The Paradox of Modern Technology in Standardizing Thermal Liver Ablation: Fostering Uniformity or Diversity?

PURPOSE: Currently, significant medical practice variation exists in thermal ablation (TA) of malignant liver tumors with associated differences in outcomes. The IMaging and Advanced Guidance for workflow optimization in Interventional Oncology (IMAGIO) consortium aims to integrate interventional oncology into the standard clinical pathway for cancer treatment in Europe by 2030, by development of a standardized low-complex-high-precision workflow for TA of malignant liver tumors. This study was conducted at the start of the IMAGIO project with the aim to explore the current state and future role of modern technology in TA of malignant liver tumors. MATERIALS AND METHODS: A cross-sectional questionnaire was conducted followed by an expert focus group discussion with core members and collaborating partners of the consortium. RESULTS: Of the 13 participants, 10 respondents filled in the questionnaire. During the focus group discussion, there was consensus on the need for international standardization in TA and several aspects of the procedure, such as planning based on cross-sectional images, the adoption of different techniques for needle placement and the importance of needle position- and post-ablative margin confirmation scans. Yet, also considerable heterogeneity was reported in the adoption of modern technology, particularly in navigational systems and computer-assisted margin assessment. CONCLUSION: This study mirrored the current diversity in workflow of thermal liver ablation. To obtain comparable outcomes worldwide, standardization is needed. While advancements in tools and software hold the potential to homogenize outcome measurement and minimize operator-dependent variability, the rapid increase in availability also contributes to enhanced workflow variation.

Multicenter and inter-software evaluation of ablative margins after thermal ablation of colorectal liver metastases.

PURPOSE: To assess the association between minimal ablative margin (MAM) and local tumor progression (LTP) following CT-guided thermal ablation of colorectal liver metastases (CRLM) in a multicenter cohort and across two confirmation software. MATERIALS AND METHODS: This multicenter retrospective study included patients who underwent CT-guided radiofrequency or microwave ablation for CRLM between 2009 and 2021 in three institutions. Three-dimensional (3D) MAM was retrospectively assessed using dedicated ablation confirmation software by automatic non-rigid (Ablation-fit) or semi-automatic rigid co-registration (SAFIR) of intraprocedural pre- and post-ablation contrast-enhanced CT scans by two independent reader teams blinded to patient outcomes. LTP was assessed on a per-tumor basis. Factors associated with LTP-free survival were assessed using multivariable Cox regression analysis. RESULTS: Overall, 113 patients (mean age: 67 ± 10 years; 78 men) who underwent thermal ablation for 189 CRLM (mean diameter: 1.9 ± 1.1 cm) met the inclusion criteria. 173/189 (92%) CRLM could be successfully analyzed using both software. Over a median follow-up of 31 months (IQR: 22-47), 21 of 173 CRLM (12.1%) developed LTP. On multivariable analysis, 3D MAM was independently associated with LTP in both software (Ablation-fit: HR 0.47, 95% CI: 0.36-0.61, p < 0.001; SAFIR: HR 0.42, 95% CI: 0.32-0.55, p < 0.001). No LTP was observed in CRLM ablated with MAM ≥ 4 mm (Ablation-fit) and ≥ 5 mm (SAFIR). The per-tumor median absolute difference in MAM quantification between both software was 2 mm (IQR: 1-3). CONCLUSION: MAM was independently associated with LTP after thermal ablation of CRLM across multicenter data and two confirmation software. Ablations achieving a MAM ≥ 5 mm were associated with local control in both software. CLINICAL RELEVANCE STATEMENT: MAMs from intraprocedural contrast-enhanced CT were independently associated with LTP after thermal ablation of CRLM across multicenter data and two confirmation software, with a margin ≥ 5 mm associated with local control in both software. KEY POINTS: Sufficient ablative margins are critical for local control following thermal ablation of CRLM. Intraprocedural CT-derived MAM was the only independent factor associated with LTP across two confirmation software. No LTP was observed in CRLM ablated with a MAM ≥ 5 mm.

Identification of A0 minimum ablative margins for colorectal liver metastases: multicentre, retrospective study using deformable CT registration and artificial intelligence-based autosegmentation.

BACKGROUND: Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting. METHODS: This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour or local tumour progression) rates by minimum ablative margin across all institutions and identifying an intraprocedural contrast-enhanced CT-based minimum ablative margin associated with a 3-year local disease progression rate of less than 1%. RESULTS: A total of 400 ablated colorectal liver metastases (median diameter of 1.5 cm) in 243 patients (145 men; median age of 62 [interquartile range 54-70] years) were evaluated, with a median follow-up of 26 (interquartile range 17-40) months. A total of 119 (48.9%) patients with 186 (46.5%) colorectal liver metastases were from international institutions B, C, and D that were not involved in the software development. Three-year local disease progression rates for 0 mm, >0 and <5 mm, and 5 mm or larger minimum ablative margins were 79%, 15%, and 0% respectively for institution A (where the software was developed) and 34%, 19%, and 2% respectively for institutions B, C, and D combined. Local disease progression risk decreased to less than 1% with an intraprocedurally confirmed minimum ablative margin greater than 4.6 mm. CONCLUSION: A minimum ablative margin of 5 mm or larger demonstrates optimal local oncological outcomes. It is proposed that an intraprocedural minimum ablative margin of 5 mm or larger, confirmed using biomechanical deformable image registration, serves as the A0 for colorectal liver metastasis thermal ablation.

Robot-Assisted 2D Fluoroscopic Needle Placement-A Phantom Study.

RATIONALE AND OBJECTIVES: To evaluate the targeting accuracy of a novel robot-assisted guidance technique relying on one pair of 2D C-arm images. MATERIAL AND METHODS: In total, 160 punctures were carried out semi-automatically by using a novel robotic device. The needle's paths were planned based on one pair of 2D fluoroscopic images from different angles. Conically shaped aluminum tips inside a gelatin-filled plexiglass phantom served as targets. The accuracy of the needle placement was assessed by taking control CTs and measuring the Euclidean distance (ED) and normal distance (ND) between the needle and the target point. In addition, the procedural time per needle placement was evaluated. RESULTS: The accomplished mean NDs at the target for the 45°, 60°, 75° and 90° angles were 1.86 mm (SD ± 0.19), 2.68 mm (SD ± 0.18), 2.19 mm (SD ± 0.18) and 1.86 mm (SD ± 0.18), respectively. The corresponding mean EDs were 2.32 mm (SD ± 0.16), 2.68 mm (SD ± 0.18), 2.65 mm (SD ± 0.16) and 2.44 mm (SD ± 0.15). The mean duration of the total procedure, including image acquisition, trajectory planning and placement of four needles sequentially, was 12.7 min. CONCLUSIONS: Robotic guidance based on two 2D fluoroscopy images allows for the precise placement of needle-like instruments at the first attempt without the need for using an invasive dynamic reference frame. This novel approach seems to be a valuable tool for the precise targeting of various anatomical structures that can be identified in fluoroscopic images.

Innovations in Image-Guided Procedures: Unraveling Robot-Assisted Non-Hepatic Percutaneous Ablation.

Interventional oncology is routinely tasked with the feat of tumor characterization or destruction, via image-guided biopsy and tumor ablation, which may pose difficulties due to challenging-to-reach structures, target complexity, and proximity to critical structures. Such procedures carry a risk-to-benefit ratio along with measurable radiation exposure. To streamline the complexity and inherent variability of these interventions, various systems, including table-, floor-, gantry-, and patient-mounted (semi-) automatic robotic aiming devices, have been developed to decrease human error and interoperator and intraoperator outcome variability. Their implementation in clinical practice holds promise for enhancing lesion targeting, increasing accuracy and technical success rates, reducing procedure duration and radiation exposure, enhancing standardization of the field, and ultimately improving patient outcomes. This narrative review collates evidence regarding robotic tools and their implementation in interventional oncology, focusing on clinical efficacy and safety for nonhepatic malignancies.

Puncture Accuracy of Robot-Assisted CT-Based Punctures in Interventional Radiology: An Ex Vivo Study.

OBJECTIVES: The purpose of this study was to assess the performance of an optically tracked robot for computed-tomography (CT)-guided needle placements in a phantom study. METHODS: In total, 240 needle punctures were carried out with the help of an optically tracked robotic device (Micromate) based on CT image datasets at three different slice thicknesses (1, 3, and 5 mm). Conically shaped targets inside a gelatin-filled plexiglass phantom were punctured. The target positioning error between the planned and actual needle trajectory was assessed by measuring the lateral positioning error (ND) between the target and the puncture needle and the Euclidean distance (ED) between the needle tip and target in control CTs. RESULTS: The mean ND and ED for the thinnest CT slice thickness were 1.34 mm (SD ± 0.82) and 2.1 mm (SD ± 0.75), respectively. There was no significant impact of target depth on targeting accuracy for ND (p = 0.094) or ED (p = 0.187). The mean duration for the planning of one trajectory and for needle positioning were 42 s (SD ± 4) and 64 s (SD ± 7), respectively. CONCLUSIONS: In this ex vivo study, the robotic targeting device yielded satisfactory accuracy results at CT slice thicknesses of 1 and 3 mm. This technology may be particularly useful in interventions where the accurate placement of needle-like instruments is required.

Local Tumour Control Following Microwave Ablation: Protocol for the Prospective Observational CIEMAR Study.

PURPOSE: Microwave ablation (MWA) is a treatment modality for colorectal liver metastases (CRLM). While potentially curative, more information is needed on factors that contribute to long-term local tumour control. The prospective multicentre observational study CIRSE Emprint Microwave Ablation Registry aims to prospectively collect real-world technical data and clinical outcomes on patients treated with MWA in CRLM. METHODS: Eligible patients are adults with up to 9 local treatment naïve CRLM of ≤ 3 cm completely treatable with either MWA alone or MWA with resection and/or radiotherapy within 8 weeks. Data are collected, at baseline, every 3 months until 12 months, and thereafter every 6 months until the end of the study. The primary outcome measure is local tumour control. Secondary outcome measures are overall survival, (hepatic-) disease-free survival, time-to-progression untreatable by ablation, systemic therapy vacation, safety, and quality of life. Covariates related to the primary outcome measure will be assessed using a stratified log-rank test and an univariable Cox proportional hazard regression. A sample size of 500 patients with 750 lesions produces a two-sided 95% confidence interval with a precision equal to 0.057. RESULTS: Between September 2019 and December 2022, 500 patients have been enrolled with at least 976 treated tumours. CONCLUSION: The prospective observational CIEMAR study will provide valuable insights into the real-world use of MWA, helping in the future patient selection and clarifying factors that may contribute to long-term local tumour control. TRIAL REGISTRATION: NCT03775980.

Multi-Probe RFA vs. Single-Probe MWA in an Ex Vivo Bovine Liver Model: Comparison of Volume and Shape of Coagulation Zones.

OBJECTIVES: To compare the volumes and shapes of the coagulation zone (CZ) of a multi-probe RFA system (three RFA electrodes) and a single-probe MWA system from the same vendor in an ex vivo bovine liver model. MATERIAL & METHODS: A total of 48 CZs were obtained in bovine liver specimens with three different ablation system configurations (single-probe MWA vs. multi-probe RFA with 20 mm inter-probe distance [confluent CZ] vs. multi-probe RFA with 50 mm inter-probe distance [three individual CZs]) at 4, 6, 8, and 10 min ablation time using a fixed ablation protocol. Ablation diameters were measured and ellipticity indices (EIs) and volumes calculated. Calculations for all systems/configurations were compared. RESULTS: Volumes and diameters increased with ablation time for all configurations. At 4 and 6 min ablation time volumes obtained with the RFA 50 mm setup, and at 8 and 10 min with the RFA 20 mm setup were the largest at 26.5 ± 4.1 mL, 38.1 ± 5.8 mL, 46.3 ± 4.9 mL, 48.4 ± 7.3 mL, respectively. The single-probe MWA could not reach the volumes of the RFA setups for any of the ablation times evaluated. EI were very similar and almost round for RFA 20 mm and single-probe MWA, and differed significantly to the more ovoid ones for the RFA 50 mm configuration. CONCLUSIONS: The multi-probe RFA system employing three electrodes achieved significantly larger ablation volumes in both configurations (confluent CZ and three individual CZs) per time as compared with a single-probe MWA system in this ex vivo bovine liver model.

Early-Stage HCC Percutaneous Locoregional Management: East versus West Perspectives.

Hepatocellular carcinoma represents an important cause of death worldwide. Early-stage hepatocellular carcinoma patients not suitable for surgery can be treated with a variety of minimally invasive locoregional interventional oncology techniques. Various guidelines in different countries address the treatment of hepatocellular carcinoma, but the actual treatment is usually discussed by a multidisciplinary tumor board in a personalized manner, leading to potential treatment differences based on Western and Eastern perspectives. The aim of this paper is to integrate literature evidence with the eminent experiences collected during a focused session at the Mediterranean Interventional Oncology (MIO) Live Congress 2023.

Study Protocol STEREOLAB: Stereotactic Liver Ablation Assisted with Intra-Arterial CT Hepatic Arteriography and Ablation Confirmation Software Assessment.

PURPOSE: This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. MATERIALS AND METHODS: This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5 cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2 years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. DISCUSSION: The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).

Stereotactic ablation: A game changer?

For both primary and metastatic liver cancer, thermal ablation represents an interesting alternative to surgery. However, except for a small fraction of patients, conventional ultrasound- and CT-guided single-probe approaches have not achieved oncologic outcomes comparable with surgery. In this overview, we describe our stereotactic ablation workflow and discuss the short- and long-term results of stereotactic radiofrequency ablation (SRFA) and stereotactic microwave ablation (SMWA) for the treatment of primary and secondary liver tumours. The advantages of this method are discussed together with a summary of the existing stereotactic techniques for thermal ablation and the clinical data that support them. Stereotactic ablation is based on an optical navigation system and a specialized aiming tool. The workflow includes advanced three-dimensional planning, precise needle/probe placements according to the plan and intraoperative image fusion to check the needle positions and the ablation margins. Stereotactic ablation offers all the advantages of a minimally invasive procedure while producing oncological results comparable with surgery. The number of locally treatable liver cancers may be significantly expanded with these cutting-edge instruments and methods. We firmly believe that it can become a cornerstone in the treatment of liver cancers.

A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma.

BACKGROUND: HCC is the leading cause of cancer in chronic liver disease. A growing body of experimental mouse models supports the notion that gut-resident and liver-resident microbes control hepatic immune responses and, thereby, crucially contribute to liver tumorigenesis. However, a comprehensive characterization of the intestinal microbiome in fueling the transition from chronic liver disease to HCC in humans is currently missing. METHODS: Here, we profiled the fecal, blood, and liver tissue microbiome of patients with HCC by 16S rRNA sequencing and compared profiles to nonmalignant cirrhotic and noncirrhotic NAFLD patients. RESULTS: We report a distinct bacterial profile, defined from 16S rRNA gene sequences, with reduced α-and ß-diversity in the feces of patients with HCC and cirrhosis compared to NAFLD. Patients with HCC and cirrhosis exhibited an increased proportion of fecal bacterial gene signatures in the blood and liver compared to NAFLD. Differential analysis of the relative abundance of bacterial genera identified an increased abundance of Ruminococcaceae and Bacteroidaceae in blood and liver tissue from both HCC and cirrhosis patients compared to NAFLD. Fecal samples from cirrhosis and HCC patients both showed a reduced abundance for several taxa, including short-chain fatty acid-producing genera, such as Blautia and Agathobacter. Using paired 16S rRNA and transcriptome sequencing, we identified a direct association between gut bacterial genus abundance and host transcriptome response within the liver tissue. CONCLUSIONS: Our study indicates perturbations of the intestinal and liver-resident microbiome as a critical determinant of patients with cirrhosis and HCC.

Towards liver segmentation in the wild via contrastive distillation.

PURPOSE: Automatic liver segmentation is a key component for performing computer-assisted hepatic procedures. The task is challenging due to the high variability in organ appearance, numerous imaging modalities, and limited availability of labels. Moreover, strong generalization performance is required in real-world scenarios. However, existing supervised methods cannot be applied to data not seen during training (i.e. in the wild) because they generalize poorly. METHODS: We propose to distill knowledge from a powerful model with our novel contrastive distillation scheme. We use a pre-trained large neural network to train our smaller model. A key novelty is to map neighboring slices close together in the latent representation, while mapping distant slices far away. Then, we use ground-truth labels to learn a U-Net style upsampling path and recover the segmentation map. RESULTS: The pipeline is proven to be robust enough to perform state-of-the-art inference on target unseen domains. We carried out an extensive experimental validation using six common abdominal datasets, covering multiple modalities, as well as 18 patient datasets from the Innsbruck University Hospital. A sub-second inference time and a data-efficient training pipeline make it possible to scale our method to real-world conditions. CONCLUSION: We propose a novel contrastive distillation scheme for automatic liver segmentation. A limited set of assumptions and superior performance to state-of-the-art techniques make our method a candidate for application to real-world scenarios.

Laser Target System in Combination with an Aiming Device for Percutaneous CT-Guided Interventions - An Accuracy Study.

RATIONALE AND OBJECTIVES: To evaluate the targeting accuracy of laser-guided punctures in combination with an aiming device for computed tomography (CT) interventions during in vitro experiments. MATERIALS AND METHODS: A total of 600 CT-guided punctures were performed using a laser target system, half of them with the additional help of an aiming device. Conically shaped targets in a plexiglass phantom were punctured. The planning CT data sets were acquired with 1.25, 2.5 and 5 mm slice thickness. Needle placement accuracy, as well as procedural time, was assessed. The Euclidean (ED) and normal distances (ND) were calculated at the target point. RESULTS: Using the aiming device, the accomplished mean ND at the target for the 1.25, 2.5 and 5 mm slice thickness was 1.76 mm (SD ± 0.92), 2.09 mm (SD ± 1.06) and 1.93 mm (SD ± 1.38), respectively. Without aiming device, the corresponding results were 2.55 mm (SD ± 1.42), 2.7 mm (SD ± 1.43) and 2.31 mm (SD ± 1.64). At a slice thickness of 1.25 mm and 2.5 mm, punctures with the aiming device were significantly more accurate for both the ED and ND as compared to the punctures without aiming device (p < 0.001). The mean time required to complete the procedure, including image acquisition, trajectory planning, the placement of 10 needles, and the control-CT scan was 24.8 min without and 29.8 min with the aiming device. CONCLUSION: The additional use of the aiming device in combination with the commercially available laser guidance system significantly increased the level of accuracy during this in vitro experiment compared to freehand passes.

Reliability of Stereotactic Radiofrequency Ablation (SRFA) for Malignant Liver Tumors: Novice versus Experienced Operators.

PURPOSE: To compare the results of a novice with those of experienced interventional radiologists (IRs) for stereotactic radiofrequency ablation (SRFA) of malignant liver tumors in terms of safety, technical success, and local tumor control. METHODS: A database, including all SRFA procedures performed in a single center between January 2011 and December 2018 was retrospectively analyzed. A total of 39 ablation sessions performed by a novice IR were compared to the results of three more experienced IRs. Comparative SRFA sessions were selected using propensity score matching considering tumor type, age, sex, tumor size, and tumor number as matching variables. Overall, 549 target tumors were treated in 273 sessions. Median tumor size was 2.2 cm (1.0-8.5 cm) for 178 hepatocellular carcinomas (HCCs) and 3.0 cm (0.5-13.0 cm) for 371 metastases. A median of 2 (1-11) tumors were treated per session. RESULTS: No significant differences were observed when comparing the results of more experienced IRs with those of a novice IR regarding the rates of major complications (6.8% [16/234] vs. 5.1% [2/39]; p = 0.477), mortality (1.3% [2/234] vs. 0% [0/39]; p = 0.690), primary technical efficacy (98.5% [525/533] vs. 98.9% [94/95]; p = 0.735), and local recurrence (5.6% [30/533] vs. 5.3% [5/95]; p = 0.886). However, the median planning/placement time was significantly shorter for the experienced IRs (92 min vs. 119 min; p = 0.002). CONCLUSIONS: SRFA is a safe, effective, and reliable treatment option for malignant liver tumors and favorable outcomes can be achieved even by inexperienced operators with minimal supervision.

Ultrasound-guided versus computed tomography-controlled periradicular injections of the first sacral nerve: a prospective randomized clinical trial.

AIM: To compare ultrasound (US)-guided versus computed tomography (CT)-controlled periradicular injections of the first sacral spinal (S1) nerve in a prospective randomized clinical trial. MATERIALS AND METHODS: Thirty-nine patients with S1-radiculopathy were consecutively enrolled for 40 periradicular injections and assigned to an US or CT guided group. Needle position after US-assisted placement was controlled by a low-dose CT-scan. Accessibility, accuracy, and intervention time were compared. The overall effect on pain was matched evaluating the visual analog scale (VAS) decrease before and one month after the intervention. RESULTS: The mean intervention time was lower in the US-group compared to the CT-group: 4.4±3.46 min (1.3-13.2) vs. 6.5±3.03 min (2.4-12.5). Using CT-controlled infiltration the mean number of needle passes was with 1.15 higher than utilizing US-guidance. The therapeutic effect (mean difference between pre- and post-intervention, VAS scores) for the CT-group was 4.85±2.52 and for the US-group 4.55±2.74 with no significant difference between the two groups (p=0.7). CONCLUSION: US-controlled infiltrations of the first sacral nerve show a similar therapeutic effect to the time consuming, and ionizing CT-controlled injections and result in a significant reduction of procedure expenditure and avoidance of radiation.

Patient-specific needle guidance templates drilled intraprocedurally for image guided intervention: feasibility study in swine.

PURPOSE: Thermal ablation of large tumors may benefit from simultaneous placement of multiple needles, but accurate placement becomes challenging as the number of needles increases. The aim of this work was to evaluate use of personalized needle guidance grid templates based on intraprocedural CT and fabricated at the point of care to implement ablation treatment plans with multiple needles in vivo. METHODS: A plastic frame was designed to hold two parallel plastic guide plates in a rigid relationship, fixed over the abdomen by a mounting arm. Steel ball targets (1.5 mm) were implanted under ultrasound in the livers of two domestic swine under general anesthesia. Following breath-hold CT of the subject and frame, the targets and frame were identified using customized 3D Slicer-based planning software. Multiple needle trajectories targeting the balls were planned, including complex off-plane trajectories. A machining program for drilling the hole pattern corresponding to the planned needle trajectories was generated. The pattern was drilled in the two plates with a numerical-controlled milling machine in the suite. The plates were attached to the frame and needles passed through the paired holes to the calculated depth. Placement accuracy was defined as needle tip-to-target distance on post-placement CT. RESULTS: The planning process and manufacturing required approximately 6 and 15 min, respectively. Needles were rapidly inserted (n = 11) to the target points without complications or traversing nontarget anatomy. The mean needle tip-to-target distance error was 3.4 ± 2.2, range 0-7 mm. CONCLUSION: Rapid and accurate needle placement was feasible using a subject-specific, custom-drilled, needle guidance grid template fabricated intraprocedurally. Targeting accuracy and performance were similar to more complex and expensive tracking systems which may enable accurate intraprocedural implementation of treatment plans in the liver or other organs. This may be of value in complex ablation cases or in areas where more advanced guidance systems are not available.

Interleukin-11 drives human and mouse alcohol-related liver disease.

OBJECTIVE: Alcoholic hepatitis (AH) reflects acute exacerbation of alcoholic liver disease (ALD) and is a growing healthcare burden worldwide. Interleukin-11 (IL-11) is a profibrotic, proinflammatory cytokine with increasingly recognised toxicities in parenchymal and epithelial cells. We explored IL-11 serum levels and their prognostic value in patients suffering from AH and cirrhosis of various aetiology and experimental ALD. DESIGN: IL-11 serum concentration and tissue expression was determined in a cohort comprising 50 patients with AH, 110 patients with cirrhosis and 19 healthy volunteers. Findings were replicated in an independent patient cohort (n=186). Primary human hepatocytes exposed to ethanol were studied in vitro. Ethanol-fed wildtype mice were treated with a neutralising murine IL-11 receptor-antibody (anti-IL11RA) and examined for severity signs and markers of ALD. RESULTS: IL-11 serum concentration and hepatic expression increased with severity of liver disease, mostly pronounced in AH. In a multivariate Cox-regression, a serum level above 6.4 pg/mL was a model of end-stage liver disease independent risk factor for transplant-free survival in patients with compensated and decompensated cirrhosis. In mice, severity of alcohol-induced liver inflammation correlated with enhanced hepatic IL-11 and IL11RA expression. In vitro and in vivo, anti-IL11RA reduced pathogenic signalling pathways (extracellular signal-regulated kinases, c-Jun N-terminal kinase, NADPH oxidase 4) and protected hepatocytes and murine livers from ethanol-induced inflammation and injury. CONCLUSION: Pathogenic IL-11 signalling in hepatocytes plays a crucial role in the pathogenesis of ALD and could serve as an independent prognostic factor for transplant-free survival. Blocking IL-11 signalling might be a therapeutic option in human ALD, particularly AH.