Imaging Features of Gallbladder Cancer
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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 char- acteristics. 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 associa- tion 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.