Treatment Of Hepatic Tumors Research Articles

Determining beta radiation doses from Y-90 microsphere for the treatment of hepatic tumors by using Monte Carlo and analytical methods

The very short range of beta radiation is a potential radiation treatment for tumor, which can preserve sensitive structures. However, due to the limited range of beta radiation, practical dosimetry of beta sources may be a point of concern, and theoretical dosimetry methods play an important role. A resin microsphere loaded with the Yttrium-90 (Y-90) radionuclide can be applied in the radioembolization of hepatic tumors. In this work, we present initial calculations of dose rates around a microsphere loaded with the Y-90 radionuclide uniformly distributed on its exterior surface. Two approaches were used to carry out the estimations: the first one by means of Monte Carlo simulations using the PENELOPE code and the second one by means of the beta-point dose function formalism. A Fortran code was developed to handle with the various quantities necessary to perform the numerical integration of the beta-point dose function. A comparison between results obtained by means of both methods indicated a maximum difference of ~5% up to the 0.3 cm distance from the center of the sphere.

HMGB1-Mediated Cell Death-A Crucial Element in Post-Hepatectomy Liver Failure.

Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models. Plasma from 96 LR patients and liver tissues from a subset of 24 LR patients were analyzed for HMGB1 levels, and associations with PHLF and liver injury markers were assessed. In a murine LR model, the HMGB1 inhibitor glycyrrhizin, was administered to assess its impact on liver regeneration. Furthermore, plasma levels of keratin-18 (K18) and cleaved cytokeratin-18 (ccK18) were quantified to assess suitability as predictive biomarkers for PHLF. Patients experiencing PHLF exhibited elevated levels of intrahepatic and circulating HMGB1, correlating with markers of liver injury. In a murine LR model, inhibition of HMGB1 improved liver function, reduced steatosis, enhanced regeneration and decreased hepatic cell death. Elevated levels of hepatic cell death markers K18 and ccK18 were detected in patients with PHLF and correlations with levels of circulating HMGB1 was observed. Our study underscores the therapeutic and predictive potential of HMGB1 in PHLF mitigation. Elevated HMGB1, K18, and ccK18 levels correlate with patient outcomes, highlighting their predictive significance. Targeting HMGB1 enhances liver regeneration in murine LR models, emphasizing its role in potential intervention and prediction strategies for liver surgery.

A Combination of Biocatalysis and Fenton-Like Reaction Induced OH• Burst for Cascade Amplification of Cancer Chemodynamic Therapy.

Chemodynamic therapy (CDT) is a novel antitumor strategy that employs Fenton or Fenton-like reactions to generate highly toxic hydroxyl radical (OH•) from hydrogen peroxide (H2O2) for inducing tumor cell death. However, the antitumor efficacy of the CDT strategy is harshly limited by the redox homeostasis of tumor cells; especially the OH • is easily scavenged by glutathione (GSH) and the intracellular H2O2 level is insufficient in the tumor cells. Herein, we propose the Mn2+-menadione (also known as vitamin K3, MK3) cascade biocatalysis strategy to disrupt the redox homeostasis of tumor cells and induce a OH• storm, resulting in enhanced CDT effect. A nanoliposome encapsulating Mn-MK3 (Mn-MK3@LP) was prepared for the treatment of hepatic tumors in this study. After Mn-MK3@LPs were taken up by tumor cells, menadione could facilitate the production of intracellular H2O2 via redox cycling, and further the cytotoxic OH • burst was induced by Mn2+-mediated Fenton-like reaction. Moreover, high-valent manganese ions were reduced by GSH and the depletion of GSH further disrupted the redox homeostasis of tumor cells, thus achieving synergistically enhanced CDT. Overall, both cellular and animal experiments confirmed that the Mn-MK3@LP cascade biocatalysis nanoliposome exhibited excellent biosafety and tumor suppression efficacy. This study may provide deep insights for developing novel CDT-based strategies for tumor therapy.

Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model

The available ablative procedures for the treatment of hepatic cancer have contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy (ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk regions. We evaluated the effectiveness of ECT in a rat model. WAG/Rij rats were randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth group served as Sham. Tumor volume and oxygenation were measured before and five days after the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were additionally analysed by histology and immunohistochemistry. The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECT-treated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups. Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups. ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days following treatment.

Spacer-Supported Thermal Ablation to Prevent Carbonisation and Improve Ablation Size: A Proof of Concept Study.

Thermal ablation offers a minimally invasive alternative in the treatment of hepatic tumours. Several types of ablation are utilised with different methods and indications. However, to this day, ablation size remains limited due to the formation of a central non-conductive boundary layer. In thermal ablation, this boundary layer is formed by carbonisation. Our goal was to prevent or delay carbonisation, and subsequently increase ablation size. We used bovine liver to compare ablation diameter and volume, created by a stand-alone laser applicator, with those created when utilising a spacer between laser applicator and hepatic tissue. Two spacer variants were developed: one with a closed circulation of cooling fluid and one with an open circulation into hepatic tissue. We found that the presence of a spacer significantly increased ablation volume up to 75.3 cm3, an increase of a factor of 3.19 (closed spacer) and 3.02 (open spacer) when compared to the stand-alone applicator. Statistical significance between spacer variants was also present, with the closed spacer producing a significantly larger ablation volume (p < 0.001, MDiff = 3.053, 95% CI[1.612, 4.493]) and diameter (p < 0.001, MDiff = 4.467, 95% CI[2.648, 6.285]) than the open spacer. We conclude that the presence of a spacer has the potential to increase ablation size.

Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing.

There is no noninvasive method to estimate lung shunting fraction (LSF) in patients with liver tumors undergoing Yttrium-90 (Y90) therapy. We propose to predict LSF from noninvasive dynamic contrast enhanced (DCE) MRI using perfusion quantification. Two perfusion quantification methods were used to process DCE MRI in 25 liver tumor patients: Kety's tracer kinetic modeling with a delay-fitted global arterial input function (AIF) and quantitative transport mapping (QTM) based on the inversion of transport equation using spatial deconvolution without AIF. LSF was measured on SPECT following Tc-99m macroaggregated albumin (MAA) administration via hepatic arterial catheter. The patient cohort was partitioned into a low-risk group (LSF ≤&amp;nbsp;10%) and a high-risk group (LSF &gt;&amp;nbsp;10%). Results: In this patient cohort, LSF was positively correlated with QTM velocity |u| (r = 0.61, F = 14.0363, p = 0.0021), and no significant correlation was observed with Kety's parameters, tumor volume, patient age and gender. Between the low LSF and high LSF groups, there was a significant difference for QTM |u| (0.0760 ± 0.0440 vs. 0.1822 ± 0.1225 mm/s, p = 0.0011), and Kety's Ktrans (0.0401 ± 0.0360 vs 0.1198 ± 0.3048, p = 0.0471) and Ve&amp;nbsp;(0.0900 ± 0.0307 vs. 0.1495 ± 0.0485, p = 0.0114). The area under the curve (AUC) for distinguishing between low LSF and high LSF was 0.87 for |u|, 0.80 for Ve and 0.74 for Ktrans. Noninvasive prediction of LSF is feasible from DCE MRI with QTM velocity postprocessing.

Percutaneous Ablation of Hepatic Tumors at the Hepatocaval Confluence Using Irreversible Electroporation: A Preliminary Study

Background: Tumors at the hepatocaval confluence are difficult to treat, either surgically or ablatively. Methods: A retrospective longitudinal study on patients ineligible for thermal ablation who underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted. Factors analyzed included patient and tumor characteristics, IRE procedure details, treatment-related complications, and prognosis. Results: Between 2017 and 2021, 21 patients at our institute received percutaneous IRE. Of the 38 lesions, 21 were at the hepatocaval confluence. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of the ablated tumors, respectively. All postcava remained perfused at follow-up, except for 1 (4.8%) hepatic vein near the lesion found to be temporarily occluded and restored within 1 month. The ratio of the maximum diameter of ablation area at 1, 3, and 6 months post procedure compared to that immediately after IRE was 0.68 (0.50–0.84), 0.49 (0.27–0.61), and 0.38 (0.25–0.59), respectively. Progression-free survival of the patients with recurrence was 121 (range, 25–566) days. Four (19.0%) patients died at the end of follow-up with median overall survival of 451.5 (range, 25–716) days. Conclusions: IRE could be a safe and effective treatment for hepatic tumors at the hepatocaval confluence. This article provides valuable prognostic data; further clinical research is needed for better prognosis.

Abstract No. 337 Novel delivery method of caffeic acid for treatment of hepatic tumors via trans arterial embolization

Previous findings have shown the combination of trans arterial embolization (TAE) therapy and caffeic acid (CA) is superior to TAE alone in the treatment of hepatocellular carcinoma (HCC) (1,2). The present study sought to develop and evaluate a novel method of CA delivery within a liquid embolic for use in a rabbit model of mCRC with liver metastases.

Complications after Thermal Ablation of Hepatocellular Carcinoma and Liver Metastases: Imaging Findings.

Tumour ablation is a strategy of treatment of hepatic tumours in patients with small hepatocellular carcinoma (HCC) (<3 cm) or in patients unfit for surgical resection. Moreover, tumor ablation can be used as an adjuvant therapy or may be used in association with resection in case of patients with poor functional liver disease. These types of treatment usually could be performed percutaneously under image guidance. The most clinically verified and used ablation modalities are Radiofrequency Ablation (RFA) and microwave ablation (MWA). However, despite both of them are considered minimally invasive techniques, they could be related to post-procedural complications. The International Working Group on Image-Guided Tumor and the Society of Interventional Radiology (SIR) identified major and minor post-ablative complications. Major complications, as vascular complications, occur in 2.2% to 3.1% of cases and include all the high risk pathological conditions which could increase the level of care or result in hospital admission or substantially prolonged hospital stay (SIR classifications C–E). Minor complications, as biliary complications, occur in 5% to 8.9% and include self-limiting conditions that are considered to be of low risk for the patient’s outcome. The purpose of this review is to summarise the main pathological ultrasound (US) and Computed Tomography (CT) findings, that may arise after ablative treatment. To simplify the analysis, the pathological pictures are divided according to the site of damage into vascular, biliary and extrahepatic complications.

Numerical mesoscale tissue model of electrochemotherapy in liver based on histological findings

Electrochemotherapy (ECT) and irreversible electroporation (IRE) are being investigated for treatment of hepatic tumours. The liver is a highly heterogeneous organ, permeated with a network of macro- and microvasculature, biliary tracts and connective tissue. The success of ECT and IRE depends on sufficient electric field established in whole target tissue; therefore, tissue heterogeneity may affect the treatment outcome. In this study, we investigate electroporation in the liver using a numerical mesoscale tissue model. We numerically reconstructed four ECT experiments in healthy porcine liver and computed the electric field distribution using our treatment planning framework. We compared the computed results with histopathological changes identified on microscopic images after treatment. The mean electric field threshold that best fitted the zone of coagulation necrosis was 1225 V/cm, while the mean threshold that best fitted the zone of partially damaged liver parenchyma attributed to IRE was 805 V/cm. We evaluated how the liver macro- and microstructures affect the electric field distribution. Our results show that the liver microstructure does not significantly affect the electric field distribution on the level needed for treatment planning. However, major hepatic vessels and portal spaces significantly affect the electric field distribution, and should be considered when planning treatments.

Comparison of short-term outcomes and invasiveness of microwave versus radiofrequency ablation for the treatment of hepatic tumors

Comparison of short-term outcomes and invasiveness of microwave versus radiofrequency ablation for the treatment of hepatic tumors

Ex vivo liver resection for liver tumors: Last resort when conventional technique is not applicable

1. Purpose: The treatment of hepatic neoplasms has undergone, in recent years, various evolution of the surgical technique and extension to the indication for resection. Many patients with liver tumors cannot benefit from resection due to the difficulty of the anatomical site of the lesion.Of these patients, only some can benefit from ex vivo hepatic resection, which consists of a complete hepatectomy, bench tumor resection and self-transplant. 2. Materials and methods: We have retrospectively evaluated PUBMED databases. Studies was evaluated from 2010 to 2020.Only very few studies analyzed “Ex situ liver resection”, “Extracorporeal liver resection”, “Liver auto-transplantation”. Conclusion: Ex vivo liver resection and autotransplantation is fesible in very few patients with unresectable hepatic tumor fit for surgery. R0 resection accounts about 60%-90% but outcomes are less satisfactory due to high complications rate of about 25% and low survival in 3 years.

Contrast-Enhanced Ultrasound: A Useful Tool to Study and Monitor Hepatic Tumors Treated With Histotripsy.

Histotripsy is a novel noninvasive nonthermal, nonionizing, and precise treatment technique for tissue destruction. Contrast-enhanced ultrasound (CEUS) improves the detection, characterization, and follow-up of hepatic lesions because it depicts accurately the vascular perfusion of both normal hepatic tissue and hepatic tumors. We present the spectrum of imaging findings of CEUS after histotripsy treatment of hepatic tumors. CEUS provides real-time information, a close approximation to the dimension of the lesion, and a clear definition of its margins. Hepatic tumors detected by ultrasound can be potentially treated using B-mode ultrasound-guided histotripsy and characterized and monitored with CEUS. CEUS has shown to be very useful after tissue treatment to monitor and assess the evolution of the treated zone. Histotripsy treated zones are practically isoechogenic and slightly heterogeneous, and their limits are difficult to establish using standard B-mode ultrasound. The use of CEUS after histotripsy showing uptake of contrast protruding into the treated zone is clinically relevant to identify residual tumors and establish the most appropriate management strategy avoiding unnecessary treatments. We here describe CEUS findings after histotripsy for hepatic tumors.

Regenerative Liver Surgery - ALPPS and Associated Techniques.

Hepatectomy is the only potentially curative treatment of hepatic tumors, but remains challenging in case of multiple, bilobar lesions and those located in the vicinity of the hepatic hilum and hepatic veins. Regenerative liver surgery utilizes the unique ability of the liver to re-grow after tissue loss and vascular deprivation. All concepts subsumed under this term aim to increase the resectability of hepatic tumors by stimulating growth of future liver remnant. Many of these techniques have evolved over the last decades. ALPPS (associated liver partition and portal vein ligation for staged hepatectomy) is an advanced technique combining portal vein ligation and parenchymal transection which gave rise to many variants, all with the common goal of extending resectability. This article reviews techniques currently available for regenerative liver surgery focusing on ALPPS, its mechanisms of liver regeneration, indications, advantages, drawbacks, results and future perspectives.

Anomalous Celiac Trunk Variation Encountered in Y-90 Radioembolization

Background: &#x0D; Yttrium-90 microsphere embolization is a selective internal radiation therapy (SIRT) used in the treatment of hepatocellular carcinoma and liver metastases. Current literature recommends lobar, or more selective, infusion of SIRT to allow for precise radiation administration and to mitigate risk of non-target embolization. Lobar infusion requires knowledge of anatomical variations of hepatic arterial supply. The trifurcation of the celiac trunk into the left gastric artery, splenic artery, and common hepatic artery is the most common presentation representing 51% to 89% of patient anatomy. A replaced right hepatic artery (RHA) arising from the superior mesenteric artery (SMA) is one of the most common variants of hepatic arterial supply with a prevalence of 10.6% to 15%. Common variations such as these are well described and easily mapped using catheter angiography, but rarer variations are not as well described and more challenging to map. &#x0D; &#x0D; Project Methods: &#x0D; Mapping catheter angiogram of the celiac trunk and SMA was obtained. Additional aortogram and CT angiogram were obtained to further elucidate patient’s anatomy. &#x0D; &#x0D; Results: &#x0D; Initial mapping angiogram was only partially successful because the RHA could not be selected. Abdominal aortogram and CT angiogram of the abdomen and pelvis revealed a replaced RHA arising directly from the distal celiac trunk. Additionally, the patient had a replaced cystic artery arising from the left hepatic artery and an arc of Buhler connecting the proximal SMA to the proximal aspect of the right hepatic artery. &#x0D; &#x0D; Conclusion: &#x0D; Radiologists need to be aware of rare variations in hepatic arterial supply for the safe and effective treatment of hepatic neoplasms, whether primary or metastatic. Description of arterial variation and informed selection of arterial branches will remain a critical aspect of improving efficiency and reducing risks of hepatic embolization procedures.

Selective internal radiation therapy of hepatic tumors: Morphologic and functional imaging for voxel-based computer-aided dosimetry

IntroductionSelective Internal Radiation Therapy (SIRT) is used for the treatment of hepatic tumors. The aim of this retrospective study was to compare two dosimetric approaches based on 99mTc-MAA SPECT/CT and 90Y PET/CT, using Simplicit90Y™ versus the supplier suggested method of activity calculation. Material and methodsA total of 19 patients underwent 21 SIRT after baseline angiography and 99mTc-MAA SPECT/CT, followed by 90Y PET/CT. Overlap between 99mTc-MAA and 90Y-microspheres was quantified with different thresholds isocontours. The perfused volume and tumor absorbed dose were estimated using Simplicit90Y™ based on SPECT/CT and PET/CT, then compared with the supplier suggested method. These data were related to overall survival to evaluate their prognostic impact. ResultsThe overlap between PET/CT and SPECT/CT was dependent on thresholds, decreasing with an increasing threshold. The overlap between the 99mTc-MAA and 90Y-microspheres biodistributions versus the tumor distribution on morphological imaging was suboptimal, in particular for small tumor volume. The tumor absorbed dose estimated after 90Y PET/CT was not different from tumor absorbed dose estimated after SPECT/CT. The Perfused lobe absorbed dose was significantly lower while the volume of the perfused lobe was significantly higher when estimated by Simplicit90Y™ compared to the supplier suggested conventional approach. A statistical parameter based on overlap between tumor and 90Y-microspheres distribution as well as tumoral dosimetry was significantly related to the overall survival. ConclusionPost-treatment imaging remains paramount to estimate the irradiation dosimetry, due to an imperfect overlap. The perfused volume could be estimated from functional imaging, given its impact on dosimetry. Finally, survival seems related to tumoral overlap and dosimetry.

Guided capture of 3-D Ultrasound data and semiautomatic navigation using a mechatronic support arm system

Abstract A common treatment for malignant hepatic tumors is radiofrequency thermal ablation (RFA); however this procedure is often exhausting and error-prone, when performed only with hand held devices. In this work, we present a new concept for a computer- and mechatronic-arm-assisted treatment of hepatic tumor with RFA. Challenging factors of state-of-the-art RFA procedures are tackled by utilizing a prototype, which combines state-of-the-art ultrasound image guidance with a mechatronic support arm system. Physicians can image and examine the human abdomen using an ultrasound capturing device which is guided by the mechatronic support arm. The mechatronic arm allows to track the ultrasound transducer via joint position encoders, so that the recorded images’ exact positions are acquired and the patient is automatically registered during imaging. Consequently, physicians can use the acquired ultrasound images to navigate in the imaged abdomen area. The established prototype enables preplanning and semi-automatic alignment of trajectories with sufficient accuracy. In addition, the arm system supports the usually lengthy, exhausting and error-prone holding of the needle during the ablation process. Based on the results of accuracy examination and expert assessments by surgeons, the established concept could be proven to be advantageous for the considered use case.

The Role of Autophagy for the Regeneration of the Aging Liver.

Age is one of the key risk factors to develop malignant diseases leading to a high incidence of hepatic tumors in the elderly population. The only curative treatment for hepatic tumors is surgical removal, which initiates liver regeneration. However, liver regeneration is impaired with aging, leading to an increased surgical risk for the elderly patient. Due to the increased risk, those patients are potentially excluded from curative surgery. Aging impairs autophagy via lipofuscin accumulation and inhibition of autophagosome formation. Autophagy is a recycling mechanism for eukaryotic cells to maintain homeostasis. Its principal function is to degrade endogenous bio-macromolecules for recycling cellular substances. A number of recent studies have shown that the reduced regenerative capacity of the aged remnant liver can be restored by promoting autophagy. Autophagy can be activated via multiple mTOR-dependent and mTOR-independent pathways. However, inducing autophagy through the mTOR-dependent pathway alone severely impairs liver regeneration. In contrast, recent observations suggest that inducing autophagy via mTOR-independent pathways might be promising in promoting liver regeneration. Conclusion: Activation of autophagy via an mTOR-independent autophagy inducer is a potential therapy for promoting liver regeneration, especially in the elderly patients at risk.

Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms

Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 μs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.

3:00 PM Abstract No. 227 A systematic review of automated feeder detection software for locoregional treatment of hepatic tumors

To report the efficacy of automated feeder detection (AFD) software for the identification and treatment of liver tumors. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional DSA and CBCT without AFD. In total, 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients, including 537 with hepatocellular carcinoma, 8 with neuroendocrine metastases, and 59 patients without a reported etiology. Reported sensitivity of AFD ranged between 86% to 98.5%, compared to DSA alone (38%-64%) or DSA in combination with CBCT (69%-81%). Three studies reported tumor response by modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines, with complete response in the range of 60-69%. AFD is a promising new technology for the identification of tumor-feeding arteries and should be considered a useful complement to conventional DSA and CBCT in the treatment of liver tumors.