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Acta Radiologica 43 (2002) 7176 Copyright C Acta Radiologica 2002

Printed in Denmark All rights reservedA C T A R A D I O L O G I C A

ISSN 0284-1851

ACCURACY OF CT IN LOCAL STAGING OF

GALLBLADDER CARCINOMA

B. S. K1, H. K. H1, I.-J. L1, J. H. K1, H. W. E1, I. Y. B1, A. Y. K1, T. K. K1,M. H. K2, S. K. L2 and W. K3

Departments of 1Diagnostic Radiology, 2Internal Medicine and 3Biostatistics and Research, University of Ulsan, Asan Medical

Center, Seoul, Korea.

Abstract

Purpose: To evaluate the accuracy of CT for staging gallbladder cancers, Key words: Gallbladder, neoplasms;especially the T-factor of the TNM staging system. CT.

Material and Methods: CT investigations of 100 patients with surgicallyproven gallbladder cancers were retrospectively analyzed. Dynamic helical CT Correspondence: Hyun Kwon Ha,was performed in 16 patients and conventional CT in the remaining 84. On Department of DiagnosticCT, three radiologists attempted tumor staging for these patients; the majority Radiology, University of Ulsan, Asanopinion was used for final decision. According to CT protocols (dynamic helical Medical Center, 3881, Poongnap-CT vs. conventional CT) and each tumor type (thickened wall/intraluminal dong, Songpa-ku, Seoul, 138736,mass/massive), the accuracy of CT staging was compared. The CT staging was Korea.correlated with the surgico-pathologic results. FAX 82 2 476 4719.

Results: The overall accuracy of CT for staging gallbladder cancers was 71%;it was 79% for T1 and T2 tumors, 46% for T3 tumors, and 73% for T4 tumors. Accepted for publication 9 October

For all three readers, the poorest accuracy was obtained in T3 tumors. No 2001.statistically significant difference was noted in the accuracy between the groupsundergoing conventional CT and dynamic helical CT. A statistically significantdifference was noted in the accuracy for staging thickened wall and intraluminalmass types of tumors (p0.05); the highest accuracy was obtained in the intra-luminal mass type (89%) and the massive type (83%), while it was 54% in thethickened wall type.

Conclusion: The accuracy of tumor staging with CT in patients with gallblad-der cancer depends on the morphological type of tumor. The poorest result isobtained in the thickened wall type.

Early diagnosis of primary gallbladder cancer is dif-

ficult to make pre-operatively because the patientsare often asymptomatic or present with signs orsymptoms of chronic cholecystitis or cholelithiasis(15). Therefore, most investigators have reportedthat the prognosis for these patients is poor evenwith surgical intervention (11). Delay in the diag-nosis of this disease is the main reason for unsatis-factory results following surgery (11). Recently, withthe development of the imaging and treatment mod-alities, it is recognized that the prognosis for gall-bladder cancer and selection of operative proceduredepend upon the depth of tumor invasion (10). Tu-

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mors confined within the mucosa or muscularis

have a relatively favorable prognosis and may becured using simple cholecystectomy or extendedcholecystectomy. However, lesions spreading be-yond the muscularis are associated with a poor out-come, and in those a more aggressive surgical ap-proach should be taken (10). For this reason, moreaccurate assessment of the depth of gallbladder can-cer invasion is important. However, there have beenlimits in the literature regarding the accuracy of CTin the staging of gallbladder cancers (12).

The purpose of this study was to evaluate theaccuracy of CT in staging gallbladder cancers.

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Material and Methods

A computerized search was conducted at our insti-tution from May 1996 to June 2000 to identifycases of gallbladder cancer. Of the 197 patientsidentified, 97 were excluded from the study for one

of the following reasons: radical surgery was notperformed (n51); CT was not available (n40);or pathologic specimens were not available (n6).Therefore, a total of 100 patients who underwentsurgery were analyzed. They included 36 men and64 women with ages ranging from 19 to 85 years(mean 57 years).

CT was obtained using Somatom Plus-S (n65)(Siemens) or Somatom Plus-4 (n35) (Siemens)units with 8- or 10-mm slices at intervals of 8 or 10mm from the diaphragm to the symphysis pubis.Contrast material (600900 ml; E-Z-CAT, 2% iod-inated, water soluble; E-Z-EM, Westbury, NY,

USA) was given orally to all patients 1 h beforeexamination. In all patients, 100120 ml of iopam-idol (Iopamiro 300; Bracco) or iopromide (Ul-travist 300; Schering) were given intravenously asa bolus (rate 2.53.0 ml/s). Examination wasstarted 70 s after the beginning of the injection in84 patients. In the remaining 16 patients, a dy-namic study using helical CT was performed withthe same volume and injection rate of contrast ma-terial; dual-phase helical CT was performed witharterial and portal phases. Arterial phase imageswere obtained at 30 s with 8- or 10-mm slices atintervals of 8- or 10-mm from the diaphragm to

the third portion of the duodenum. Portal phaseimages were obtained at 70 s with 8- or 10-mmslices at intervals of 8- or 10-mm from the dia-phragm to the symphysis pubis.

On CT, the primary features of gallbladder can-cers were divided into three types: intraluminalmass (polypoidal mass protruding into the lumen);thickened gallbladder wall (infiltrating mass thatmanifested as wall thickening without an obviousmass); and massive type (mass almost filling thegallbladder lumen) (6). According to the surgico-pathological TNM classification (1), the tumors

were staged as follows: T1 (tumor invading the mu-cosa or muscle layer); T2 (tumor invading the per-imuscular connective tissue without extension be-yond the serosa); T3 (tumor invading beyond theserosa but less than 2 cm into the liver); and T4(tumor extending more than 2 cm into the liver).

Because it was impossible to discriminate tumorinvasion within the gallbladder wall, we did noattempt to separate T1 from T2 tumors. In ad-dition, both N and M stagings were also not con-sidered for tumor staging. Pericholecystic infil-tration was considered to be present if the fat sur-

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rounding the gallbladder was infiltrated by linearstrandings. Hepatic invasion was considered to bepresent if the hepatic parenchyma near the gall-bladder bed revealed a mass with altered attenu-ation and contour deformity.

Without knowledge of the final surgico-path-

ological results, three radiologists independentlyperformed tumor staging on CT for the 84 patientswho underwent conventional CT. In the remaining16 patients (who underwent dynamic helical CT),tumor staging as well as contrast enhancementpattern of the lesions (i.e., hyperattenuated, hy-poattenuated, or isoattenuated compared with ad- jacent hepatic parenchyma) were independentlyinterpreted by the same readers on each arterialand portal phase in a blinded fashion. In addition,the incidence of transient enhancement of hepaticparenchyma adjacent to the gallbladder fossa wasanalyzed on the arterial phase. We also compared

the accuracy of CT staging according to the CTprotocol (dynamic helical CT vs. conventional CT)and types of gallbladder cancer. Lastly, CT stagingwas correlated with surgico-pathological results.When CT interpretations for staging and otherfindings differed among the three readers, the ma-jority opinion was applied as the final decision.

To compare the accuracy of staging of CT pro-tocol and each tumor type, a statistical analysiswas performed using the logistic regression modelfor tumor type and Fishers exact two-tailed testfor CT protocol. A p-value of less than 0.05 wasconsidered to indicate a statistically significant dif-

ference.

Results

Of 100 patients, 50 were of the thickened gallblad-der wall type, 44 the intraluminal mass type, and6 the massive type (Table 1). The surgico-patholog-ical tumor staging for these 100 patients was asfollows: T1 (n19) and T2 (n48) tumors in 67;T3 tumors in 22; and T4 tumors in 11. Of 67 pa-tients with T1 or T2 tumors, there was the thicken-

Table 1

Surgical-pathologic tumor stages according to types ofgallbladder cancer

Surgical- Tumor types Patients, n

pathol. stageThickened Intraluminal Massive

wall mass

T1, T2 29 33 5 67

T3 15 7 0 22

T4 6 4 1 11

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Fig. 1. Gallbladder cancer (T1 tumor on surgico-pathologicstaging) in a 49-year-old woman. Contrast-enhanced CT showsa soft tissue mass () in the gallbladder lumen without anyevidence of disruption of the wall and pericholecystic infil-tration. (Correctly staged by all three readers.)

Fig. 2. Gallbladder cancer (T2 tumor on surgico-pathologicstaging) in a 49-year-old woman. Contrast-enhanced CT showsdiffuse, uneven thickening () of the gallbladder wall withfocal disruption and pericholecystic infiltration ( ). Gallstone

in the gallbladder. (Two of three readers overstaged this case asa T3 tumor.)

ed wall type in 29, the intraluminal mass type in33, and the massive type in 5. Of 22 patients withT3 tumor, the thickened wall and intraluminalmass types were seen in 15 and 7, respectively. Of11 patients with T4, the thickened wall type wasnoted in 6, the intraluminal type in 4, and themassive type in 1 (Table 1).

Table 2 shows the overall accuracy of tumor sta-

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ging by the three readers, 70% for reader I, 67%for reader II, and 64% for reader III. For all threereaders, the poorest result was obtained for T3 tu-mors.

Table 3 shows the results of the surgico-patho-logic and CT tumor staging. The overall accuracy

of CT for staging gallbladder cancers was 71% (71/100). Sixty-seven patients with T1 or T2 tumorswere correctly staged on CT in 53 cases (79%) (Fig.1) and overstaged in 14 cases (21%) (Fig. 2).Twenty-two patients with T3 tumor were correctlystaged in 10 cases (46%) (Fig. 3), understaged in 8(36%) (Fig. 4), and overstaged in 4 (18%). Eleven

Fig. 3. Gallbladder cancer (T3 tumor on surgico-pathologicstaging) in a 58-year-old woman. Contrast-enhanced CT showsan irregularly shaped soft tissue mass (P) in the gallbladderlumen with evidence of an irregular serosal surface and minimalpericholecystic infiltration (). (Correctly staged by all threereaders.)

Fig. 4. Gallbladder cancer with focal hepatic invasion (T3 tu-mor on surgico-pathologic staging) in a 53-year-old woman.Contrast-enhanced CT shows irregular thickening ( ) of thegallbladder wall without any definite evidence of hepatic tumorinvasion. At surgical biopsy the focal lesion in the liver ()proved to be a hemangioma. (Two of three readers understagedthis case as stage T1 or T2.)

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patients with T4 tumor were correctly staged in 8cases (73%) and understaged in 3 (27%). Overall,overstaging (n18/100) was more common thanunderstaging (n11/100).

In 16 patients who underwent dynamic helicalCT, the gallbladder cancers appeared to be isoat-

tenuated in 9, hyperattenuated in 6, and hypoat-tenuated in 1 on the arterial CT phase. Transientenhancement in the hepatic parenchyma near thegallbladder was identified in 10 patients on the ar-terial phase. On portal phase CT, the gallbladdertumors appeared as hypoattenuated lesions in 12patients, hyperattenuated in 2, and isoattenuatedin 2. Therefore, the lesion-to-liver contrast was in-

Table 2

Tumor staging on CT, comparison of accuracy of thethree readers

Surgical- Reader

pathol.I II IIIstage

n % n % n %

T1, T2 53/67 79 49/67 73 47/67 70

T3 9/22 41 10/22 45 9/22 41

T4 8/11 73 8/11 73 8/11 73

Overall 70/100 70 67/100 67 64/100 64

Table 3

CT and surgical-pathologic stages, comparison in 100patients with gallbladder cancer

Surgical- CT stage Pat.,

pathol. nT1, T2 T3 T4stage

n % n % n %

T1, T2 53 79 10 15 4 6 67

T3 8 36 10 46 4 18 22

T4 1 9 2 18 8 73 11

Table 4

CT accuracy for staging gallbladder cancer, comparison with CTprotocol

Surgical- CT protocol

pathol.Conventional CT, n84 Dynamic CT, n16stage

U C O U C O

T1 or T2 0 42 13 0 11 1

T3 3 10 6 2 0 1

T4 3 7 0 0 1 0

Total, n and (%) 6 (7) 59 (70) 19 (23) 2 (13) 12 (75) 2 (13)

Uunderstaging, Ccorrect, Ooverstaging.

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Fig. 5. Gallbladder cancer (T2 tumor on surgico-pathologicstaging) in a 62-year-old woman. a) Arterial phase CT showsisoattenuated, poorly marginated soft tissue mass ( ) in thegallbladder lumen. Faintly enhanced hepatic parenchyma ()adjacent to the gallbladder fossa. Mild dilatation of the com-mon bile duct ( ) caused by benign stricture of the distal com-mon bile duct was proven with ampullary biopsy. (The arterialphase alone overstaged by all three readers as T3.) b) Portalphase CT showing the tumor mass ( ) in the gallbladder hy-

poattenuated and more clearly demonstrated on this imagethan in the arterial phase. Hyperattenuated hepatic paren-chyma seen on (a) becomes isoattenuated on (b). (The portalphase correctly staged by all three readers.)

creased on the portal phase. The tumors were cor-rectly staged in 9 patients on the arterial phase andin 12 patients on the portal phase (Fig. 5). Com-bined use of both arterial and portal phase CTresulted in a correct staging in 12 patients; the ar-terial phase helical CT did not improve the results

of tumor staging. The results of the comparison ofCT accuracy for staging gallbladder cancers ac-cording to the CT protocol are shown in Table 4.There was no statiscally significant difference inthe overall accuracy between the groups whounderwent conventional CT and dynamic CT in-vestigations (p0.05).

When considering the relationship between themorphological tumor types and CT tumor staging,there were some noticeable differences (Table 5).Of the 50 patients with the thickened wall type, 27(54%) were correctly staged on CT. In contrast, 39

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Table 5

CT accuracy for staging gallbladder cancer, comparison to tumor types

Surgical- Tumor types

pathol.Thickened wall, n50 Intraluminal mass, n44 Massive, n6stage

U C O U C O U C O

T1, T2 0 17 12 0 32 1 0 4 1

T3 6 7 2 2 3 2 0 0 0

T4 3 3 0 0 4 0 0 1 0

Total, n and (%) 9 (18) 27 (54) 14 (28) 2 (4) 39 (89) 3 (7) 0 5 (83) 1 (17)

Uunderstaging, Ccorrect, Ooverstaging

(89%) of the 44 patients with the intraluminal masstype were correctly staged. Of the 6 patients withthe massive type of tumor, 5 cases were correctelystaged by CT (83%). There was a statistically sig-

nificant difference of the accuracy in CT stagingbetween the groups of the intraluminal mass andthe thickened wall type (p0.05). However, therewas no statistically significant difference in the ac-curacy between the groups of intraluminal massand massive type (p0.05) and between the groupswith the thickened wall and the massive type(p0.05).

Discussion

The need for accurate pre-operative staging ofgallbladder cancer cannot be overemphasized, not

only for the patients prognosis but also for se-lecting the optimal surgical strategy. The mediansurvival for T1 and T2 tumors has been reportedto be significantly better than for T3 and T4lesions (3). P et al. (14) have also shownthat the average survival time of patients with gall-bladder cancer dropped from 21.8 months forstage III to 3.5 months for stage IV. Therefore, itis generally agreed that the single most importantfactor for survival is the extent of tumor at thetime of diagnosis.

Despite of the merits of CT for characterizing

and defining tumor extent, there have been rela-tively few reports evaluating the accuracy of CT inthe staging of gallbladder cancers (especially of theT-factor of the TNM staging system) (9). In ourstudy, the overall accuracy of CT for staging gall-bladder cancers was 71%; 79% for T1 and T2 tu-mors, 46% for T3 tumors, and 73% for T4 tumors.As CT overstaged in 18 of our 100 patients andunderstaged in 11, overstaging appears to be amore common problem. All three interpretersshowed similar overall accuracy rates for tumorstaging with the poorest results for T3 tumors.

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This indicates that CT has a significant limitationfor determining the presence or absence of mini-mal pericholecystic tumor infiltration. It may beattributed to the fact that the CT interpreters com-

monly confused pericholecystic inflammatory in-filtration or partial volume averaging-related mar-ginal blurring of the gallbladder wall with tumorinfiltration. Furthermore, microinvasion of alesion toward the liver is commonly missed on CT.In fact, there was a selection bias in our study aswe excluded patients who were inoperable due toadvanced tumor stages. However, although the in-clusion of these patients might have improved ourresults, use of conventional CT may not overcomeits inherent limitation.

In order to improve the accuracy of pre-operat-ive staging of gallbladder cancer, various other in-

vestigative modalities have been utilized. One re-port (4) showed that the overall accuracy of sono-graphy was 38%; the accuracy for T3 tumors was69% but was only 31% for T4 tumors. Accordingto that report, only 1 patient was overstaged whilethe majority of patients were understaged. Thus,H et al. (4) concluded that sonographyunderestimated tumor status. O et al.(13), who compared sonography and CT in the sta-ging of gallbladder cancers, reported the sensitivityof sonography for determining liver invasion to be68%. They did not find CT to be superior to sono-

graphy, and sonography also appeared to haveconsiderable limitations for staging gallbladdercancers.

To improve the accuracy of CT for tumor sta-ging, other techniques can be used. Recently, thedynamic CT study has been widely used for char-acterizing abdominal lesions. However, our studyshowed that application of dynamic CT did notimprove the diagnostic accuracy. In 9 of our 16patients, the gallbladder cancers appeared as isoat-tenuated lesions on the arterial phase. In contrast,they were hypoattenuated on the portal phase in

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12 patients. Therefore, the lesion-to-liver contrastwas increased in the portal phase, thereby improv-ing the CT determination of tumor invasion intothe pericholecystic space and the liver. Moreover,the common occurrence of transient hyperattenu-ation in the hepatic parenchyma adjacent to the

gallbladder, which might result from coexistingcholecystitis, caused some confusion in staging thetumors. CT features of homogenous hyperattenu-ation on the arterial phase and isoattenuationcompared with surrounded hepatic parenchyma onthe portal or late phases would help differentiatingtransient hyperattenuation from tumor invasion(7). Recent advent of multidetector-row CT per-mits a more rapid acquisition of thinner collimatedimages than is possible with conventional CT. Inaddition, high quality three-dimensional imagescan be obtained with volume data (5). In this re-gard, use of narrow collimation of section thick-

ness and three-dimensional images are promisingfor improving the diagnostic accuracy of tumorstaging, as this technique may not only improvethe detection of minimal pericholecystic tumor in-filtration but also minimize the partial volume av-eraging effect.

Gallbladder cancers are usually classified intothree types: massive; thickened wall; and in-traluminal mass (6). In our study, the type of gall-bladder cancer affected the accuracy of CT for tu-mor staging. The accuracy was much higher (89%vs. 54%) in the intraluminal mass type than in thethickened wall type. This is attributable to the fact

that in the intraluminal mass type of tumor the inci-dence of pericholecystic tumor infiltration is lowand the extent of areas which should be observed ismore localized than in the thickened wall type. Ac-cording to a series ofA et al. (2), the intralumi-nal mass type of tumor is less invasive than the othertypes of tumor and rarely invades the serosa if notgrown to a considerable size. Therefore, intralumin-al types of tumor seem to have a better prognosis.Our results, demonstrating that 33 of the 44 intralu-minal mass types belonged to T1 or T2 tumors, maysupport this assumption (2).

The size of a polypoid mass is also reported tobe closely correlated with tumor spread and conse-quently with the prognosis (9). A polypoid tumorof more than 1 cm in diameter is more likely to bemalignant, whereas tumors less than 1 cm are moreoften benign and are commonly cholesterol polyps(8).

In conclusion, the accuracy of tumor staging in

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patients with gallbladder cancer by using CT de-pends on the morphological types of tumor withthe poorest accuracy in the thickened wall type.

ACKNOWLEDGEMENT

We thank Bonnie Hami (Department of Radiology, The Uni-versity Hospitals Health System, Cleveland, OH, USA) for edi-torial assistance in preparing this manuscript.

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