Local Ablative Techniques Research Articles

Microwave tumors ablation: Principles, clinical applications and review of preliminary experiences

Local ablative techniques have been developed to enable local control of unresectable tumors. Ablation has been performed with several modalities including ethanol ablation, laser ablation, cryoablation, and radiofrequency ablation. Microwave technology is a new thermal ablation technique for different types of tumors, providing all the benefits of radiofrequency and substantial advantages. Microwave ablation has been applied to liver, lung, kidney and more rarely to bone, pancreas and adrenal glands. Preliminary works show that microwave ablation may be a viable alternative to other ablation techniques in selected patients. However further studies are necessary to confirm short- and long-term effectiveness of the methods and to compare it with other ablative techniques, especially RF.

OPTIMIZING THE APPROACH TO PATIENTS WITH POTENTIALLY RESECTABLE LIVER METASTASES FROM COLORECTAL CANCER

Liver metastases are a common event in colorectal carcinoma. Significant advances have been made in managing these patients in the last decade, including improvements in staging and surgical techniques, an increasing armamentarium of chemotherapeutics and multiple local ablative techniques. While combination chemotherapy significantly improves median patient survival, surgical resection provides the only prospect of cure and is the focus of this review. Interpretation of published work in this field is challenging, particularly as there is no consensus to what is resectable disease. Of particular interest recently has been the use of neoadjuvant treatment for downstaging and downsizing disease in patients with initially unresectable liver metastases, in the hope of response leading to potentially curative surgery. This review summarizes the recent developments and consensus guidelines in the areas of staging, chemotherapy, local ablative techniques, radiation therapy and surgery, emphasizing the multidisciplinary approach to this disease and ongoing controversies in this field and examines the changing paradigms in the management of colorectal hepatic metastases.

Interdisziplinäres Management resektabler kolorektaler Lebermetastasen

Lebermetastasen sind die häufigste Rezidivlokalisation nach Primäroperation eines kolorektalen Karzinoms. Ist die Leber einziger Metastasierungsort und sind die Herde lokal operabel, gilt die Leberresektion heute als Standardverfahren. Sie weist eine geringe perioperative Mortalität auf und ermöglicht teilweise lange Überlebenszeiten. Auch wiederholte Resektionen von Leberrezidiven sind möglich und erfolgversprechend. Der Nutzen einer adjuvanten Chemotherapie nach potenziell kurativer Leberresektion ist derzeit noch nicht gesichert, Patienten sollten nur im Rahmen klinischer Studien behandelt werden. Gleiches gilt für die neoadjuvante Chemotherapie. Lokal ablative Verfahren können die Resektion ersetzen oder ergänzen, doch sind derzeit noch keine evidenzbasierten Empfehlungen möglich. OncoSurge™ ist ein neu entwickeltes, auf Studiendaten und Expertenwissen basierendes Entscheidungsmodell, das die Beurteilung der individuellen Eignung von Patienten zur Lebermetastasenresektion vereinfachen soll.

Comparison Between Local Ablative Therapy and Chemotherapy for Non-Resectable Colorectal Liver Metastases: A Prospective Study

There is a growing interest for the use of local ablative techniques in patients with non-resectable colorectal liver metastases. Evidence on the efficacy over systemic chemotherapy is, however, extremely weak. In this prospective study we aim to assess the additional benefits of local tumour ablation. A consecutive series of 201 colorectal cancer patients, without extrahepatic disease, that underwent laparotomy for surgical treatment of liver metastases, were prospectively followed for survival and HRQoL. At laparotomy three groups were identified: patients in whom radical resection of metastases proved feasible, patients in whom resection was not feasible and received local ablative therapy, and patients in whom resection or local ablation was not feasible for technical reasons and who received systemic chemotherapy. Patients in the chemotherapy and in local ablation group were comparable for all prognostic variables tested. For the local ablation group overall survival at 2 and 5 years was 56 and 27%, respectively (median 31 months, n = 45), for the chemotherapy group 51 and 15%, respectively (median 26 months, n = 39) (P = 0.252). After resection these figures were 83 and 51%, respectively (median 61 months, n = 117) (P < 0.001). The median DFS after local ablation was 9 months, HRQoL was restored within 3 months. Patients after local ablation gained far more QALY's (317) than in the chemotherapy group (165) (P < 0.001). Although overall survival did not reached statistical significance, the median DFS of 9 months suggests a beneficial effect of local tumour ablation for non-resectable colorectal liver metastases. Moreover, compared with systemic chemotherapy more QALY's were gained after local ablative therapy.

Current Status of Local Ablative Techniques in the Treatment of Pancreatic Cancer

Current Status of Local Ablative Techniques in the Treatment of Pancreatic Cancer

Combining Local and Regional Therapeutic Modalities to Treat Hepatic Malignancies

Hepatocellular carcinoma and metastatic colon cancer have proven to be challenging problems in oncology today. Currently multiple treatment options are available for treating patients with these diseases, and for this reason, a multimodality and multidisciplinary approach is needed to optimize the effectiveness of treatment. Local ablation techniques along with intra-arterial therapy may be complementary and therefore increase survival in patients being treated for hepatocellular carcinoma and metastatic colon cancer. With proper patient selection, further improvement in treatment outcomes can be achieved when these techniques are combined with surgical resection and multidrug systemic chemotherapy. Therefore, it is imperative that interventional radiologists work closely with our colleagues in other medical and surgical specialties to provide our patients with the best possible treatment options.

Emerging Local Ablation Techniques

Local ablation technologies for hepatic malignancy have developed rapidly in the past decade, with advances in several percutaneous or externally delivered treatment methods including radiofrequency ablation, microwave ablation, laser ablation, and high-intensity focused ultrasound. Research has focused on increasing the size of the ablation zone and minimizing heat-sink effects. More recent developments include improvements in treatment planning and navigation with integration of several imaging modalities, as well as automated delivery of the ablation through robotics. These improvements will allow increased consistency in treatment delivery and will facilitate translation to the community setting. Combination therapies with multimodality guidance are on the cutting edge of image-guided, minimally invasive cancer therapies. Local ablation is being combined with regional therapies, such as arterial chemoembolization and local activation of systemically administered drugs, with promising results. Potential combinations with local ablation also include external radiation therapy and antitumor immune modulation. Image-guided oncology is emerging as an important part of the interventional radiology practice, thanks in part to the innovation and imaging background that lies at the roots of our discipline.

Treatment for multiple bilobar liver metastases of colorectal cancer

Recent advances have extended indications for hepatectomy to include multiple bilobar colorectal liver metastases (CLM). Staging systems based on the biological malignancy of primary and metastatic tumors provide appropriate indications for hepatectomy in CLM. However, suitability for resection in patients with complex and extensive hepatic metastases is controversial. A medline search was performed to identify papers reporting the resection for CLM. Techniques, indication, and results were reviewed. If the anticipated remnant liver volume is small (25-40% of total), suggesting a high risk of postoperative liver failure, portal vein embolization (PVE) is recommended prior to hepatectomy. However, curative resections are not always possible. Specifically in synchronous multiple bilobar CLM, two-stage hepatectomy, comprising bilateral hepatectomy and primary resection with or without PVE, can prevent growth of ipsilateral metastatic nodules in the remnant liver and reduce surgical risk. Several local ablation techniques can complement surgery if hepatic resection alone increases the risk of postoperative liver failure or is not curative. Chemotherapy combined with targeted treatment can suppress recurrence and extend indications for hepatectomy by reducing the size and number of primary irresectable tumors. PVE or staged procedure combining with local ablation or neoadjuvant, downstaging or adjuvant therapies extends indications for hepatectomy to include multiple bilobar CLM. The 5-year survival rate for multiple bilobar CLM treated with alternating hepatectomy and chemotherapy is comparable to the values reported for single and hemilateral CLM.

Fabrication of a cell array on ultrathin hydrophilic polymer gels utilising electron beam irradiation and UV excimer laser ablation

Most of the surface patterning methods currently applied are based on lithography techniques and microfabrication onto silicon or glass substrates. Here we report a novel method to prepare patterned surfaces on polystyrene substrates by grafting ultrathin cell-repellent polymer layers utilising both electron beam (EB) polymerisation and local laser ablation techniques for microfabrication. Polyacrylamide was grafted onto tissue culture polystyrene (TCPS) dishes using EB irradiation. Water contact angles for these PAAm-grafted TCPS surfaces were less than 10° ( cos θ = 0.99 ) with PAAm grafted amounts of 1.6 μg/cm 2 as determined by ATR/FT-IR. UV excimer laser (ArF: 193 nm) ablation resulted in the successful fabrication of micropatterned surfaces composed of hydrophilic PAAm and hydrophobic basal polystyrene layers. Bovine carotid artery endothelial cells adhered only to the ablated domains after pretreatment of the patterned surfaces with 15 μg/mL fibronectin at 37 °C. The ablated domain sizes significantly influenced the number of cells occupying each domain. Cell patterning functionality of the patterned surfaces was maintained for more than 2 months without loss of pattern fidelity, indicating that more durable cell arrays can be obtained compared to those prepared by self-assembled monolayers of alkanethiols, as described in previous reports. The surface fabrication techniques presented here can be utilised for the preparation of cell-based biosensors as well as tissue engineering constructs.

Review of Asian experience of thermal ablation techniques and clinical practice

The field of image-guided tumour ablation has gained great attention from Asian physicians because it represents a safe and effective technique for many commonly seen tumours in this population, showing minimal morbidity and excellent local control rates. Based on the current survey data from Asian physicians who are currently performing image-guided tumour ablation, thermal ablation has been mainly performed for patients with unresectable liver tumours. Radiofrequency ablation has replaced many other local ablation techniques such as microwave or ethanol ablation in treating small focal hepatic tumours for the last 5 years. Surgery and transcatheter arterial chemoembolization also have a unique role as curative and palliative treatment options for patients with more extensive tumour burden. Although radiofrequency ablation represents a paradigm shift in local therapy, more sophisticated strategies to enhance the therapeutic efficacy are necessary and more randomized and controlled investigations to estimate its clinical benefit are warranted.

Non-resective ablation therapy for hepatocellular carcinoma: effectiveness measured by intention-to-treat and dropout from liver transplant waiting list.

Orthotopic liver transplantation (OLT) for patients with small hepatocellular carcinoma (HCC) is widely accepted, and the usefulness of local ablation techniques as a bridge for liver transplantation is still under investigation. From December 1997 to February 2003, patients with cirrhosis and T0-T1-T2-T3 stage HCC received multi-modality ablative therapy (MMT) for the treatment of their HCC and were evaluated for OLT; listed, and transplanted when an allograft became available. MMT included radiofrequency ablation (RFA), and/or Trans-Arterial Chemo-Embolization (TACE), and alcohol (EtOH) ablation, followed by Trans-Arterial Chemo-Infusion (TACI), with repeated treatments based on follow up hepatic magnetic resonance imaging (MRI) during the waiting period for OLT. A total of 135 HCC patients were seen at our center within this time frame. The intention-to-treat group included 33 (24.4%) patients with T0, T1, T2, T3 HCC and cirrhosis. There were 31 men and two women. The mean age was 53.6 +/- 7.2 yr. All patients received MMT with a mean of 2.90 +/- 1.5 procedures per patient. Tumor-node-metastasis (TNM) stages at time of listing were: T0 in one patient, T1 in nine patients, T2 in 17 patients, and T3 in six patients. Twenty-eight (85%) patients have received OLT. Five (12.19%) patients were listed and removed (dropout) from the transplant waiting list after waiting 5, 5, 5, 8, and 14 months respectively. The waiting time of the HCC listed group was 9.1 +/- 14.8 months with a mean follow up of 32 months. OLT patient survival and cancer-free survival are 92.9% and 95.24%, respectively; the overall survival of intention-to-treat group was 79% at 32 months follow up. Predictors of dropout included an alpha-fetoprotein (AFP, >400 ng/mL) and T3 HCC stage. Aggressive ablation therapy with a short transplant waiting time optimizes the use of OLT for curative intent in selective cirrhotic HCC patients.

The use of a “Liquid” electrode in hepatic electrolysis

Background The use of direct current electrolysis as a local nonthermal ablative technique for colorectal liver metastases promises to be a simple, safe, and effective therapy. Under general anesthesia, electrolysis is presently limited to tumors smaller than 5 cm, due to the protracted nature of its administration. In an attempt to enhance the effect of electrolysis, a direct current was passed through a preinjected bolus of acetic acid. Methods The effect of a combination of electrolysis and an injection of acetic acid was tested in the liver of eight normal pigs. The volumes of necrosis caused were analyzed. Results Acetic acid independently produced a volume of necrosis but did not provide a volumetric or rate advantage when used in combination with a direct current. Statistically, the only main effect on the volume of necrosis was a result of electrolysis. Conclusion The use of 50% acetic acid to augment the efficacy of direct current electrolysis cannot be recommended.

Cryotherapy for liver tumors: current status, perspectives, clinical results, and review of literature.

Cryotherapy has gained importance as a locally ablative treatment option for patients with non-resectable liver tumors, especially metastases from colorectal cancer. We have used this technique since 1996 for the treatment of 77 patients with malignant liver tumors. Patient data was prospectively recorded and follow-up was until September 2002 or death. Fifty-five patients had colorectal cancer liver metastases, 16 metastases from other primaries and 6 had hepatoma. Forty patients had cryotherapy only and 37 had an additional liver resection. Morbidity and mortality were 22% and 1.3%, respectively. In 68% of patients with colorectal liver metastases and an elevated serum carcinoembryonic antigen-level preoperatively, it returned to the normal range following cryosurgery. For all 77 patients, median survival was 28 months with a 3- and 5-year-survival rate of 39% and 26%, respectively, and median survival was 29 months with a 3- and 5-year-survival rate of 44% and 26%, respectively, for the 55 patients with colorectal liver metastases. Local recurrence at the cryosite was observed in 13 of 65 patients (20%) with initially complete treatment. For cryotherapy to further establish as a treatment for malignant liver tumors in a time where many new local ablative techniques are developing, different goals need to be achieved. The trauma of the procedure and local treatment failure need to be minimized and survival results need to be optimized. Published studies and new possible fields of research regarding these goals are discussed.

Non-Surgical Treatment Options in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the commonest malignancies in South East Asia and indeed worldwide. Despite the high prevalence of the disease, surgical resection, the only proven cure is an option for only a small proportion of patients, less than 20%. Liver cirrhosis is the most common cause of HCC and necessitates the preservation of as much liver as possible, resulting in local ablative techniques, intraarterial and systemic therapy providing an important treatment modality. This review article discusses the trials that exist between non-surgical treatment options for the treatment and palliation of HCC, as well as the rational and the mechanism of their use. It is hoped that through a better understanding of the current modalities available to surgeons in this complex disease that future trials and research will help develop both systemic and local therapy options.

Histopathological changes after microwave coagulation therapy for patients with hepatocellular carcinoma: review of 15 explanted livers

Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT observed in explanted livers in relation to CT findings. A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Explanted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections. Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. Histologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas. Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body-like inflammatory reaction and fibrosis. Pathologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed.

Histopathological changes after microwave coagulation therapy for patients with hepatocellular carcinoma: review of 15 explanted livers

Objectives Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT observed in explanted livers in relation to CT findings. Methods A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Explanted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections. Results Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. Histologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas. Conclusions Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body–like inflammatory reaction and fibrosis. Pathologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed.

Local Ablative Treatments for Liver Metastases: The Current Situation

Surgical resection is the optimal treatment for liver metastases. However, due to their multifocality and/or insufficient remnant liver volume, the majority of liver metastases are unresectable. For this reason, several local ablative techniques have been developed, aiming to produce selective tumour destruction and thus increase the rate of patients amenable to curative-intent treatments. Among these techniques, cryoablation and radiofrequency ablation only have proven to have a curative potential, while transarterial chemoembolization and alcohol injection should be considered as palliative options only. The local recurrences after cryoablation and radiofrequency are equivalent, inferior to 10%, highly dependent of selection criteria. In contrast, morbidity is significantly increased after cryoablation, leading most of the teams to prefer the radiofrequency approach. Two major limitations for radiofrequency are, first, the risk to provoke heat biliary lesion in case of matastases located proximally to hilar plate, and second, the risk of insufficient ablation due to a cooling effect in case of metastases near to major vessels. Keeping in mind these limitations, selective use of radiofrequency may offer a significant benefit by allowing complete tumour clearance in patients with unre-sectable liver metastases.

Radiofrequency ablation of liver tumors: Influence of technique and tumor size

Background. Radiofrequency thermal ablation (RFA) of liver tumors is done by both radiologists and surgeons by using various techniques for a variety of indications. This report describes our initial experience with RFA in 45 patients with hepatic malignancies. Methods. Patients with primary or secondary hepatic malignancies who were not candidates for resection underwent ultrasound-guided RFA under general anesthesia. End points were recurrence within or adjacent to the ablation zone or new hepatic or extrahepatic lesions. Product limit survival estimates for both ablation site recurrence-free survival and disease-free survival were calculated and compared for tumor size (less than 4 cm or 4 cm or greater), operative approach (percutaneous, laparoscopy, or open), and tumor type (hepatocellular cancer, colorectal cancer, or other metastatic disease). Results. Patients with hepatocellular cancer (n = 11) and with secondary hepatic malignancies (n = 34) had 84 lesions ablated with a median follow-up of 12 months. Largest ablated tumor size of 4 cm or greater (P <.001) and the percutaneous approach (P <.02) were associated with worse ablation site recurrence-free survival but not overall disease-free survival (P =.06). The 15 patients with colorectal cancer had worse disease-free survival compared with other tumor types (P <.01). Conclusions. RFA of hepatic malignancies can be done by using a percutaneous, laparoscopic, or open approach. Local control appears superior for tumors less than 4 cm and when an open surgical approach is used. The difficulty in achieving prolonged disease-free survival, especially in colorectal cancer, underscores the need to investigate multimodality approaches that include local ablative techniques. Future RFA studies should consider tumor size, operative technique, and tumor type in trial design. (Surgery 2002;132:605-12.)

Modern alternatives to resection of metastases--MR-guided laser-induced thermotherapy (LITT) and other local ablative techniques

In patients with liver metastases of different primaries modern local ablative techniques such as laser-induced thermotherapy (LITT) and radiofrequency ablation (RF) are minimal invasive therapy options, if the patients were no candidates for liver surgery. A maximum of 5 cm lesion diameter and not more than 5 metastases without extrahepatic are treatable. MR-guided LITT is currently performed by means of implantable percutaneous catheter systems in local anesthesia and with outpatient management. RF is performed sometimes in general anesthesia and a hospital admission for some days. Liquid irrigated application systems are available both for LITT and for radiofrequency therapy and realized necrosis diameter up to 6 cm. At present LITT enables a local tumor control better than 98% for localized liver metastases without extrahepatic spreading patterns. In a group of 846 patients the average survival times were 4.0 years for patients with liver metastasis from different primary tumors. The data for RF ablation confirm the high value for tumor control for hepatocellular carcinomas with poorer results for liver metastases. Percutaneous MR-guided LITT permits good tumor control of liver metastases smaller than 5 cm and less than 5 in number with an improvement of survival times.

Radiofrequency ablation of fetal cervical teratoma

Background: Highly vascular fetal tumors can lead to death before viability as a result of vascular steal syndrome. Open fetal surgery is associated with significant risks for prematurity and maternal morbidity. Various local ablative techniques have been tried to reduce tumor vascularity, with variable success. Radiofrequency ablation has been performed for sacrococcygeal teratoma, but cervical teratoma poise further significant challenges with its proximity to vital neck structures.Purpose: This is the first report in which percutaneous radiofrequency ablation was used to reduce tumor vascularity in a human fetus with a large cervical teratoma.Methods: A partly solid, partly cystic neck tumor was first detected in a 19‐week fetus. The tumor grew rapidly and caused signs of cardiac decompensation by 26 weeks. After extensive counseling and ethics discussion, operation was performed at 28 weeks under general anesthesia. Radiofrequency ablation to the solid component of the tumor was performed with a nine‐prong retractable needle electrode with thermal couples (RITA), deployed to a maximum diameter of 5 cm. The operation was uneventful and fetal condition was monitored throughout the procedure.Results: Tumor growth was arrested temporarily with improvement of the cardiac status. Re‐growth of the tumor was noted after 32 weeks, necessitating delivery at 33 weeks. Postnatal investigation showed extensive tumor infiltration into the neck tissues and probable liver metastases. Biopsy showed immature teratoma, and chemotherapy was considered to be futile. Intensive care was withdrawn and the baby died 6 days after delivery.Conclusions: Radiofrequency ablation of fetal tumor in utero can reduce blood flow sufficiently to reverse high‐output fetal heart failure. Cervical tumors poise extra challenges with its proximity to vital neck structures. With careful and meticulous placement of the probe, ablation can be performed without injury to surrounding tissues. Experience in this area is preliminary and all such experiences should be reported.