Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer.

BACKGROUND: Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin. METHODS: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg(-1) verteporfin. After 60-90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently. RESULTS: In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm(3) at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy. CONCLUSIONS: Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.

Radiofrequency ablation in the treatment of breast cancer liver metastases.

Minimally invasive, image-guided thermal ablation is gaining acceptance for the treatment of solid tumour deposits and its use is increasing. This overview discusses one method of thermal ablation in one palliative setting; the local control of breast cancer liver metastases (BCLM) using radiofrequency ablation. Breast cancer is common and over half of all women diagnosed with metastatic disease develop BCLM. The mainstay of therapy remains chemotherapy and supportive care, which may prolong survival to a median of 18-24 months. Despite breast cancer being considered a systemic disease, surgical series of metastectomy for BCLM have shown a survival advantage. Despite this, surgery for BCLM is rarely practiced due to the associated morbidity for a relatively meagre survival benefit. Similarly, radiofrequency ablation has been used for local control of BCLM; the reported series show a median survival of between 30 and 60 months, with no treatment-related deaths and only three serious treatment-related adverse events in 164 patients reported. Despite this, scepticism remains over the efficacy of BCLM ablation due to the heterogeneity of patient inclusion and selective nature of reporting. Randomised trials are needed to formulate robust evidence-based recommendations and direct the necessary allocation of health care resources. Whether or not local ablative treatment of BCLM conveys a survival advantage is an important consideration. However, in this non-curative setting, it is essential that other outcome measures are carefully evaluated in conjunction with survival, including symptoms (local and constitutional), quality of life and psychological morbidity. To these ends, a randomised, multicentre trial to assess best medical therapy alone versus best medical therapy plus radiofrequency ablation in patients presenting with newly diagnosed BCLM with or without the presence of stable extra-hepatic disease will shortly be underway.

Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation.

There is little published long-term survival data for patients with colorectal liver metastases treated with radiofrequency ablation (RFA). We present a multivariate analysis of 5-year survival in 309 patients (198 male, aged 64 (24-92)) treated at 617 sessions. Our standard protocol used internally cooled electrodes introduced percutaneously under combined US and CT guidance/monitoring. The number and size of liver metastases, the presence and location of extrahepatic disease, primary resection, clinical, chemotherapy and follow-up data were recorded. Data analysis was performed using SPSS v.10. On multivariate analysis, significant survival factors were the presence of extrahepatic disease (p < 0.001) and liver tumour volume (p = 0.001). For 123 patients with five or less metastases of 5 cm or less maximum diameter and no extrahepatic disease median survival was 46 and 36 months from liver metastasis diagnosis and ablation, respectively; corresponding 3- and 5-year survival rates were 63%, 34% and 49%, 24%. Sixty-nine patients had three or less tumours of below 3.5 cm in diameter and their 5-year survival from ablation was 33%. There were 23/617(3.7%) local complications requiring intervention. Five-year survival of 24-33% post ablation in selected patients is superior to any published chemotherapy data and approaches the results of liver resection.

Early indicators of treatment success after percutaneous radiofrequency of pulmonary tumors.

We retrospectively reviewed the imaging of patients after radiofrequency ablation (RFA) of lung metastases performed at our institution to assess the usefulness of ground glass opacification (GGO) margin for the prediction of complete tumor ablation. From January 2004 to March 2007, patients were identified where there was a postprocedure thin collimation scan to allow multiplanar reformatting, either immediately or at 24 h and at least 6 months of imaging follow-up. Thirty-six tumors in 22 patients were identified. The scans were assessed for the presence and width of GGO margin, and minimal and maximal dimensions were measured. A second reviewer, blinded to the outcome of the postprocedure assessment, reviewed the follow-up imaging for recurrence. The recurrence group had larger tumors (p = 0.045) and smaller mean minimal GGO margin width (p = 0.0001). Multivariate binary regression analysis confirmed that the minimal GGO margin was significantly (p < 0.005) associated with tumor recurrence. Receiver operator characteristic curve analysis suggests a cutoff of 4.5 mm for complete tumor ablation. There was substantial agreement (kappa = 0.759) between the site of absent GGO margin and the site of tumor recurrence. The point on the tumor surface where there is no GGO margin is likely to be the site of future recurrence. In our experience, a circumferential GGO margin of >5 mm is the minimal margion required to ensure complete tumor ablation.

Lung tumour ablation - where are we now?

Ablation of lung tumours is the fastest expanding area within interventional oncology. Radiofrequency, laser, microwave and cryotherapy have all been shown to be effective. Which of these ablation technologies becomes the preferred technique for lung tumours remains to be seen.

Imaging appearances following thermal ablation.

Radiofrequency ablation (RFA) has an increasingly important role in the management of a number of solid tumours. Treatments usually take place at specialist centres that draw patients from a wide geographical area, but follow-up imaging is often undertaken at the referring institution. This review aims to describe and illustrate the range of normal and abnormal post-ablative appearances encountered in the most commonly treated organs, i.e. liver, lung, and kidney, to equip radiologists with the necessary knowledge for confident interpretation of post-ablation imaging in this diverse patient group.

Quantitative secretin MRCP (MRCPQ): results in 215 patients with known or suspected pancreatic pathology.

Secretin magnetic resonance cholangiopancreatography quantification (MRCPQ) of pancreatic exocrine function correlates well with steatorrhoea and conventional, non-invasive function tests. We report MRCPQ results in a variety of pancreatic conditions. A total of 215 patients [107 male, mean age 46 years (14-78)] were studied. A multi-slice MRCP sequence was performed before and at 2-min intervals after 0.1 ml/kg IV secretin. Change in small intestinal water volume was plotted against time and the flow rate derived from the gradient. Patients were classified using clinical history, MRCP, MR imaging, computed tomography (CT) [150/215 (70%)] and endoscopic retrograde cholangiopancreatography (ERCP) [56/215 (26%)] findings but not MRCPQ results. Mean, standard deviation and 95% confidence intervals were calculated. The one way ANOVA and Student's t-test were used for statistical analysis. Seventy-six patients had chronic pancreatitis, 26 were post-surgical, 34 post-acute pancreatitis, six atrophic pancreatopathy, eight with obstruction, 15 divisum, ten sphincter of Oddi dysfunction, 26 normal and 14 miscellaneous. Significant differences were observed between normals (mean+/-SD; 7.4 +/- 2.9 ml/min) and severe chronic pancreatitis (5.3 +/- 2.4) (P = 0.018), pancreatic atrophy (3.8 +/- 3.1) (P = 0.013) or duct obstruction (5.3 +/- 2.4) (P = 0.047)) and between moderate (7.0 +/- 3.0) (P = 0.03) and severe chronic pancreatitis. MRCPQ can be used to quantify function across the spectrum of pancreatic disease and showed significant differences between several different pathologies.

Analysis of the factors associated with radiofrequency ablation-induced pneumothorax.

AIM: To define the characteristics most likely to result in radiofrequency ablation (RFA)-induced pneumothorax. METHODS AND MATERIALS: CT-guided RFA was performed in 79 tumours in 55 lungs in 37 patients, 16 were women, mean age 62 years (range 34-83). Three had primary lung cancer, 34 had metastases. The number, size, and location of tumours, electrode type, treatment parameters, length of electrode trajectory through aerated lung, background emphysema, prior interventions, and use of positive-pressure ventilation were analysed. The size, timing of any pneumothoraces, and intervention were recorded. RESULTS: Pneumothorax occurred in 21 of the 25 lungs treated (38%), 18 immediate and three delayed. Seventeen of the 21 (81%) occupied less than 30% of the hemithorax, whereas in four cases >31% was involved. Eight of the 55 (15%) pneumothoraces required aspiration. The length of the electrode trajectory through aerated lung in those who developed a pneumothorax was 5.4+/-4.7cm versus 1.9+/-2.7 in those who did not (p=0.001). The mean number of tumours ablated was higher in the pneumothorax group, 1.7+/-1 versus 1.3+/-0.6 (p=0.03), as was the number of electrode positions, 6+/-3.9 versus 3.6+/-2.2 (p=0.01). On multivariate analysis only the needle trajectory through aerated lung was significant (p=0.04). CONCLUSIONS: The number of tumours, electrode positions, and the anticipated electrode trajectory through aerated lung impacts on the likelihood of a pneumothorax. These considerations should be factored into patient selection, the choice of approach, and trajectory used in RFA.

Radiofrequency ablation (RFA) as a cytoreductive strategy for hepatic metastasis from breast cancer.

INTRODUCTION: Patients with liver metastasis from breast cancer have a poor prognosis, although this may be improved by hepatectomy in a selected group with disease confined to the liver. We evaluate the effectiveness of radiofrequency ablation (RFA) as a cytoreductive strategy in the management of liver metastasis from primary breast cancer. PATIENTS AND METHODS: Nineteen patients with hepatic metastasis from primary breast cancer underwent RFA of their liver lesions between April 1998 and August 2004. RESULTS: The median age of the patients was 52 years (range, 32-69 years), 8 had disease confined to the liver, with 11 having stable extrahepatic disease in addition. Seven patients with disease confined to the liver at presentation are alive, as are 6 with extrahepatic disease, median follow-up after RFA was 15 months (range, 0-77 months). Survival at 30 months was 41.6%. In addition, 7 patients followed up for a median of 14 months (range, 2-29 months) remain alive and disease-free. RFA failed to control hepatic disease in 3 patients. RFA was not associated with any mortality or major morbidity. CONCLUSIONS: Control of hepatic metastasis from breast cancer is possible using RFA and may lead to a survival benefit, particularly in those patients with disease confined to the liver.

Diagnosis of duct disruption and assessment of pancreatic leak with dynamic secretin-stimulated MR cholangiopancreatography.

OBJECTIVE: The management of pancreatic duct disruption is complex and depends on several factors including the cause, morphology, and degree of disruption. ERCP can show duct disruption in as many as 75% of patients but is invasive and cannot detect disruption beyond an obstruction. We studied the role of secretin MR cholangiopancreatography in patients with suspected pancreatic duct disruption. CONCLUSION: Secretin MR cholangiopancreatography is a safe, noninvasive test that can provide additional useful information about duct integrity and facilitate management.

Image guided tumour ablation.

Several different technologies have been employed for the local ablation of tissue by thermal techniques. At the present time the most widely favoured technique is radiofrequency ablation (RFA) but developments in other techniques, e.g. microwave may change this. In many countries RFA or percutaneous ethanol injection (PEI) are accepted therapies for patients with Childs Pugh Class A or B cirrhosis and early hepatocellular carcinoma (HCC). Results for RFA in large series of patients with liver metastases from colon cancer are very promising. Five-year survival rates of 26% from the time of first ablation and 30% from the diagnosis of liver metastases for patients with limited (<6, <5 cm) liver disease who are not surgical candidates compares well with post resection series where 5-year survival rates vary between 29% and 39% in operable candidates. Sufficient experience has now been gained in lung and renal ablation to show that these are minimally invasive techniques which can produce effective tumour destruction with a limited morbidity. More novel areas for ablation such as adrenal or pelvic recurrence are being explored.

Complications of percutaneous therapy.

Percutaneous tumour ablation is a minimally invasive, image guided procedure which attracts a low morbidity (2%-10%) and procedure-related deaths are exceptional. As such it can be offered to patients who could not withstand more invasive procedures such as surgical resection. Complications can be divided into systemic and local, those related to the anatomical area and those specific to the ablative technique or the particular tumour type. Most ablation experience has been gained using radiofrequency in the liver for metastases or hepatocellular carcinoma. Newer applications include ablation of inoperable lung primary or metastatic disease and renal cell carcinoma. The most common complications are haemorrhage, super-added infection or collateral damage. Tumour dissemination, whilst a theoretical risk, is very unusual.

CT mapping of the distribution of saline during radiofrequency ablation with perfusion electrodes.

PURPOSE: During radiofrequency (RF) ablation, adjunctive saline increases the size of the ablation zone and therefore electrodes that simultaneously deliver current and saline have been developed, but the addition of saline also results in an irregular ablation zone. Our aim was to study the distribution of saline during RF ablation. METHODS: Four patients were treated: 3 with liver metastases and 1 with hepatocellular carcinoma (HCC). Two different perfusion electrodes were used: a high-perfusion-rate, straight electrode (Berchtold, Germany) and a low-perfusion-rate, expandable electrode (RITA Medical Systems, USA). The saline perfusate was doped with non-ionic contrast medium to render it visible on CT and the electrical conductivity was measured. CT scans were obtained of each electrode position prior to ablation and repeated after ablation. Contrast-enhanced CT was performed 18-24 hr later to demonstrate the ablation zone. All treatments were carried out according to the manufacturer's recommended protocol. RESULTS: The addition of a small quantity of non-ionic contrast did not alter the electrical conductivity of the saline. Contrast-doped saline extravasated beyond the tumor in all 3 patients with metastases but was limited in the patient with HCC. In some areas where saline had extravasated there was reduced enhancement on contrast-enhanced CT consistent with tissue ablation. One patient treated with the high-perfusion-rate system sustained a jejunal perforation requiring surgery. CONCLUSION: Saline can extravasate beyond the tumor and with the high-perfusion-rate system this resulted in an undesirable extension of the ablation zone and a complication.

The use of radiofrequency in cancer.

Radiofrequency ablation (RFA) provides an effective technique for minimally invasive tissue destruction. An alternating current delivered via a needle electrode causes localised ionic agitation and frictional heating of the tissue around the needle. Image-guided, percutaneous ablation techniques have been developed in most parts of the body, but the most widely accepted applications are for the treatment of hepatocellular carcinoma (HCC) in early cirrhosis, limited but inoperable colorectal liver metastases, inoperable renal cell carcinoma and inoperable primary or secondary lung tumours. The procedures are well tolerated and the complication rates low. Patients with coexistent morbidity who are not suitable for surgery are often able to undergo RFA. Most treatments in the lung, kidney and for HCC are performed under conscious sedation with an overnight hospital stay or as a day-case. Larger more complicated ablations, for example, in hepatic metastases may require general anaesthesia. Limitations of RFA include the volume of tissue that can be ablated in a timely fashion, that is, most centres will treat 3-5 tumours up to 4-5 cms in diameter. Early series reporting technical success and complications are available for lung and renal ablation. Liver ablation is better established and 5-year survival figures are available from several centres. In patients with limited but inoperable colorectal metastases, the 5-year survival ranges from 26 to 30% and for HCC it is just under 50%. In summary, RFA provides the opportunity for localised tissue destruction of limited volumes of tumour; it can be offered to nonsurgical candidates and used in conjunction with systemic therapy.

Radiofrequency ablation of neuroendocrine liver metastases: the Middlesex experience.

BACKGROUND: Current treatment options for neuroendocrine liver metastases are not widely applicable or not that effective. Image-guided thermal ablation offers the possibility of a minimally invasive, albeit palliative, treatment that decreases tumor volume, preserves most of the normal liver, and can be repeated several times. We report our experience with image-guided thermal ablation in 25 patients with unresectable liver metastases. METHODS: Since 1990 we have treated 189 tumors at 66 treatment sessions in 25 patients (12 female, 13 male; median age, 56 years; age range, 26--78 years). Thirty treatments were performed with a solid-state laser, and 36 treatments were performed with radiofrequency ablation. All but one treatment was performed percutaneously under image guidance. Sixteen patients had metastases from carcinoid primaries, three from gastrinoma, two from insulinoma, and four from miscellaneous causes. Fourteen of 25 had symptoms from hormone secretion. RESULTS: Imaging follow-up was available in 19 patients at a median of 21 months (range, 4--75 months). There was a complete response in six patients, a partial response in seven, and stable disease in one; hence, tumor load was controlled in 14 of 19 patients (74%). Relief of hormone-related symptoms was achieved in nine of 14 patients (69%). The median survival period from the diagnosis of liver metastases was 53 months. One patient with end-stage cardiac disease died after a carcinoid crisis. There were eight (12%) complications: five local and three distant, four major and four minor. CONCLUSIONS: As a minimally invasive, readily repeatable procedure that can be used to ablate small tumors, preferably before patients become severely symptomatic, radiofrequency ablation can provide effective control of liver tumor volume in most patients over many years.

Radiofrequency ablation of colorectal liver metastases.

BACKGROUND: Untreated patients with colorectal liver metastases rarely survive 3 years, and the 3-year survival rate for patients treated with chemotherapy is 3%. The best survival rates are for the small subgroup that has operable disease, i.e., 39% at 5 years. Radiofrequency ablation (RFA) offers a new opportunity to destroy liver metastases in patients who are not surgical candidates because of disease distribution or comorbidity. METHODS: Acceptance criteria were a maximum of four or five liver lesions with a maximum diameter of 4 or 5 cm and no evidence of active extrahepatic disease. Nearly all treatments were performed percutaneously using ultrasound, computed tomography, or magnetic resonance imaging (or some combination) for guidance and monitoring. RFA is a minimally invasive procedure that can be readily repeated. General anesthesia facilitates the procedure but is not essential. Multiple overlapping ablations are required to ensure optimal treatment in all but the smallest tumors. RESULTS: In our cohort of 167 patients with colorectal liver metastases, 73 fulfilled the optimal acceptance criteria (5 or fewer tumors that were

Radio-frequency ablation of colorectal liver metastases in 167 patients.

The objective of this paper is to report our results from a prospective study of 167 patients with colorectal liver metastases treated with radio-frequency ablation (RFA). Three hundred fifty-four treatments were performed in 167 patients, 99 males, mean age 57 years (34-87). The mean number of metastases was 4.1 (1-27). The mean maximum diameter was 3.9 cm (1-12). Fifty-one (31%) had stable/treated extra-hepatic disease. Treatments were performed under general anaesthesia using US and CT guidance and single or cluster water-cooled electrodes (Valleylab, Boulder, CO). All patients had been rejected for or had refused surgical resection. Eighty percent received chemotherapy. Survival data were stratified by tumour burden at the time of first RFA. The mean number of RFA treatments was 2.1 (1-7). During a mean follow-up of 17 months (0-89), 72 developed new liver metastases and 71 developed progressive extra-hepatic disease. There were 14/354 (4%) major local complications and 22/354 (6%) minor local complications. For patients with < or =5 metastases, maximum diameter < or =5 cm and no extra-hepatic disease, the 5-year survival from the time of diagnosis was 30% and from the time of first thermal ablation was 26%. Given that the 5-year survival for operable patients is a median of 32%, our 5-year survival of 30% is promising.