ReviewGrowth rate and malignant potential of small gallbladder polyps – Systematic review of evidence
Introduction
Gallbladder polyp (GBP) is a growth protruding into its lumen from the inner gall bladder wall. Standard ultrasound (US) features of a GBP are: protrusion of internal gall bladder wall of similar echogenicity as that of the gallbladder wall and hyperechoic compared with the surrounding bile, lack of mobility, and no associated acoustic shadowing.1
An appreciable number are actually pseudopolyps, representing focal accumulation of cholesterol or adherent calculi, but whilst US features suggestive of a pseudopolyp have been described, an overlap of pseudopolyps with both true polyps and gallstones is common, making US differentiation difficult.2
GBPs are reportedly diagnosed in up to 5% of the general population, with frequency increasing due to more patients having US scans and a better US technology.3
True GBPs can be non-neoplastic or neoplastic. Non-neoplastic polyps comprise hyperplastic and inflammatory polyps. Neoplastic polyps can be benign or malignant; the benign ones being adenomas, adenomyomas, leiomyomas, fibromas, and lipomas, whilst malignant tumours being adenocarcinoma, squamous cell carcinoma, and mucinous cystadenoma.
Although adenomas are benign, they are seen as being pre-malignant, with an adenoma-carcinoma sequence proposed.4
Four out of five cases of gall bladder cancer (GBC) are diagnosed at an advanced stage, with 5-year survival rates being <15% for tumours invading muscularis mucosae or beyond.5 It is not known how many GBCs are preceded by a GBP, but clearly differentiating the non-neoplastic from malignant or premalignant polyp is extremely important. This distinction, however, constitutes a major diagnostic challenge. Malignancy is more frequent in polyps with diameters of 10 mm or greater, presence of coexisting gall stones, solitary and symptomatic polyps, congenital and some acquired biliary anomalies, in females and with increasing patient age.6, 7, 8, 9 Some studies have shown an increase in prevalence of GBPs in certain ethnicity.10 Of these factors, size of at least 10 mm is the predictor of malignancy in pre-existing GBPs. Majority of incidentally detected GBPs, however, are less than 10 mm in size and are often too small to allow accurate characterisation.
Current practice regarding the management of GBPs consists of cholecystectomy for lesions with a diameter of 10 mm or greater, and US follow-up for lesions smaller than 10 mm.
However, the threshold size above which polyps should be followed, the interval of follow-up, and its overall duration remain controversial. The knowledge about the long-term natural history of smaller than 10 mms GBPs is limited and there is no evidence based guidelines.11
The primary aims of this systematic review were to identify, appraise and synthetise the evidence on whether:
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GBPs smaller than 10 mms grow over time when followed up
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growth of a GBP smaller than 10 mms, as identified on US, is an indicator of malignancy.
Section snippets
Inclusion and exclusion criteria
The inclusion and exclusion criteria used for studies is outlined below (Table 1).
Study identification
We searched Medline and Embase via the Evidence Search databases. Papers published between January 1976 and January 2012 were included. The references for all included articles were reviewed and any relevant abstracts and full text articles were obtained and included in the review. Full search strategy is available from the authors.
Study selection
The initial list of titles followed by the abstracts for those studies which met
Search results
The database search returned 478 studies (Medline search identified 376 studies and Embase search identified 102 studies). 56 were duplicates.
On the basis of screening of titles 299 articles were deemed not relevant and thus excluded.
123 remaining abstracts were reviewed. On the basis of screening of the abstracts 112 papers were excluded as not fulfilling the inclusion criteria. Full text of 11 studies was obtained.
One study which used endoscopic US follow up of GBPs detected on transabdominal
Discussion
Ten studies satisfied the inclusion criteria aiming to assess change in size of GBP over time.
They had variable design, follow up duration and reporting formats.
Nine studies concluded that the risk of development of malignancy in small polyps was low and that there was no correlation between growth and development of malignancy. One study18 cautioned that even small <10 mms polyps can harbour malignancy, and indeed seven of 418 cholecystectomy specimens contained gallbladder malignancy in
Conclusion
Level II-2 and below evidence on rate of growth of small GBPs <10 mms exists in the literature. It indicates that growth does occur in a significant minority of small GBPs, but it is slow. Due to deficient reporting and small numbers of cases, the correlation between growth of GBP and development of malignancy cannot be established using currently available evidence. Malignancy can be present in polyps <10 mms although it is significantly more frequent in polyps >10 mms. Cholecystectomy for
Acknowledgements
The authors would like to thank Michelle Madden, Clinical Information Specialist, Edge Hill University LIRC, and Dan Lythgoe, Medical Statistician, Liverpool CR-UK Centre, for their kind help with the methodology.
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