Gallbladder Polyps: Prospective Study

Transcription

1 Gallbladder Polyps: Prospective Study Judith A. Collett, FRACP, Richard B. Allan, DMU, Richard J. Chisholm, FRACR, Ian R. Wilson, FRACP, Michael J. Burt, FRACP, Bruce A. Chapman, FRACP The aim of this study was to describe the natural history of gallbladder polyps. Thirty-eight subjects who had been previously identified as having gallbladder polyps in an epidemiologic study of gallstone prevalence in 627 diabetic subjects and matched controls were followed longitudinally. Follow-up sonograms were obtained on 33 and 22 of the 38 subjects at 2 and 5 years, respectively. Prevalence for gallbladder polyps in this population was 6.7%, with a marked male predominance (odds ratio 2.3). No statistical difference in prevalence was found between diabetic subjects and nondiabetic controls. Ninety percent of the polyps were less than 10 mm in diameter, with no polyp being larger than 12 mm. During the follow-up period no changes suggestive of malignant transformation were observed. In conclusion, we found that gallbladder polyps were relatively common and that few significant changes occurred over a 5 year period. In asymptomatic subjects in whom gallbladder polyps less than 10 mm in diameter are found incidentally, the likelihood of malignant transformation is low. KEY WORDS: Gallbladder, polyps; Polyps, gallbladder. Widespread use of sonography has led to the identification of an increasing number of polypoid lesions of the gallbladder. Initial information about these lesions came from postmortem studies and surgical series and showed that the majority are cholesterol polyps. 1,2 More recently prevalence studies in healthy populations have been published, 3 5 and these have found prevalence rates of 4 to 6%. The increasing availability of, and technical improvements in, sonography Received September 11, 1997, from the Departments of Gastroenterology (J.A.C., M.J.B., B.A.C.) and Radiology (R.B.A.), R.J.C.), Christchurch Hospital, Christchurch, New Zealand; and Wakefield Clinic (I.R.W.), Wellington, New Zealand. Revised manuscript accepted for publication December 7, Address correspondence and reprint requests to B. A. Chapman, FRACP, Department of Gastroenterology, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand. have led to the clinical dilemma of what to do when an incidental finding of gallbladder polyps is made in an asymptomatic patient. We report a 5 year follow-up study of subjects in whom polyps were found incidentally and show that the natural history of these lesions without surgical intervention is benign. METHODS In 1989 we performed an epidemiologic study of gallstone prevalence in an outpatient diabetic population and compared the findings with an age- and sex-matched control group. 6 Three hundred and nine diabetic subjects and 318 age- and sex-matched controls were recruited. Excluding 63 subjects who had previously had a cholecystectomy, sonograms 1998 by the American Institute of Ultrasound in Medicine J Ultrasound Med 17: , /98/$3.50

2 208 GALLBLADDER POLYPS J Ultrasound Med 17: , 1998 of the gallbladder were obtained in 564 subjects. Informed consent was obtained, and the study approved by the Regional Health Authority Ethics Committee. All sonographic examinations were performed on an Acuson 128 (Acuson, Mountain View, CA) using phased array sector and curvilinear array probes with frequencies of 2.5, 3.5, and 5.0 MHz. All patients fasted for at least 8 hours prior to the ultrasonographic scan. A standard sonography protocol was followed for all examinations. The gallbladder was imaged in longitudinal and transverse planes in the supine or left decubitus position (depending on body habitus, bowel gas, or gallbladder position). Imaging in the standing erect position was performed on all subjects. The field of view and transmission focusing were optimized for gallbladder imaging in each case. A standard sequence of hard copy images was obtained for review and reporting. Four experienced operators (a qualified sonographer [R.B.A.], two senior radiology residents, and a consultant radiologist [R.J.C.]) performed the sonographic studies. Interpretation and reporting of the sonograms were performed primarily by one consultant radiologist (R.J.C.) using the hard copy record and a worksheet of findings completed at the time of sonography. Data from the reports were entered on a computerized database designed specifically for the study. Standard sonographic criteria were used for the diagnosis of gallbladder lesions as polyps 7 : the lesion had to be immobile, nonshadowing, hyperechoic compared to the surrounding bile, and attached to the gallbladder wall. Any lesions that did not fulfill all of these criteria were not reported as polyps. The maximum diameter of the polyps was measured using electronic calipers and rounded to the nearest millimeter. Subjects in whom polyps had been identified were recontacted after 2 years and invited to return for a follow-up sonogram. The same technique was used with the same equipment. Five years after the initial sonogram subjects were again invited to return for a second follow-up sonogram. The same technique was applied using an Acuson XP10 with phased array sector and curvilinear array probes with frequencies of 2.5, 3.5, 4, and 5 MHz. All followup scans were performed by one qualified sonographer (R.B.A.) and reported by one consultant radiologist (R.J.C.). Statistical analysis was performed using In-Stat software. Two-tailed P values were obtained using chi-square, Fisher s exact test, and the Mann- Whitney U test. P values less than 0.05 were considered significant. RESULTS A total of 627 subjects aged between 30 and 75 years were enrolled. Of these 63 had undergone previous cholecystectomy. Therefore 564 subjects were scanned, of whom 309 were diabetic and 318 were controls. In six subjects, all diabetic, the gallbladder could not be identified. Of incidental note, a significantly higher prevalence of gallstones was found in diabetic subjects than in controls (32.7% versus 20.8%, P < chi-square). 6 Thirty-eight subjects were initially identified as having gallbladder polyps, of whom 33 (86.8%) were rescanned at 2 years (two had died, two refused, one not contactable), and 30 still had polyps. Twenty-two of these 30 (57.9% of the original group) were rescanned at 5 years (three refused, five not contactable). The mean age of those with gallbladder polyps (male, 56 year; female, 57 years) was similar to that of the whole study group (male, 56 years; female, 54 years). Excluding the 63 subjects who had undergone previous cholecystectomy (13 male, 50 female), the prevalence rate for gallbladder polyps was 6.7% (8.5% for men, 3.9% for women). Sixteen nondiabetic controls, as compared to 22 diabetic subjects, had gallbladder polyps, but this difference was not statistically significant (P = 0.32). Twenty-five of 293 male subjects and 13 of 334 female subjects had polyps, which shows a significant male predominance (P < 0.05) and an odds ratio of 2.3 (confidence interval of 1.2 to 4.6). The highest prevalence was seen in the 40 to 59 years age bracket for men, whereas for women prevalence was similar in all age groups. No evidence of increasing prevalence with increasing age was found (Fig. 1). Ten of the 38 patients (nine male, one female) identified as having gallbladder polyps also had gallstones (Fig. 2). Despite this, there was no increased likelihood of having gallbladder polyps in those with cholelithiasis (P = 0.72). In three subjects, polyps were no longer visualized on subsequent examinations. Two of the three subjects had gallstones present on initial examination, and the other developed a gallstone subsequently. Gallbladder wall thickening (defined as greater than 3 mm in thickness) was not a feature in any of the subjects with polyps. Although on first examination 24% of subjects had multiple polyps, on subsequent examinations the number of subjects with multiple polyps increased to 37% and 59% at 2 and 5 years, respectively. The mean diameter of the largest polyp in each subject varied from 3.9 mm at first examination to 5.4 mm

3 J Ultrasound Med 17: , 1998 COLLETT ET AL 209 DISCUSSION Figure 1 Gallbladder polyp prevalence (%) according to age and sex. and 5.0 mm at 2 and 5 years, respectively. No significant difference was found in the size distribution between solitary and multiple polyps (P = 0.95). No polyp was larger than 12 mm in diameter (Fig. 3), and in 90% the diameter of the largest polyp was less than 10 mm (Fig. 4). In one patient polyp size increased from 4 mm to 10 mm over 2 years, but this polyp had slightly decreased in size to 8 mm 6 months later at an additional examination, and the patient refused further follow-up at 5 years. In three other patients with polyps 10 mm or greater in diameter, the size remained stable in two patients, but the third refused a second sonogram. The terminology relating to gallbladder tumors remained confused until a simplified classification of benign tumors and pseudotumors was proposed by Christensen and Ishak 1 in The majority of polyps are cholesterol polyps, 7,8 but adenomas may make up as many as 10% of lesions 8 11 and have recently been confirmed to have malignant potential. 2 Unfortunately, no firm sonographic features are known that can distinguish cholesterol polyps from adenomas. However, some sonographic features exist that may predict malignant potential, such as size greater than 10 mm, 8,9 rapid growth rate, 12,13 sessile appearance, 9,11 and gallbladder wall thickening. 12 Previous authors have proposed earlier detection by diagnostic sonography as the best way of improving mortality rates from gallbladder cancer, 14 as surgical outcome has been related to size of tumor and depth of invasion. 12,15 Malignant change in gallbladder adenomas has been well documented. 2 In view of this, a surveillance policy, using biennial sonography in asymptomatic patients who have gallbladder polyps without malignant features, has been suggested for recommendation. 16 However, this policy is not practical in communities with limited resources and increased awareness of cost-effectiveness in medicine. It may also create unwarranted fears in the subjects under such scrutiny. Moreover, gallbladder cancers in Western populations occur in less than to 0.016% of the population per year, 2,17 whereas gallbladder polyps are a relatively frequent occurrence. Figure 2 A, Gallbladder containing coexistent polyp and gallstones. B, Scanning in the erect position allows confirmation of the gallstones by demonstrating their movement to the dependent fundus. A B

4 210 GALLBLADDER POLYPS J Ultrasound Med 17: , 1998 Figure 3 Solitary 11 mm gallbladder polyp, which demonstrated no significant change in size over a 5 year interval. Figure 4 Changes in gallbladder polyp size over time. The prevalence of gallbladder polyps in our study (8.5% male, 3.9% female) was similar to the findings of Segawa and coworkers in an apparently healthy Japanese population undergoing mass sonographic screening (6.28% male, 3.51% female). 5 Segawa and colleagues study also noted the highest prevalence to be in middle-aged men, as was our finding. This male predominance was not found in a random Scandinavian population (4.6% male, 4.3% females), 3 which had prevalence rates similar to those in a study of Japanese male selfdefense officials aged 48 to 56 years (5.3%). 4 The reasons for this difference are not immediately apparent, but the high female cholecystectomy rate in our study group (male-female ratio, 1:3.8) may partly account for the discrepancy in the prevalence of polyps between the sexes. At the initial sonographic examination most polyps were solitary. This is in accordance with Jorgensen and Jensen s experience. 3 However, Kubota and associates retrospective review of cholecystectomy specimens showed that only 25% of cholesterol polyps were solitary, compared with 88% of adenomas or cancers. 9 This discrepancy may simply reflect the limitations of ultrasonography in identifying very small polyps or may be the result of different population groups, as Kubota and coauthors study was a retrospective review of patients who underwent cholecystectomy for polypoid gallbladder lesions. The increase in subjects with multiple polyps seen in this study is unlikely to have resulted from technical factors as the frequency range used for the all scans was similar and was limited more by body habitus than by probe availability, the resolution of systems used was not significantly different, and all operators were experienced and technically proficient using a standardized protocol. The distribution of polyp size based on the diameter of the largest polyp was similar in our study to that found by Shinchi and collaborators 4 and by Jorgensen and Jensen, 3 with the majority of polyps measuring less than 10 mm. In Kubota and associates study of cholecystectomy specimens, the mean sizes were as follows cholesterol polyps, 8.8 mm; adenomas, 6.9 mm; cancers, 25.7 mm, and inflammatory polyps, 4 mm. 9 In five of 12 patients who had repeat sonograms in their study, 9 maximum diameter increased 1.5 to 4 times over 4 to 12 months, and these all patients had cancers. Our study showed only one subject in whom the polyp grew 1.5 times over 2 years, and when this person had an additional sonogram 6 months later, the polyp had diminished in size. Kubota and colleagues found 57% of the cholesterol polyps to be less than 10 mm; however, 75% of adenomas and 13% of the cancers also were also less than 10 mm. 9 When polyps were less than 5 mm and hyperechoic, in Shinchi and coworkers study, they were arbitrarily regarded as cholesterol polyps. 4 However it can be seen that the number or size of lesions alone is unhelpful in determining the histologic nature of polyps seen on ultrasonograms. We were unable to draw clinicopathologic conclusions regarding the nature of polyps in our group, since, at last scan, none of the patients had proceeded to cholecystectomy. Other features associated with increased likelihood of malignant change are gallbladder wall thickening and sessile rather than pedunculated

5 J Ultrasound Med 17: , 1998 COLLETT ET AL 211 appearance. No gallbladder wall thickening was seen in any of our subjects with polyps, and none of the polyps had a sessile appearance. Although our 5 year follow-up rate at 58% was disappointing, our 2 year follow-up rate was good at 87%, and we were able to show that no significant change occurs in the nature of the polyps between the two subsequent sonograms. The value of a prospective longitudinal study even with a moderately high attrition rate cannot be underestimated. The use of diabetic subjects is unlikely to have skewed our results as they were age- and sex-matched by controls, and the difference in gallbladder polyp rates between the two groups was not statistically significant. Although the mean size of the largest polyp showed a statistically significant increase between the first and subsequent examinations, this is unlikely to be clinically significant as a variation of 1 mm in polyp diameter could easily be attributable to technical factors. The absence of polyps in three patients on first follow-up examination may represent technical difficulties, since the diagnostic sensitivity of ultrasonography for polyps is reduced in the presence of gallstones. 10 An alternative explanation, especially for the patient who subsequently was found to have a gallstone only, as postulated by Christensen and Ishak, 1 is that these polyps with narrow, delicate pedicles become detached and form a nidus for future calculus formation. In this study, we have been able to observe the natural history of incidentally found polypoid lesions of the gallbladder. We found few of the features that might predict adenomas with malignant potential. Based on the results of this study the likelihood of malignant transformation of polyps less than 10 mm in diameter is low. 4. Shinchi K, Honjo H, Hirohata T: Epidemiology of gallbladder polyps: An ultrasonographic study of male selfdefence officials in Japan. Scand J Gastroenterol 29:7, Segawa K, Arisawa T, Niwa Y, et al: Prevalence of gallbladder polyps among apparently healthy Japanese: Ultrasonographic study. Am J Gastroenterol 87:630, Chapman B, Wilson I, Frampton C, et al: The prevalence of gallbladder disease in diabetes mellitus. Dig Dis Sci 41:2222, Lichtenstein J: The gallbladder: What if it s not stones? Semin Roentgenol 26:209, Koga A, Watanabe K, Fukuyama T, et al: Diagnosis and operative indications for polypoid lesions of the gallbladder. Arch Surg 123:26, Kubota K, Bandai Y, Noie T, et al: How should polypoid lesions of the gallbladder be treated in the era of laparoscopic cholecystectomy? Surgery 117:481, Yang HL, Sun YG, Wang Z: Polypoid lesions of the gallbladder: Diagnosis and indications for surgery. Br J Surg 79:227, Ishikawa O, Ohhigashi H, Imaoka S, et al: The difference in malignancy between pedunculated and sessile polypoid lesions of the gallbladder. Am J Gastroenterol 84:1386, Koga A, Yamuchi S, Izumi Y, et al: Ultrasonographic detection of early and curable carcinoma of the gallbladder. Br J Surg 72:728, Tsuchiya Y: Early carcinoma of the gallbladder: Macroscopic features and US findings. Radiology 179:171, Koga A, Yamauchi S, Nakayama F: Primary carcinoma of the gallbladder. Am Surgeon 51:529, Nevin J, Moran T, Kay S, et al: Carcinoma of the gallbladder: staging, treatment, and prognosis. Cancer 37:141, Aldridge M, Bismuth H: Gallbladder cancer: The polypcancer sequence. Br J Surg 77:363, Ministry of Health: Cancer New Registrations and Deaths New Zealand Health Information Service, 1995 REFERENCES 1. Christensen A, Ishak K: Benign tumors and pseudotumors of the gallbladder. Arch Pathol 90:423, Kozuka S, Tsubone M, Yasui A, et al: Relation of adenoma to carcinoma in the gallbladder. Cancer 50:2226, Jorgensen T, Jensen K: Polyps in the gallbladder: A prevalence study. Scand J Gastroenterol 25:281, 1990