Thermal Ablation Of Liver Metastases Research Articles

Comparison of percutaneous ablation and hepatectomy for liver metastasis: A single center retrospective study.

To investigate the current treatment for liver metastasis and clarify the indications for percutaneous thermal ablation for liver metastasis. Ninety-two patients were enrolled and retrospectively analyzed. The patients underwent hepatectomy and/or percutaneous thermal ablation for liver metastases between January 2012 and December 2018. Twenty-six patients who underwent ablation treatment and seven patients who underwent both ablation and hepatectomy were included in the ablation treatment group (group A). We compared these patients with 59 patients who underwent hepatectomy only (group H). Subgroup analyses were performed between ablation (group AC) for colorectal liver metastasis and hepatectomy (group HC) for colorectal liver metastasis in 17 and 53 patients, respectively. The percentage of liver metastases other than colorectal cancer in group A was higher than that in the group H. Maximum tumor size in group A was significantly smaller than that in group H. Similarly, the patients in group AC were significantly older and demonstrated higher total bilirubin, lower serum albumin, and lower platelet counts than those in group HC. Overall survival was poorer in the AC group than that in the HC group. However, no differences were observed at metastasis ≤2 cm in size. Percutaneous thermal ablation was performed for many cancer types than hepatectomy. It is performed in elderly patients. We suggested that ablation for colorectal liver metastasis sized ≤2 cm is a suitable indication.

Outcomes after curatively intended treatment of limited peritoneal metastases and thermal ablation for liver metastases from colorectal cancer.

Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2 % of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice. This was a retrospective national cohort study. All patients were treated at Aarhus University Hospital; the only CRS+HIPEC centre in Denmark. We included CRC patients managed with curative intent for simultaneously diagnosed PM and LM in the period January 2016- December 2021. LM was treated with RFA as first choice, if possible. Survival was calculated by the Kaplan-Meier method. A total of 25 patients were included, the median agewas 60 years (range 43-75 years) and 15 (60 %) were females. The median peritoneal cancer index was 7 (range 0-12), the median number of LM was 1 (range 1-3). Ablation was performed as the only treatment for LM in 18 (72 %) patients. After a median follow-up time of 17.1months (range4-36months), the median OS was 28.6months (95 % confidence interval (Cl) 15.8;36.1), 1-year OS was 84.0 % (95 % Cl 62.8;93.7). Median DFS was 6.1months (95 % Cl 4.0;10.3). Median LOS was ten days (range 5-26days). Both 30-day and 90-day mortality were 0 %. The selected treatment modality (RFA) for CRC patients with both LM and PM was safe. However, DFS was low. Further research is warranted to investigate if RFA is as effective as LM resection.

Radiofrequency and microwave ablation controls hepatic oligoprogression of advanced gastroenteropancreatic neuroendocrine tumors.

In progression of multifocal liver metastases of gastroenteropancreatic neuroendocrine tumors (GEP-NET) escalation of systemic therapy is indicated. The aim of this retrospective study was to investigate the potential of local thermal ablation in hepatic oligoprogression and otherwise stable disease in GEP-NET. Patients with hepatic oligoprogression and otherwise stable disease, who underwent radiofrequency ablation (RFA) or microwave ablation (MWA) for local control, were included in the study. Thermal ablation was performed while maintaining the ongoing systemic therapy or without addition of a systemic therapy. The effectiveness of this therapeutic approach was evaluated by determination of local treatment success, improvement of progression-free survival (PFS) and the safety. Seventeen thermal ablation procedures were performed in 13 patients with well differentiated NET including seven ileum NET, four pancreatic NET, one appendix NET and one rectum NET. RFA and MWA of liver metastases were well tolerated without major complications. Thermal ablation resulted in an estimated median PFS of 62.6 weeks (mean 50.5 weeks; range 10.1-78.9 weeks) per procedure. In four patients, two ablation procedures were performed throughout the course of their disease resulting in an estimated median PFS of 69.1 weeks (mean 71.6 weeks; range 10.1-123.1 weeks) per patient. Start or change of systemic therapy could be delayed up to 123.1 weeks by using thermal ablations for isolated progression of single liver metastases. 88% of thermal ablations prolonged PFS. Thermal ablation of liver metastases in a non-curative intent has the potential to provide focal growth control and to prolong PFS in GEP-NET patients with hepatic oligoprogression.

Thermal ablation of the most challenging cases of liver metastases.

Patient selection for image-guided thermal ablation of liver metastases has to be taken in a multidisciplinary tumor board given the extreme complexity of cancer metastatic disease, and the numerous treatment options offered to oligometastatic patient today.The role of image-guided thermal ablation increases over years in the treatment of liver metastases. In order to fulfill the expected outcomes which are to have a local control rate equivalent to surgery, interventional oncologist have to take every measure that will help when treating most challenging metastases including image guidance, anesthesia, respiration monitoring, ablation technique, confirmation software that can favor positive outcomes, and in some way to render challenging metastases easy to treat.

Gata6+ resident peritoneal macrophages promote the growth of liver metastasis

Emerging evidence suggests that resident macrophages within tissues are enablers of tumor growth. However, a second population of resident macrophages surrounds all visceral organs within the cavities and nothing is known about these GATA6+ large peritoneal macrophages (GLPMs) despite their ability to invade injured visceral organs by sensing danger signals. Here, we show that GLPMs invade growing metastases that breach the visceral mesothelium of the liver via the “find me signal”, ATP. Depleting GLPMs either by pharmacological or genetic tools, reduces metastases growth. Apoptotic bodies from tumor cells induces programmed cell death ligand 1 (PD-L1) upregulation on GLPMs which block CD8+ T cell function. Direct targeting of GLPMs by intraperitoneal but not intravenous administration of anti-PD-L1 reduces tumor growth. Thermal ablation of liver metastases recruits huge numbers of GLPMs and enables rapid regrowth of tumors. GLPMs contribute to metastatic growth and tumor recurrence.

How Compatible Are Immune Checkpoint Inhibitors and Thermal Ablation for Liver Metastases?

Simple SummaryAlthough immune checkpoint inhibitors (ICIs) have achieved great progression in cancer treatment, the efficacy of ICI monotherapy is still limited. Meanwhile, the negative efficacy of thermal ablation for liver metastases is the high rate of local tumor progression. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, thermal ablation and ICI can boost the immune response against cancer cells as one of the positive synergy effects. The findings of preclinical and clinical research have provided supportive evidence for the combination of ICIs with thermal ablation reversing T-cell exhaustion and demonstrating synergy. However, the clinical feasibility of immune response activation by combination therapy with ICI monotherapy and thermal ablation appears to be limited, it may be not very common phenomena.Cancer immunotherapy, which reactivates the weakened immune cells of cancer patients, has achieved great success, and several immune checkpoint inhibitors (ICIs) are now available in clinical practice. Despite promising clinical outcomes, favorable responses are only observed in a fraction of patients, and resistance mechanisms, including the absence of tumor antigens, have been reported. Thermal ablation involves the induction of irreversible damage to cancer cells by localized heat and may result in the release of tumor antigens. The combination of immunotherapy and thermal ablation is an emerging therapeutic option with enhanced efficacy. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, the combination of immuno-oncology (IO) therapy and thermal ablation may be mutually beneficial. In preclinical and clinical studies, the combination of ICI and thermal ablation significantly inhibited tumor growth, and synergistic antitumor effects appeared to prolong the survival of patients with secondary liver cancer. However, evidence for the efficacy of ICI monotherapy combined with thermal ablation is currently insufficient. Therefore, the clinical feasibility of immune response activation by ICI monotherapy combined with thermal ablation may be limited, and thermal ablation may be more compatible with dual ICIs (the IO–IO combination) to induce strong immune responses.

Abstract No. 19 Optimal timing of cytotoxic chemotherapy when combined with thermal ablation of liver metastases

Adjuvant versus neoadjuvant chemotherapy has been extensively discussed in the surgical literature, but much less is known about the optimal timing of peri-ablation chemotherapy. Here, we examine whether the timing of peri-ablation chemotherapy (adjuvant versus neoadjuvant) affects outcomes.

MINIMALLY INVASIVE TECHNOLOGIES IN TREATMENT OF COLORECTAL CANCER WITH LIVER METASTASES

Purpose: to explore the results of application of minimally invasive technologies in treatment of colorectal cancer with liver metastases. Materials and methods: results of treatment of 55 patients with colorectal cancer with liver metastases (T2-3N0-1M1) were analyzed. 25 patients, who underwent laparoscopic procedures on the colon with atypical liver resection or radiofrequency thermal ablation of liver metastases with interstitial chemotherapy and laparoscopic catheterization umbilical vein, formed the study group. 30 patients, who underwent open surgery, formed the control group. Chemotherapy was performed for both groups of patients (drugs was injected through the umbilical vein in the study group and through a peripheral vein in the control group). Results: laparoscopic approach led to reliable decrease of postoperative complications and improvement in the life quality of patients during the postoperative period (p<0,05). Summary: minimally invasive combination treatment reduced the rate of progression by 32% and increase the time to disease progression for 7 months (p <0,05) in the study group.

Thermal ablation of liver metastases from colorectal cancer: radiofrequency, microwave and laser ablation therapies.

Surgery is currently considered the treatment of choice for patients with colorectal cancer liver metastases (CRLM) when resectable. The majority of these patients can also benefit from systemic chemotherapy. Recently, local or regional therapies such as thermal ablations have been used with acceptable outcomes. We searched the medical literature to identify studies and reviews relevant to radiofrequency (RF) ablation, microwave (MW) ablation and laser-induced thermotherapy (LITT) in terms of local progression, survival indexes and major complications in patients with CRLM. Reviewed literature showed a local progression rate between 2.8 and 29.7 % of RF-ablated liver lesions at 12-49 months follow-up, 2.7-12.5 % of MW ablated lesions at 5-19 months follow-up and 5.2 % of lesions treated with LITT at 6-month follow-up. Major complications were observed in 4-33 % of patients treated with RF ablation, 0-19 % of patients treated with MW ablation and 0.1-3.5 % of lesions treated with LITT. Although not significantly different, the mean of 1-, 3- and 5-year survival rates for RF-, MW- and laser ablated lesions was (92.6, 44.7, 31.1 %), (79, 38.6, 21 %) and (94.2, 61.5, 29.2 %), respectively. The median survival in these methods was 33.2, 29.5 and 33.7 months, respectively. Thermal ablation may be an appropriate alternative in patients with CRLM who have inoperable liver lesions or have operable lesions as an adjunct to resection. However, further competitive evaluation should clarify the efficacy and priority of these therapies in patients with colorectal cancer liver metastases.

Contrast-enhanced ultrasound in planning thermal ablation of liver metastases: Should the hypervascular halo be included in the ablation volume?

Introduction Liver metastases often exhibit a hypervascular halo during the arterial phase of contrast-enhanced ultrasonography (CEUS). This finding has no correlates on baseline gray-scale imaging, and it has never been characterized. The aim of this study was to identify the features of this halo and determine whether it should be included in the ablation volume during thermal ablation procedures. Materials and methods We prospectively enrolled 25 patients referred to our department for thermal ablation of liver metastases. Before treatment all patients underwent CEUS, and the maximum diameter of the metastatic lesion was measured before administration of the ultrasound contrast agent and during the arterial and portal venous phases of the contrast contrast-enhanced study. Maximum diameters in the different vascular phases were compared with the Turkey–Kramer test. Two biopsies were obtained from each lesion with a 21-gauge needle: 1) one from the center of the metastasis to confirm the diagnosis and 2) one from the hypervascular peripheral halo identified in the arterial phase at CEUS. Results The mean (±standard deviation) maximum lesion diameter was 2.67 ± 1.2 cm before contrast agent injection, 3.50 ± 1.4 cm during the arterial phase, and 2.71 ± 1.2 cm during the venous phase. The difference between maximum diameters measured before contrast enhancement and in the arterial phase was highly significant (mean: 0.84 ± 0.45 cm, p < 0.0001). Histological examination of halo specimens revealed inflammatory infiltrates with no evidence of tumor infiltration in 24/25 (96%) cases and normal hepatic parenchymal tissue in the 25th specimen. Discussion The hypervascular halo surrounding liver metastases during the arterial phase of CEUS represents a chronic inflammatory infiltrate, not tumor infiltration. However, since chronic inflammation appears to promote neovascularization and the production of tumoral growth factors, it seems wise to include the hypervascular halo in the intended-to-treat volume when planning the ablation procedure.

Alignment of sparse freehand 3-D ultrasound with preoperative images of the liver using models of respiratory motion and deformation

We present a method for alignment of an interventional plan to optically tracked two-dimensional intraoperative ultrasound (US) images of the liver. Our clinical motivation is to enable the accurate transfer of information from three-dimensional preoperative imaging modalities [magnetic resonance (MR) or computed tomography (CT)] to intraoperative US to aid needle placement for thermal ablation of liver metastases. An initial rigid registration to intraoperative coordinates is obtained using a set of US images acquired at maximum exhalation. A preprocessing step is applied to both the preoperative images and the US images to produce evidence of corresponding structures. This yields two sets of images representing classification of regions as vessels. The registration then proceeds using these images. The preoperative images and plan are then warped to correspond to a single US slice acquired at an unknown point in the breathing cycle where the liver is likely to have moved and deformed relative to the preoperative image. Alignment is constrained using a patient-specific model of breathing motion and deformation. Target registration error is estimated by carrying out simulation experiments using resliced MR volumes to simulate real US and comparing the registration results to a "bronze-standard" registration performed on the full MR volume. Finally, the system is tested using real US and verified using visual inspection.

Double contrast MRI of thermally ablated liver metastases.

To investigate the ability of double contrast MRI (enhancement with iron oxide and gadopentetate dimeglumine) to increase the difference in contrast between various tissues after thermal ablation of liver metastases. 12 patients were imaged after MR-guided laser-induced thermotherapy (LITT). Imaging was performed with a 1.5T MR system. Nonenhanced, iron oxide-enhanced and double contrast images were acquired using T (1)-weighted GRE and T (2)-weighted TSE sequences. Iron oxide imaging was performed 10 min after injection of 1.4 ml ferucarbotran (Resovist(R), Schering AG Berlin, Germany) and double contrast imaging 60 sec after the additional injection of 0.1 mmol/kg body weight gadopentetate dimeglumine (Magnevist(R), Schering AG Berlin, Germany). Qualitative and quantitative assessment was performed on induced necroses, residual or recurrent tumor tissue and metastatic tissue untreated at the time of the study. Iron oxide-enhanced T (1) GRE images demonstrated the highest contrast between ablated hyperintense tissue and iron accumulating and resultant hypointense liver parenchyma. Due to Gd enhancement, double contrast T (1)-weighted GRE images displayed the highest change in signal intensity in vital tumor tissue compared to ablated tissue and iron oxide accumulating liver parenchyma (p < 0.01). First observations indicate that LITT of hepatic metastases can be better followed with double contrast MRI, which displays increased contrast due to Gd enhancement of perfused tumor tissue and signal intensity loss in iron oxide accumulating hepatic parenchyma. Induced necrosis does not change its signal intensity at all after injection of iron oxide and Gd-containing contrast media.

Registration of freehand 3D ultrasound and magnetic resonance liver images

We present a method to register a preoperative MR volume to a sparse set of intraoperative ultrasound slices. Our aim is to allow the transfer of information from preoperative modalities to intraoperative ultrasound images to aid needle placement during thermal ablation of liver metastases. The spatial relationship between ultrasound slices is obtained by tracking the probe using a Polaris optical tracking system. Images are acquired at maximum exhalation and we assume the validity of the rigid body transformation. An initial registration is carried out by picking a single corresponding point in both modalities. Our strategy is to interpret both sets of images in an automated pre-processing step to produce evidence or probabilities of corresponding structure as a pixel or voxel map. The registration algorithm converts the intensity values of the MR and ultrasound images into vessel probability values. The registration is then carried out between the vessel probability images. Results are compared to a “bronze standard” registration which is calculated using a manual point/line picking algorithm and verified using visual inspection. Results show that our starting estimate is within a root mean square target registration error (calculated over the whole liver) of 15.4 mm to the “bronze standard” and this is improved to 3.6 mm after running the intensity-based algorithm.

Laser‐induced thermotherapy (LITT) of liver metastases: MR‐guided percutaneous insertion of an MRI‐compatible irrigated microcatheter system using a closed high‐field unit

To evaluate the efficacy and safety of a new MRI-compatible irrigated laser microcatheter system for thermal ablation of liver metastases. The new microcatheter system consists of a titanium needle with a diameter of 1.5 mm and a surrounding Teflon catheter with an outer diameter of 1.8 mm (5.5 F). In vitro laser-induced coagulation of bovine liver tissue was performed to determine the optimal perfusion rate of cooling saline flow, maximum laser energy, and ablation time. Laser-induced thermotherapy using the new microcatheter system, an Nd:YAG laser (Dornier), and a flexible laser light guide (Somatex GmbH, Berlin, Germany) was performed in 28 patients with liver metastases. Percutaneous insertion and positioning of multiple microcatheters in the lesion and monitoring of therapy was performed with a closed high-field MRI scanner using T1-weighted gradient-echo sequences during breath-hold. A perfusion rate of 0.75 mL/minute, a laser energy of 15 W, and an ablation time of 20 minutes were found suitable to achieve safe and sufficient ablation of metastatic tissue. The mean volume of induced coagulation in vitro was 23.9 mL. Ablation of liver metastases in patients was technically and clinically successful. The new microcatheter system allows for both catheter placement and monitoring of therapy using a single imaging modality. This shortens the procedure and enables more precise puncture and therapy of liver metastases. Due to the miniaturized design of the catheter and the real-time monitoring, the procedure is minimally invasive and very well tolerated by patients. This new technique seems to be a safe and feasible alternative in treating liver metastases.

Thermische Ablation von Lebermetastasen: Aktueller Stand und Perspektiven

To present thermal ablation of liver metastases via laser induced thermotherapy. Different technical procedures of thermal ablation and online monitoring are used, as there are the MR-guided laser induced thermotherapy (LITT) and the radiofrequency ablation thermotherapy (RF). In a prospective non randomized study 606 patients with liver metastases were treated via MR-guided laser induced thermotherapy. Inclusion criteria were the exclusion of extrahepatic tumor spread and a number of metastases lower than 5 and a size lower than 50 mm in diameter. The local tumor control rate in the 3 month and 6 month control study was 98.3%, the complication rate 3.5% (clinically relevant: 1.2%). The mean survival rate was 40.9 months for all patients with liver metastases without statistically relevant differences for various primaries, like colorectal carcinoma, breast cancer and various other tumors. Results for radiofrequency are so far limited with incidence of a higher local tumor recurrence rate versus LITT. MR-guided LITT results in a high local tumor control rate with improved survival.