Transabdominal ultrasound and endoscopic ultrasound for detection of gallbladder polyps and differentiating between polyp types

Background
The gallbladder is an organ situated close to the liver. It stores bile, produced by the liver, before it is released to the small bowel for digestion. Abnormal growths inside the gallbladder, called 'gallbladder polyps', can develop. Most polyps (90%) are harmless; these are called pseudo polyps. The remaining are true polyps and can be cancerous, have cancer-like parts (precancerous dysplastic polyps), or be benign, but they can potentially turn into cancer. Dysplastic polyps and cancerous polyps should be treated. Most people also treat benign polyps because of their potential to become cancerous. Treatment is done by removal of the gallbladder with the polyp within (cholecystectomy). To decide which patients should undergo surgery, it is important to (1) be certain that a gallbladder polyp is present, (2) know whether it is a true or pseudo polyp, and (3) whether a polyp is (pre)cancerous. Transabdominal ultrasound (TAUS), which uses ultrasound waves to differentiate between tissues, and endoscopic ultrasound (EUS), ultrasound attached to an endoscope introduced into the small intestine through the mouth and stomach, are the two tests currently used to detect gallbladder polyps and identify the type of gallbladder polyps.

We performed a thorough search for studies that reported the accuracy (ability) of TAUS and EUS for the detection of gallbladder polyps and for differentiating between true and pseudo polyps, and between (pre)cancerous and benign polyps.

Study characteristics
A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and did not use a combination of TAUS and EUS. Six studies (16,260 participants) used TAUS for diagnosis of gallbladder polyps. No studies on the diagnosis of gallbladder polyps by EUS were found. Six studies (1,078 participants) used TAUS and three studies (209 participants) used EUS for differentiating between true and pseudo polyps. Four studies (1,009 participants) used TAUS and three studies (351 participants) used EUS for differentiating between (pre)cancerous and benign polyps.

Key results
In a general population of 1000 people (in which 6.4% have a gallbladder polyp), TAUS will overdiagnose 37 people without a polyp as having a polyp, and in 7 people with a polyp, the polyp will be missed. In a population of 1000 people with a gallbladder polyp, of which 10% have a true polyp, 189 people with a pseudo polyp will be indicated as having a true polyp by TAUS, and 90 people by EUS. These people may be treated, which is not necessary. In 32 people, the true polyp will be misclassified as a pseudo polyp by TAUS and in 15 people by EUS. These people would not be treated, while they may need treatment. In a population of 1000 people with a gallbladder polyp, of which 5% have a (pre)cancerous polyp, 105 people with a benign polyp will be indicated as having a (pre)cancerous polyp by TAUS, and 75 people by EUS. These people may be overtreated for a (precursor of) cancer, which is not there. In 11 people, the (pre)cancerous polyp will be misclassified as a benign polyp by TAUS, and in 7 people by EUS. These participants may not receive proper treatment for their (precursor of) cancer. TAUS will correctly diagnose 956 out of 1000 people regarding the presence or absence of gallbladder polyps. For differentiating between polyp types, fewer people will be correctly diagnosed by TAUS, leading to unnecessary treatment for pseudo polyps and neglect of (pre)cancerous polyps. There was insufficient evidence that EUS is better than TAUS in differentiating between true and pseudo polyps and between (pre)cancerous and benign polyps.

Quality of evidence
All studies were either at high or unclear risk of bias and 13 studies had either high or unclear applicability concerns. This may undermine the validity of the studies.

Future research
Further studies of high methodological quality and with clearly reported criteria for diagnosis of gallbladder polyps, true polyps, and (pre)cancerous polyps are necessary.

Authors' conclusions: 

Although TAUS seems quite good at discriminating between gallbladder polyps and no polyps, it is less accurate in detecting whether the polyp is a true or pseudo polyp and dysplastic polyp/carcinoma or adenoma/pseudo polyp. In practice, this would lead to both unnecessary surgeries for pseudo polyps and missed cases of true polyps, dysplastic polyps, and carcinomas. There was insufficient evidence that EUS is better compared to TAUS in differentiating between true and pseudo polyps and between dysplastic polyps/carcinomas and adenomas/pseudo polyps. The conclusions are based on heterogeneous studies with unclear criteria for diagnosis of the target conditions and studies at high or unclear risk of bias. Therefore, results should be interpreted with caution. Further studies of high methodological quality, with clearly stated criteria for diagnosis of gallbladder polyps, true polyps, and dysplastic polyps/carcinomas are needed to accurately determine diagnostic accuracy of EUS and TAUS.

Read the full abstract...
Background: 

Approximately 0.6% to 4% of cholecystectomies are performed because of gallbladder polyps. The decision to perform cholecystectomy is based on presence of gallbladder polyp(s) on transabdominal ultrasound (TAUS) or endoscopic ultrasound (EUS), or both. These polyps are currently considered for surgery if they grow more than 1 cm. However, non-neoplastic polyps (pseudo polyps) do not need surgery, even when they are larger than 1 cm. True polyps are neoplastic, either benign (adenomas) or (pre)malignant (dysplastic polyps/carcinomas). True polyps need surgery, especially if they are premalignant or malignant. There has been no systematic review and meta-analysis on the accuracy of TAUS and EUS in the diagnosis of gallbladder polyps, true gallbladder polyps, and (pre)malignant polyps.

Objectives: 

To summarise and compare the accuracy of transabdominal ultrasound (TAUS) and endoscopic ultrasound (EUS) for the detection of gallbladder polyps, for differentiating between true and pseudo gallbladder polyps, and for differentiating between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder in adults.

Search strategy: 

We searched the Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded, and trial registrations (last date of search 09 July 2018). We had no restrictions regarding language, publication status, or prospective or retrospective nature of the studies.

Selection criteria: 

Studies reporting on the diagnostic accuracy data (true positive, false positive, false negative and true negative) of the index test (TAUS or EUS or both) for detection of gallbladder polyps, differentiation between true and pseudo polyps, or differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps. We only accepted histopathology after cholecystectomy as the reference standard, except for studies on diagnosis of gallbladder polyp. For the latter studies, we also accepted repeated imaging up to six months by TAUS or EUS as the reference standard.

Data collection and analysis: 

Two authors independently screened abstracts, selected studies for inclusion, and collected data from each study. The quality of the studies was evaluated using the QUADAS-2 tool. The bivariate random-effects model was used to obtain summary estimates of sensitivity and specificity, to compare diagnostic performance of the index tests, and to assess heterogeneity.

Main results: 

A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and not as a combination of tests. All studies were at high or unclear risk of bias, ten studies had high applicability concerns in participant selection (because of inappropriate participant exclusions) or reference standards (because of lack of follow-up for non-operated polyps), and three studies had unclear applicability concerns in participant selection (because of high prevalence of gallbladder polyps) or index tests (because of lack of details on ultrasound equipment and performance). A meta-analysis directly comparing results of TAUS and EUS in the same population could not be performed because only limited studies executed both tests in the same participants. Therefore, the results below were obtained only from indirect test comparisons. There was significant heterogeneity amongst all comparisons (target conditions) on TAUS and amongst studies on EUS for differentiating true and pseudo polyps.

Detection of gallbladder polyps: Six studies (16,260 participants) used TAUS. We found no studies on EUS. The summary sensitivity and specificity of TAUS for the detection of gallbladder polyps was 0.84 (95% CI 0.59 to 0.95) and 0.96 (95% CI 0.92 to 0.98), respectively. In a cohort of 1000 people, with a 6.4% prevalence of gallbladder polyps, this would result in 37 overdiagnosed and seven missed gallbladder polyps.

Differentiation between true polyp and pseudo gallbladder polyp: Six studies (1078 participants) used TAUS; the summary sensitivity was 0.68 (95% CI 0.44 to 0.85) and the summary specificity was 0.79 (95% CI 0.57 to 0.91). Three studies (209 participants) used EUS; the summary sensitivity was 0.85 (95% CI 0.46 to 0.97) and the summary specificity was 0.90 (95% CI 0.78 to 0.96). In a cohort of 1000 participants with gallbladder polyps, with 10% having true polyps, this would result in 189 overdiagnosed and 32 missed true polyps by TAUS, and 90 overdiagnosed and 15 missed true polyps by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (relative sensitivity 1.06, P = 0.70, relative specificity 1.15, P = 0.12).

Differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder: Four studies (1,009 participants) used TAUS; the summary sensitivity was 0.79 (95% CI 0.62 to 0.90) and the summary specificity was 0.89 (95% CI 0.68 to 0.97). Three studies (351 participants) used EUS; the summary sensitivity was 0.86 (95% CI 0.76 to 0.92) and the summary specificity was 0.92 (95% CI 0.85 to 0.95). In a cohort of 1000 participants with gallbladder polyps, with 5% having a dysplastic polyp/carcinoma, this would result in 105 overdiagnosed and 11 missed dysplastic polyps/carcinomas by TAUS and 76 overdiagnosed and seven missed dysplastic polyps/carcinomas by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (log likelihood test P = 0.74).

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