Interstitial Therapy Research Articles

Laparoscopic liver resections for hepatocellular carcinoma. Is it a feasible option for patients with liver cirrhosis?

Laparoscopic surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver, above all for patients with hepatocellular carcinoma (HCC) and cirrhosis. This approach mainly includes diagnostic procedures and interstitial therapies. However, we believe there is room for laparoscopic liver resections in well-selected cases. The aim of this study is to assess: (a) the risk of intraoperative bleeding and postoperative complications, (b) the safety and the respect of oncological criteria, and (c) the potential benefit of laparoscopic ultrasound in guiding liver resection. A prospective study of laparoscopic liver resections for hepatocellular carcinoma was undertaken in patients with compensated cirrhosis. Hepatic involvement had to be limited and located in the left or peripheral right segments (segments 2-6), and the tumor had to be 5 cm or smaller. Tumor location and its transection margins were defined by laparoscopic ultrasound. From January 1997, 22 out of 250 patients with HCC (9%) underwent laparoscopic liver resections. The mean patient age was 61.4 years (range, 50-79 years). In three patients, conversion to laparotomy was necessary. The laparoscopic resections included five bisegmentectoies (2 and 3), nine segmentectomies, two subsegmentectomies and three nonanatomical resections for extrahepatic growing lesions. The mean operative time, including laparoscopic ultrasonography, was 199 +/- 69 min (median, 220; range, 80-300). Perioperative blood loss was 183 +/- 72 ml (median, 160; range, 80-400 ml). There was no mortality. Postoperative complications occurred in two out of 19 patients: an abdominal wall hematoma occurred in one patient and a bleeding from a trocar access in the other patient requiring a laparoscopic re-exploration. Mean hospital stay of the whole series was 6.5 +/- 4.3 days (median, 5; range, 4-25), while the mean hospital stay of the 19 laparoscopic patients was 5.4 +/- 1 (median, 5; range, 4-8). Laparoscopic treatment should be considered in selected patients with HCC and liver cirrhosis in the left lobe or segments 5 and 6 of the liver. It is clear that certain types of laparoscopic resection are feasible and safe when carried out by adequately skilled surgeons with appropriate instruments.

CT-Guided Brachytherapy (CTGB) versus Interstitial Laser Ablation (ILT) of Colorectal Liver Metastases

To compare local tumor control after percutaneous tumor ablation by interstitial laser therapy (ILT) or CT-guided brachytherapy (CTGB). In a matched pair analysis including 18 patients with 36 liver metastases of colorectal primary, both ILT and CTGB were performed in different lesions. The following matching factors were considered: (i) tumor size ≤ 5 cm, and (ii) execution of chemotherapy after tumor ablation. Primary endpoint was local tumor control. Treated lesions were identical in terms of tumor size and all matching criteria were fulfilled in all patients except for the performance of adjuvant chemotherapy. Median follow-up was 14 months (3–24 months) for both groups. Only five of 18 patients (28%) demonstrated local tumor progression after CTGB, whereas in ten of 18 patients (56%) tumor progression was found after ILT. Differences encountered were significant for all patients (p = 0.04), whereas in those who fulfilled all matching criteria (n = 14) the level of statistical significance was not reached (p = 0.23). CTGB demonstrated superior local tumor control compared to ILT in long-term follow-up.

WE-C-351-01: Characterization of Gold Nanoshells for Thermal Therapy Using MRI

Purpose: To investigate the development of light activated gold nanoshells as mediators for highly conformal photothermal therapy of soft‐tissue tumors with an emphasis on illustrating how results from MR‐guidance in phantoms, in vivo small and large animals have helped demonstrate feasibility and shape the therapeutic approach. Method and Materials: Experiments were performed on a 1.5T MRI.Temperature was measured in real‐time using MR thermography based on the proton resonance frequency shift. Nanoshell phantoms were employed to evaluate effects of concentration and size on distribution of heat when activated by an 808‐nm laser and quantitatively correlated to a 3D finite element model. Passive (enhanced permeability and retention) and active (EGFR receptor) targeting was studied in tumor xenografts. Feasibility of interstitial therapy delivery was investigated in a large animalmodel of braincancer using a canine sarcomamodel.Results: Numerical modeling of heating of gold‐silica nanoshells in phantom correlated excellently with observed MR measured heating patterns. SEM results indicate that passive accumulation of nanoshells (∼140 nm) results in large concentrations near tumor microvasculature (corroborated by MR heating and dynamic enhancement patterns) and this results in statistically significant increase in temperature (21±4°C) over controls after 3 minutes at 4 W/cm2 in a PC3 xenograph. Intravenous injection of these nanoshells into a dog model of cancer resulted in selective heating of the target tumor observable on MRI. EGFR receptor targeting allowed increased uptake of smaller nanoshells (<30 nm) versus non‐targeted nanoshells. Addition of iron‐oxide cores facilitated MR imaging of nanoshells in addition to heating. Conclusion:Gold nanoshells effect a more conformal thermal therapy delivery, as confirmed in a large animalmodel of braincancer. MR temperature imaging and guidance is an invaluable tool in the investigation and development of this emerging thermal therapy technique as it moves from Petri dish to patient.

Tolerance of the aorta using intraoperative iodine-125 interstitial brachytherapy in cancer of the lung

Purpose A retrospective review to assess the efficacy and morbidity of surgical resection and 125I interstitial lung brachytherapy placed in approximation to the aorta. Methods and materials The records and postoperative films of 278 patients who had undergone intrathoracic 125I brachytherapy at our institution were reviewed. All patients had undergone a gross total resection of a non–small-cell lung cancer using segmental resection, wedge resection, or sublobar resection. Frozen section margins of resection were required to be negative before the intraoperative delivery of the implant. Of those reviewed, 29 patients were implanted with 125I impregnated Vicryl mesh that contacted greater than 50% with the aorta. Implants consisted of 125I seeds sewn into a nomographically guided geometric array. Only implants where 50% or greater of the implant volume directly approximated the aorta were selected for inclusion into this study. The mean aortic volume receiving the entire prescribed dose was 17.2 cc (mean surface area = 34.4 cm 2) and the mean prescribed dose was 114 Gy (range, 85–120) over the permanent life of the implant calculated by isodose curve distribution at a depth of 0.5 cm from the plane of the implant. Five patients have received postoperative mediastinal dose supplementation with external beam irradiation to further address occult mediastinal nodal disease not revealed during the intraoperative frozen section analysis. Results All patients tolerated the surgery and brachytherapy well with no perioperative mortality. With a median followup of 45.3 months (range, 1–117), 1 of the 29 patients suffered a fatal hemorrhage from suspected great vessel rupture. A review of this case demonstrated that the interstitial therapy had been supplemented with 4500 cGy of external irradiation, which overlapped a small portion of the implant volume overlying the aorta. No other patients suffered even minor events referable to the implant and have continued to do well without symptomatic evidence of chronic sequelae as of the publication of this article or the time of their death. Local control has been achieved in all patients still living and had been achieved in all patients who died from subsequent progression of metastatic disease or other cause. Conclusions Interstitial 125I intrathoracic brachytherapy is a safe and effective method when used with sublobar resection in high-risk stage I non–small-cell lung cancer patients and may be used even in situations that require placement of the sources in close approximation to the aorta. The tolerance of the aorta seems to be greater than previously thought, and may well exceed 12,000 cGy over the permanent life of the interstitial implant. Interstitial 125I brachytherapy can safely be used to deliver significant radiation dose in direct contact with the aorta but supplemental, overlapping external beam irradiation should be avoided.

Methods for geometric and nonlinear optimization of the structure of interstitial implants for interstitial x-ray therapy of malignant tumors

In 1990 G. K. Edmundson suggested a geometric optimization method for determination of the effective structure of interstitial implants. In 1997 Y. Anacak, M. Essassolak, A. Aydin, et al. used this method for two-level interstitial implantation. It was shown in their work that the geometric optimization method provided higher efficiency of the dose distribution than conventionally used dose distributions produced by interstitial implants with equal exposure times. In 1983 the problem of optimization of the interstitial implant structure was formulated in our works. Its mathematical interpretation was also suggested. The goal of this work was to show that the geometric optimization method does not always provide high efficiency of the dose distribution, even in comparison with conventionally used dose distributions produced by interstitial implants with equal exposure times. The interstitial implant structure can be optimized by solving special mathematical programming problems.

Impact of intraoperative ultrasonography in laparoscopic liver surgery

Laparoscopic surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver. This mainly includes diagnostic procedures, interstitial therapies, and treatment of liver cysts. However, the authors believe there is room for a laparoscopic approach to the liver in selected cases. A prospective study of laparoscopic liver resections was undertaken with patients who had preoperative diagnoses of benign lesion and hepatocellular carcinoma with compensated cirrhosis. The inclusion criteria required that hepatic involvement be limited and located in the left or peripheral right segments (segments 2-6), and that the tumor be 5 cm or smaller. The location of the tumor and its transection margin were defined by laparoscopic ultrasound (LUS). From December 1996, 17 (5%) of 313 liver resections were included in the study. There were 5 benign lesions and 12 hepatocellular carcinomas in cirrhotic patients. The mean age of the study patients was 59 years (range, 29-79 years). The LUS evaluation identified the presence of new hepatocellular carcinoma nodules in two patients (17%). The resections included 1 bisegmentectomy, 8 segmentectomies, 3 subsegmentectomies, and 3 nonanatomic resections. The mean operative time, including laparoscopic ultrasonography, was 156 +/- 50 min (median, 150 min; range, 60-250 min), and the perioperative blood loss was 190 +/- 97 ml. There was no mortality. Conversion to laparotomy was necessary for two patients. Postoperative complications were experienced by 3 of 15 patients, all of them cirrhotics. One of the patients had a wall hematoma, and the remaining two patients had bleeding from a trocar access requiring a laparoscopic reexploration. The mean hospital stay for the whole series was 6.9 +/- 4.9 days (median, 6 days; range, 2-25 days) and 5.6 +/-1.4 days (median, 6 days; range, 2-8 days) for the 15 laparoscopic patients. Laparoscopic treatment should be considered for selected patients with benign and malignant lesions in the left lobe or frontal segments of the liver. Evaluation by LUS is indispensable to guarantee precise determination of the segmental tumor location and the relationship of the tumor to adjacent vascular or biliary structures, excluding adjacent or adjunctive new lesions. The evolution of laparoscopic hepatectomies probably will depend on the development of new techniques and instrumentations.

Percutaneous Laser Ablation of Small Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) arising in cirrhosis is one of the most common malignant tumors in the world showing wide geographical variations in prevalence. In this review we will focus on Percutaneous Laser Ablation (PLA), the ablative method of choice for HCC nodules (up to 4 cm) at our Institutions. PLA was performed with a continuous-wave neodymium yttrium-aluminium-garnet laser that operated at a wavelength of 1.064 μm. According to lesion volume, one to four 300 μm optic fiber (s) advanced in 21-g needle were positioned into the target lesions under US guide. A single optimal laser illumination was considered when 1800 Joules/fiber were delivered in 6 min. at 5 W. The interventional procedure was performed under conscious sedation, on an inpatient basis. Spiral triphasic TC was used to assess effectiveness of treatment. According to our observation high rates of tumor necrosis (90%) may be achieved in small HCC nodule (up to 4 cm) with 1 to 3 illuminations in 1 to 2 sessions. In our study the mortality rate turned out to be 0.6% whereas major complications occurred in 0.4% of cases. Local tumor progression rate was of 15% and 49% respectively patients who developed new lesions within five years of follow-up. The 1-, 2-, 3-, 4-, and 5-year cumulative survival rates were 89%, 75%, 52%, 43%, and 27%, respectively. The independent predictors of survival were found to be tumor grading, bilirubin levels £ 2.5 mg/dl and the achievement of complete tumor ablation. On the other hand, complete necrosis could be achieved more frequently due to some factors such as HCC grading (well differentiated forms at histology), lesion location, easy to reach operators skills and in case the HCC nodule was naive (newly diagnosed and not previously treated). Our findings suggested that PLA is an effective and safe percutaneous treatment modality for HCC nodules up to 4 cm. Keywords: Lasers, interstitial therapy Liver, interventional procedures Liver neoplasms, Liver neoplasms, therapy

Salvage hepatic resection after incomplete interstitial therapy for primary and secondary liver tumours

When the response to percutaneous ablation therapy (PAT) of liver tumours is incomplete, surgery may be undertaken as a salvage therapy. To validate the safety and effectiveness of salvage hepatectomy, patients who had undergone PAT or no treatment before hepatectomy were compared. Of 137 patients who had hepatectomy for primary and secondary tumours, 21 had undergone PAT and 116 had surgery as primary treatment. Tumour features and the incidence of liver cirrhosis were similar in the two groups. Peroperative mortality and major morbidity rates were zero and 5 per cent (one of 21) respectively among patients who had PAT before surgery, and 0.9 per cent (one of 116) and zero in those who did not. Duration of operation (mean 495 versus 336 min; P<0.001), clamping time (mean 81 versus 53 min; P<0.001), blood loss (mean 519 versus 286 ml; P=0.004), need for blood transfusion (six of 21 patients versus nine of 116; P=0.001), and rates of thoracophrenolaparotomy (eight of 21 versus 14 of 116; P<0.001) and resection of other tissues (six of 21 versus nine of 116; P<0.001) were significantly higher in the PAT group. Hepatectomy after incomplete PAT is safe and effective, but more extensive procedures are necessary. The effect of salvage hepatectomy on long-term outcome is still unclear.

Early use of a phosphodiesterase inhibitor after brachytherapy restores and preserves erectile function

To investigate whether the early use of phosphodiesterase inhibitors (PDEIs) after brachytherapy (BT) is associated with better erectile function, as of men potent before BT 38-70% have erectile dysfunction afterward. We evaluated a prospectively created database of 2500 patients who had had BT at our institution since 1992. We measured baseline age, cancer stage, Gleason grade, prostate specific antigen (PSA) level at diagnosis, implant type, use of neoadjuvant and adjuvant hormonal suppression therapy, use of external beam radiotherapy in conjunction with interstitial therapy, and follow-up PSA levels. Men were stratified by their use of PDEIs at <1 year (early group) or >1 year after implantation (late group). We excluded all men who did not have baseline Sexual Health Inventory for Men (SHIM) scores and at least one follow-up SHIM score; the latter were obtained at 6-month intervals after BT. Data were analysed using the Mann-Whitney U-test. In all, 210 men met the inclusion criteria; 85 began using PDEIs within a year of BT, and 125 started after a year. The mean time to PDEI use was 191 days in the early and 595 days in the late group. The median age was 62 years in the early and 63 years in the late group (P = 0.02). Baseline Gleason scores did not differ, nor did PSA levels between the groups. Of men in the early group, 48% received neoadjuvant and/or adjuvant hormonal suppression therapy, vs half of men in the late group. Baseline SHIM scores were not significantly different, nor were scores at the first two follow-up assessments, but the scores at 18-36 months after BT were significantly different. The early use of PDEIs after BT is associated with a significant improvement in and maintenance of erectile function compared with late use. Men undergoing BT should be encouraged to use PDEIs early after implantation, to preserve erectile function.

Right inferior phrenic vein indicating the right hepatic vein confluence into the inferior vena cava

Background Limiting backflow bleeding from the hepatic veins is a priority when performing hepatectomy. However, hepatic vein encirclement is difficult, especially in re-resection. We verified the presence and trajectory of the right inferior phrenic vein (RIPV), which could be a useful anatomic landmark to guide surgeons in targeting the extrahepatic right hepatic vein (RHV) before dissection. Methods Between May 2001 and January 2005, 100 consecutive patients with liver tumors were enrolled and underwent hepatectomy: 77 patients underwent surgery for tumors located in the right hemiliver. Results RIPV was detected in all but 1 patient (99%), and its trajectory was always guided toward the extrahepatic RHV. The only patient in whom RIPV was not detected had undergone prior liver resection and interstitial therapies for colorectal cancer liver metastases. Conclusions Apart from exceptional conditions, detection of the RIPV is always feasible and allows safe surgical dissection while approaching the extrahepatic RHV before hepatic resection.

Reporting Standards for Percutaneous Thermal Ablation of Renal Cell Carcinoma

WITH the increasing incidence of renal cell carcinoma (RCC) in the United States and the increasing proportion of patients with tumors detected at an early stage (1–5), nephron-sparing approaches are becoming more popular. These alternatives to radical nephrectomy include partial nephrectomy, wedge resection, and, more recently, in situ thermal ablation. Five-year survival rates after partial nephrectomy are equivalent to those after radical nephrectomy (6–8), supporting the rationale of in situ tumor destruction to further reduce morbidity and invasiveness. In situ thermal destruction of RCC uses techniques that destroy tumor tissue through heating (eg, radiofrequency [RF] ablation, microwave ablation, laser interstitial therapy, high-intensity focused ultrasound [US]) or freezing (eg, cryotherapy). Each of these techniques relies on controlled energy delivery to minimize collateral damage to normal renal parenchyma and other surrounding structures. In the United States, RF ablation and cryoablation are currently the most widely used techniques for in situ RCC destruction. Thermal ablation of RCC may be performed percutaneously, laparoscopically, or through open surgery. Our current understanding of the role of percutaneous thermal ablation in the management of primary RCC is limited by a paucity of prospective studies (9,10). Given the relative newness of this technology, most series to date report short-term or midterm outcomes, with no reports extending to 5 years of survival outcomes. No randomized trials have been performed to date comparing thermal ablation against a gold standard (ie, partial nephrectomy) or against other thermal ablation techniques. The optimal size range of RCC amenable to thermal ablation has not been clearly defined and is closely related to anatomic factors that influence the ability to deposit sufficient thermal dose to coagulate tissue, including proximity to major vessels and the urinary collecting system, which can act as a heat sink. The kidney has approximately four times the blood flow of the liver, so convective heat loss during thermal ablation is potentially significant (11). The role of percutaneous thermal ablation compared with laparoscopic or open thermal ablation also remains a topic of controversy. The combination of thermal ablation with other imageguided therapies (eg, transcatheter embolization) and adjuvant therapies such as chemotherapy and antiangiogenic agents for larger RCCs in patients who are poor operative candidates is another potential use of this technique. Although most recent reports of percutaneous RCC ablation have involved RF ablation, other ablation technologies are now available with percutaneous applicators (eg, cryoablation, microwave, laser interstitial therapy), and reporting standards should be uniform for all forms of energy-based ablation. This document provides recommended reporting standards for physicians performing percutaneous thermal ablation of primary RCC and will serve as a template in the design of clinical trials to further evaluate this technology. From the Section of Vascular and Interventional Radiology, Department of Radiology (T.W.I.C.), New York University School of Medicine, New York, New York; Department of Radiology (S.F.M.), University of Western Ontario, Peterborough Regional Health Center, Peterborough, Ontario, Canada; Department of Radiology, Gastrointestinal/Genitourinary Division (D.A.G.), Massachusetts General Hospital; Department of Radiology (S.N.G.), Beth Israel Deaconess Medical Center, Boston; Department of Radiology (C.J.G.), Lahey Clinic Medical Center, Burlington; Department of Radiology (D.A.P.), University of Massachusetts Memorial Health Care, Worcester, Massachusetts; Department of Radiology (T.B.K.), University of California San Diego Medical Center, San Diego, California; Department of Radiology (D.S.), The Reading Hospital and Medical Center, Reading, Pennsylvania; and Department of Radiology (J.F.C.), University of Colorado Health Sciences Center, Denver, Colorado. Received June 19, 2006; revision requested June 19; final revision received June 29; and accepted July 3. Address correspondence to T.W.I.C., c/o Tricia McClenny, Society of Interventional Radiology, 3975 Fair Ridge Dr, Suite 400 North, Fairfax, VA 22033; E-mail: mcclenny@sirweb.org

Energy ablative techniques for treatment of small renal tumors

The success of partial nephrectomy for the treatment of small renal cancers has led to the development of energy ablative technologies, which are less invasive alternatives for performing nephron-sparing surgery. Currently, cryoablation and radiofrequency ablation are the two most reported technologies. Both technologies use very different means to cause cellular injury. Additionally, three newer technologies, high-frequency ultrasound ablation, laser interstitial therapy, and microwave therapy are emerging in the literature. Three- and 4-year data for cryoablation and radiofrequency ablation are now becoming available. On the basis of these studies, it is clear that ablative technologies can be effective treatments for select small renal tumors. It is also evident that both percutaneous and laparoscopic approaches offer minimal morbidity. As long-term (5 years and greater) outcome data for ablative technologies accumulate, we are likely to see an increase in clinical reports, including more patients who may be candidates for extirpative surgery. Technology will advance, leading to smaller probes with larger treatment zones, making it possible to treat larger tumors and potentially even tumors in the advanced disease state.

Magnetic resonance–guided interstitial therapy for vaginal recurrence of endometrial cancer

To evaluate the feasibility and to describe the acute toxicity of a real-time intraoperative magnetic resonance (MR)-image guided interstitial approach to treating vaginal recurrence of endometrial cancer. From February 2004 to April 2005, 10 patients with recurrent endometrial cancer underwent MR-guided interstitial brachytherapy. Parameters evaluated included needle placement, dose-volume histograms (DVH), and complications. Magnetic resonance-image guidance resulted in accurate needle placement. Tumor DVH values included median volume, 47 cc; V100, 89%; V150, 61%; V200, 38%; D90, 71 Gy; and D100, 60 Gy. DVH of organs at risk resulted in a median D2cc of external beam and brachytherapy dose (% of brachytherapy prescription): bladder, 75Gy(3) (88%); rectum, 70Gy(3) (87%); and sigmoid, 56Gy(3) (41%). All patients experienced either a Grade 1 or 2 acute toxicity related to the radiation; only 1 patient had Grade 3 toxicity. No toxicities were attributable to the use of MR guidance. Real-time MR guidance during the insertion of interstitial needles reduces the likelihood of an inadvertent insertion of the needles into the bladder and the rectum. Three-dimensional dosimetry allows estimation of the dose to organs at risk. Toxicities are limited.

1154: Laparoscopic ultrasonography for abdominal tumors

Accurate preoperative staging of gastrointestinal malignancies is of major importance in the decision for adequate stage-related therapy. There is evidence that laparoscopy in combination with laparoscopic ultrasound (L-LUS) is more accurate in the detection of intraabdominal tumors than conventional preoperative imaging. Staging L-LUS is a minimally invasive technique that reveals local tumor extent and intraabdominal disseminated tumor spread. Therefore, laparoscopic ultrasound is an ideal adjunct to laparoscopy because this technique may compensate for the lack of tactile feedback with laparoscopic instruments. The concept of using ultrasound through a laparoscopic access for liver tumors was first described by Yamakawa et al. in 1958, but it was only since the end of the 1980s that laparoscopic ultrasound probes were introduced in the clinical practice. Currently available data indicate that L-LUS provides information similar to that obtained by intraoperative ultrasound and can identify lesions that are too small to be visible by preoperative imaging techniques. Furthermore, L-LUS also allows performance of US-guided biopsy or interstitial therapies as ethanol injection, cryoablation or radiofrequency thermal ablation in the same session. Laparoscopic radiofrequency represents a safe and effective treatment for patients with hepatocellular carcinoma not amenable to surgical resection, especially when the percutaneous approach to the lesion is deemed very difficult or impossible. Better protection of vital structures and a more accurate staging are major advantages of this approach. In the future, these advantages and the possibility to perform a more aggressive approach (in association with local vascular exclusion) could favor a more extensive use of the laparoscopic radiofrequency. More recently, some series of laparoscopic segmentectomy were reported; the authors showed that laparoscopic resections are feasible and safe in selected patients with left-sided and right-peripheral lesions requiring limited resections. Staging L-LUS can also provide a significant effect in the multimodal approach to a population of patients undergoing regional treatment of hepatic colorectal metastases. Staging L-LUS also acts as a bridge to a potential laparoscopic approach of both primary colon tumor and liver metastases. Patients with hilar cholangiocarcinoma and gallbladder cancer frequently have unresectable disease that is not apparent on preoperative imaging studies. L-LUS can correctly identify unresectable disease and prevents unnecessary laparotomy in about one third of patients. Color-coded Doppler imaging can be very valuable for the assessment of resectability in patients with pancreatic cancer. Current data confirm that laparoscopic ultrasound is capable of enhancing the accuracy of staging laparoscopy. Compared to standard laparoscopy, a combination of both techniques markedly increases the sensitivity of staging laparoscopy in the determination of unresectable disease. This is of major importance in the assessment of occult liver metastases and lymph node involvement. Laparoscopic ultrasonography improves the diagnostic accuracy compared to conventional imaging techniques and should be considered as integral part of staging laparoscopy. It may help in choosing the most suitable treatment for the patient. However, a steep learning curve for L-LUS has been reported, and a training workshop experience with LUS will be needed to improve both accuracy rates and LUS technique.

Optical properties of sol-gel fiber optic applicators for laser interstitial therapy

A new type of applicator for interstitial laser coagulation is proposed in this paper. The new fiber optic applicator is made by removing the original fiber cladding and replacing it with a sol-gel coating. The sol-gel coating was prepared from the silicate precursor TEOS (tetraethylorthosilicate), mixed with ethanol in acid, which catalyzes hydrolysis. The material is produced with the factor R = 20, where R denotes the number of solvent moles to the number of TEOS moles. In these studies, optical fibers were used from Laser Components (core diameter 400 µm, HCS, low OH). The external jacket was mechanically removed, leaving a remaining 2-cm length of bare fiber. The modified dip-coating method was used to cover the bare fibers with sol-gel material. Two types of applicators were produced: pure sol-gel coated devices and applicators with sol-gel coating doped with photosensitive dyes. The photodynamic activity of chlorophyll-based Photolon and Protoporphyrin IX (PPIX) incorporated within the sol-gels was studied spectrophotometrically. It was demonstrated that sol-gel applicators are capable of performing laser interstitial coagulation using a semiconductor cw laser at 980 nm. It was also demonstrated that the incorporated photosensibilizers retain their photochemical activity.

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

Docetaxel (Taxotere) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human (U87 and U80 glioma) and rat brain-tumor (9L gliosarcoma and F98 glioma) cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n=15, median survival 39.1 days) had significantly improved survival over control animals (n=12, median survival 22.5 days, P=0.01). Similarly, animals receiving BCNU polymers (n=15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P=0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n=14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P=0.003). We conclude that locally delivered docetaxel shows promise as a novel anti-glioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.

Organ preservation using interstitial radiation therapy for base of tongue cancer: University of Cincinnati experience

Organ preservation using interstitial radiation therapy for base of tongue cancer: University of Cincinnati experience

Cancer therapy-associated CNS neuropathology: an update and review of the literature

Standard therapeutic options for brain tumors include surgery, radiation, and chemotherapy. Unfortunately, these same therapies pose risks of neurotoxicity, the most common long-term complications being radiation necrosis, chemotherapy-associated leukoencephalopathy, and secondary neoplasms. These side effects remain difficult to predict, but are associated with risk factors that include patient age, therapeutic modality and dosage, genetic background, and idiosyncratic predispositions. Experimental treatments designed to enhance efficacy and to minimize neurotoxicity include molecularly targeted, genetic, stem cell, and immune therapies. Newer modifications in radiation and drug delivery include stereotactic radiosurgery, interstitial therapy such as intracavitary brachytherapy and gliadel wafer placement, 3D conformal radiation, boron neutron capture therapy, radiosensitizers, blood-brain barrier disrupting agents, and convection enhanced delivery. Toxicities associated with these newer modalities have yet to be fully investigated and documented. Additionally, a number of recently implemented radiographic techniques such as PET and SPECT imaging have enhanced the ability to distinguish recurrent tumor from radiation necrosis. Nevertheless, post-therapeutic brain biopsies and autopsies remain the gold standard for assessing neurotoxicity, therapeutic efficacy, tumor progression, and the development of secondary neoplasms. At the same time, treatment-associated changes such as tumor necrosis, vasculopathy, inflammation, and cytologic atypia can pose significant diagnostic pitfalls, particularly if the pathologist is not provided a detailed therapeutic history. Therefore, it is critical to recognize the full spectrum of cancer therapy-associated neuropathology, the topic of the current review.

Role of interstitial therapy in the treatment of liver cancer

Conventional palliative management of inoperable focal hepatic tumours remains unsatisfactory. Interstitial techniques such as cryotherapy, alcohol injection, low power laser hyperthermia and interstitial radiotherapy offer alternative approaches. Cryotherapy is an effective and precise technique for inducing tumour necrosis. It can only be performed at laparotomy making it relatively invasive and retreatment impractical. Alcohol is cheap and can be injected percutaneously. However, inhomogeneous distribution produces imprecise and nonreproducible lesions. Low power laser hyperthermia produces precise and reproducible areas of necrosis that are roughly spherical in shape. At present, this technique is most effective for small tumours. Interstitial radiotherapy remains the least evaluated of all the interstitial techniques. Unlike cryotherapy and low power laser hyperthermia, the biological effect of ethanol injection and interstitial radiotherapy cannot be monitored in real time by ultrasound. With the exception of cryotherapy, all methods can be applied percutaneously with low morbidity and mortality. None of these techniques is established, but they may offer the prospect of cure in cases where all areas of tumour can be positively identified and fully treated. However, in most instances the intention is to control the growth of relatively small discrete volumes of tumour within the hepatic parenchyma.

Accuracy and conformity of stereotactically guided interstitial brain tumour therapy using I-125 seeds

Objective: To assess the accuracy of the stereotactic implantation procedure of catheters containing I-125 seeds in brain tumours and investigate the effect of catheter deviations on the dose distribution in patients. Methods: A randomised sample ( n=37) of all patients treated with I-125 seeds in our department between 6/1994 and 2/2002 was examined. Intraoperative X-ray images were used to measure deviations of implanted I-125 seed catheters from their planned positions and the influence on dose conformity, tumour surface dose and dose burden of surrounding healthy brain tissue was determined. Results: The mean spatial target point deviation was 2.0 mm (maximum 4.1 mm, SD 0.9 mm) and in 54.1% of the cases, reduction of the planned dose was greater than 5%. Target point deviations less than 1.5 mm have only minor influence on surface dose and conformity. Results indicated that in 10.8% of the cases the realized dose distribution showed a ‘slight deviation’, according to the guideline criteria for external radiosurgery of the Radiation Therapy Oncology Group. In 89.2% of the patients the applied dose conformed to the target volume. Conclusions: Stereotactically guided interstitial irradiation with I-125 seeds can be used to treat brain tumours and metastases with high conformity comparable to radiosurgery. The observed deviations of the stereotactically implanted I-125 seed catheters from their planned target points were smaller when compared to frameless procedures. In order to maintain the required spatial accuracy of 1.5 mm in interstitial therapy using I-125 seeds, it appears necessary to optimise stereotactic instruments further.