Imaging Features of Gallbladder Cancer

COLLECTIVE REVIEWS

An Often Overlooked Diagnosis: Imaging Features of Gallbladder Cancer

Charles Henry Caldow Pilgrim, MBBS (Hons), PhD, FRACS, Ryan T Groeschl, MD, Sam G Pappas, MD, FACS, T Clark Gamblin, MD, MS, FACS

Up to 50% of patients with gallbladder carcinoma The controversy surrounding gallbladder polyps and (GBCA) do not have the diagnosis identified on initial their association with malignancy continues unabated. imaging and erroneously proceed to simple cholecystec- Numerous studies continue to try in vain to separate tomy as the first surgical procedure.1 A more careful those lesions that are neoplastic from those that are not. consideration of the imaging findings should allow Whether this is a valuable endeavor remains to be shown, a higher number of patients to be identified preopera- as the vast majority of GBCA do not arise from adenoma- tively, and should subsequently translate to more patients tous polyps, and the vast majority of polyps are not being referred for appropriate preoperative workup and adenomatous. Our focus on polyps might be better definitive oncological management. Patients with T3 directed toward preoperatively identifying GBCA, as it GBCA should be readily diagnosed even with simple more commonly presents as relatively nonspecific gall- transabdominal ultrasonography (US), as these lesions, bladder wall thickening. This can be the presenting char- by definition, invade into the liver, and although T2 acteristic in at least three quarters of patients, with less lesions might be more subtle, many of these lesions than one quarter manifesting polypoid masses.4 should also be identifiable to the astute eye if attention is paid to some fundamental details of the imaging characteristics. Of particular note is the nature of gallbladder Polyps wall thickening, which is described in this review. T1b It is currently accepted that gallbladder polyps >10 mm lesions will no doubt continue to pose a diagnostic warrant cholecystectomy to reduce the incidence of problem; fortunately, no detriment to long-term malignancy, although the evidence base for this is weak. outcomes has been displayed after re-resection for a post- The logic is that removing polyps removes adenoma operative diagnosis for this stage of disease.2 Preoperative and removing adenoma minimizes progression to assessment of depth of invasion, although a critical deter- GBCA. However, the vast majority of polyps are not minant to guide extent of liver resection required for an adenoma. Additionally, the vast majority of GBCA do R0 resection,3 is particularly difficult in GBCA, given not arise from adenoma but rather arise from dysplastic the lack of a submucosa, and also the peculiarity of the lesions.5 This 10-mm threshold is challenged from time normal extension of an epithelial lining into the muscular to time, and lowering to 6 mm was recently suggested layer at times (as manifest by Rokitansky-Aschoff by Zielinski and colleagues.6 However, their own data sinuses). Certain CT features can be useful in this regard, showed that 36 of 130 polypoid lesions they identified and any patient with US characteristics that are suspicious on US were not even present on the final cholecystectomy for malignancy should proceed to additional investigation specimen. Additionally, there were only 15 true polyps in rather than to cholecystectomy in the first instance. this cohort and 3 cancers, all of which showed additional features clearly suggestive of malignancy (ie, invasion into the liver, vascularity, sessile shape, or presence in association with primary sclerosing cholangitis)6 and therefore CME questions for this article available at would easily be captured by a selective approach based http://jacscme.facs.org on features of risk of malignancy other than size. These Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, data demonstrated that there were twice as many polyps Editor-in-Chief, has nothing to disclose. visualized that turned out not to exist, as there were Received August 18, 2012; Revised September 27, 2012; Accepted true polyps. In addition, in almost one quarter of cases September 27, 2012. From the Department of Surgery, Division of Surgical Oncology, Medical (22%), US overestimated the size of the lesion by College of Wisconsin, Milwaukee, WI. 4 mm or more. Lowering the threshold to 6 mm does Correspondence address: Charles Henry Caldow Pilgrim, MBBS (Hons), not seem justified based on these data. PhD, FRACS, Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, A large cohort of 346 patients followed for a mean of WI 53226. email: [email protected] 5.4 years either clinically or with US demonstrated the

ª 2013 by the American College of Surgeons ISSN 1072-7515/12/$36.00 Published by Elsevier Inc. 333 http://dx.doi.org/10.1016/j.jamcollsurg.2012.09.022 334 Pilgrim et al Imaging for Gallbladder Cancer J Am Coll Surg

cohorts of polyps. All polyps >3 cm in the cohort described Abbreviations and Acronyms by Park and colleagues were malignant.8 Few surgeons GBCA ¼ gallbladder carcinoma would be comfortable observing a gallbladder lesion EUS ¼ endoscopic ultrasonography >2 cm (let alone >3 cm), and it is lesions smaller than ¼ US ultrasonography this where the clinical equipoise about the appropriateness XGC ¼ xanthogranulomatous cholecystitis of surgery lies. To estimate the malignant rate in lesions <20 mm, Cho benign nature of virtually all gallbladder polyps in and colleagues analyzed 88 patients with gallbladder Western series. Of the 149 undergoing US scanning, polyps in this size category who underwent preoperative only one single polyp increased in size (from 3 mm to endoscopic ultrasonography (EUS) and had confirmatory 5 mm) and more than one third were not present on cholecystectomy.10 They identified hypoechoic foci in subsequent scanning. Of those proceeding to surgery, 91% of patients with neoplastic polyps and only 11% of more than two thirds did not have a polyp of any kind those with non-neoplastic polyps.10 However, in a more on final pathological examination. Whether this repre- recent study of 134 patients with gallbladder wall thick- sents resolution of the polyp or initial misdiagnosis is ening (rather than polyps), the differences in rates of difficult to establish. In total, there were only 3 adenomas hypoechoic foci did not differentiate between neoplastic detected (1 of which was 7 to 9 mm, the other 2 were and non-neoplastic thickening.11 The usefulness of this >10 mm in size). Gallbladder carcinoma did not develop imaging characteristic remains to be clearly defined. in any of the patients followed clinically (for a mean of In fact, despite EUS being considered superior to 8 years).7 The authors conclude that the presence of conventional US for imaging gallbladder lesions because GBCA resulting from or associated with incidentally of its higher operating frequency enabling higher- detected polyps is extremely low, and that incidental resolution imaging of small lesions,11,12 the usefulness of polyps <6 mm do not need to be followed up at all.7 the modality at all in the investigation of gallbladder This important work is the largest series of polyps fol- polyps remains in question. Endoscopic US performs lowed up in a Western setting, and clearly demonstrates poorly for lesions <10 mm, with only 40% accuracy in that almost no polyp ever progresses to cancer. The base- a series of 94 patients in which there was a particularly line incidence of GBCA in the geographic location does, high rate of neoplasia in small lesions (17% of those however, need to be taken into account, and polyps in between 5 and 10 mm were neoplastic).13 For lesions higher-risk groups, such as females in Northern India >10 mm, the diagnostic accuracy of EUS (86%) was or Chile, need to be viewed with much greater concern. not shown to be better than that of newer high- Conversely, most Western centers have low rates of resolution transabdominal US (90%) in another series GBCA and a more liberal approach can safely be taken.7 of 144 patients.12 Recent advances in contrast-enhanced In stark contrast, Park and colleagues8 report on 105 US are also expected to increase capability for early diag- so-called polyps in 98 patients, 33 of whom had GBCA, nosis via the transabdominal route.14 It is anticipated that from a center in Korea. This alarmingly high rate must high-resolution transabdominal US will become an be tempered by considering that the mean size of the malig- invaluable diagnostic modality for the differential diag- nant diagnoses was 3.8 cm and the range went up to 12 cm nosis of polypoid gallbladder lesions and early GBCA.1 in this study. It is clearly inappropriate to consider a 12-cm Although additional evaluation of EUS is probably war- mass in the same cohort as a 6-mm pedunculated polyp. ranted, recent improvements in transabdominal tech- Not surprisingly, size and sessile morphology were highly niques, combined with the more invasive nature of predictive of malignancy. Including 3.8-cm sessile masses EUS, will likely limit the role of EUS for investigating in a cohort of polyps will always increase the rate of malig- gallbladder polyps in the future. Endoscopic US does nant diagnoses found, as these lesions are obviously GBCA offer potential to biopsy polyps and/or suspicious nodes, until proven otherwise. In fact, in another study of T2 and the description of biopsy of gallbladder lesions from GBCA, the mean tumor size was only 2.8 cm (and these an endobiliary approach (from within the gallbladder) has tumors by definition had already spread beyond the gall- also been successfully reported in a small series from bladder wall into the subserosa).9 Including patients with Japan.14 Although technically difficult, this at least large sessile masses only confuses the issue about the rate appears to have some validity in terms of accuracy of of malignant diagnoses among truly polypoid lesions. An tissue diagnosis, however, advantages of this technique upper size limit of perhaps 2 cm should be introduced in over percutaneous biopsy remain to be shown. an attempt to more accurately define the rate of malignancy Another imaging modality that has been assessed in an in a clinically meaningful way when describing series and attempt to separate benign from malignant polyps between Vol. 216, No. 2, February 2013 Pilgrim et al Imaging for Gallbladder Cancer 335

1 and 2 cm in size is PET scanning. Both visual assessment the careful assessment of the nature of gallbladder wall of the gallbladder vs liver uptake and the ratio of gallbladder thickening, and will also frequently document evidence polyp/liver standardized uptake values were statistically of distant nodal or metastatic spread. Multiphase equally efficacious in determining malignancy in a series imaging, particularly with a portal venous phase (65 to of 50 patients with gallbladder lesions, including 20 with 75 seconds after intravenous contrast injection), provides GBCA.15 In this study, 18F-fluorodeoxyglucose activity optimal visualization of enhancement patterns.16,17 was scored positive if discernibly more avid than adjacent Although it is widely accepted that a 10-mm polyp liver parenchyma, and negative if lower or visually indis- should raise concerns about the presence of GBCA, it is cernible. This technique can help to identify those lesions underappreciated that the same value of 10-mm of wall requiring additional workup before surgery. thickening is of equal or greater importance for the likeli- It is apparent that gallbladder lesions do not need to be hood of malignancy in that context. There is emerging removed simply because they are polypoid, especially if evidence that CT findings related to the nature of gall- they are small. On the other hand, if they display features bladder wall thickening can differentiate benign from suggestive of malignancy, such as local invasion, vascu- malignant causes4,16 and can also assign T stage with larity, sessile shape, or are associated with enlarged some degree of accuracy preoperatively.17 regional lymph nodes, then they should be treated as In their excellent article on the subject, Kim and cancer rather than as a polyp, necessitating additional colleagues describe 5 distinct patterns of wall enhance- imaging investigation and appropriate oncologic surgery. ment on CT that correlate well with the differentials of The argument that the low morbidity of cholecystec- GBCA, adenomyomatosis, and acute and chronic chole- tomy combined with the high lethality of GBCA should cystitis (Table 1). Their study was based on 78 patients indicate an operation for polyps is nonsensical. If polyps with a gallbladder wall in excess of 3 mm thick, including are not the precursors of most cases of gallbladder malig- 29 with GBCA.16 A heterogeneously enhancing thick, nancy, then removing all polyps as soon as they are iden- one-layer pattern (type 1) or a strongly enhancing thick tifiable will have little to no impact on the incidence of inner layer (>2.6 mm) with a weakly enhancing or non- GBCA. Almost all of these lesions are of no consequence enhancing thin outer layer (<3.4 mm, type 2) were found and can be easily, safely, and appropriately managed to be most sensitive and specific for GBCA,16 and this conservatively. There are many reasons why patients makes biological sense. GBCA arises from the mucosa, with polypoid lesions of the gallbladder do warrant chole- and acute and chronic cholecystitis are manifest as inflam- cystectomy, for example, abdominal symptoms or mation and edema of the whole gallbladder wall, in concurrent gallstones. These are excellent indications for particular the serosa. As such, thickening localizing to operation and there is no argument here. Let us put to those areas would be anticipated to reflect the various rest, however, the concept that all polypoid lesions of relevant pathologies. Enhancement of the mucosal lining the gallbladder require urgent cholecystectomy to prevent also makes intuitive sense for GBCA, as the vascular rampant progression toward GBCA, a condition that tumor increases arterial flow and, in cholecystitis, the clearly arises only occasionally from this pathology, and arterial supply is compromised by edema and inflamma- which much more commonly arises surreptitiously from tion leading to reduced enhancement of this layer. A dysplastic lesions presenting only as thickening of the diffusely thickened single layer as described for type 1 gallbladder wall. Table 1. Computed Tomography Features of Gallbladder Gallbladder wall thickening Wall Thickening with Likely Differential Diagnosis16 Far more commonly than a polypoid mass, GBCA pres- Most common ents simply as nonspecific gallbladder wall thickening. Type Description diagnosis The diagnosis in this context is, however, rarely consid- 1 Heterogeneously enhancing Gallbladder cancer thick one layer ered, given the frequency with which the inflammatory 2 Strongly enhancing thick Gallbladder caner conditions of acute and chronic cholecystitis are encoun- inner layer (2.6 mm) tered daily by general surgeons and hepatobiliary Weakly enhancing/nonenhancing surgeons alike.16 The diagnosis can be challenging because thin outer layer (3.4 mm) of this common differential and also because the findings 3 Borderline pattern Adenomyomatosis on US are generally nonspecific.16 Additional imaging is 4 Weakly enhancing thin inner layer Chronic cholecystitis usually necessary to delineate the nature of gallbladder Nonenhancing thin outer layer wall thickening, but unfortunately this is undertaken all 5 Weakly enhancing thin inner layer Acute cholecystitis too infrequently. Multidetector CT is ideally suited to Nonenhancing thick outer layer 336 Pilgrim et al Imaging for Gallbladder Cancer J Am Coll Surg would be expected to represent a more advanced GBCA, One benefit of EUS over CT has been the ability to where the whole thickness of the wall has been replaced concurrently perform fine-needle aspiration at the same with tumor. Irregularity and focal involvement of the sitting. A systematic review including a total of 9 studies gallbladder wall were also identified as features suggesting and 284 patients demonstrated EUS fine-needle aspira- malignancy.16 These findings were confirmed in another tion to have a pooled sensitivity of 84% and a pooled cohort of 125 patients (18 of whom had GBCA) in which specificity of 100%.19 Certainly, EUS fine-needle aspira- a thickened gallbladder wall with type 1 enhancement tion can provide a tissue diagnosis for patients with unre- pattern was significantly associated with malignancy.4 sectable GBCA,20 but what advantage this can have over All of these features should be readily apparent to the percutaneous biopsy remains to be shown. At the present trained eye from both the departments of radiology and time, abnormalities detected on abdominal US should surgery. stimulate CT in the first instance, as EUS does not give A similar earlier study had assessed magnetic resonance the same breadth of information about metastases, and Half-Fourier Acquisition Singleshot Turbo spinEcho is insufficient on its own in the preoperative workup sequence in 144 patients with gallbladder wall thickening before hepatic resection. and described 4 distinct layered patterns (Table 2). Type With careful observation of cross-sectional imaging 4 (diffuse nodular thickening without layering, a similar features, even early-stage tumors can therefore be anticipated description to CT type 1 thickening outlined here) was before their penetration into the deeper muscular layers of associated with GBCA. One particular advantage of this the gallbladder. This area truly represents an opportunity study was the use of Half-Fourier Acquisition Singleshot for clinicians to do better for earlier diagnosis of GBCA. Turbo spinEcho sequence images, which are the source images for magnetic resonance cholangiography, meaning Adenomyomatosis and xanthogranulomatous the test is routinely and widely available currently.18 cholecystitis However, a benefit of MRI over CT has yet to be Two other pathologies in which the differential diagnosis demonstrated. from GBCA is extremely difficult are xanthogranuloma- In addition to these wall-enhancement characteristics, tous cholecystitis (XGC) and adenomyomatosis. The simple thickness appears to be an important and often latter diagnosis displays, by definition, epithelial cells in overlooked feature to consider. The mean gallbladder the muscular layer of the gallbladder and the nature of wall thickness was 6.5 mm and 19.4 mm for non- these cells as benign or malignant is almost impossible neoplastic and neoplastic gallbladder wall thickening as to predict on imaging alone. In a similar manner, tumor measured by EUS, respectively, in a series of 130 speci- involvement of Rokitansky-Aschoff sinuses makes differ- mens including 13 GBCA.11 These measurements were entiation of mucosal from muscular invasive tumors similar to those in another study where the mean wall impossible (as these sinuses normally extend into muscle). thickness of GBCA measured by CT was 13.6 mm in Magnetic resonance can have a role in differentiating comparison with 6.6 mm for benign conditions.4 Based these pathologies, with a reported sensitivity and speci- on multivariate analysis from the first study, gallbladder ficity of 83% and 100% in a small study comparing wall thickening >10 mm and hypoechoic internal echo- 14 patients with cholecystitis, adenomyomatosis, or genecity were independent predictive factors for polyps from 15 patients with GBCA using high b-value neoplastic wall thickening on EUS, although there was diffusion weighted imaging,21 although additional studies no advantage over CT in terms of accuracy.11 will be required. The particular difficulty in differentiating XGC comes Table 2. Magnetic Resonance Imaging Features of Gall- from the fact that the inflammatory infiltration can often 18 bladder Wall Thickening with Likely Differential Diagnosis extend into the adjacent liver, hepatic flexure of the colon, Most common or duodenum, mimicking malignancy radiologically and Type Description diagnosis pathologically.22 The pathology is thought to relate to bile 1 Two layers Chronic cholecystitis Thin hypointense inner layer being forced under pressure into the gallbladder wall Thick hyperintense outer layer through mucosal ulceration or rupture of Rokitansky- 2 Two layers Acute cholecystitis Aschoff sinuses, when there is gallbladder or cystic duct Ill-defined margins obstruction.22 One key pathological difference again relates 3 Multiple hyperintense cystic Adenomyomatosis to the mucosal layer. Xanthogranulomatous cholecystitis spaces in wall predominantly occurs in the gallbladder wall, with the 4 Diffuse nodular thickening Gallbladder cancer mucosal surface overlying the lesion either remaining intact without layering or being only focally denuded. The mucosal line in GBCA Vol. 216, No. 2, February 2013 Pilgrim et al Imaging for Gallbladder Cancer 337 on the other hand is often disrupted as the malignancy Table 4. Computed Tomography Features Suggesting progresses, which can be visualized on CT.22 Gallbladder Cancer Complicated by Cholecystitis Rather Than Simple Cholecystitis in a Series of 26 Patients with the Five CT features found to be suggestive of XGC have Former Diagnosis Matched with 25 Patients with the Latter25 been described as diffuse gallbladder wall thickening, Features suggesting gallbladder cancer a continuous mucosal line, intramural hypoattenuated Higher frequency of nodal involvement (65% vs 16.7%) nodules, and the absence of macroscopic hepatic invasion More extensive wall thickness (8.9 mm vs 5.9 mm) or intrahepatic bile duct dilation (Table 3). The combina- Focal irregularity in wall thickness tion of any 3 of these 5 findings provided excellent accu- Less distension of gallbladder (volume 71 mL vs 95 mL) racy for the differentiation of XGC from GBCA in 18 patients with the first diagnosis compared with 17 with 22 helping to differentiate the diagnoses can be available from the second. In this study, the wall thickness itself was 25 not found to be different between the 2 diagnoses. Using careful consideration of the axial scan images. EUS, only a disrupted mucosal line was found to be With this in mind, there should be an opportunity to significantly different in a smaller study of 15 patients diagnose GBCA earlier by paying greater attention to the with XGC or GBCA.20 initial US imaging, and proceeding to more detailed axial Positron emission tomography scanning as a modality scanning when suspicion arises that a case is not straight- is not helpful in differentiating XGC from GBCA as flu- forward. Forewarned, and so long as there is willingness orodeoxyglucose is not specific for malignant cells, and and capacity to proceed to hepatectomy and lymphade- can accumulate in inflammatory lesions that also display nectomy for established GBCA, the surgeon can then increased glucose metabolism.23 Hepatobiliary iminodi- proceed to open operation with planned intraoperative acetic acid scanning can also similarly demonstrate frozen section for confirmation of the disease. Even if false-positive results, with the classic pericholecystic rim the diagnosis is in error, an open cholecystectomy for sign being reported in cases of malignancy as well eventual cholecystitis where there was concern for malig- cholecystitis.24 nancy cannot be criticized. Consideration of wall layering can be useful for differentiating GBCA from simple cholecystitis as described here, Established gallbladder carcinoma but to complicate matters, the diagnoses of acute or chronic In those few cases where the diagnosis of GBCA is estab- cholecystitis and GBCA can be concurrently established. In lished preoperatively, an accurate assessment of T, N, and fact, up to 25% of GBCA can present in this manner and M stage is critical to plan treatment and surgery when a malignant diagnosis can be evident in up to 1% of appropriate. patients with cholecystitis.25 Even in this extremely difficult Ultrasonography has a relatively high sensitivity for situation, CT has still been demonstrated to show features detection of advanced stages of the tumor, but is limited that might be suggestive of GBCA (Table 4). In a series of in the diagnosis of early lesions and unreliable for staging.26 26 patients with cholecystitis complicating GBCA Accurate diagnosis of the early stages of disease is more reli- matched with patients with simple cholecystitis alone, ably performed with CT. Techniques such as multiplanar suggestive features of malignancy included a higher reconstruction can add additional value to the interpreta- frequency of nodal involvement (65% in GBCA vs tion of standard axial CT images and, in one study of 16.7% of cholecystitis), more extensive thickness 118 patients with GBCA, this improved the accuracy of (8.9 mm vs 5.9 mm) or focal irregularity in thickness. T staging from 72% to 85%.17 Unfortunately, one of the Less gallbladder distension resulting from the infiltrating more critical elements in planning surgery is the differen- process reducing gallbladder compliance was also seen tiation of T1 from T2 lesions and, in this regard, the sensi- and helped point to a malignant diagnosis (gallbladder tivity dropped to 64% in this study by Kim and volume 71 mL in GBCA vs 95 mL in cholecystitis). In colleagues.17 Similarly, lesions can be overstaged in the summary, even in this difficult situation, valid information presence of concurrent inflammation or adenomyomatosis. Overtreating T1b lesions as T2 GBCA is probably Table 3. Computed Tomography Features of Xanthogra- inconsequential, however, T1a lesions are curatively nulomatous Cholecystitis22 resected with simple laparoscopic cholecystectomy and it Diffuse gallbladder wall thickening would be preferable to avoid open liver resection with lym- Continuous mucosal line phadenectomy in this context. Intramural hypoattenuated nodules The significance of local nodal disease on postoperative Absence of macroscopic hepatic invasion scanning is particularly difficult to ascertain after chole- Absence of intrahepatic bile duct dilation cystectomy for unexpected GBCA, as differentiating 338 Pilgrim et al Imaging for Gallbladder Cancer J Am Coll Surg malignant nodal involvement from inflammation is currently is, and be aware that there are defined CT and almost impossible. Para-aortic nodal involvement is MRI descriptions of wall changes that can separate the however much less likely to be attributable to the postop- diagnoses of GBCA from acute and chronic cholecystitis erative state in this context.25 The presence of enlarged and adenomyomatosis. nodes before any surgery, on the other hand, is more ominous for malignancy, and involvement of nodal Author Contributions groups beyond the hepatoduodenal ligament is viewed Study conception and design: Pilgrim, Groeschl, Pappas, as a contraindication to surgery in some patients, as there Gamblin have traditionally been very few long-term survivors Drafting of manuscript: Pilgrim, Gamblin among patients with N2 nodal disease,27 and this N Critical revision: Pilgrim, Groeschl, Pappas, Gamblin staging classifies patients as stage IVB disease in the current 7th edition of the AJCC Cancer Staging Manual.28 REFERENCES The role of PET in GBCA has not been studied suffi- 1. Barreto SG. Improving the preoperative diagnostic yield of gallbladder cancers. Ann Surg 2010;252:572; author reply ciently to make conclusive statements about its clinical 29 572 573. value, however, there is some work suggesting this 2. Shih SP, Schulick RD, Cameron JL, et al. Gallbladder cancer: modality might be superior to CT in the detection of the role of laparoscopy and radical resection. Ann Surg 2007; occult metastatic disease. In a study of 99 patients with 245:893e901. biliary tract tumors, including 16 with GBCA, PET 3. Pilgrim C, Usatoff V, Evans PM. A review of the surgical strat- correctly identified metastatic disease in 18 of 19 patients egies for the management of gallbladder carcinoma based on T stage and growth type of the tumour. Eur J Surg Oncol 2009; overall who were shown to have metastases (sensitivity 35:903e907. 94%) compared with only 12 of 19 lesions identified 4. Tongdee R, Maroongroge P, Suthikeree W. The value of with CT (sensitivity 63%). In this article, metastatic MDCT scans in differentiation between benign and malignant disease was present in 6 of 16 patients with GBCA, but gallbladder wall thickening. J Med Assoc Thai 2011;94: e the sensitivity and specificity of PET for this specific 592 600. 30 5. Adsay NV. Neoplastic precursors of the gallbladder and extra- tumor type were not given. Although the positive hepatic biliary system. Gastroenterol Clin North Am 2007;36: predictive value was also higher for nodal disease, PET 889e900, vii. actually picked up only one additional case over CT 6. Zielinski MD, Atwell TD, Davis PW, et al. Comparison of and therefore added little to this domain of staging. surgically resected polypoid lesions of the gallbladder to their In the postoperative setting after incidental GBCA, pre-operative ultrasound characteristics. J Gastrointest Surg 2009;13:19e25. PET has also been shown to demonstrate utility in iden- 7. Corwin MT, Siewert B, Sheiman RG, Kane RA. Incidentally tifying metastatic disease and contraindicating additional detected gallbladder polyps: is follow-up necessary? Long- surgery; however, it was no better than CT in identifying term clinical and US analysis of 346 patients. Radiology residual locoregional disease.31 2011;258:277e282. 8. Park KW, Kim SH, Choi SH, Lee WJ. Differentiation of non- neoplastic and neoplastic gallbladder polyps 1 cm or bigger with multi-detector row computed tomography. J Comp Assist CONCLUSIONS Tomogr 2010;34:135e139. With a more critical consideration of the common finding 9. Choi SB, Han HJ, Kim CY, et al. Surgical outcomes and prog- of gallbladder wall thickness, and with a more liberal nostic factors for T2 gallbladder cancer following surgical e approach to obtaining more than simply US for these resection. J Gastrointest Surg 2010;14:668 678. 10. Cho JH, Park JY, Kim YJ, et al. Hypoechoic foci on EUS are patients, we can potentially increase our detection of simple and strong predictive factors for neoplastic gallbladder early-stage GBCA before cholecystectomy. Clinical atten- polyps. Gastrointest Endosc 2009;69:1244e1250. tion should focus on this imaging characteristic rather than 11. Kim HJ, Park JH, Park DI, et al. Clinical usefulness of endo- unnecessary concern about the rare adenomatous gall- scopic ultrasonography in the differential diagnosis of gall- e bladder polyp that even more rarely becomes malignant. bladder wall thickening. Dig Dis Sci 2012;57:508 515. 12. Jang JY, Kim SW, Lee SE, et al. Differential diagnostic and staging The role of PET scanning is evolving and can have poten- accuracies of high resolution ultrasonography, endoscopic tial to characterize 1 to 2 cm gallbladder polyps and also to ultrasonography, and multidetector computed tomography for identify occult metastatic disease in patients with known gallbladder polypoid lesions and gallbladder cancer. Ann Surg malignancy. However, the mainstay of workup for these 2009;250:943e949. patients should be CT. Clinicians should realize that a 13. Cheon YK, Cho WY, Lee TH, et al. Endoscopic ultrasonography does not differentiate neoplastic from non-neoplastic small gall- gallbladder wall in excess of 10 mm should be treated bladder polyps. World J Gastroenterol 2009;15:2361e2366. with at least the same (if not greater) suspicion for 14. Inui K, Yoshino J, Miyoshi H. Diagnosis of gallbladder harboring malignancy as the 10-mm gallbladder polyp tumors. Intern Med 2011;50:1133e1136. Vol. 216, No. 2, February 2013 Pilgrim et al Imaging for Gallbladder Cancer 339

15. Lee J, Yun M, Kim KS, et al. Risk stratification of gallbladder 23. Makino I, Yamaguchi T, Sato N, et al. Xanthogranulo- polyps (1-2 cm) for surgical intervention with 18F-FDG PET/ matous cholecystitis mimicking gallbladder carcinoma with CT. J Nucl Med 2012;53:353e358. a false-positive result on fluorodeoxyglucose PET. World J 16. Kim SJ, Lee JM, Lee JY, et al. Analysis of enhancement pattern Gastroenterol 2009;15:3691e3693. of flat gallbladder wall thickening on MDCT to differentiate 24. Achong DM. Pericholecystic rim sign on PET/CT secondary gallbladder cancer from cholecystitis. AJR Am J Roentgenol to locally invasive gallbladder carcinoma. Clin Nucl Med 2008;191:765e771. 2010;35:720e721. 17. Kim SJ, Lee JM, Lee JY, et al. Accuracy of preoperative 25. Liang JL, Chen MC, Huang HY, et al. Gallbladder carcinoma T-staging of gallbladder carcinoma using MDCT. AJR Am J manifesting as acute cholecystitis: clinical and computed tomo- Roentgenol 2008;190:74e80. graphic features. Surgery 2009;146:861e868. 18. Jung SE, Lee JM, Lee K, et al. Gallbladder wall thickening: 26. Furlan A, Ferris JV, Hosseinzadeh K, Borhani AA. Gallbladder MR imaging and pathologic correlation with emphasis on carcinoma update: multimodality imaging evaluation, staging, layered pattern. Eur Radiol 2005;15:694e701. and treatment options. AJR Am J Roentgenol 2008;191: 19. Wu LM, Jiang XX, Gu HY, et al. Endoscopic ultrasound- 1440e1447. guided fine-needle aspiration biopsy in the evaluation of bile 27. Kondo S, Nimura Y, Hayakawa N, et al. Regional and duct strictures and gallbladder masses: a systematic review para-aortic lymphadenectomy in radical surgery for advanced and meta-analysis. Eur J Gastroenterol Hepatol 2011;23: gallbladder carcinoma. Br J Surg 2000;87:418e422. 113e120. 28. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer 20. Hijioka S, Mekky MA, Bhatia V, et al. Can EUS-guided Staging Manual. 7th ed. New York: Springer; 2010. FNA distinguish between gallbladder cancer and xanthogranu- 29. Sacks A, Peller PJ, Surasi DS, et al. Value of PET/CT in the lomatous cholecystitis? Gastrointest Endosc 2010;72:622e627. management of primary hepatobiliary tumors, part 2. AJR 21. Sugita R, Yamazaki T, Furuta A, et al. High b-value diffusion- Am J Roentgenol 2011;197:W260eW265. weighted MRI for detecting gallbladder carcinoma: prelimi- 30. Lee SW, Kim HJ, Park JH, et al. Clinical usefulness of 18F- nary study and results. Eur Radiol 2009;19:1794e1798. FDG PET-CT for patients with gallbladder cancer and chol- 22. Goshima S, Chang S, Wang JH, et al. Xanthogranulo- angiocarcinoma. J Gastroenterol 2010;45:560e566. matous cholecystitis: diagnostic performance of CT to differ- 31. Shukla PJ, Barreto SG, Arya S, et al. Does PET-CT scan have entiate from gallbladder cancer. Eur J Radiol 2010;74: a role prior to radical re-resection for incidental gallbladder e79ee83. cancer? HPB (Oxford) 2008;10:439e445.