 33932, Shreveport, Louisiana 71130.

686

well as the inability to determine in the individual patient whether disease is active or quiescent. To investigate these diagnostic limitations, a study utilizing the ultrasonically measured gallbladder wall as an independent diagnostic criteria for biliary tract disease was initiated. Encouraging preliminary results of this study have previously been reported (3, 4). The purpose of this report is to present the results of a prospective blinded study of the utility and accuracy of gallbladder wall thickness as a predictor of disease in 106 patients with cholecystitis.

MATERIALS AND METHODS

One hundred six consecutive patients operated on at the U.S. Public Health Service Hospital in Seattle from November 1978 through March 1980, who had preoperDigestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

0163-2116/81/0800-0686503.00/19 1981DigestiveDiseaseSystems, Inc.

B I L I A R Y TRACT SONOGRAPHY

Fig 1. Normal gallbladder wall, 2' mm thick (arrow); gb = gallbladder; k = kidney; 1-cm scale between dots.

ative cholecystosonograms, form the basis of this report. All biliary sonograms were performed using a Unirad digital gray scale scanner with either a 3.5 MHz shortfocus, 3.5 MHz long-focus, or 5.0 MHz long-focus transducer. The technique of scanning has previously been reported in detail (3). To review briefly, in the fasting or NPO state using mineral oil as a coupling agent, scans were obtained in longitudinal, subcostal oblique and decubitus positions. Once the gallbladder was identified, patients were placed in the left lateral decubitus position to facilitate identification of the gallbladder wall and document movement of intraluminal contents. Gravity displacement of the intraluminal contents towards the cystic duct was performed to reduce possible distortion of gallbladder wall thickness measurements by biliary sludge or gravel. Once the gallbladder wall had been adequately visualized sonographically, measurements of the free peritoneal surface were preferentially recorded in the region of the fundus (Figures 1 and 2). Measurements were recorded to the nearest 0.5 mm. In cases where the wall thickness was not uniform, representative measurements were taken and the largest measurement recorded. In a blinded fashion, similar measurements were performed at surgery on the excised gallbladder, which had been opened along the peritoneal surface from the fundus to the cystic duct. Using ophthalmology calipers graded Digestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

into millimeters, the thickest area in the fundic region of the gallbladder was measured. The control population consisted of fasting patients with normal oral cholecystograms or patients who had undergone abdominal or pelvic sonography for n0ngastrointestinal complaints, in whom the gallbladder wall could be sonographically visualized. Patients with ascites or acute abdominal complaints were excluded, as well as patients with recent or remote symptoms consistent with biliary tract disease. If asymptomatic cholelithiasis was found, these patients also were excluded. Slightly less than half the patients who met these criteria had a gallbladder wall that could be distinctly identified. Only these patients with a distinct and measurable gallbladder wall were included in the control population. On the basis of clinical presentation, hospital course, and operative findings, patients were divided into two groups: patients with acute or chronic cholecystitis. Patients with asymptomatic cholelithiasis were placed i n the chronic group, as well as patients with biliary colic, even if nasogastric suctioning and intravenous fluids were temporarily required. Histologic criteria were not used to distinguish between the acute and chronic groups because of their poor discriminating ability (5). The correlation and relationships between the histologic appearance of the gallbladder wall and the operative appearance and

687

DEITCH

~~iii!~~'84 !iil~il

Fig 2. Gallbladder wall, 5 mm thick. Arrow illustrates thickness of gallbladder wall in patient with acalculous cholecystitis.

clinical presentation of these patients will be the subject of a separate report. Lastly, patient were divided into calculous and acalculous groups. This study was approved by Human Subjects Committee of the University of Washington.

RESULTS One hundred six consecutive patients operated on over a 17-month period for acute or chronic cholecystitis were studied prospectively. Of these patients, 103 had both preoperative sonograms performed and direct measurements of the gallbladder wall taken at surgery, and they form the basis of the study group. Two patients did not have their gallbladder walls measured at surgery, one patient did not have a preoperative sonogram, and these were excluded from analysis. Of the 103 patients, 88 had sonographically visible gallbladder walls. In 95% of these patients, the measurements agreed within 1 mm of independent and blind measurements made at surgery (Table 1). Six of the 15 patients whose gallbladder walls were not sonographically visible had technically indequate studies. Eight of the

688

remaining nine patients had small, shrunken, stonefilled gallbladders in which the shadows cast by the calculi obscured the gallbladder wall (Figure 3). One patient had a pericholecystic abscess contiguous with the gallbladder which obscured the gallbladder wall. Separating patients by the thicknesses of their gallbladder walls, a clear distinction between the control and surgical groups could be seen (Table 2). Of the control group, 93% had thin walls (2.5 mm or less), 6% had intermediate walls (3.0 mm), while only 1% had thick walls (3.5 mm or thicker). In contrast 18% of the surgical patients had thin walls, 24% had intermediate walls, and 58% had thick walls. There was minimal overlap between normal and diseased gallbladders in the thick-walled group, but there was considerable overlap in the thin and intermediate walled groups. If the surgical group was further divided into patients with acute versus chronic cholecystitis, then only in the chronic group was there any significant overlap with the control population. In the acute cholecystitis group, 22 of 23 patients (94.5%) had thick gallbladder walls versus 1% of the control population. Seven of these Digestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

BILIARY TRACT SONOGRAPHY TABLE 1. CORRELATION BETWEEN SURGICAL AND ULTRASONIC MEASUREMENTS OF GALLBLADDER WALL THICKNESS IN 88 PATIENTS Number o f patients

Difference between surgical and ultrasonic measurements (mm)

Percentage o f total (%)

35 19 30 4

Same 0.5 1.0 1.5

40 21.5 (61.5)* 34 (95.5) 4.5 (100)

*Cumulative percentage of population in parenthesis.

23 patients had acute acalculous ch01ecystitis. Six of these patients had thick gallbladder walls, and one patient had an intermediately thickened wall. The surgical measurements of 15 patients whose gallbladder walls were not sonographically visible were not significantly different from 88 patients whose walls were identified. Thirteen of these patients had chronic cholecystitis, and the distribution of their wall thicknesses were as follows: 4, thin; 3, intermediate; and 6, thick-walled. The remaining two patients had acute cholecystitis, and both had thick gallbladder walls.

In order to evaluate the clinical usefulness of gallbladder wall thickness as an independent diagnostic criteria, its sensitivity and specificity were determined (Table 3). The specificity of the test was 99% if a 3-mm-thick wall was considered the upper limit of normal. In contrast, if a 3-mm gallbladder wall was considered diseased, then the specificity decreased to 93%; however, the sensitivity increased from 45% to 75% in the subgroup of patients with chronic cholecystitis and from 94.5% to 100% in patients with acute cholecystitis. Other variables evaluated to determine their relationship to gallbladder wall thickness were the presence or absence of infection, pancreatitis, or elevated liver function tests. Of the total surgical subgroup, 22% had positive gallbladder wall or bile cultures, as did 10% of patients with chronic cholecystitis and 60% of patients with acute cholecystitis group (72% acalculous, 55% calculous). Patients with positive cultures did not have thicker walls than patients with sterile cultures in either the acute or chronic groups. Twenty-six percent of patients had either abnormal liver function tests (bilirubin, SGPT, SGOT, or alkaline phosphatase) or in-

Fig. 3. Small, shrunken gallbladder filled with calculi (c). Shad-owing (sh) of. calculi obscure gallbladder wall. Digestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

689

DEITCH TABLE 2. RELATIONSHIPOF THICKNESSOF GALLBLADDERWALL TO PRESENCEOR ABSENCE OF DISEASE Gallbladder wall thickness (ram)

Control

Acute cholecystitis

Chronic cholecystitis

2.5 (thin) 3.0 (intermediate) 3.5 (thick)

93 (93%) 6 (6%) 1 (1%)

0 1 22

16 (25%) 20 (30%) 29 (45%)

creased serum amylase preoperatively, as did 17% of the chronic group and 56% of the acute group. No difference in wall thickness was found between patients with acute cholecystitis on the basis of serum chemistries, although 70% of the chronic cholecystitis group with elevated chemistries had gallbladder walls in the thick range versus 40% with normal chemistries. DISCUSSION Biliary tract sonography has proven to be a reliable and accurate diagnostic test for biliary tract disease; however, the determination of disease has been based primarily on the echogenic properties of calculi contained within the gallbladder. This accounts for two major limitations of biliary sonography, specifically an inability to diagnose acalculous cholecystitis and an inability in the individual patient to determine whether acute or chronic cholecystitis was present. A prospective blinded study of gallbladder wall thickness was begun to determine the relationship of gallbladder wall thickness to disease and to determine its clinical limitations as an independent diagnostiC criteria. In 1978, Marchal et al (6) reported two patients with sonographical!y visualized gallbladder walls that were thickened and described this thickening as a new diagnostic sign. Handler (7), in 1979, reported on a series of 117 patients in whom an attempt was made to visualize songraphicaUy the TABLE 3. ACCURACYOF GALLBLADDERWALL THICKNESSAS A PREDICTOROF DISEASE Thickness (mm)

Specificity* Sensitivity? (total group) Chronic cholecystitis Acute cholecystitis Overall accuracy

3.0

3.5

93/100 (93%) 72/88 (82%) 49/65 (75%) 22/22 (100%) 165/188 (88%)

99/100 (99%) 51/88 (58%) 29/65 (45%) 2 2 / 2 3 (94.5%) 150/188(80%)

*Specificity = (true test negative/all negatives in population). ?Sensitivity = (true test positives/all positives in population).

690

gallbladder wall. Forty of these patients were considered normal, and ten had visible gallbladder walls which measured 2 mm or less in thickness. Of the abnormal group, 17 of 77 patients (22%), had sonographically visualized gallbladder walls which ranged in thickness from 3 to 10 mm. Nine of these 17 patients had surgical verification of their ultrasonic findings, seven with calculi and two with acalculous cholecystitis. On the basis of this series, Handler considered 3 mm to be the upper limit of normal for the ultrasonically visualized gallbladder wall. On the other hand, Lee et al (8) did not find cholecystosonography accurate in detecting thickened gallbladder walls. In his retrospective study just 39% of 23 surgical specimens with pathologically thickened gallbladder walls could be identified sonographically. Therefore, he stated that ultrasound was a relatively insensitive method for visualizing the gallbladder wall. The criticism leveled by Lee et al, at the inability of ultrasound to visualize the gallbladder wall consistently, does not appear to be warranted based on a retrospective study since, unless the gallbladder wall is actively searched for sonographically, it will not be consistently identified. Adequate visualization of the gallbladder wall requires a conscious effort on the part of the technician or radiologist performing the procedure. This is especially true in patients with multiple calculi, since the shadowing produced by these calculi may obscure the gallbladder wall (Figure 3). Only by perserverance and modifying the technique of examination to fit the individual being examined can the gallbladder wall be consistently visualized. The overall visualization rate of patients in the surgical group in the current study was 86%. During the early phase of the study only 75% of the examinations were technically adequate, but as the technician gained experience, her ability to visualize the gallbladder wall increased considerably and technically inadequate examinations during the last half of this study were less than 5%. Although the above review of the literature does not show a consensus of opinion on the ability of ultrasound to visualize Digestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

BILIARY TRACT SONOGRAPHY the gallbladder wall, these differing opinions were based on only 34 patients in three studies who had their ultrasonic predictions verified surgically. Before gallbladder wall thickness can be accepted as an independent diagnostic criteria, it must satisfy two conditions. First, ultrasound must be able to accurately measure the gallbladder wall and, second, a specific measure of the gallbladder wall thickness should reliably separate normal from diseased gallbladders. In the present study, 95% of patients with sonographically visible gallbladder walls had ultrasonic and surgical measurements that agreed within 1 mm (Table 1). It therefore appeared that cholecystosonography could accurately and reliably measure the gallbladder wall noninvasively. The second question remained, could the normal gallbladder be distinguished from the diseased gallbladder solely on the basis of a thickened wall? To answer this question the sensitivity (ability to identify patients with disease) and specificity (ability to identify patients without disease) of this test was determined (Table 3). For simplicity a gallbladder wall less than 3.0 mm was considered thin, at 3.0 mm it was considered intermediate, and if larger than 3.0 mm, thick. A thick gallbladder wall (3.5 mm or more) had a specificity of 99% and a sensitivity of 94.5% in diagnosing acute cholecystitis. The sensitivity could have been increased to 100% if the intermediately thick gallbladder walls were considered diseased; however, commensurate with this increase in sensitivity a concomitant decrease in specificity would have occurred (to 93%). From these data it appeared that the presence of a thickened or intermediate gallbladder wall could accurately separate patients with acute cholecystitis from the normal patient population, although some overlap between patients with acute and chornic cholecystitis was found. The standard contrast radiographic tests cannot reliably diagnose acute cholecystitis, especially if acalculous; however, sonography, by noninvasively visualizing the gallbladder wall and documenting the presence of thickening, can identify patients with active disease. Therefore, using gallbladder wall thickness as a diagnostic criteria, patients with acute acalculous cholecystitis could be reliably diagnosed. This is critically important in postoperative and trauma patients in whom acute acalculous cholecystitis is often occult and frequently lethal. Mortality rates as high as 70% (9) have been reported in this disease. This high mortality rate reflects the frequent absence of local signs and symptoms Digestive Diseases and Sciences, Vol. 26, No. 8 (August ]981)

prior to gallbladder perforation and the development of peritonitis. Indeed systemic symptoms predominate over local complaints in over 75% of the patients studied. Currently, once the diagnosis of postoperative or posttraumatic acalculous cholecystitis is suspected, the standard diagnostic test is an exploratory laparotomy (9). The use of cholecystosonography in this patient population could identify patients with cholecystitis even in the absence of calculi by visualizing a thickened gallbladder wall. If the gallbladder wall is not thickened, even if calculi are present, exploratory laparotomy might be avoided. A second potential clinical use of gallbladder wall thickness would be to evaluate the patient with known calculi who is a poor operative risk or in whom medical jaundice is clinically suspected in spite of the presence of gallstones. Patients with probable alcoholic hepatitis or pancreatitis and concomitant gallstones are a common clinical example of this latter problem. In both clinical situations, the presence of a thin gallbladder wall would give support to the nonoperative management of these patients. On the other hand, if the gallbladder wall was thickened, then acute cholecystitis would be more likely and surgical consultation could be obtained. Radionuclide imaging of the hepatobiliary system with technetium-based scintiscans has recently been employed in the differential diagnosis of jaundice (10) as well as in the diagnosis of acute cholecystitis (11). Radionuclide imaging has not proved superior to sonography in the differential diagnosis of jaundice since the overall accuracy of this screening test is just 84%, which is inferior to results obtained with sonography (10). Thus in the jaundiced patient with abdominal pain I feel that sonography should be the initial diagnostic test performed. Szlabick et al (11) have recently reported a retrospective study of 271 patients with acute abdominal pain who had hepatobiliary scanning performed to diagnose or exclude acute cholecystitis. The authors defined an abnormal scan as one in which the gallbladder failed to visualize within 1 hr of injection of the radionuclide while the proximal gastrointestinal tract and biliary tree were opacified and patent. In 91% of their patient population the test could be diagnostically interpreted and 98.7% of the patients with an abnormal scan who underwent surgery had the presence of biliary tract disease verified. However, 9% of their patient population had diagnostically indeterminate examina-

691

DEITCH tions, and 60% of this group had surgically verified acute cholecystitis. The authors concluded that ultrasonography should be used in this subset of patients with indeterminate scintiscans to determine if acute cholecystitis is present or not. Although the results of this study are very encouraging, overall I believe ultrasonography should be the initial diagnostic test performed in patients with suspected acute cholecystitis. The reasons for this are several. First, sonography is a purely anatomic examination which is not affected by hepatic reserve and is not dependent on hepatic excretion of a contrast agent. Thus sonography can be accurately performed in patients with minimal liver reserve and/or significant jaundice. Hepatobiliary scanning requires the injection of a radionuclide plus multiple sequential examinations to yield a diagnostic study. Sonography, in contrast, requires no injectate and can be completed at the initial examination. Also, if the biliary tract is sonographically normal, other contiguous abdominal organs such as the liver and pancreas can be examined. In contrast to patients with acute cholecystitis, less than half the patients with chronic cholecystitis were correctly diagnosed using a thick (3.5 mm or wider) gallbladder wall as a diagnostic criteria. The majority of these patients had calculi which could be visualized and documenting that the gallbladder wall was thickened was not clinically important in most patients. Although in patients with suspected chronic acalculous cholecystitis, visualization of gallbladder wall might be a helpful diagnostic test, only three patients in this series had chronic acalculous cholecystitis. None had thick gallbladder walls, although two were in the intermediate range; the third was thin. If the intermediately thick gallbladder wall was considered diseased, then the specificity of this test would have been 93% with an overall sensitivity for all patients with chronic cholecystitis, calculous and acalculous, of 75%. Two of the three patients with chronic acalculous cholecystitis would have been correctly diagnosed using 3.0 mm as a diagnostic criteria. Thus, it appears reasonable to conclude that an intermediately thickened or thick gallbladder wall, combined with a clinical picture of chronic cholecystitis, would reliably indicate patients who might benefit from elective cholecystectomy, even in the absence of calculi. In fact, the problem of diagnosing chronic acalculous cholecystitis may become more difficult with the widespread use of biliary ultrasound, ie, the diagnosis of chronic acalculous cholecystitis has been based on

692

nonvisualization of the gallbladder after a doubledose oral cholecystogram in patients with biliary tract symptoms. Yet, nonvisualization of the gallbladder has a false positive rate of 17% (12), and therefore many investigators recommend the routine use of ultrasound to verify the presence of biliary tract disease in patients with nonvisualizing oral cholecystograms preoperatively to avoid unnecessary surgery (2). Thus, in patients with chronic acalculous cholecystitis this ultrasonic second opinion might only muddy the water rather than clear it. In this situation, the presence or absence of a thickened gallbladder wall might help in managing the individual patient. Other variables besides the clinical diagnosis of acute or chronic cholecystitis were evaluated to determine their relationship to gallbladder wall thickness. These variables included the presence or absence of infected bile, and whether liver chemistries or serum amylase were normal or elevated on admission. In the group of patients with acute cholecystitis, none of these variable were important. In the chronic cholecystitis group, 70% of patients who had elevated serum amylase or liver chemistries had thick gallbladder walls compared to only 40% of patients with normal serum chemistries. Clinically, the significance of these findings is still under study. There are limitations with using gallbladder wall thickness as a diagnostic test. First, there was a 14% nondiagnostic rate. Six of these 15 nondiagnostic tests were purely technical failures where the gallbladder wall was obscured by intestinal gas or contiguous structures. Eight of the remaining nine patients with nondiagnostic tests had small, shrunken, stone-filled gallbladders while one patient had a pericholecystic abscess that was contiguous with the gallbladder wall and obscured it. Yet in 13 of these 15 patients the sonographic study was adequate to diagnose cholelithiasis. Secondly, there are several entities that can sonographically mimic a thickened gallbladder wall. These include biliary sludge, cholesterolosis, and small nonshadowing stones or gravel. Therefore, the technique of performing the examination is critical, especially the maneuver of placing the patient in the left lateral decubitus position to allow sludge and gravel to move dependently with gravity. Only a carefully performed sonogram will furnish a true picture of the gallbladder wall. Other factors than primary disease of the gallbladder can result in apparent ultrasonic thickening of the gallbladder wall. These Digestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

BILIARY TRACT SONOGRAPHY factors i n c l u d e a s c i t e s (2) or the p r e s e n c e of h y p o a l b u m i n e m i a , e s p e c i a l l y in p a t i e n t s w i t h a l c o h o l i c liver d i s e a s e (13).

REFERENCES 1. Crow HC, Bartrum RJ, Foote SR: Expanded criteria for the ultrasonic diagnosis of gallstones. J Clin Ultrasound 4:289293, 1976 2. Deitch EA, Engel JM: Ultrasound in elective biliary tract surgery. Am J Surg 140:277-283, 1980 3. Engel JM, Deitch EA, Sikkema WW: Gallbladder wall thickness; ultrasonic accuracy and relationship to disease. Am J Radiol 134:907-909, 1980 4. Deitch EA, Engel JM: Acute acalculous cholecystitis; ultrasonic diagnosis. Am J Surg August 1981 5. Andrews E: Pathologic changes of diseased gallbladders, a new classification. Arch Surg 31:767-793, 1935 6. Marchal G, Crolla D, Baurt AL, Fevery J, Kerremanns R:

Digestive Diseases and Sciences, Vol. 26, No. 8 (August 1981)

Gallbladder wall thickening; a new sign of gallbladder disease visualized by gray scale cholecystosonography. J Clin Ultrasound 6:177-179, 1978 7. Handler SJ: Ultrasound of gallbladder wall thickening and its relation to cholecystitis. Am J Radiol 132:581-585, 1979 8. Lee SK, Nelson GL, Koehler RE, Stanley RJ: Cholecystosonography; accuracy pitfalls and unusual findings. Am J Surg 129:223-228, 1980 9. Dupriest RW, Khanesja SC, Cowley RA: Acute cholecystitis complicating trauma. Ann Surg 189:84-89, 1979 10. Fonseca C, Rosenthall L, Greenberg D, Hernandez M, ArzoumanianA: Differential diagnosis of jaundice by 99mTCIDA hepatobiliary imaging. Clin Nucl Med 4:135-142, 1979 11. Szlabick RE, Catto JA, Fink-BennettD, Ventura V: Hepatobiliary scanning in the diagnosis of acute cholecystitis. Arch Surg 115:540-544, 1980. 12. Mujahed Z, Evans JA, Whales PJ: The nonopacified gallbladder on oral cholecystography. Radiology 112:1-4, 1974 13. Fiske CE, Liang FC, Brown TW: Ultrasonographic evidence of gallbladder wall thickening in association with hypoalbuminemia. Radiology 135:713-716, 1980.

693