Comparison of a coaxial versus non-coaxial liver biopsy technique in an oncological setting: diagnostic yield, complications and seeding risk

Image-guided percutaneous liver biopsy (PLB) is a commonly used minimally invasive technique to retrieve tissue, usually for diagnostic purposes. In the realm of precision medicine [1, 2], the demand for PLB is increasing as clinical cancer trials mandate advanced genetic and molecular tissue analyses to appropriately select and monitor patients for tailored cancer treatment [3]. Therefore, acquisition of sufficient tissue is essential and usually obtained via PLB at different time points during treatment. Yet, special consideration is needed for the fact that more and sometimes larger tissue cores are required [4], which may increase the complication rate and the discomfort for the patient when using the standard non-coaxial PLB technique (NC-PLB) due to multiple needle passes through the liver capsule. Although several studies have shown that PLB is safe, well tolerated and can be performed in an outpatient setting [5‐12], the published literature on image-guided PLB is quite heterogeneous in terms of patient profile, underlying hepatic pathology, biopsy-related technical features and definitions of complications, making a direct comparison between studies difficult. In a cancer population, the possibility of tumour seeding has to be considered besides general complications such as post-biopsy bleeding. Only a few studies [13‐15] have investigated the risk and frequency of tumour seeding after PLB using different biopsy techniques. The coaxial liver biopsy technique (C-PLB), which involves placing a larger outer sheath needle into the target tissue, through which subsequent biopsies are taken using a slightly smaller needle, has been proposed to decrease the risk of tumour seeding and complications in liver biopsies [14]. To date, no direct comparative study between a C-PLB and NC-PLB in an oncological setting has been performed. Therefore, the purpose of this paper was to assess the diagnostic yield, safety and seeding risk of a C-PLB versus a NC-PLB technique in a cancer patient cohort.

Image-guided PLB plays a pivotal role in clinical cancer practice, enabling the collection of sufficient tissue for diagnostic purposes and advanced tissue analyses. In the realm of precision medicine, more and larger cores, often obtained before and at different time points during treatment, are required to perform the vast amount of genomic, transcriptomic and immunohistochemical analyses inherent to this field [4]. In this study, we showed that the use of C-PLB allowed for significantly more tissue sampling with fewer complications and a lower seeding rate than NC-PLB.

The diagnostic accuracy of both C-PLB and NC-PLB achieved the UK national audit standard of > 90% [11], with no significant difference between either technique.

Regarding complications, pain was the most frequently reported complaint as expected [12, 17]. Patients experienced less pain after C-PLB than NC-PLB and this is probably directly attributable to the lower number of passes through the liver capsule, reducing capsular pain. In line with previous large cohort studies [12], major complications were uncommon. For instance, a post-biopsy bleeding occurred only in 1.2% of cases, which is comparable with the results of Cui et al [5], who reported a bleeding risk of 1.43% in a cohort of 26,941 cancer patients across the USA. In this and most other studies, the impact of procedural factors such as biopsy technique, number of passes and needle size was not assessed. The single study comparing bleeding rates between a coaxial and non-coaxial biopsy technique [18], the latter with and without gel foam plugs, could not show a significant difference in complication rate. However, two cases of major bleeding necessitating embolisation and resulting in one patient’s death occurred after an unplugged biopsy. Similarly, the one patient requiring arterial embolization (0.1%) for bleeding in our study underwent a NC-PLB. In addition, a large prospective study [19] showed that the risk of bleeding rises with an increasing number of multiple passes. Hence, we believe that C-PLB with Gelfoam plugs does have its merit to decrease the risk of serious post-biopsy bleeding by minimising the number of capsular passes while still allowing for more tissue collection. Pulmonary embolism is an infrequent but major complication and occurred more often in our study than in previous reports. Most likely, this is attributable to the hypercoagulability inherent to cancer, putting patients at higher risk of thromboembolic events [20], in combination with the cessation of anticoagulation prior to the procedure.

Our study is the first and the largest to date to specifically and systematically evaluate the risk of tumour seeding post-PLB in cancer patients with a variety of histopathological aetiologies. Seeding was uncommon in the current study, occurring in only 13 out of 630 patients with imaging follow-up (2%) and only observed in the context of significant disease progression elsewhere in these patients. Even then, lesions along the biopsy track were very small and, in fact, only picked up on re-reviewing the images and none were diagnosed prospectively in the original radiology reports. This suggests that seeding may not have been the driving force for disease progression in patients having a biopsy of metastatic liver lesions. The limited number of studies investigating the seeding risk after PLB of metastases focused on breast and colon cancer [13, 15, 21, 22]. Chen et al [15] who evaluated all post-biopsy imaging in a cohort of 433 PBL of colon and breast metastasis found that none of the breast cancer patients presented with seeding, yet a 6% (17 of 278 patients) seeding rate was seen after PLB of colorectal metastases. In older retrospective studies comprising less than 51 patients, the risk of seeding post-PLB of colorectal metastasis was even higher ranging 10–16% [13, 21, 22]. These studies mainly sampled tissue by fine-needle aspiration and NC-PLB. In contrast to these results, we only found seeding in 3 out of 151 (2%) colorectal cancer patients after PLB. Instead, the seeding cases occurred in other tumour types, with a relatively higher ratio of occurrence in melanoma and GIST. We hypothesise the biopsy technique used may be crucial in decreasing tumour seeding along biopsy tracts. Using a coaxial system, there is only one penetration of the liver capsule with no direct contact with the metastasis when placing the coaxial needle at the edge of the target lesion. The fully automatic core biopsy needle samples the lesion and is retracted through the coaxial needle which protects the liver parenchyma and the soft tissues from tumour seeding. The risk of seeding in our study was significantly lower in those patients where a coaxial needle system was used. This is supported by the findings of Maturen et al [14], who did not have a single case of seeding after the use of a coaxial needle system for PLB of hepatocellular carcinoma (HCC), while a previous meta-analysis [23] found an overall seeding risk of 2.7% post-PLB in HCC.

Our study has several limitations. Firstly, this was a retrospective study and therefore there may have been a selection bias. However, all consecutive liver biopsies performed in our institutions in the given period were included in the analysis. Secondly, the choice of the biopsy technique reflected the radiologist preference and results may have been influenced by individual performances. Nevertheless, all biopsies were performed by experienced operators in both groups. Thirdly, the vast majority of the patients received systemic anticancer treatment post-liver biopsy which may have delayed or eliminated the occurrence of tumour seeding. Also, only a few patients had oligometastatic disease, and therefore, it’s not possible to estimate the seeding risk and its impact on survival in patients on a potential curative pathway. Nevertheless, our results do reflect standard oncology practice and the standard of care in our institution can be expected worldwide. Fourthly, no histological confirmation of suspected seeding lesions was obtained. As these were usually seen in a context of generalised progressive disease, sampling of these lesions would result in additional stress for patients with no added value to the clinical management, and was therefore deemed unethical. Finally, as the biopsy track is not identifiable on subsequent imaging, the course of the needle was estimated based on lesion location and available procedural imaging and reports. We tried to define the maximum possible seeding rate accepting that all lesions identified in the biopsy track were true positives, although some could actually represent disease progression. Therefore, the seeding rate in our study could be slightly overestimated, which only underscores the fact that seeding is very uncommon and should not be reason not to perform a PLB.

In conclusion, we found that C-PLB is of particular interest in the oncological setting and for clinical cancer trials. More and larger tissue cores can be obtained repeatedly in the same patient in safely manner with a lower risk of complications and seeding than NC-PLB.