Surgical extirpation of liver tumors remains a proven approach in the management of metastatic tumors to the liver, particularly those of colorectal origin. Ablative, non-resective therapies are an increasingly attractive primary therapy for liver tumors as they are generally better tolerated and result in far less morbidity and mortality. Ablative therapies preserve greater normal liver parenchyma allowing better post-treatment liver function and are particularly appropriate for treating subsequent liver-specific tumor recurrence. This article reviews the current status of ablative therapies for non-hepatocellular liver tumors with a discussion of many of the clinically available approaches.

Surgical resection of limited colorectal liver disease improves long-term survival and can be curative in a subset of selected cases. Image-guided percutaneous ablation therapies have emerged as safe and effective alternative options for selected patients with unresectable colorectal liver metastases (CLM) that can be ablated with margins. Ablation causes focal destruction of tissue and has increasingly been shown to provide durable eradication of tumors.

A selective review of literature was conducted in PubMed, focusing on recent studies reporting on the safety, efficacy, and long-term outcomes of percutaneous ablation modalities in the treatment of CLM. The present work gives an overview of the different ablation techniques, their current clinical indications, and reported outcomes from most recently published studies. The 'test of time' concept for using ablation as a first local therapy is also described.

There are several thermal ablative tools currently available, including radiofrequency ablation (RFA), microwave ablation, and cryoablation. Most data to date originated from the application of RFA. Adjuvant thermal ablation in the treatment of oligometastatic colon cancer liver disease offers improved oncologic outcomes. The ideal CLM amenable to percutaneous ablation is a solitary tumor with the largest diameter up to 3 cm that can be completely ablated with a sufficient margin. 5-year overall survival rates up to 70% after ablation of unresectable CLM have been reported. Pathologic confirmation of complete tumor necrosis with margins over 5 mm provides best long-term local tumor control by thermal ablation.

Current evidence suggests that percutaneous ablation as adjuvant to chemotherapy improves oncologic outcomes of patients with CLM. For small tumors that can be ablated completely with clear margins, percutaneous ablation may offer outcomes similar to those of surgery.

Percutaneous imaging-guided cryoablation (PICA) is a recently developed technique, which applies extreme hypothermia to destroy tumours under close imaging surveillance. It is minimally invasive, safe, repeatable, and does not interrupt or compromise other oncologic therapies. It presents several advantages over more established heat-based thermal ablation techniques (e.g. radiofrequency ablation; RFA) including intrinsic analgesic properties, superior monitoring capability on multi-modal imaging, ability to treat larger tumours, and preservation of tissue collagenous architecture. There has been a recent large increase in reports evaluating the utility of PICA in a wide range of patients and tumours, but systematic analysis of the literature is challenging due to the rapid pace of change and predominance of extensively heterogeneous level III studies. The precise onco-therapeutic role of PICA has not been established. This narrative review outlines the available evidence for PICA in a range of tumours. Current indications include curative therapy of small T1a renal tumours; curative/palliative therapy of small primary/secondary lung tumours where RFA is unsuitable; palliation of painful bone metastases; and urologic treatment of organ-confined prostate cancer. There is growing evidence to support its use for small hepatic tumours, and encouraging results have been obtained for breast tumours, extra-abdominal desmoid tumours, and management of higher-stage tumours and oligometastatic disease. However, the overall evidence base is weak, effectively restricting PICA to cases where standard therapy and RFA are unsuitable. As the technique and evidence continue to mature, the benefits of this emerging technique will hopefully become more widely available to cancer patients in the future.

Increasing data on treatment of liver metastases with locoregional therapies have solidified the expanding role of interventional radiologists (IRs) in the treatment of liver metastases from colorectal cancer. Ablative approaches such as radiofrequency ablation and microwave ablation have shown durable eradication of tumors. Catheter-directed therapies such as transarterial chemoembolization, drug-eluting beads, yttrium-90 radioembolization, and intra-arterial chemotherapy ports represent potential techniques for managing patients with unresectable liver metastases. Understanding the timing and role of these techniques in multidisciplinary care of patients is crucial. Implementation of IRs for consultation enables better integration of these therapies into patients' overall care.

The aim of the present study was to analyze the impact of cryosurgery (CRYO) on liver metastases compared to other thermoablative techniques. In a rat liver metastases model, evidence for tumor cell spread was analyzed comparing CRYO, radiofrequency ablation (RFA), and laser-induced thermotherapy (LITT).

In an experimental study, we compared cell spillage in the washout of isolated perfused rat livers undergoing thermal ablation. Within the same model, CC531-GFP rat liver tumors were treated with CRYO, RFA, or LITT and the number of vital tumor cells within the perfusate was measured. Matrix metalloproteinases (MMP-2, MMP-9) were analyzed after in vivo ablation of rat colorectal liver metastases in the third experimental model.

Our data showed pronounced washout of cells after CRYO with a higher amount of intravascular cells and cell detritus compared to RFA and LITT. Only the effluent fluid of cryosurgery-treated livers revealed GFP-stained tumor cells. MMP-2 and MMP-9 expression was significantly higher after cryosurgery than after RFA and LITT.

When using thermoablative techniques, intravascular metastatic cell spillage is highest in CRYO, and increased expression of matrix metalloproteinases may further facilitate tumor cell spread. Therefore, RFA and LITT may be preferable whenever surgical resection of liver tumors is impossible.

Only 15% of patients with colorectal liver metastases (CLM) are candidates for curative hepatectomy at time of diagnosis, limited by anatomical location and tumor burden. Ablative therapies may extend this. This study reports a single institution's long-term experience with hepatic cryotherapy for advanced CLM.

Between April 1990 and June 2009, 304 patients were curatively treated with cryotherapy. Survival was estimated by Kaplan-Meier method. Prognostic factors for survivals were determined by using univariate and multivariate analyses.

A total of 293 patients were included into analysis. The median number of lesions treated per patient was three (range, 1-13). The median overall survival was 29 (range, 3-220) months. The 1-, 3-, 5-, and 10-year survivals were 87%, 41.8%, 24.2%, and 13.3%, respectively. A total of 161 patients developed intrahepatic recurrences: cryosite (23%); edge recurrence (14%); and within the liver remnant (78%). The median disease-free survival (DFS) was 9 (range, 1-220) months. The 1-, 3-, 5-, and 10-year DFS rates were 37.9%, 17.2%, 13.4%, and 10.8%, respectively. Univariate analysis identified four factors that significantly affect survival: node-positive primary tumor (p=0.001), preoperative CEA level (p<0.001), number of lesions (p<0.001), and use of neoadjuvant chemotherapy (p<0.001). However, only primary tumor nodal status was independently prognostic (hazards ratio=2.023; 95% confidence interval, 1.444-2.835; p<0.001).

Hepatic cryotherapy seems to be a safe and effective ablative technique for the treatment of colorectal liver metastases and may offer long-term survival in otherwise unresectable disease.

The standard treatment for colorectal liver metastases (CRLM) is surgical resection. Only 20-30% of patients are deemed suitable for surgery. Recently, much attention has focused on ablative therapies either to treat unresectable CRLM or to extend the margins of resectability. This review aims to assess the long-term outcome and complication rates of various ablative therapies used in the management of CRLM.

A literature search was performed of electronic databases including Medline, Cochrane Collaboration Library and the National Library of Medicine's ClinicalTrials.gov. Inclusion criteria were ablation for CRLM with minimum 1 year follow-up and >10 patients, published between January 1994 and January 2010.

In all, 226 potentially relevant studies were identified, of which 75 met the inclusion criteria. Cryotherapy (26 studies) had local recurrence rates of 12-39%, with mean 1-, 3- and 5-year survival rates of 84%, 37% and 17%. The major complication rate ranged from 7% to 66%. Microwave ablation (13 studies) had a local recurrence rate of 5-13%, with a mean 1-, 3- and 5-year survival of 73%, 30% and 16%, and a major complication rate ranging from 3% to 16%. Radiofrequency ablation (36 studies) had a local recurrence rate of 10-31%, with a mean 1-, 3- and 5-year survival of 85%, 36% and 24%, with major complication rate ranging from 0% to 33%.

Ablative therapies offer significantly improved survival compared with palliative chemotherapy alone with 5-year survival rates of 17-24%. Complication rates amongst commonly used techniques are low.

The therapeutic concept for hepatic metastases is mainly based on surgical resection and systemic chemotherapy. Considering technical respectability, oncological significance and limiting comorbidities, only 10-30% of patients with hepatic metastases can undergo surgery with a curative intention. Patients assessed as being non-resectable qualify in general for (palliative) chemotherapy. However, for many patients surgical therapy of the liver is no longer possible due to medical or technical reasons, nevertheless, the total tumor load is still limited, which makes an interventional, local ablative therapy approach promising, with and without chemotherapy. Thus, various interventional-radiological, minimally invasive techniques could be successfully established as oncological therapy components besides surgery and chemotherapy. These types of intervention encompass mainly chemotherapy (percutaneous alcohol instillation, transarterial chemoembolization and transarterial chemotherapy), thermotherapy (radiofrequency, laser and microwave ablations) and radio-ablative procedures (radio-embolization, selective internal radiation therapy SIRT, interstitial and catheter-guided brachytherapy). Incorporating these procedures into therapeutic multimodal concepts inaugurates a significantly broadened therapy spectrum with a clear additional improvement in patient prognosis.

Thermoablation is a local therapy that is effective in in situ destruction of colorectal liver metastasis while preserving surrounding normal liver tissue. It is less invasive compared to surgery, easy to use, and can be repeated. The therapy provides local control of unresectable disease and is an alternative therapy for small resectable lesions in patients with insufficient hepatic reserve after resection or coexistent comorbid conditions. It can artificially increase the resection margin thus increasing the number of patient candidate for resection. When used in conjunction with liver resection it clears the liver of multiple lesions that are surgically inaccessible or unresectable. Main limitations of the treatment are local recurrence of the disease, treatment-related complications, and questionable impact on patient. Outcome of therapy can be improved when used as part of multimodality treatment.

The global incidence of liver cancer is greater than a million cases a year. Surgical resection where applicable is still the standard of care for these patients. Various liver-directed regional therapies have been developed in an effort to treat the vast majority of unresectable liver tumors. This article reviews the principles behind various ablation therapies currently available for malignant liver tumors and their outcomes.

Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue. This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions. Two important motivations for adjuvant use are: (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site). This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo. The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including: thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators. The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.

Ablation techniques for unresectable liver carcinomas have evolved immensely since their introduction. Results of studies involving these techniques are restricted to reports of patient case series, which are often not presented in a standardised manner. This review aims to summarise the major studies in ablation technologies and present them in a way that may make comparison between the major modalities easier.

All major databases (Medline, Cochrane, Embase and Pubmed) were searched for studies using microwave, radiofrequency or cryoablation to treat unresectable liver tumours. Only studies with at least 30 patients and 3-year follow-up were included. Complication, recurrence and survival rates of all studies are summarised and presented.

It is difficult to compare ablation modalities, as probe design and energy sources have evolved rapidly over the last decade. Ablation offers an invaluable palliative option and in some cases it may offer rates of cure approaching that of surgical resection with lower morbidity and mortality. Perhaps the time has come, therefore, for prospective large-scale randomised control trials to take place comparing ablation modalities to each other and surgical resection.

Untreated colorectal liver metastases (CLMs) have a dismal prognosis. Surgery remains the gold standard of treatment, but many patients will have inoperable disease at presentation. Until recently, the outlook for such patients was bleak. The purpose of this review was to report on available options in the treatment CLMs, which would be considered unresectable by conventional evaluation.

Inclusion criteria were articles published in English-language journals reporting on either retrospective or prospective cohorts of patients undergoing treatment for conventionally inoperable CLM. Main outcome measures were survival, resectability rates, morbidity and mortality following treatment of the patients' disease.

Improved chemotherapy regimes and other innovative treatments have opened up new options for such patients and may even render conventionally inoperable disease resectable. The aim of treatment should be down-staging of metastases to achieve resectability, however, other treatments such as ablation may be also be used (either alone or in conjunction with resection).

A nihilistic attitude to the patient with seemingly inoperable liver metastases should be discouraged. Discussion of such patients at multi-disciplinary meetings is essential in order to plan and monitor treatments.

We proposed for the first time a surgical term, the nanocryosurgery, for efficient tumor treatment through combining the theories of cyrosurgery and nanotechnology. Simulations were performed on the combined phase change bioheat transfer problems in a single cell level and its surrounding tissues, to explicate the difference of transient temperature response between conventional cyrosugery and nanocyrosurgery. According to theoretical interpretation and existing experimental measurements, intentional loading of nanoparticles with high thermal conductivity into the target tissues can lower the final temperature significantly, increase the maximum freezing rate, and enlarge the ice volume obtained in the absence of nanoparticles. In addition, introduction of nanoparticle-enhanced freezing could also make conventional cyrosurgery more flexible in many aspects such as artificially interfering in the size, shape, image and direction of iceball formation. The concepts of nanocyrosurgery may offer new opportunities for future tumor treatment.

Surgical resection is the gold standard in the treatment of resectable colorectal liver metastases (CRLM). In several centers, resection is being replaced by radiofrequency ablation (RFA), even though there is no evidence yet from randomized trials to support this. The aim of this study was to critically review the oncological evidence for and against the use of RFA for resectable CRLM.

An exhaustive review of RFA of colorectal metastases was carried out.

Five-year survival data after RFA for resectable CRLM are not available. Percutaneous RFA is associated with worse local control, worse staging, and a small risk of electrode track seeding when compared with resection (level V evidence). For tumors </=3 cm, local control after surgical RFA is equivalent to resection, especially if applied by experienced physicians to nonperivascular tumors (level V evidence). There is indirect evidence for profoundly different biological effects of RFA and resection.

A subgroup of patients has been identified for whom local control after RFA might be equivalent to resection. Whether this is true, and whether this translates into equivalent survival, remains to be proven. The time has come for a randomized trial.

In situ ablation of colorectal liver metastases is frequently assessed for palliative treatment only. The establishment of clinically relevant lesion size and a lack of long-term survival data were regarded as main limitations to using them with curative intention. In contrast to surgical liver resection, whose oncological findings seem to have remained unchanged over the years, the in situ ablation methods have considerably changed technically and clinically in the last few years.

The aim of the paper was to point out experimental and clinical data underlining the impact of in situ ablation for potentially curative treatment of colorectal liver metastases.

On the basis of experimental data, the aim of complete local tumor control (R0 ablation) can only be obtained if additional energy is applied after reaching the tumor-adapted maximal coagulation volume. Analogous to the oncological safety margin in surgical resection, we defined this decisive energy difference as the "energy safety margin" for in situ ablation. The energy safety margin is the energy that must be additionally applied after reaching the plateau in the energy/volume curve to achieve complete tumor coagulation. In addition to that, in situ ablation should be combined with temporary interruption of hepatic perfusion whenever possible to prevent intralesional recurrences. In this way, the thermoprotective mechanism of hepatic perfusion can be effectively eliminated. With restrictions, the survival data after ablation in specialized centers is comparable to surgical resection with concomitantly lower morbidity and mortality. Based on recent findings and with the corresponding expertise in the field of ablation and state-of-the-art equipment, ablation is, thus, an alternative to surgical resection. The combined application of surgical resection and ablation is also a suitable method for increasing the R0 rate and thus helps improve the prognosis of treated patients. In summary, it can be said that in situ ablation is a useful expansion of the therapeutic spectrum of liver metastases and can be applied as an alternative to or in combination with surgical resection.

Hepatic cryosurgery is useful for patients with hepatic metastases from colorectal cancer confined to the liver but considered unresectables because of the number and location of lesions. While encouraging results were reported following cryosurgery for unresectable liver metastases we considered particularly valuable to examine the safety and effectiveness of cryosurgery in patients with resectable and unresectable metastases from colorectal cancer.

Between January 1997 and September 2005, 53 patients with liver metastases from colorectal cancer underwent hepatic cryosurgery at our institution. Hepatic metastases were resectable in 31 (58.5%) patients and unresectable in 22 (41.5%).

A total of 136 liver metastases were treated in 53 patients. The size of treated lesions ranged from 0.5 to 10 cm (mean 2.7). There were 2 postoperative deaths (3.8%) from massive bleeding and from cryoshock. The overall morbidity rate was 66%. The median follow-up was 24.8 months. The overall survival rate at 12 months was 86.1%, at 48 months it was 27%. No significant difference was found between survival rates in patients with resectable or unresectable metastases. Among 31 patients with resectable liver metastases 7 (22.6%) patients developed recurrence at the site of cryosurgery.

Survival rates were comparables between patients with resectable and unresectable metastases but a high complication rate and a substantial rate of local recurrence following cryosurgery should caution against its use to treat resectable disease.

Local ablative techniques have been used for several decades in the treatment of colorectal liver metastases and are gaining more and more interest. At this time radiofrequency ablation is the most popular local ablative technique with interesting results on local tumour control, disease free and overall survival. However, the exact place in the treatment of non-resectable colorectal liver metastases and its possible place in the treatment of resectable liver metastases has still to be defined. This article describes the feasibility, advantages and disadvantages of radiofrequency ablation, together with the results of the most cited articles, to form a critical review on the use of this technique in the treatment of colorectal liver metastases.