CT-guided biopsies of unspecified suspect intrahepatic lesions: pre-procedure Lipiodol-marking improves the biopsy success rate

The institutional review board (IRB) approved this retrospective cohort study with a waiver for written informed consent. Inclusion criteria were as follows: unclear and suspect hepatic lesion, CT-guided biopsy of the hepatic lesion, unenhanced, IV contrast or previous Lipiodol-angiography for lesion marking, age 18 and above. All patients who met the inclusion criteria (Figure 1) were included. We excluded all patients with a time interval between CT-guided biopsy and Lipiodol-angiography of more than two months (n = 18) or an abort of the CT intervention during the examination due to lack of lesion visibility or sufficient biopsy window (n = 23).

FIGURE 1.

Data were evaluated for the whole study population, and a comparison of the three groups, unenhanced (group 1), Lipiodol enhanced (group 2), and IV contrast medium enhanced (group 3) was performed. Only patients who were not eligible for an ultrasound-guided biopsy or after an unsuccessful ultrasound-guided biopsy were referred to the radiology department for a CT-guided intervention. The interdisciplinary tumor board made the decision to biopsy. The enhancement protocol was selected at the time of the decision for biopsy based on several parameters and experience. Patients with lesions expected to be displayed well in unenhanced CT, either by size, location, or based on previous imaging, were planned for an unenhanced biopsy. A contrast protocol was determined in patients with lesions that might be more challenging to display in unenhanced CT. The decision for contrast protocol, Lipiodol (Example given in Figure 2) vs. IV contrast medium (e.g., Figure 3), was also based on the lesions’ location and parameters (e.g., size, architecture with visible changes in the liver parenchyma). Small lesions and lesions with a challenging location were more likely marked with Lipiodol due to a more long-lasting uptake which enables a secure identification during the whole examination, while IV contrast might have been washed out. In clinical practice, more intravenous contrast applications were performed in the early years of the study period. In the last years, more patients were examined using a previous intra-arterial enhancement by Lipiodol based on good local experience. The study population and the three groups were subdivided by lesion size and occurrence of liver cirrhosis.

FIGURE 2.

FIGURE 3.

All patients received a transcutaneous CT-guided biopsy of the hepatic lesion using the same 128-multislice CT scanner [SOMATOM Definition AS, Siemens Healthineers] for image acquisition. The interventions were performed by interventional radiologists with more than five years of experience in CT-guided interventions. The obtained core biopsies were histopathologically analyzed by the local Institute for Pathology. Successful biopsy was defined as histopathological findings other than typical liver tissue or non-specific findings. Based on our experience, Lipiodol does not affect the analysis of the specimen.

Before the examination, the coagulation profile was checked. Patients who were planned for an application of IV contrast medium were screened for contraindications, e.g., reduced renal function or hyperthyroidism. The use of oral anticoagulants was prohibited based on national guidelines. No changes to institutional guidelines (standard operating procedures) were made. If patients were planned for IV contrast, 60 ml of contrast agent [Imeron® 350, Bracco] were administered with an application rate of 3–5 mL/s. We used a fixed delay of 60 s until the first planning scan was initiated.

After the patients received the first planning scan, the access path was planned using a standard 3D-CT workstation [syngo.via, Siemens Healthineers] without software modifications. In the case of multiple lesions with a similar suspect appearance, the lesion with the best reachability was defined as the target. Based on the biopsy planning, the cutaneous entry point was marked. After introducing the coaxial needle, the lesion approach was performed under image guidance. A coaxial approach was used for CT-guided intervention. This approach is characterized by combining two needles: a puncture sheath [17 G, Puncture Sheath, Somatex® Medical Technologies, Germany] and a biopsy handy [18 G, Biopsy Handy, Somatex® Medical Technologies, Germany]. The sheath - a thicker, shorter needle (5cm, 10 cm, or 15 cm) is inserted down to the anterior edge of the lesion. Then, the biopsy handy - a thinner, longer needle (10 cm, 15 cm, or 20 cm) is introduced through the sheath. Finally, the biopsy needle is inserted 2 cm into the edge of the lesion for tissue sampling. Three or four samples can be taken using the thinner biopsy needle. After the examination, additional CT single shots were performed to rule out immediate complications like bleeding or pneumothorax. Afterward, the patients had bed rest for 2 hours, a laboratory check of the blood parameters, and an ultrasound follow-up after 6 hours to rule out potential complications such as capsular hematoma or any other signs of bleeding.

In patients with a prior Lipiodol-marking, the angiography was performed at a minimum interval of 12 hours before the biopsy. The angiographic approach was according to our standard procedure for hepatic interventions (Figure 2A).¹² The same team of interventional radiologists with over five years of experience conducted all interventions. The angiographic approach was through the femoral artery in all cases. After the introduction of the catheter [Boston Scientific], contrast medium iomeprol [Imeron®, Bracco] was used to display the abdominal and hepatic vessels. Following this, an overview angiography was performed. The superior mesenteric artery and celiac trunk were selectively catheterized, including an indirect portography to demonstrate vascular anatomy, ensure the portal vein's patency, and rule out portal vein thrombosis. Then, super-selective catheterization of the segmental and subsegmental hepatic branches was performed using a microcatheter [Progreat®, Terumo] for approach and precise placement. Lipiodol [Lipiodol Ultra-Fluid®, Guerbet] was administered as a tumor visualizer and transient embolic agent until stasis with a maximum amount of 15 ml. After the procedure, all patients were transferred to our ward for a minimum of 24-hour surveillance.

Patient data were retrieved from the electronic patient record (Orbis, Dedalus Healthcare), imaging data from the local radiology information system (RIS, GE Healthcare), and picture archiving and communication system (PACS, GE Healthcare). We included patients who matched the inclusion criteria and received a CT-guided biopsy between 01/2010 and 12/2018.

Demographic data, underlying hepatic diseases, and liver cirrhosis were analyzed. Based on the CT images, lesion diameter, number of lesions, and lesion localization were noted. In patients with a prior Lipiodol angiography, the Lipiodol enhancement of the lesions was evaluated (visible or non-visible). During the CT-guided intervention, the puncture path (lateral-intercostal, anterolateral, anterior-subcostal, dorsolateral), length cutis-to-lesion, and liver capsule-to-lesion were measured. Dose-length-product (DLP) and the number of images of the entire examination, which includes the planning scan and the post-procedure scan, as well as for puncture sequence, including scans for needle placement, positioning, and sample acquisition, were noted and compared. This differentiation was made to achieve optimal comparability, as the differences in radiation exposure are caused by the required placement and positioning scans. For the angiography, the dose-area-product (DAB) was noted. The major endpoint of this study was the evaluation of the hitting rate, defined by histopathological findings other than healthy liver tissue. Successful biopsy findings were defined as follows: hemangioma, focal nodular hyperplasia, regenerative nodule, granuloma, adenoma, necrosis, and all types of malignancies. Unsuccessful biopsies were defined as healthy liver tissue, steatosis, inflammatory disease, fibrosis, and toxic damage.

IBM SPSS statistics version 24 (IBM) was used for statistical analysis. For continuous data, median, mean, standard deviation, minimum, maximum, and range were calculated. For all continuous data, results were calculated for the whole study group and the three cohorts. The Chi-square test was used to test for differences in the successful biopsies between the three cohorts. In the first step, the whole study population was analyzed. In the second step, different subgroups (e.g., lesions < 20 mm, liver cirrhosis) were compared in detail.

Further, the Chi-square test was used to check for differences in the distribution of attributes within the groups. Correlations were calculated according to Spearman-Rho. P-values less than 0.05 was considered statistically significant. A logistic regression analysis was performed to screen for potential factors within the demographic factors influencing the lesion hitting rate.

Patient records were also screened for complications, during the intervention or within the 24-hour surveillance. Complications were rated according to the severity score based on SIR's latest classification: 0 = no complications, 1 = mild adverse events (no/non-substantial therapy required), 2 = moderate adverse event (substantial treatment required), 3 = severe adverse events (escalation of care), 4 = life-threatening or disabling event, 5 = patient death. Complication score was evaluated for the whole study population and the subgroups.²⁰

Six hundred-seven patients, 358 men (59%) and 249 women (41%) (mean age 61 years; SD ± 12.04; range 22–86 years) with unclear suspect liver lesions, were retrospectively evaluated. In 321 patients (52.9%), the biopsy was obtained with unenhanced imaging, 145 lesions were prior marked with Lipiodol (23.9%), and 141 patients received IV contrast for the intervention (23.2%) (Figure 1). Liver cirrhosis was histopathologically diagnosed in 188 patients (33.0%). Patient characteristics are displayed in detail in Table 1.

Most patients had a known hepatic disease (n = 310, 51.1%). The most common disease was hepatitis C in 101 cases (16.6%). Other more frequent preexisting hepatic diseases were toxic liver damage (n = 48, 7.9%), non-alcoholic steatohepatitis (NASH) (n = 34, 5.6%), and hepatitis B infection (n = 28, 4.6%). No pre-existing hepatic disease was reported in 297 patients (48.9%).

Based on patient medical records and the planning CT scan for the biopsy, 297 patients (48.9%) had a solitary suspect hepatic lesion, while 310 (51.1%) had two or more lesions. The target lesions were localized in all liver segments, with the majority found in liver segments 4 and 6 (each n = 112, 18.5%), and no differences according to the Chi-square test were seen between the three groups (p = 0.052). The mean lesion size was 29 ± 18 mm (range 4–116 mm). Target lesion smaller than 20 mm was seen in 229 patients (31.5%), and lesion smaller than 10 mm was seen in 38 patients (6.3%) (Table 1).

Access path was in 335 cases (55.2%) from lateral-intercostal, in 224 patients (36.9%) from anterior-subcostal, in 44 cases (7.2%) from anterior-lateral subcostal and in 4 cases (0.7%) from dorsal-lateral intercostal. The mean access path length from cutis to the lesion was 83 mm (± 26 mm), and within the liver from capsule to lesion, 43 mm (± 26 mm). Per patient, 2.6 probes were obtained in mean (± 1.3), equal across all groups assessed by the Chi-square test (p = 0.307) (Table 2). Regarding the visual aspect, all lesions previously marked in the angiography were seen in the biopsy-CT, either by lesion enhancement or circular enhancement of the surrounding tissue.

The target lesion was successfully biopsied in 444 patients (73.1%). In 163 patients (26.9%), the biopsy probe revealed healthy liver tissue defined as non-hitting of the target lesion. For group 1 with unenhanced CT, the biopsy was successful in 73.8% (n = 232). Group 2, with a prior Lipiodol-marking of the target lesion, showed the significantly highest hitting rate with 79.3% (n = 115) (Figure 2). The lowest hitting rate was seen in group 3 with IV contrast medium with 65.2% (n = 92) (Figure 3). The difference between all three groups was stated as significant (p = 0.037). In patients with liver target lesions smaller than 20 mm, the successful hitting rate was significantly higher after Lipiodol-marking compared to unenhanced or intravenous contrast-enhanced images (71.2%, 65.5%, and 47.7%, respectively) (p = 0.021). The location within the liver based on the liver segment model had no impact on the lesion hitting rate (p = 0.107) (Figure 4).

FIGURE 4.

The presence of liver cirrhosis showed no significant impact on the overall success of liver biopsy in all three groups (p = 0.94). In the subset of patients without liver cirrhosis, a successful biopsy was highest in the Lipiodol group, 74.4%, compared to 71.5% in the unenhanced group and 58.5% using IV contrast (p = 0.049).

Patients with a known malignant disease also showed a significant difference comparing the three procedures. A successful biopsy was possible in 83.0% (n = 39) using Lipiodol-marking, in 68.2% (n=131) unenhanced, and in 58.3% (n = 35) with IV contrast medium (p = 0.024). The entity of the biopsied lesion did not impact the hitting rate by showing no significant difference between the protocols.

Based on the performed logistic regression analysis, the lesion diameter (regression coefficient 0.023, p = 0.048) and the number of obtained probes (r = 0.199, p = 0.047) significantly impacted the hitting rate. Age and length of the puncture path, from cutis or liver capsule to lesion, revealed no significant impact.

Histopathological results revealed that the major malignant disease was HCC in 155 cases (25.5%). Inflammatory changes in the liver tissue were found to lead the non-malignant changes in 134 patients (22.1%). Appendix 1 shows the high variability of the diagnosed diseases.

Overall DLP was 498.31 mGycm² in mean (± 429.53 mGycm²) for the complete examination, including control and post-procedure scan. In the unenhanced group 1, 361.00 mGycm² (± 166.55 mGycm²), in the Lipiodol-marking group 2, 411.27 mGycm² (± 517.87 mGycm²), and in the IV contrast-medium group 3 900.27 mGycm² (± 495.55 mGycm²), reaching a significant difference with higher exposure in group 3 (p = 0.019).

Only counting the applied radiation during the biopsy scans, which contain the scans for needle placement, positioning, and sample acquisition, overall DLP was 80.07 mGycm² in mean (± 57.97 mGycm²), in group 1 with 79.69 mGycm² in mean (± 59.98 mGycm²), in group 2 with 88.19 mGycm² in mean (± 56.33 mGycm²) and group 3 with 72.59 mGycm² in mean (± 56.37 mGycm²), showing no significant differences (p = 0.053). The total amount of the intervention (i)-sequences was n = 34.4 (± 24.0), in group 1 n = 34.6 (± 23.8), in group 2 n = 37.7 (± 23.4), and in group 3 n = 30.6 (± 24.7) equal across all groups (p = 0.182) (Table 2).

For the previously performed angiography in group 2 to mark the lesion with Lipiodol, an overall DAP of 10421 cGycm² in mean (± 10277 cGycm²) was noted.

In 599 patients, no treatment-related complication was stated in the patient's medical record. Eight patients presented with a grade 1 complication: 3 patients with sub-capsular bleeding (0.5%), minimal hemorrhagic fluid edge surrounding the liver in 2 patients (0.3%), bleeding in the access path (1 patient, 0.2%), bleeding in the tumor (1 patient, 0.2%), and circulatory problems due to orthostatic problems (1 patient, 0.2%). No complications of grade 2 or higher were seen related to the intervention. No significant differences in the occurrence of complications were reported (p = 0.870). Details are given in Table 2.