Personalized cancer therapies increase demand on tissue sampling. Besides establishing the nature of a lesion, staging, therapy-monitoring, research and clinical oncological studies are based on biopsies1,2,3,13. Larger tissue volume samples on the one hand provide more adequate information about tumor architecture/microenvironment and enable multiple analyses2,14, but may lead to increased bleeding risk and mortality on the other15,16,17. Therefore, complication management of percutaneous biopsies is important.
Overall major complication-rate in liver biopsy ranges between 0.3 and 3.3%18. Thereof, rate of major bleeding events range between 0.5–1.2%, though it is elevated in tumor patients (1.6%), the female sex, and advanced age15,19. Procurement of more than two biopsies was reported to elevate the risk for bleeding16,17,20. A number of > 4 biopsies is associated with a threefold higher risk of major bleeding events16.
Percutaneous needle biopsy can be performed in coaxial and non-coaxial technique. Coaxial technique, as chosen in this investigation, offers several procedural advantages. Besides collection of multiple samples in a single puncture, it has been reported to reduce bleeding risk (one puncture of the organ capsule) and prevent tumor cell seeding1. Even though this technique introduces a larger access route, it has not been associated with higher complication rates1,21,22. Additionally, coaxial technique allows for tract plugging, an effective tool in bleeding management/prevention.
Compared to literature, the rate of major bleeding events in our cohort was within acceptable margins (0.7% vs. 0.5–1.2%), even though our patients demonstrated an elevated risk profile (76% tumor patients; median number of biopsies, 4 [range 1–11]; 53% females; median age, 63.0).
Minor bleedings were reported in 4.3% (plugged, n = 11/214; unplugged, n = 2/86), which is also within acceptable margins (0–10.9%)23. Haage and colleagues described one subcapsular hematoma and one moderate bleeding from the biopsy tract in a study of 1999 without tract plugging24. Thus, the self-limiting hematoma rate in their study was notably lower, although the biopsy tract was not plugged with a gelatin sponge slurry. A possible explanation for this finding might be the higher number of samples per biopsy obtained in our study cohort in comparison to Haage et al., who in general obtained only one biopsy sample for pathological diagnosis.
The number of biopsies (plugged group, 4 [range 1–10]; unplugged group, 3 [range 1–11]) had a significant impact on bleeding events (P = 0.038; OR = 1.395, 95% CI lower = 1.018, 95% upper = 1.913), which is concordant with the pertinent literature, where significant influence on major hemorrhage was found16,17,20. In comparison to Boyum et al., our study cohort was rather small (n = 300 vs. n = 5011) and risk of major bleeding events in general is low. The number of samples per biopsy did not demonstrate a significant difference regarding major bleeding events in our cohort (P = 0.883), but did show a correlation for minor bleeding events (P = 0.020; OR = 1.501, 95% CI lower = 1.066, 95% upper = 2.113).
Beside gelatin sponge slurry, biopsy tract embolization can also be achieved with other materials, e.g. embolization coils, autologous blood clots, microfibrillary collagen, or gelatin sponge in rolled form1,9,25,26. One advantage of gelatin sponge slurry in contrast to e.g. coils is that it is absorbed completely within weeks. Risks of dislocation, delayed local infection, or imaging artefacts associated with permanent foreign bodies can therefore be avoided27.
Comparison of gelatin sponge and other absorbable embolizates has so far not been performed for liver biopsy tract plugging. Gelatin sponge was compared to microfibrillary collagen for tract embolization following percutaneous transhepatic islet cell transplantation and found to be inferior9. However, gelatin in this study was introduced into the biopsy tract in rolled form and not mixed as a suspension. It is possible, that gelatin suspension leads to a more adequate embolization due to a more sufficient distribution than the application of rolled gelatin sponges. An advantage of gelatin sponge over microfibrillary collagen, however, is the notably lower cost (< $ 4 at our institution vs. approx. $ 180.00 in 2016). Besides these advantages, preparation of gelatin sponge slurry is fast and easy, especially in emergency cases. Severe adverse events induced by gelatin sponge slurry like anaphylaxis are rare (< 0.5%)27,28 and did not occur in any of our patients.
As described we performed non-contrast CT immediately after the intervention in order to detect post-procedural complications. It is arguable that post-interventional hemorrhage can also be detected sonographically forgoing the need for additional radiation exposure. However, there are inherent limitations of sonography in our patient cohort of mostly elderly, critically ill patients who were often unable to perform deep inspiration, adequate breath holds, or demonstrated meteorism. Therefore, we opted for postinterventional non-contrast enhanced CT. From a procedural point of view postinterventional non-contrast enhanced CT not only provides a basis for evaluation of complications without the need for repositioning the patient. It can also be followed by immediate contrast-enhanced CT angiography in case any complications are suspected without time loss and thus also provides the basis for adequate and immediate intervention (e.g., immediate transfer to angiography for further treatment).
This study is limited by its retrospective character. Furthermore, our sample size of 300 patients was rather small, in particular with regard to overall low rates of major bleedings following liver biopsy. Therefore, further validation of our data should be the subject of larger cohorts. In our institutional setting, a randomized trial of tract plugging in the presence of active bleeding from the biopsy site was not justifiable, though it would be an ideal study design to test the efficiency and safety of gelatin sponge slurry. Some post-procedural complications might not be reported to us due to follow-up treatment in another institution, especially in patients with a more distant place of residence. The amount of gelatin sponge slurry applied can only be estimated. Only the use of gelatin sponge slurry, not the amount was documented. To our knowledge, no comparative study between plugged and unplugged biopsy tract exists, therefore this study addresses an important gap of knowledge.
