Management of gallbladder polyps

Gallbladder polyps (GPs) have an estimated prevalence of approximately 0.3–12.3% [1, 2], which varies widely in different regions of the world. They are rarely symptomatic [3, 4] and are mainly incidental findings. Until recently it was generally assumed that polyps in the gallbladder have the potential to grow and become cancerous over many decades [5]. However, a recent population-based study found out that the natural history of polyps is to grow over time, and polyps even more than 10 mm in size are rarely associated with gallbladder cancer (GBC; [6]). The majority of GPs are classified as pseudo or cholesterol polyps. They have no malignant potential and, therefore, do not require follow-up or intervention. Past studies assumed that “true” GPs occur in 5% of cases [1, 2, 7] and are subject to the adenoma–carcinoma sequence [8]. Although rare, malignancy is significantly more common among polyps of 10 mm or greater in size [2, 7]. It is therefore generally accepted that from this size up, GPs have to be removed surgically, preferably by laparoscopic cholecystectomy [2, 9, 10]. Nevertheless, it remains uncertain how many polyps in the gallbladder ultimately progress and become cancerous. The aforementioned recently published study involving more than 600,000 patients reported a very low incidence of GBC in GP carriers, which was interestingly comparable to patients without GPs [6].

This review discusses recent findings on the central role of imaging in diagnosis and discrimination between “true” and pseudo polyps and their treatment. Given the low incidence of true polyps, the decision for laparoscopic cholecystectomy must be balanced against its postoperative morbidity, which is moderate but severe when bile duct injuries occur. The recommendations of recent guidelines are not uniform and rely on a low level of evidence due to the small numbers, short follow-up, and current data not being taken into account in the referenced studies. The white paper of the American College of Radiology, for example, recommends yearly follow-up for polyps sized 7–9 mm and consultation for cholecystectomy in the case of a polyp growth [9]. The American Society for Gastrointestinal Endoscopy also recommends indefinite yearly monitoring for GPs [11], and a joint guideline from various European societies recommended surgery for all polyps larger than 10 mm and those larger than 6 mm with risk factors as well as 5 years of follow-up for all other polyps [10]. In view of recent findings, there appears to be a need for a revision of existing guidelines, in particular concerning periodic ultrasonography of GPs to detect GBC proactively.

Accurate imaging plays a significant role in the diagnosis and treatment of GPs. In addition to the differential diagnostic delineation of gallstones, sludge, or physiological variants of the gallbladder mucosa [12, 13], imaging should be able to differentiate between true and pseudo polyps. It is reported that ultrasonography is not accurate (less than 70% sensitivity) in differentiating polyps (true or pseudo polyps) from gallstones [12]. Yet the distinction between adenomas and non-adenomas is still made after the operation. The preoperative examination, therefore, is required to show a high degree of accuracy in order to make a reliable treatment recommendation. Also, radiation exposure plays a role in the repeated use of imaging, for example, during follow-up observations. The primary modalities discussed include ultrasound, computed tomography, and magnetic resonance imaging.

Malignant polyps are generally larger than benign ones (mean diameter 27.97 ± 2.46 mm vs. 8.56 ± 0.36 mm, respectively [14, 15]). Even though the development of malignant GPs seems to be overestimated, polyp size is the major risk factor. From a diameter of 10 mm, the risk of malignancy increases with a probability of 37–55% [34]. Since, as mentioned above, the sensitivity and specificity of the most appropriate examination also increase with the size of the polyp, the diameter of the GPs is the decisive factor in their management. It is accepted practice and is reflected in relevant guidelines, such as the European Society of Gastrointestinal and Abdominal Radiology (ESGAR; [10]), that patients with polyps of 10 mm or more in size should be treated with cholecystectomy [7, 15, 35]. However, it should be emphasized that evidence from controlled randomized studies is still lacking. There are also conflicting findings in reviews. It was shown that a significant number of polyps smaller than 10 mm have malignant potential, or even already show carcinoma [36, 37]. However, none of the cancerous polyps was smaller than 5 mm. Some authors, therefore, call for a cholecystectomy at a size of 6 mm. Due to the postoperative morbidity following cholecystectomy, there is a risk of overtreatment, which is why this procedure has not been generally accepted.

Follow-up imaging may have a limited benefit. In the most extensive population-based study to date, most GBCs were diagnosed in the first year after the detection of polyps and GBC did not appear to depend on the presence of polyps [6]. However, it is frequently believed that true polyps grow faster and therefore can be detected and removed much earlier through careful follow-up so that radiological monitoring is recommended in the case of a polyp size of less, but also more, than 10 mm [15]. Nevertheless, there is no consensus about the size of the polyps nor the frequency or duration of follow-up examinations. Small sample sizes limit studies of the evolution of GPs, and polyp growth seems to be a part of its natural history [6]. A large proportion of polyps remain constant in size for years, even over more extended periods of observation [15, 35]. A sudden increase in the size of true as well as pseudo polyps was only observed in studies with minimal case numbers [4].

It remains unclear whether polyps in the gallbladder have the potential to grow and become cancerous over many decades. Gaps in the available evidence to support the current guidelines for the treatment of GPs are outlined. The relevant radiological examination with the most reliable evidence is conventional percutaneous US, which is widely available, repeatable, and without radiation exposure. Optional additions such as the hrUS or eUS are promising modalities to further discriminate between true and pseudo polyps, and thus to assess the risk of malignancy and to support clinicians in their decision-making process.

Although the risk of a malignant polyp is related to size, it remains uncertain how many polyps ultimately progress and become cancerous. The indication for cholecystectomy, which is strongly recommended for polyps of 10 mm in size or greater, means that a considerable number of unnecessary operations are accepted. The evidence for smaller GPs is of even lower quality. Studies suggest that asymptomatic polyps smaller than 10 mm do have the capacity to become cancerous and surgery is recommended for risk factors such as PSC, solitary and sessile polyps, even from a size of 5 mm. For polyps smaller than 10 mm without risk factors, a follow-up at least every 2 years with percutaneous US seems to be appropriate. The indication for cholecystectomy should be discussed with the patient in the case of dynamic polyp growth. To date, no studies have been conducted to assess the adherence and effects of following these guidelines. Therefore, more extensive retrospective and prospective studies must be done to determine the success of GP treatment according to current guidelines.