Liver Ablation Research Articles

The Effect of Microwave and Radiofrequency Ablation (MWA/RFA) on Liver Volume in Patients with Primary and Secondary Liver Tumours: A Retrospective Analysis

PurposeIt is known that thermal liver ablation can induce liver hypertrophy. However, exact impact in liver volume remains unclear. The aim of this study is to assess the influence of radiofrequency or microwave ablation (RFA/MWA) on liver volume in patients with primary and secondary liver lesions. Findings can be relevant in assessing the potential extra benefit of thermal liver ablation in preoperatively performed liver hypertrophy inducing procedures, such as portal vein embolization (PVE).MethodsBetween January 2014–May 2022, 69 invasive treatment naïve patients with primary (n = 43) or secondary/metastatic (n = 26) liver lesions (in all segments, except in segments II/III) treated percutaneously by RFA/MWA were included. Total liver volume (TLV), segment II + III volume (serving as “distant liver volume”), ablation zone volume and absolute liver volume (ALV, calculated by subtracting the ablation zone volume from the TLV) were the study outcomes.ResultsALV in patients with secondary liver lesions increased to a median percentage of 106.87% (IQR = 99.66–113.03%, p = 0.016), volume of segments II/III increased to a median percentage of 105.81% (IQR = 100.06–115.65%, p = 0.003). ALV and segments II/III in patients with primary liver tumours remained stable, with a median percentage of 98.72% (IQR = 92.99–108.35%, p = 0.856) and 100.43% (IQR = 92.85–109.41%, p = 0.699), respectively.ConclusionIn patients with secondary liver tumours, ALV and segments II/III increased after MWA/RFA by an average of approximately 6%, while ALV in patients with primary liver lesions remained unchanged. Besides the curative intent, these findings indicate the potential added benefit of thermal liver ablation on FLR hypertrophy inducing procedures in patients with secondary liver lesions.Level of evidence Level 3, non-controlled retrospective cohort study.Graphical abstract

Clinical outcomes and cost of open, laparoscopic, and percutaneous ablation for hepatocellular carcinoma.

Open (OA), laparoscopic (LA), and percutaneous (PA) ablation are all ablation approaches for hepatocellular carcinoma (HCC) utilized in the United States today. However, it remains unclear today which approach is (A) most effective, (B) cost-efficient, and (C) nationally practiced. In-hospital mortality and cost were collected from the National Inpatient Sample (NIS) database for patients undergoing liver ablation from 2011 to 2018. Secondary outcomes included length of stay, disposition, and perioperative composite complications. We used inverse probability of treatment weighting (IPTW) to adjust for differences in patient and hospital baseline characteristics. One thousand and one hundred and twenty-five LA, 1221 OA, and 1068 PA liver ablations were analyzed. After IPTW, in-hospital mortality risk was significantly lower in PA versus OA cohorts (0.57% vs. 2.90%, p < 0.001) and reduced among PA patients, yet not significantly different from the LA cohort (0.57% vs. 1.64%, p = 0.056). The median length of hospital stay was significantly lower in the PA and LA group compared to OA (2 days vs. 6 days, p < 0.001). The median hospitalization costs were significantly lower for PA ($44,884 vs. $90,187, p < 0.001) and LA ($61,445 vs. $90,187, p < 0.001) compared to OA. Moreover, we found significant regional differences regarding the use of each ablation approach, with the Midwest having the lowest rates of PA and LA. Among patients hospitalized after ablation for HCC, PA leads to the lowest hospital cost. Both PA and LA result in lower peri-operative morbidity and mortality relative to OA. Despite these reported advantages, there are significant regional differences with respect to ablation availability suggesting the need to promote the standardization of best practices.

Intraoperative Ultrasound in Minimally Invasive Laparoscopic and Robotic Pediatric Surgery: Our Experiences and Literature Review.

Ultrasound (US) is a non-invasive imaging technique frequently used to examine internal organs and superficial tissues, and invaluable in pediatric patients. In a surgical setting, intraoperative ultrasound allows to highlight anatomical structures in detail during traditional open and minimally invasive surgery, thanks to the use of specific probes. In fact, laparoscopic and robotic ultrasonography requires the development of specialized transducers that fit through laparoscopic trocars. In adults, laparoscopic ultrasound is used during cholecystectomy before dissection of the triangle of Calot, to guide liver biopsies and ablation procedures and for the staging of patients with pancreas adenocarcinoma. However, the applications in the pediatric field are still limited. This paper aims to share our preliminary experience with ultra-sound in minimally invasive laparoscopic and robotic pediatric surgery, describing two cases in which intra-operative ultrasound was applied, and to present a review of the literature on the state of the art of the actual uses in pediatric surgery.

Impact of frailty on long-term outcomes after liver resection for hepatocellular carcinoma in elderly patients: A prospective study

BackgroundsFrailty affects short-term outcomes after liver resection in elderly patients. However, frailty's effects on long-term outcomes after liver resection in elderly patients with hepatocellular carcinoma (HCC) are unknown. MethodsThis prospective, single-center study included 81 independently living patients aged ≥65 years scheduled to undergo liver resection for initial HCC. Frailty was evaluated according to the Kihon Checklist, a phenotypic frailty index.” We investigated and compared postoperative long-term outcomes after liver resection between patients with and without frailty. ResultsOf the 81 patients, 25 (30.9%) were frail. The proportion of patients with cirrhosis, high serum alpha-fetoprotein level (≥200 ng/mL), and poorly differentiated HCC was higher in the frail group than in the nonfrail group (n = 56). Among the patients with postoperative recurrence, the incidence of extrahepatic recurrence was higher in the frail group than in the nonfrail group (30.8% vs. 3.6%, P = 0.028). Moreover, the proportion of patients who underwent repeat liver resection and ablation for recurrence who met the Milan criteria tended to be lower in the frail group than in the nonfrail group. Although there was no difference in disease-free survival between the two groups, the overall survival rate in the frail group was significantly worse than that in the nonfrail group (5-year overall survival: 42.7% vs. 77.2%, P = 0.005). Results of the multivariate analysis indicated that frailty and blood loss were independent prognostic factors for postoperative survival. ConclusionFrailty is associated with unfavorable long-term outcomes after liver resection in elderly patients with HCC.

Abstract CT003: IMbrave050: Phase 3 study of adjuvant atezolizumab + bevacizumab versus active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation

Abstract Background: The risk of HCC recurrence after liver resection or ablation with curative intent is 70-80% within 5 years, indicating an unmet need for effective adjuvant therapies. Atezolizumab (atezo) with bevacizumab (bev) is the standard of care for unresectable HCC based on the IMbrave150 study, which demonstrated statistically significant and clinically meaningful improvements in overall survival (OS), progression-free survival, and objective response rate versus sorafenib (Finn NEJM 2020, Cheng J Hepatol 2022). On the basis of the antitumor activity of atezo + bev and its capacity to positively modulate the tumor microenvironment, IMbrave050 was designed to evaluate the efficacy of adjuvant atezo + bev in delaying or preventing recurrence in patients (pts) with high-risk HCC. Methods: IMbrave050 (NCT04102098) enrolled pts with HCC at high risk of recurrence following resection or ablation. High-risk criteria were based on tumor burden (tumor size and number), vascular invasion, and tumor differentiation. Pts were randomized to Arm A (atezo + bev) or Arm B (active surveillance). Stratification factors included geographic region (Asia-Pacific excluding Japan vs rest of world) and a composite factor encompassing the number of high-risk features, curative procedure, and use of optional adjuvant TACE (allowed for one cycle following resection). Pts in Arm A received atezo 1200 mg + bev 15 mg/kg IV q3w for a period of one year or 17 cycles. Pts in Arm B underwent active surveillance for one year and were eligible to crossover to atezo + bev following independent review facility (IRF) confirmation of recurrence. The primary endpoint was IRF-assessed recurrence-free survival (RFS). Secondary efficacy endpoints included OS; investigator-assessed (INV) RFS; RFS and OS according to PD-L1 status; and time to extrahepatic spread and/or macrovascular invasion. Results: The ITT population included 334 pts each in Arms A and B. Baseline demographics were well balanced between arms. At interim analysis, with a median follow-up of 17.4 mo (cut off date: Oct 21, 2022), the primary endpoint was met with an IRF-RFS HR of 0.72 (95% CI, 0.56, 0.93; P=0.0120), and results were generally consistent across clinical subgroups. INV-RFS was similar (HR, 0.70; 95% CI, 0.54, 0.91). The safety of atezo + bev was generally manageable and consistent with the well-established safety profile of each therapeutic agent and with the underlying disease. Conclusions: Atezo + bev is the first adjuvant regimen to demonstrate a statistically significant and clinically meaningful improvement in RFS vs active surveillance in pts at high risk of disease recurrence following resection or ablation. The benefit:risk profile of atezo + bev favors the use of this regimen as an adjuvant therapy and has potential to set a new standard of care in adjuvant HCC. Citation Format: Pierce Chow, Minshan Chen, Ann-Lii Cheng, Ahmed O. Kaseb, Masatoshi Kudo, Han Chu Lee, Adam Yopp, Jian Zhou, Lu Wang, Xiaoyu Wen, Jeong Heo, Won Young Tak, Shinichiro Nakamura, Kazushi Numata, Thomas Uguen, David Hsiehchen, Edward Cha, Stephen P. Hack, Qinshu Lian, Jessica Spahn, Chun Wu, Shukui Qin. IMbrave050: Phase 3 study of adjuvant atezolizumab + bevacizumab versus active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT003.

PO-03-063 A POLYACRYLAMIDE (PAA) GEL PHANTOM FOR STUDYING CATHETER ABLATION

Benchtop studies are often used to evaluate cardiac ablation techniques, and commonly utilize ex-vivo animal tissues. While widely available, ex-vivo animal tissues do not consistently replicate live atrial tissue physical properties, adding variability. Tissue mimicking phantoms have been used in non-cardiac ablation studies, but their mechanical and electrical properties may not mimic cardiac tissue. Furthermore, analysis of ablation lesions ex-vivo has been limited to 2D measurements of lesion cross-sections, precluding lesion volume measurement and limiting accuracy. Polyacrylamide (PAA) gels, which have modifiable elasticity, and similar thermal and electrical properties to live human tissues, have been used to study liver ablation. The addition of bovine serum albumin (BSA) – a protein that coagulates when heated beyond a set temperature – has also been shown to provide optical and MRI contrast in ablated gels. The aim of this study was to develop a reproducible atrial tissue phantom with realistic elasticity, friction, and electrical impedance, enabling in-vitro replication of cardiac ablation lesions and 3D quantification using high resolution MRI scans. Gels were mixed with acrylamide concentrations from 3% to 12% (g/mL) and 2% BSA. Resulting Young's moduli and coefficients of friction were measured with a custom tester. Reference frictional properties of ex-vivo porcine aortic specimens were measured using the same methods. Reference elasticity values were derived from the literature. Gels were ablated in saline with 20-40W of power, for 20-40s, with 10-20g of contact force. Baseline impedances were set to 125Ω by titrating the salinity of the bath. Finally, gels were imaged using a 3D T2-weighted sequence on a 3T MRI scanner. The elasticity and friction of the fabricated gels are reported in Table 1, along with reference values. 10.5-12% acrylamide PAA gel phantoms matched live contractile tissue elasticity, and simulated realistic atrial tissue frictional and electrical properties. Ablations were made optically visible by the coagulation of coagulated BSA (Fig 1a) and appeared hypointense on T2-MRI (Fig 1b), enabling automated 3D analysis by thresholding. Measured lesion dimensions were comparable to those reported in prior literature. PAA gel phantoms enabled in-vitro replication of cardiac lesions with realistic mechanical and electrical properties. The addition of BSA facilitated optical verification of lesions and 3D quantification using MRI.Tabled 1Table 1: Reference and measured physical properties of gel phantoms and ex-vivo aortae as compared to literature valuesPhysical PropertyReferenceMeasured ValueMaterialValueMaterialValueYoung's Modulus (kPa)Ex-vivo porcine left atrium28.0% PAA gel32.6In-vivo human left ventricle20-200.210.5% PAA gel68.1In-vivo skeletal muscle6.2-108.612.0% PAA gel108.0Coefficient of FrictionEx-vivo porcine aorta0.02-0.046Ex-vivo porcine aorta0.058±0.024Agarose gel0.03510.5% PAA gel0.023±0.0014 Open table in a new tab

Transcatheter CT arteriography-guided irreversible electroporation of locally advanced pancreatic adenocarcinoma: A pictorial essay.

Visibility of the tumour and its surroundings during the ablative procedure is crucial for optimal treatment planning, needle placement, ablation zone coverage and postprocedural control. The use of transcatheter CT arteriography providing real-time image guidance has proven to be of additional value for thermal liver ablation. The general advantages of the technique could be of value for other indications and ablation techniques as well, especially when requiring multiple needle placements in the vicinity of precarious vascular structures. This pictorial essay presents six clinical cases that illustrate transcatheter CT arteriography guidance during the treatment of locally advanced pancreatic cancer with irreversible electroporation. The illustrations highlight the technique's ability to improve visibility of vascular structures and the advantage of real-time monitoring and treatment of intraprocedural vascular complications. The use of transcatheter CT arteriography can support the interventionalist with respect to periprocedural safety and accuracy of electrode placement for pancreatic irreversible electroporation.

A survey of liver ablation amongst UK interventional radiologists

To characterise training for, and conduct of, image-guided liver tumour ablation amongst UK interventional radiologists. A web-based survey of British Society of Interventional Radiology members was carried out between 31 August to 1 October 2022. Twenty-eight questions were designed, covering four domains: (1) respondent background, (2) training, (3) current practice, and (4) operator technique. One hundred and six responses were received, with an 87% completion rate and an approximate response rate of 13% of society members. All UK regions were represented, with the majority from London (22/105, 21%). Seventy-two out of 98 (73%) were either extremely or very interested in learning about liver ablation during training, although levels of exposure varied widely, and 37/103 (36%) had no exposure. Performed numbers of cases also varied widely, between 1-10 cases and >100 cases per operator annually. All (53/53) used microwave energy, and most routinely used general anaesthesia (47/53, 89%). Most 33/53 (62%) did not have stereotactic navigation system, and 25/51(49%) always, 18/51 (35%) never, and 8/51(16%) sometimes gave contrast medium (mean 40, SD 32%) after procedures. Fusion software to judge ablation completeness was never used by 86% (43/55), sometimes used by 9% (5/55), and always used by 13% (7/55) of respondents. Although there are high levels of interest in image-guided liver ablation amongst UK interventional radiologists, training arrangements, operator experience, and procedural technique vary widely. As image-guided liver ablation evolves, there is a growing need to standardise training and techniques, and develop the evidence base to ensure high-quality oncological outcomes.

Robotic versus freehand CT-guided radiofrequency ablation of pulmonary metastases: a comparative cohort study

PurposeRadiofrequency ablation (RFA) is a curative treatment option for small lung metastases, which conventionally involves multiple freehand manipulations until the treating electrode is satisfactorily positioned. Stereotactic and robotic guidance has been gaining popularity for liver ablation, although has not been established in lung ablation. The purpose of this study is to determine the feasibility, safety, and accuracy of robotic RFA for pulmonary metastases, and compare procedures with a conventional freehand cohort.MethodsA single center study with prospective robotic cohort, and retrospective freehand cohort. RFA was performed under general anesthesia using high frequency jet ventilation and CT guidance. Main outcomes were (i) feasibility/technical success (ii) safety using Common Terminology Criteria for Adverse Events (iii) targeting accuracy (iv) number of needle manipulations for satisfactory ablation. Robotic and freehand cohorts were compared using Mann–Whitney U tests for continuous variables, and Fisher’s exact for categorical variables.ResultsThirty-nine patients (mean age 65 ± 13 years, 20 men) underwent ablation of 44 pulmonary metastases at single specialist cancer center between July 2019 and August 2022. 20 consecutive participants underwent robotic ablation, and 20 consecutive patients underwent freehand ablation. All 20/20 (100%) robotic procedures were technically successful, and none were converted to freehand procedures. There were 6/20 (30%) adverse events in the robotic cohort, and 15/20 (75%) in the freehand cohort (P = 0.01). Robotic placement was highly accurate with 6 mm tip-to-target distance (range 0–14 mm) despite out-of-plane approaches, with fewer manipulations than freehand placement (median 0 vs. 4.5 manipulations, P < 0.001 and 7/22, 32% vs. 22/22, 100%, P < 0.001).ConclusionsRobotic radiofrequency ablation of pulmonary metastases with general anesthesia and high frequency jet ventilation is feasible and safe. Targeting accuracy is high, and fewer needle/electrode manipulations are required to achieve a satisfactory position for ablation than freehand placement, with early indications of reduced complications.

Complications Associated with Image-Guided Percutaneous Thermal Ablation of Liver Tumors

AbstractImage-guided thermal ablation of liver cancer is a well-established treatment for patients with primary or secondary liver tumors. While the safety profile for liver ablations is high, several procedure-related complications can occur. An awareness of the potential complications, their recognition, and management are essential for the interventionist who performs liver ablation. This review will describe some of the most frequently encountered complications associated with image-guided thermal ablation of hepatic malignancies.

Neoadjuvant chemotherapy does not increase risk for anastomotic leak for simultaneous resection of primary colon cancer with synchronous liver metastasis: A NSQIP-colectomy analysis.

In patients with colon cancer with synchronous liver metastasis, treatment algorithms are complex and often require multidisciplinary evaluation. Neoadjuvant therapy is frequently utilized, but there is an unclear relationship with postoperative outcomes in patients with simultaneous resection. This is a retrospective cohort study from the National Surgical Quality Improvement Program and Targeted Colectomy databases. All patients with stage IV colon cancer undergoing simultaneous colectomy with synchronous liver metastasis resection or ablation between 2015 and 2019 were identified and categorized into subgroups based on receipt of neoadjuvant chemotherapy. Multivariable logistic regression was utilized to assess for risk factors of anastomotic leaks and serious postoperative complications. We identified 1006 patients who underwent simultaneous colectomy and liver operations. Of those, 418 (41.6%) received neoadjuvant chemotherapy within 90 days of surgery, while 588 (58.4%) had simultaneous upfront surgery. On multivariable logistic regression, neoadjuvant therapy was not associated with postoperative anastomotic leaks (odds ratio [OR]:1.30; p = 0.39) or serious complications (OR: 1.04; p = 0.82). Neoadjuvant therapy does not increase postoperative complications in simultaneous colon and liver resections. These results may alleviate concerns regarding postoperative morbidity in the decision-making process of administering neoadjuvant therapy.

Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.

Abstract No. 49 Motion Compensation in 3D MRI-US Fusion Using Fast Deformable Registration: A Feasibility Study for Real-Time Intervention

The heterogeneity of hepatocellular carcinoma may be better seen with magnetic resonance imaging (MRI) compared with CT due to its high soft tissue contrast, providing precise tumor targets during therapy, while ultrasound (US) remains as the imaging modality for real-time guidance. Image fusion methods existing in clinical workflows involve rigid registration only and fail to compensate for liver motion in US. In this work, we present a hybrid deformable fusion method to align pre-interventional 3D MRI and interventional 3D US in real-time. Multimodal pre-interventional MRI (pMRI) and US (pUS) volumes were obtained from 3 human volunteers using a simultaneous MRI-US acquisition system, with an MR-compatible, hands-free US probe. pMRI and pUS volumes were aligned using conventional deformable registration, as it is not time critical. Deep learning (DL)–based registration was used for real-time fusion of pUS to iUS, and consecutive iUS volumes in near real time. The predicted DL deformation fields were used to deform the pMRI to match each US volume. US data with respiration were collected at a temporal resolution of 4.2 volumes/sec. 1600 US volumes from one volunteer was used for DL training. The hybrid deformable registration method was evaluated for pMRI and 20 US volume alignments for each volunteer. Mean Euclidean distance error between expert placed landmarks and predicted positions of landmarks after image alignment were computed. Table 1 shows the mean landmark error (LE) and computation times for the hybrid (HDR) and conventional deformable registration (CDR) method aligning pMRI and 20 US volumes. Feasibility of a multimodal hybrid deformable registration method with clinically acceptable registration accuracy and low latency was shown. The method for motion compensation may improve tumor targeting in interventional procedures including liver ablation.

Treatment of recurrent hepatocellular carcinoma following liver resection, ablation or liver transplantation

Treatment of recurrent hepatocellular carcinoma following liver resection, ablation or liver transplantation

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise.

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year, with an estimated 5-year survival rate of 30%-35% after diagnosis. Hepatocellular carcinoma (HCC) constitutes a significant subtype of liver cancer (approximate75%) and is considered primary liver cancer. Treatment for liver cancer mainly depends on the stage of its progression, where surgery including, hepatectomy and liver transplantation, and ablation and radiotherapy are the prime choice. For advanced liver cancer, various drugs and immunotherapy are used as first-line treatment, whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins. Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are second-line therapy. Various metabolic and signaling pathways such as Notch, JAK/ STAT, Hippo, TGF-β, and Wnt have played a critical role during HCC progression. Dysbiosis has also been implicated in liver cancer. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

Monitoring of thermal lesions in ultrasound using fully convolutional neural networks: A preclinical study

Accurate monitoring of thermal ablation regions is an important guarantee for successful ablation treatment, which mainly depends on the subjective judgment of radiologists in current clinical practice. This work innovatively applied fully convolutional neural networks (FCNs) for detection and monitoring of thermal ablation regions in ultrasound (US) and comprehensively compared the performance of VGG16-FCN, U-Net, UNet++, Attention U-Net, MultiResUNet, and ResUNet, which have shown outstanding performance in medical image segmentation. The input of the models was US echo envelope data backscattered from the ablated regions. Excised porcine liver ablation dataset and clinical liver tumors ablation dataset were respectively used to evaluate the prediction ability of the models. With 1000 excised porcine liver ablation samples for training and 200 samples for testing, the UNet++ achieves both the highest Dice score (DSC) of 0.7824 ± 0.1098 and the best Hausdorff distance (HD) of 2.70 ± 1.38 mm. Additionally, considering potential clinical usage, we also tested the model generalizability by training on the excised dataset and testing on the clinical data, in which we obtained the performance with the highest DSC obtained by the ResUNet and the best HD by the UNet++. Our comparative study suggests that both UNet++ and ResUNet have relatively outstanding segmentation performance among all compared models, which are potential candidates for automatic segmentation of thermal ablation regions in US during clinical ablation treatment.

Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish.

The liver is a highly regenerative organ, yet the presence of a dedicated stem cell population remains controversial. Here, we interrogate a severe hepatocyte injury model in adult zebrafish to define that regeneration involves a stem cell population. After near-total hepatocyte ablation, single-cell transcriptomic and high-resolution imaging analyses throughout the entire regenerative timeline reveal that biliary epithelial cells undergo transcriptional and morphological changes to become hepatocytes. As a population, biliary epithelial cells give rise to both hepatocytes and biliary epithelial cells. Biliary epithelial cells proliferate and dedifferentiate to express hepatoblast transcription factors prior to hepatocyte differentiation. This process is characterized by increased MAPK, PI3K, and mTOR signaling, and chemical inhibition of these pathways impairs biliary epithelial cell proliferation and fate conversion. We conclude that, upon severe hepatocyte ablation in the adult liver, biliary epithelial cells act as facultative liver stem cells in an EGFR-PI3K-mTOR-dependent manner.

Use of Contrast Media During CT-guided Thermal Ablation of Colorectal Liver Metastasis for Procedure Planning is Associated with Improved Immediate Outcomes.

The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes. This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used to estimate effects of pre-ablation CECT on residual unablated tumor, 3D-MAM, and local tumor progression-free survival (LTPFS). Pre-ablation CECT was acquired in 71/173 (41%) sessions. Residual unablated tumor was present in one (0.9%) versus nine tumors (6.6%) ablated with versus without using pre-ablation CECT, respectively (p = 0.024). Pre-ablation CECT use decreased the odds of residual disease on first follow-up by 78% (CI95% [5, 86]) and incomplete ablation (3D-MAM ≤ 0mm) by 58% (CI95% [13, 122]). The odds ratio for residual unablated tumor for larger CLM was lower when pre-ablation CECT was used (odds ratio 1.0 with pre-ablation CECT vs. 2.52 without). Pre-ablation CECT use was not associated with improvements on LTPFS. Pre-ablation CECT is associated with improved immediate outcomes by significantly reducing the incidence of residual unablated tumor and by mitigating the risk of incomplete ablation for larger CLM. We recommend performing baseline intra-procedural pre-ablation CECT as a standard imaging protocol. Level 3 (retrospective cohort study).

PFKFB3-mediated Pro-glycolytic Shift in Hepatocellular Carcinoma Proliferation.

Metabolic reprogramming, in particular, glycolytic regulation, supports abnormal survival and growth of hepatocellular carcinoma (HCC) and could serve as a therapeutic target. In this study, we sought to identify glycolytic regulators in HCC that could be inhibited to prevent tumor progression and could also be monitored invivo, with the goal of providing a theragnostic alternative to existing therapies. An orthotopic HCC rat model was used. Tumors were stimulated into a high-proliferation state by use of off-target liver ablation and were compared with lower-proliferating controls. We measured invivo metabolic alteration in tumors before and after stimulation, and between stimulated tumors and control tumors using hyperpolarized 13C magnetic resonance imaging (MRI) (h13C MRI). We compared metabolic alterations detected by h13C MRI to metabolite levels from exvivo mass spectrometry, mRNA levels of key glycolytic regulators, and histopathology. Glycolytic lactate flux increased within HCC tumors 3 days after tumor stimulation, correlating positively with tumor proliferation as measured with Ki67. This was associated with a shift towards aerobic glycolysis and downregulation of the pentose phosphate pathway detected by mass spectrometry. MRI-measured lactate flux was most closely coupled with PFKFB3 expression and was suppressed with direct inhibition using PFK15. Inhibition of PFKFB3 prevents glycolytic-mediated HCC proliferation, trackable by invivo h13C MRI.

Virtual Treatment Zone From Cone Beam CT Commonly Alters Treatment Plan and Identifies Tumor at Risk for Under-Treatment in US or US Fusion-Guided Microwave Ablation of Liver Tumors.

Tumor ablation is included in several major cancer therapy guidelines. One technical challenge of percutaneous ablation is targeting and verification of complete treatment, which is prone to operator variabilities and human imperfections and are directly related to successful outcomes, risk for residual unablated tumor and local progression. The use of "Prediction Ablation Volume Software" may help the operating Interventional Radiologist to better plan, deliver, and verify before the ablation, via virtual treatment zones fused to target tumor. Fused and superimposed images provide 3-dimensional information from different timepoints, just when that information is most useful. The aim of this study is to evaluate the technical success and efficacy of an ablation treatment flowchart provided by a cone beam computed tomography (CBCT) "Prediction Ablation Volume Software." This is a single-center retrospective study. From April 2021 to January 2022, 29 nonconsecutive evaluable patients with 32 lesions underwent liver ablation with Prediction Ablation Volume Software. Each patient was discussed in a multidisciplinary tumor board and underwent an enhanced computed tomography or magnetic resonance imaging approximately 1 month before the procedure, as well as ∼1 month after. Technical success was defined as treatment of the tumor according to the protocol, covered completely by the Prediction Ablation Volume. Technical efficacy was defined as assessment of complete ablation of the target tumor at imaging follow up (∼1 month). Technical success, technical efficacy, and procedural factors were studied. Technical success was achieved in 30 of 32 liver lesions (94%), measuring 20 mm mean maximum diameter. The antenna was repositioned in 16 of 30 (53%) evaluable target lesions. Residual tumor was detected at 1 month imaging follow up in only 4 of 30 (13%) of the treated lesion. Technical efficacy was of 87% in this retrospective description of our process. The implementation of a CBCT Prediction Ablation Volume Software and flowchart for the treatment of liver malignancies altered the procedure, and demonstrated high technical success and efficacy. Such tools are potentially useful for procedural prediction and verification of ablation.