Lukas Philipp Beyer

Percutaneous Ablation of Hepatic Tumors Using Irreversible Electroporation: A Prospective Safety and Midterm Efficacy Study in 34 Patients.

PURPOSE To evaluate the safety and efficacy of percutaneous irreversible electroporation (IRE) of primary and secondary liver cancer unsuitable for resection or thermal ablation. MATERIALS AND METHODS In this prospective, single-center study, 65 malignant liver tumors (hepatocellular carcinoma, n = 33; cholangiocellular carcinoma, n = 5; colorectal cancer metastasis, n = 22; neuroendocrine cancer metastasis, n = 3; testicular cancer metastasis, n = 2) in 34 patients (27 men, 7 women; mean age, 59.4 y ± 11.2) were treated. Local recurrence-free survival (LRFS) according to the Kaplan-Meier method was evaluated after a median follow-up of 13.9 months. RESULTS Median tumor diameter was 2.4 cm ± 1.4 (range, 0.2-7.1 cm). Of 65 tumors, 12 (18.5%) required retreatment because of incomplete ablation (n = 3) or early local recurrence (n = 9). LRFS at 3, 6, and 12 months was 87.4%, 79.8%, and 74.8%. The median time to progressive disease according to modified Response Evaluation Criteria In Solid Tumors was 15.6 months. Overall complication rate was 27.5% with six major complications and eight minor complications. Major complications included diffuse intraperitonal bleeding (n = 1), partial thrombosis of the portal vein (n = 1), and liver abscesses (n = 4). Minor complications were liver hematomas (n = 6) and clinically inapparent pneumothoraces (n = 2). CONCLUSIONS IRE showed promising results regarding therapeutic efficacy for the percutaneous treatment of liver tumors; however, significant concerns remain regarding its safety.

Factors associated with short-term local recurrence of liver cancer after percutaneous ablation using irreversible electroporation: a prospective single-center study.

PURPOSE To evaluate the risk factors associated with short-term local recurrence of malignant liver lesions after irreversible electroporation (IRE). MATERIALS AND METHODS Thirty-nine consecutive patients (79 malignant liver lesions) were treated with IRE, of whom 14 were excluded from the analysis (including 12 without 6 mo of follow-up and two with incomplete ablation). The remaining 25 patients (aged 59.4 y ± 11.2) had 48 malignant liver lesions, including 22 hepatocellular carcinomas (HCCs), six cholangiocellular carcinomas, and 20 metastatic liver cancers. Multivariate analyses were used to evaluate the associations of risk factors with early recurrence. The characteristics of patients, lesions, and IRE procedures were assessed by logistic regression. RESULTS Fourteen of the 48 treated lesions (29.2%) showed early local recurrence after 6 months. Tumor volume (< 5 cm(3) vs ≥ 5 cm(3); P = .022) and underlying disease type (HCC, cholangiocellular carcinoma, or metastatic disease; P = .023) were independently associated with early local recurrence. However, distances to the surrounding portal veins (< 0.5 cm vs ≥ 0.5 cm; P = .810), hepatic veins (P = .170), hepatic arteries (P = .761), and bile ducts (P = .226) were not significantly associated with local recurrence. CONCLUSIONS Because short distances to the surrounding vessels were not associated with early local recurrence, percutaneous IRE might provide an alternative treatment option for perivascular tumors. However, patients with larger tumor volumes appeared to be poor candidates for percutaneous IRE. Regarding the different types of treated lesions, patients with HCC had significantly better outcomes.

Stereotactically-navigated percutaneous Irreversible Electroporation (IRE) compared to conventional IRE: a prospective trial.

Purpose. The purpose of this study was to compare CT-navigated stereotactic IRE (SIRE) needle placement to non-navigated conventional IRE (CIRE) for percutaneous ablation of liver malignancies. Materials and Methods. A prospective trial including a total of 20 patients was conducted with 10 patients in each arm of the study. IRE procedures were guided using either CT fluoroscopy (CIRE) or a stereotactic planning and navigation system (SIRE). Primary endpoint was procedure time. Secondary endpoints were accuracy of needle placement, technical success rate, complication rate and dose-length product (DLP). Results. A total of 20 IRE procedures were performed to ablate hepatic malignancies (16 HCC, 4 liver metastases), 10 procedures in each arm. Mean time for placement of IRE electrodes in SIRE was significantly shorter with 27 ± 8 min compared to 87 ± 30 min for CIRE (p < 0.001). Accuracy of needle placement for SIRE was higher than CIRE (2.2 mm vs. 3.3 mm mean deviation, p < 0.001). The total DLP and the fluoroscopy DLP were significantly lower in SIRE compared to CIRE. Technical success rate and complication rates were equal in both arms. Conclusion. SIRE demonstrated a significant reduction of procedure length and higher accuracy compared to CIRE. Stereotactic navigation has the potential to reduce radiation dose for the patient and the radiologist without increasing the risk of complications or impaired technical success compared to CIRE.

Irreversible Electroporation of Malignant Hepatic Tumors - Alterations in Venous Structures at Subacute Follow-Up and Evolution at Mid-Term Follow-Up

Purpose To evaluate risk factors associated with alterations in venous structures adjacent to an ablation zone after percutaneous irreversible electroporation (IRE) of hepatic malignancies at subacute follow-up (1 to 3 days after IRE) and to describe evolution of these alterations at mid-term follow-up. Materials and Methods 43 patients (men/women, 32/11; mean age, 60.3 years) were identified in whom venous structures were located within a perimeter of 1.0 cm of the ablation zone at subacute follow-up after IRE of 84 hepatic lesions (primary/secondary hepatic tumors, 31/53). These vessels were retrospectively evaluated by means of pre-interventional and post-interventional contrast-enhanced magnetic resonance imaging or computed tomography or both. Any vascular changes in flow, patency, and diameter were documented. Correlations between vascular change (yes/no) and characteristics of patients, lesions, and ablation procedures were assessed by generalized linear models. Results 191 venous structures were located within a perimeter of 1.0 cm of the ablation zone: 55 (29%) were encased by the ablation zone, 78 (41%) abutted the ablation zone, and 58 (30%) were located between 0.1 and 1.0 cm from the border of the ablation zone. At subacute follow-up, vascular changes were found in 19 of the 191 vessels (9.9%), with partial portal vein thrombosis in 2, complete portal vein thrombosis in 3, and lumen narrowing in 14 of 19. At follow-up of patients with subacute vessel alterations (mean, 5.7 months; range, 0 to 14 months) thrombosis had resolved in 2 of 5 cases; vessel narrowing had completely resolved in 8 of 14 cases, and partly resolved in 1 of 14 cases. The encasement of a vessel by ablation zone (OR = 6.36, p<0.001), ablation zone being adjacent to a portal vein (OR = 8.94, p<0.001), and the usage of more than 3 IRE probes (OR = 3.60, p = 0.035) were independently associated with post-IRE vessel alterations. Conclusion Venous structures located in close proximity to an IRE ablation zone remain largely unaffected by this procedure, and thrombosis is rare.

Adverse effects of irreversible electroporation of malignant liver tumors under CT fluoroscopic guidance: a single-center experience.

PURPOSE We aimed to describe the frequency of adverse events after computed tomography (CT) fluoroscopy-guided irreversible electroporation (IRE) of malignant hepatic tumors and their risk factors. METHODS We retrospectively analyzed 85 IRE ablation procedures of 114 malignant liver tumors (52 primary and 62 secondary) not suitable for resection or thermal ablation in 56 patients (42 men and 14 women; median age, 61 years) with regard to mortality and treatment-related complications. Complications were evaluated according to the standardized grading system of the Society of Interventional Radiology. Factors influencing the occurrence of major and minor complications were investigated. RESULTS No IRE-related death occurred. Major complications occurred in 7.1% of IRE procedures (6/85), while minor complications occurred in 18.8% (16/85). The most frequent major complication was postablative abscess (4.7%, 4/85) which affected patients with bilioenteric anastomosis significantly more often than patients without this condition (43% vs. 1.3%, P = 0.010). Bilioenteric anastomosis was additionally identified as a risk factor for major complications in general (P = 0.002). Minor complications mainly consisted of hemorrhage and portal vein branch thrombosis. CONCLUSION The current study suggests that CT fluoroscopy-guided IRE ablation of malignant liver tumors may be a relatively low-risk procedure. However, patients with bilioenteric anastomosis seem to have an increased risk of postablative abscess formation.

Continuous Dynamic Registration of Microvascularization of Liver Tumors with Contrast-Enhanced Ultrasound

Aim. To evaluate the diagnostic value of quantification of liver tumor microvascularization using contrast-enhanced ultrasound (CEUS) measured continuously from the arterial phase to the late phase (3 minutes). Material and Methods. We present a retrospective analysis of 20 patients with malignant (n = 13) or benign (n = 7) liver tumors. The tumors had histopathologically been proven or clearly identified using contrast-enhanced reference imaging with either 1.5 T MRI (liver specific contrast medium) or triphase CT and follow-up. CEUS was performed using a multifrequency transducer (1–5 MHz) and a bolus injection of 2.4 mL sulphur hexafluoride microbubbles. A retrospective perfusion analysis was performed to determine TTP (time-to-peak), RBV (regional blood volume), RBF (regional blood flow), and Peak. Results. Statistics revealed a significant difference (P < 0.05) between benign and malignant tumors in the RBV, RBF, and Peak but not in TTP (P = 0.07). Receiver operating curves (ROC) were generated for RBV, RBF, Peak, and TTP with estimated ROC areas of 0.97, 0.96, 0.98, and 0.76, respectively. Conclusion. RBV, RBF, and Peak continuously measured over a determined time period of 3 minutes could be of valuable support in differentiating malignant from benign liver tumors.

Irreversible Electroporation Ablation of Malignant Hepatic Tumors: Subacute and Follow-up CT Appearance of Ablation Zones

PURPOSE To describe findings on contrast-enhanced computed tomography (CT) images of malignant hepatic tumors 24-72 hours after percutaneous ablation by irreversible electroporation (IRE) and at midterm follow-up. MATERIALS AND METHODS Retrospective analysis of 52 malignant liver tumors-30 primary hepatic tumors and 22 hepatic metastases-in 34 patients (28 men and 6 women, mean age 64 y) treated by IRE ablation was performed. Ablation zones were evaluated by two examiners in a consensus reading by means of a dual-phase CT scan (consisting of a hepatic arterial and portal venous phase) performed 24-72 hours after IRE ablation and at follow-up. RESULTS During the portal venous phase, ablation zones either were homogeneously hypoattenuating (n = 36) or contained heterogeneously isoattenuating or hyperattenuating (n = 16) foci, or both, in a hypoattenuating area. Of 52 lesions, 38 included gas pockets. Peripheral contrast enhancement of the ablation defect was evident in 23 tumors during the arterial phase and in 36 tumors during the portal venous phase. Four tumors showed intralesional abscesses after the intervention. At follow-up (mean, 4.7 mo), the mean volume of the ablation defects was reduced to 29% of their initial value. CONCLUSIONS Because normal findings on contrast-enhanced CT images after IRE ablation may be very similar to the typical characteristics of potential complications following ablation, such as liver abscesses, CT scans must be carefully analyzed to distinguish normal results after intervention from complications requiring further treatment.

Microwave ablation of large HCC lesions: Added value of CEUS examinations for ablation success control

PURPOSE To assess the value of dynamic contrast enhanced ultrasound (CEUS) for the detection of residual tumor tissue day 1 after microwave ablation (MWA) of large hepatocellular carcinoma (HCC) compared to MRI. MATERIAL AND METHODS 30 consecutive patients (5 females, 25 males, mean age 64 years, age range 54-73 years) with an untreated HCC lesion larger than or equal to 3 cm underwent percutaneous MWA between 03/2014 and 04/2016. 1 patient was excluded because of an artificial pacemaker. All remaining 29 patients underwent 3-T MRI with liver-specific contrast agent and CEUS 1 day after ablation to detect residual tumor tissue. The 6-week follow-up including CEUS and MRI was defined as the reference standard. RESULTS Complete ablation was achieved in 23 of 29 treated lesions (79%). The sensitivities and specificities for the detection of residual tumor tissue on day 1 were 100% and 83% for CEUS and 87% and 67% for MRI resp. without the differences being statistically significant. CONCLUSION CEUS allows a reliable assessment of therapeutic success of percutaneous ablation of large HCC lesions one day after the ablation. Its ability to visualize reactive periablation perfusion changes in real-time might be of advantage in the depiction of residual tumor tissue when compared to MRI imaging alone.

Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors

Aim of this retrospective analysis was to evaluate the survival times after percutaneous irreversible electroporation (IRE) in inoperable liver tumors not amenable to thermal ablation. 71 patients (14 females, 57 males, median age 63.5 ± 10.8 years) with 103 liver tumors were treated in 83 interventions using IRE (NanoKnife® system). The median tumor short-axis diameter was 1.9 cm (minimum 0.4 cm, maximum 4.5 cm). 35 patients had primary liver tumors and 36 patients had liver metastases. The Kaplan-Meier method was employed to calculate the survival rates, and the different groups were compared using multivariate log-rank and Wilcoxon tests. The overall median survival time was 26.3 months; the median survival of patients with primary land secondary liver cancer did not significantly differ (26.8 vs. 19.9 months; p = 0.41). Patients with a tumor diameter >3 cm (p < 0.001) or more than 2 lesions (p < 0.005) died significantly earlier than patients with smaller or fewer tumors. Patients with hepatocellular carcinoma and Child-Pugh class B or C cirrhosis died significantly earlier than patients with Child-Pugh class A (p < 0.05). Patients with very early stage HCC survived significantly longer than patients with early stage HCC with a median survival of 22.3 vs. 13.7 months (p < 0.05).

Intrasurgical dignity assessment of hepatic tumors using semi-quantitative strain elastography and contrast-enhanced ultrasound for optimisation of liver tumor surgery.

OBJECTIVE To evaluate the efficacy of strain elastography (SE) using semi-quantitative measurement methods compared to constrast enhanced ultrasound during liver tumor surgery (Io-CEUS) for dignity assessment of focal liver lesions(FLL). MATERIAL AND METHODS Prospective data acquisition and retrospective analysis of US data of 100 patients (116 lesions) who underwent liver tumor surgery between 10/2010 and 03/2016. Retrospective reading of SE color patterns was performed establishing groups depending on dominant color (>50% blue = stiff, inhomogenous, >50% yellow/red/green = soft tissue). Semi-quantitative analysis was performed by Q-analysis based on a scale from 0 (soft) to 6 (stiff). 2 ROIs were placed centrally, 5 ROIs in the lesions surrounding tissue. Io-CEUS was performed by bolus injection of 5-10 ml sulphurhexaflourid microbubbles evaluating wash-in- and -out- kinetics in arterial, portal venous and late phase. Histopathology after surgical resection served as goldstandard. RESULTS 100 patients (m: 65, f: 35, mean age 60.5 years) with 116 liver lesions were included. Lesions size ranged from 0.5 to 8.4 cm (mean 2.42 cm SD±1.44 cm). Postoperative histology showed 105 malignant and 11 benign lesions. Semi-quantitative analysis showed central indurations of >2.5 in 76/105 cases suggesting malignancy. 7 benign lesions displayed no central indurations correctly characterized benign by SE. ROC-analysis and Youden index showed a sensitivity of 72.4% and specificity of 63.6% assuming a cut-off of 2.5. Io-CEUS correctly characterized 103/105 as malignant. Sensitivity was 98%, specificity 72.7%. CONCLUSION Strain elastography is a valuable tool for non-invasive characterization of FLLs. Semi-quantitative intratumoral stiffness values of >2.5 suggested malignancy. However, sensitivity of Io-CEUS in detecting malignant lesions was higher compared to SE. In conclusion SE should be considered for routine use during intraoperative US in addition to Io-CEUS for optimization of curative liver surgery.