MR-guided laser-induced thermotherapy (LITT) of liver tumours: experimental and clinical data

MR-guided laser-induced interstitial thermotherapy (LITT) is a percutaneous, minimally invasive treatment modality for treating liver lesions/metastases, soft tissue tumours and musculoskeletal lesions. In this group, MR-guided LITT is currently performed under local anaesthesia on an out-patient basis with a specially designed saline-cooled laser application system. Nd:YAG laser (1064?nm wave length) was used for tumour ablation. Magnetic resonance imaging (MRI) using both open and closed MR units has proven clinically effective in validating the exact positioning of optical fibres. It also allows for real time-monitoring of thermal effects and the evaluation of treatment-induced coagulation necrosis. In liver tumours, percutaneous MR-guided LITT achieves a local tumour control rate of 98.7% at 3 months post-therapy and 97.3% at 6 months with metastases smaller than 5?cm in diameter. The mean survival rate for 1259 patients with 3440 metastases treated with 14 694 laser applications at the institute (calculated with the Kaplan-Meier method) was 4.4 years (95% confidence interval: 4.1–4.8?years) and median survival was 3.00 years. No statistically significant difference in survival rates was observed in patients with liver metastases from colorectal cancer vs metastases from other primary tumours. The rate of clinically relevant side effects and complications requiring secondary treatment was 2.2%. The clinical use of MR guided LITT (size<5?cm, number<5) is justified in patients with liver metastases of colorectal and/or breast cancers if the inclusion criteria are carefully observed. Further indications for MR guided LITT include recurrent cancer lesions in the head and neck, lung metastases and bone and soft tissue lesions.     

Magnetic resonance-guided percutaneous microwave coagulation therapy for liver metastases of breast cancer in a case

Real-time magnetic resonance (MR) imaging enables the application of percutaneous microwave coagulation for high-risk patients with metastatic liver tumours. The tumours, local vessels and bile ducts can be observed clearly in three-dimensional sections and a sufficient surgical margin can be confirmed on the MR image even during the coagulation procedure. MR-guided percutaneous microwave coagulation therapy is effective for treatment of not only primary liver tumours but also metastatic breast cancers in the liver, which are not diffuse but discrete, and difficult to treat with only chemo-and endocrine therapy. We report a 44-year-old Japanese woman who underwent modified radical mastectomy for right breast cancer (T1c N0 M0 Stage I). Three years after the operation, she developed two metastatic liver tumours and was treated by MR-guided percutaneous microwave coagulation, achieving a complete response (CR) without any recurrence for 15 months as of the present. The most beneficial aspect of MR-guided percutaneous microwave coagulation is its safety. It is only minimally invasive and can be repeated. This therapy, therefore promises to prolong the disease free period. Additional clinical trials will be valuable to delineate the effectiveness and safety of MR-guided percutaneous microwave coagulation therapy for controlling the liver metastases of breast cancer.     

Repeated transarterial chemoembolisation using different chemotherapeutic drug combinations followed by MR-guided laser-induced thermotherapy in patients with liver metastases of colorectal carcinoma

Background:

To evaluate a treatment protocol with repeated transarterial-chemoembolisation (TACE) downsizing before MR-guided laser-induced interstitial thermotherapy (LITT) using different chemotherapeutic combinations in patients with unresectable colorectal cancer (CRC) liver metastases.

Methods:

Two hundred and twenty-four patients were included in the current study. Transarterial-chemoembolisation (mean 3.4 sessions per patient) was performed as a downsizing treatment to meet the LITT requirements (number⩽5, diameter <5 cm). The intra-arterial protocol consisted of either Irinotecan and Mitomycin (n=77), Gemcitabine and Mitomycin (n=49) or Mitomycin alone (n=98) in addition to Lipiodol and Embocept in all patients. Post TACE, all patients underwent LITT (mean 2.2 sessions per patient).

Results:

Overall, TACE resulted in a mean reduction in diameter of the target lesions of 21.4%. The median time to progression was 8 months, calculated from the start of therapy and the median local tumour control rate was 7.5 months, calculated as of therapy completion. Median survival of patients calculated from the beginning of TACE was 23 months (range 4–110 months), in patients treated with Irinotecan and Mitomycin the median was 22.5 months, Gemcitabine and Mitomycin 23 months and Mitomycin only 24 months with a statistically significant difference between the groups (P<0.01).

Conclusion:

Repeated TACE offers adequate downsizing of CRC liver metastases to allow further treatment with LITT. The combined treatment illustrates substantial survival rates and high local tumour control with statistically significant differences between the three protocols used. Further randomised trials addressing the current study results are required.     

Ablation therapy of non-colorectal cancer lung metastases: retrospective analysis of tumour response post-laser-induced interstitial thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA)

Purpose: To retrospectively compare the local tumour response and survival rates in patients with non-colorectal cancer lung metastases post-ablation therapy using laser-induced thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA).

Material and methods: Retrospective analysis of 175 computed tomography (CT)-guided ablation sessions performed on 109 patients (43 males and 66 females, mean age: 56.6 years). Seventeen patients with 22 lesions underwent LITT treatment (tumour size: 1.2–4.8?cm), 29 patients with 49 lesions underwent RFA (tumour size: 0.8–4.5?cm) and 63 patients with 104 lesions underwent MWA treatment (tumour size: 0.6–5?cm). CT scans were performed 24-h post-therapy and on follow-up at 3, 6, 12, 18 and 24 months.

Results: The overall-survival rates at 1-, 2-, 3- and 4-year were 93.8, 56.3, 50.0 and 31.3% for patients treated with LITT; 81.5, 50.0, 45.5 and 24.2% for patients treated with RFA and 97.6, 79.9, 62.3 and 45.4% for patients treated with MWA, respectively. The mean survival time was 34.14 months for MWA, 34.79 months for RFA and 35.32 months for LITT. In paired comparison, a significant difference could be detected between MWA versus RFA (p?=?0.032). The progression-free survival showed a median of 23.49?±?0.62 months for MWA,19.88?±?2.17 months for LITT and 16.66?±?0.66 months for RFA (p?=?0.048). The lowest recurrence rate was detected in lesions ablated with MWA (7.7%; 8 of 104 lesions) followed by RFA (20.4%; 10 of 49 lesions) and LITT (27.3%; 6 of 22 lesions) p value of 0.012. Pneumothorax was detected in 22.16% of MWA ablations, 22.73% of LITT ablations and 14.23% of RFA ablations.

Conclusion: LITT, RFA and MWA may provide an effective therapeutic option for non-colorectal cancer lung metastases with an advantage for MWA regarding local tumour control and progression-free survival rate.     

Improving laser-induced thermotherapy of liver metastases--effects of arterial microembolization and complete blood flow occlusion.

INTRODUCTION: A prerequisite for an oncologically curative application of laser-induced thermotherapy (LITT) of liver metastases is complete tumor destruction. This increased effectiveness was achieved experimentally by combining LITT with interrupted hepatic perfusion. The aim of this study was to evaluate whether an interventional selective arterial microembolization might be as effective as complete blood flow occlusion using an open Pringle's maneuver. PATIENTS AND METHODS: We included patients with unresectable colorectal liver metastases. LITT was performed without interrupted hepatic perfusion (control group) compared to LITT in combination with interrupted perfusion either by embolization of intraarterial degradable starch microspheres (DSM) (percutaneous access) or by complete hepatic inflow occlusion (Pringle's maneuver; open access). Online monitoring was performed using intraoperative ultrasound or MRI. Volumetric techniques were used to assess metastases and postinterventional lesions. RESULTS: Fifty-six patients with 104 metastases (control group (25), DSM (37), and Pringle (42)) were treated. The preinterventional tumor volumes were significantly smaller than the postinterventional lesion volumes (control group: 9.8 vs. 25.3 cm3; DSM: 9.5 vs. 65.4 cm3; Pringle: 12.9 vs. 76.5 cm3). The morbidity rate was 21.4% without treatment-related mortalities. After 6 months follow-up, tumor recurrence was diagnosed in 6 patients (control group (4), LITT with DSM (1), and Pringle (1)). CONCLUSIONS: Combining LITT with blood flow occlusion leads to a significant increase in lesion size. The application of DSM offers a safe and effective alternative to the open access with Pringle's maneuver. Compared to LITT-monotherapy, this modality achieves significantly larger thermal lesions with the need of fewer applications.     

Thymidine phosphorylase and dihydropyrimidine dehydrogenase protein expression in colorectal cancer.

It is essential for actively proliferating cells to increase their rate of DNA synthesis to progress through the cell cycle. This is reflected in the increased uracil usage that is a common feature in solid tumours. Thymidine phosphorylase (TP) anabolises formation of pyrimidine nucleosides available for DNA synthesis, whereas dihydropyrimidine dehydrogenase (DPD) catabolises the degradation of pyrimidine bases, thereby reducing levels of uracil and thymine available for DNA synthesis. In addition, tissue levels of TP or DPD have been associated with the clinical efficacy of pyrimidine anti-metabolites commonly used in the treatment of colorectal cancer. There is little information, however, on the relative expression or degree of co-ordinated regulation of either protein in primary or metastatic colorectal cancer. DPD and TP protein levels were measured in 15 primary colorectal carcinomas, 10 colorectal liver metastases and 25 adjacent uninvolved tissues. DPD was reduced in 67% (10/15) of colorectal tumours (mean tumour/normal = 0.52) and in all liver metastases (mean tumour/normal = 0.41) compared with the corresponding normal tissue. In contrast, TP was increased in 80% (12/15) of colorectal tumours (mean tumour/normal = 18.91) and in all metastases (mean tumour/normal = 3.70). TP and DPD protein expression were highly variable in uninvolved and tumour tissues. The ratio of TP:DPD was higher in 87% of colorectal tumours and in all liver metastases compared with the adjacent uninvolved tissues. This suggests the presence of co-ordinated regulation of these pyrimidine metabolic enzymes and offers a strategy for optimising the use of pyrimidine-based chemotherapy.     

Hepatic resection for secondary tumours

The role of liver resection for secondary tumours is reviewed, with particular reference to secondary disease from primary colorectal cancer. While there are no controlled trials producing direct evidence of improved survival following resection, figures on five year survivors without resection are anecdotal. Numerous series now report five year survival of up to 50% following resection, instances of five year survival without resection are now fallen to around 5% in most major series. Factors which adversely affect survival after resection seem to be poor tumour clearance, number of metastases and possibly Dukes' C primary tumours. Other factors, including the extent of resection and size of the tumour, may affect perioperative morbidity and mortality but should not influence long-term survival. Resectional treatment is rapidly gaining an established position in the treatment of colorectal secondaries, and may be considered also for some non-colorectal lesions, particularly endocrine tumours.     

CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours

To analyze prospectively the interventional and clinical aspects of computed tomography-guided direct intratumoural injection of a novel chemotherapeutic administration and the parenchymal changes of tumour and necrosis in malignant liver tumours. Eight patients with 17 colorectal liver metastases were treated with a mean of 5.1 injections and nine patients with 13 hepatocellular carcinoma nodules with a mean of 3.1 treatments with computed tomography guided local applications of a novel cisplatin/epinephrine gel. This application provides a higher local and lower systemic drug concentration. Volumes of tumour and necrosis prior and after treatment were measured by computer generated volumetric analysis. Contrast enhanced studies verified pretherapeutic viable tumour volumes with a value of 77.4 ml in the metastases and 29.2 ml in the hepatocellular carcinoma nodules. Intratumoural drug application resulted in a significant increase of necrosis and a decrease in viable tumour volume to be 68.3 ml in metastases and 14.5 ml in hepatocellular carcinoma. Local therapy control rate for the follow up to 6 months was 38 and 71% for the group of metastases and hepatocellular carcinoma, respectively. Direct intratumoural injection of cisplatin/epinephrine injectable gel is a feasible and good tolerated method and results in the development of a statistically significant increase in necrosis in malignant liver tumours. For hepatocellular carcinoma a higher local therapy control rate compared to colorectal metastases can be reported.     

Interventionelle Tumordestruktion durch thermische Verfahren

The aim of this article is to present interventional therapy methods based on thermal ablation, such as radiofrequency ablation (RFA), laser-induced thermotherapy (LITT) and microwave ablation (MWA) for palliative therapy of secondary malignant liver and lung tumors. This report provides information on data about local tumor control rates, survival data, progression-free survival (PFS) and complications. In liver metastases of colorectal carcinoma (CRC) the local tumor control rate is 85% for RFA, 95% for LITT and 93% for MWA, long-time survival is 22 months for RFA, 37 months for LITT and 32 months for MWA, progression-free survival is 84 months for RFA, 97 months for LITT and 93 months for MWA. Recent studies showed improved results with combined systemic and regional chemotherapy (e.g. TACE). Local recurrences of head and neck malignoma, lymph node infiltration and pelvic neoplasia are less frequent indications for tumor ablation.     

The safety and efficacy of microwave ablation for the treatment of CRC pulmonary metastases

Purpose: Microwave ablation (MWA) is a recently developed thermal ablation technique that has been used for the treatment of different types of tumours. In the present study, we retrospectively evaluated the safety and efficacy of CT-guided percutaneous MWA for the treatment of colorectal cancer (CRC) pulmonary metastases.

Materials and methods: From June 2010 to June 2015, 48 unresectable lesions in 32 patients with CRC pulmonary metastases were subjected to CT-guided MWA. Imaging follow-up was with contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT.

Results: Oncologic imaging showed that 42 (87.5%) of the 48 lesions in the 32 patients were completely ablated. Needle track metastatic seeding was not found, and no patient deaths occurred within 30?d after ablation. The mean hospital stay was 3?d (range, 2–7?d). Pneumothorax was the most frequent complication and occurred in 6 (12.5%) of the 48 lesions. The median survival time was 31?months (95% CI: 15.4–46.6). The 1-, 2- and 3-year survival rates were 79.5%, 63.1% and 44.4%, respectively. Univariate Cox regression analysis showed that tumour size, disease-free interval (DFI) and number of tumours were significantly related to the overall survival time (p?=?.007, p?=?.022 and p?=?.030, respectively). Multivariate analysis showed that tumour size was an independent prognostic factor for survival (p?=?.017).

Conclusion: CT-guided percutaneous MWA is a safe and effective minimally invasive method for treating CRC pulmonary metastases.     

Site-specific effect of chemotherapy in patients with breast cancer.

The efficacy of cytotoxic therapy in different anatomical sites can be studied by analyzing the anatomical distribution of recurrences following adjuvant therapy or the rate of response according to site of metastasis. Cumulated data from 7 adjuvant studies showed that the relative reduction in the rate of recurrence was 37% for local and regional recurrences versus 25% for distant metastases. There are only sparse and inconclusive data concerning the anatomical pattern of recurrence according to type of adjuvant chemotherapy. Thus, the majority of trials have not demonstrated significant differences in distribution of metastases in patients receiving different types of adjuvant systemic therapy. The available data on the rate of response in relation to metastatic site showed higher response rates in soft tissue metastases (55%), compared to visceral and bone metastases (40%). Cumulated data from 12 trials showed no differences in response rates between different soft tissue lesions (skin, subcutaneous tissue, lymph nodes, breast), or between metastases demonstrated by paraclinical tests (lung, liver, bone). However, there was a tendency for soft tissue lesions to have a higher response rate (55-60%) than visceral and bone metastases (31-44%). The reason for the observed differences is unknown. At the time of diagnosis soft tissue lesions may be smaller (with better blood supply) than visceral lesions. This might increase the likelihood of response, since experimental data show that the response rate is inversely correlated with tumour burden and tumour size. Another explanation is based on the hypothesis of site-specific clonal selection of tumour cells, which differ with respect to sensitivity to cytotoxic agents. However, the observed differences can also be ascribed to methodological errors or differences in assessing response of tumours at specific sites. Thus, the false positive response rate in soft tissue lesions, evaluated by physical examination, is approximately 20% compared with less than 10% in lung lesions evaluated by x-rays.     

Human chorionic gonadotropin in colorectal cancer and its relationship to prognosis

The presence of human chorionic gonadotropin in large bowel cancers was studied immunohistochemically using an immunoperoxidase technique. HCG-positive tumour cells were present in 42 of 194 adenocarcinomas examined (22.0% of colon cancer and 21.2% of rectal cancers). On histological grading, the hCG-positive rate tended to rise as the degree of differentiation decreased. HCG was detected more frequently in cancers invading the total bowel wall (27%) than in those invading the partial wall (17.1%). Lymph node, liver or peritoneal metastases were present more frequently in hCG-positive tumours than in hCG-negative tumours. Furthermore, there was an intimate correlation between the presence of hCG-positive tumour cells and CEA doubling times in nine cases with untreated liver metastasis. The survival rate for patients with tissue hCG-positive cells was lower than for those with hCG-negative tumours. Thus, the presence of tissue hCG in colorectal cancers may be a biological marker of prognostic significance.     

The results of 1115 patients with colorectal cancer treated over an 8-year period in a single hospital

The results of treatment of 1115 patients with colorectal cancer, from one hospital, are presented. The mean age of the patients was 67.24 (+/- 0.35 SEM) years and there were the same number of male and female patients. Forty per cent of patients were admitted as an emergency, and 67% of the tumours were in the rectum or sigmoid colon. 46.7% of the patients were considered to have undergone a 'curative' resection. Six per cent of the tumours were Dukes' Stage A lesions; 37% were Stage B and 57% Stage C. Twenty-six per cent had liver metastases. The overall hospital mortality was 21.5% and the operative mortality 14%. One-third of the patients admitted as an emergency died during their first admission. The overall 5-year survival was 25.8%; those with Dukes' Stage A tumours had a 5-year survival of 82.1%, Stage B 53.6% and Stage C 12.8%. The sex, site of tumour or duration of symptoms had no effect on prognosis.     

Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1

The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer.     

Percutaneous radiofrequency ablation for malignant liver tumours in challenging locations

Purpose: To evaluate the treatment results of radiofrequency ablation (RFA) for primary and metastatic malignant liver tumours in challenging locations and also to present the treatment strategy that was used in these cases. Patients and Methods: From January 2007 to January 2010, we performed CT‐guided RFA on 528 lesions in 402 patients (265 men and 137 women; mean age 65.1 years, range 19–82 years) with liver tumours (primary and metastatic) of which 98 lesions in 84 patients (55 men and 29 women; mean age 67.8 years, range 33–82 years) were located in challenging locations, defined as less than 5 mm from a large vessel or an extrahepatic organ (heart, lung, gall bladder, right kidney or gastrointestinal tract). The sizes of the tumours ranged 1.5–6 cm. We used two different RFA systems with an expandable needle electrode (RITA; Rita Medical Systems, Inc, Mountain View, CA, USA and MIRAS; Invatec S.r.l., Roncadelle, Italy).The tumours were considered as ablated completely if no viability was found on dual‐phase dynamic contrast‐enhanced CT at 1 month after RFA. Results: Complete ablation was obtained in 89.7% (88/98) of the high‐risk located lesions, while 10 (10.3%) of the lesions were managed with repeated RFA because of tumour residue. The 1‐, 2‐ and 3‐year survival rates were 82.6, 67.3 and 54.1%, respectively. Minor complications occurred in eight of the 84 patients (9.5%), including small sub‐capsular haematoma in four, small pleural effusion in three and partial liver infarction in one. Local tumour progression rate was 9.2% (9/98). Conclusion: RFA is a safe and effective method of treatment of primary and metastatic liver tumours even located in challenging locations when performed by a well‐trained and experienced interventional radiologist.     

Twelve colorectal cancer cell lines exhibit highly variable growth and metastatic capacities in an orthotopic model in nude mice

Orthotopic tumour models for colorectal cancer are a complementary tool for the study of tumours in vivo. They are more closely related to human cancer than are subcutaneous tumour models, since evaluation of spontaneous metastasis formation is possible. In the present study, fragments of subcutaneous xenografts established from 12 well-described and generally available colorectal cancer cell lines were implanted in the caecum of nude mice and tumour growth and metastatic events registered. The results showed considerable differences between the cell lines with respect to take rate, tumour growth and metastatic ability. This resulted in variable disease progression that seemingly reflects clinically relevant heterogeneity. The most common metastatic findings were mesenteric lymph-node metastases, occurring at variable frequency in tumour-bearing mice with 10 out of 12 cell lines, whereas only one line gave rise to liver metastases, in two of 10 animals. The study provides useful background information on the 12 colorectal cancer cell lines in a clinically relevant orthotopic tumour model.     

MR-guided laser-induced thermo-ablation of liver tumors: clinical experiences and therapy control concepts

Minimally-invasive, laser-induced interstitial thermotherapy (LITT) of solid tumors represents a valid alternative to surgical procedures such as tumor resections. Within the framework of a palliative study on 16 patients, a total of 25 metastases in the liver were treated in an open MR system (0.5 T). The intraoperative scanner design allows patient-based navigation, decisive for a safe applicator positioning, as well as temperature monitoring and direct inspection of the therapy result, without need for patient transfer or repositioning. Although the MR thermometry applied in the open scanner assisted LITT monitoring, the current accuracy of temperature data was not sufficient to serve automatic irradiation control. Therefore, an experimental monitoring and control system was developed in a closed MR scanner (1.5 T) featuring a calibrated MR thermometry. The system provides also an interface to the laser system, allowing the automatic off/on switching of the laser power according to preoperatively defined control criteria. The basic functionality of the automatic laser control was successfully demonstrated with laser ablation experiments of liver samples using irradiation parameters close to typical clinical values.     

Percutaneous Electrochemotherapy in Primary and Secondary Liver Malignancies – Local Tumor Control and Impact on Overall Survival

BackgroundLocal nonsurgical tumor ablation currently represents a further option for the treatment of patients with liver tumors or metastases. Electrochemotherapy (ECT) is a welcome addition to the portfolio of local therapies. A retrospective analysis of patients with liver tumors or metastases treated with ECT is reported. Attention is given to the safety and efficacy of the treatment over time.Patients and methodsEighteen consecutive patients were recruited with measurable liver tumors of different histopatologic origins, mainly colorectal cancer, breast cancer, and hepatocellular cancer. They were treated with percutaneous ECT following the standard operating procedures (SOP) for ECT under general anaesthesia and muscle relaxation. Treatment planning was performed based on MRI preoperative images. The follow-up assessment included contrast-enhanced MR within at least 1–3 months after treatment and then after 5, 7, 9, 12, and 18 months until progression of the disease or death.ResultsOnly mild or moderate side effects were observed after ECT. The objective response rate was 85.7% (complete response 61.9%, partial 23.8%), the mean progression-free survival (PFS) was 9.0 ± 8.2 months, and the overall survival (OS) was 11.3 ± 8.6 months. ECT performed best (PFS and OS) in lesions within 3 and 6 cm diameters (p = 0.0242, p = 0.0297)_. The effectiveness of ECT was independent of the localization of the lesions: distant, close or adjacent to vital structures. Progression-free survival and overall survival were independent of the primary histology considered.ConclusionsElectrochemotherapy provides an effective valuable option for the treatment of unresectable liver metastases not amenable to other ablative techniques.Key words: electrochemotherapy, liver metastases     

Radiofrequency ablation permits an effective treatment for colorectal liver metastasis.

BACKGROUND: Radiofrequency ablation (RFA) has become an important adjunct to modern liver surgery. However, scant knowledge on long-term outcome of RFA for colorectal liver metastasis is available, nowadays. METHODS: This is a prospective clinical study of patients with liver metastasis of colorectal cancer who were treated by RFA between April 1, 1998, and November 30, 2004. Forty-seven patients with 147 liver metastases were treated with RFA in a total of 70 interventions. A metastasis resection was not feasible in 80% of the interventions. All the patients were followed up at regular intervals with contrast-enhanced computed tomography (CT) and laboratory tests including carcinoembryonic antigen (CEA). RESULTS: No RFA-related mortality occurred. The median follow-up time after the diagnosis of liver metastasis was 33 months. The RFA-related morbidity was 7%. After the RFA, the expected median overall survival rate is, to date, 39 months. Overall survival rates at 1, 2 and 3 years were 88%, 80% and 57%, respectively. Local recurrence rates reached 8.8% overall and 1.6% for metastasis smaller than 3cm in diameter. No local recurrence occurred for metastasis smaller than 3cm in diameter if treated with the newest RFA device. CONCLUSIONS: Excellent local tumour control was achieved with radiofrequency ablation of small liver metastasis. The expected overall survival rate of patients with RFA for unresectable or non-resected colorectal liver metastasis improved in comparison with the survival rate reported following the natural course (best supportive care) or chemotherapy. The low local recurrence rate of metastases of less than 3cm challenges the results obtained by the more invasive treatment of conventional liver surgery.     

Scanning electron microscopy study of the blood supply of human colorectal liver metastases

AIMS: The failure of hepatic artery directed treatment of colorectal liver metastases may reflect a major portal venous contribution to tumour blood supply. This study provides ultrastructural details of the blood supply of colorectal liver metastases and their association with the portal vein and hepatic artery. METHODS: Resected liver specimens from six patients with colorectal liver metastases were examined by histology and scanning electron microscopy (SEM), following vascular resin casting. RESULTS: Nine metastatic colorectal adenocarcinomas were identified. The main feature of all tumours on SEM was direct communication between hepatic sinusoids and tumour vessels. A direct portal venous connection with tumour vessels was observed in a single specimen, whilst a direct arteriole connection was not identified. CONCLUSIONS: It appears that both the hepatic artery and portal vein contribute to the blood supply of colorectal liver metastases through sinusoidal connections with tumour specific blood vessels. SEM provides useful additional information on the morphological features of tumour vasculature.