Changes in Local Hepatic Blood Perfusion During Interstitial Laser-Induced Thermotherapy of Normal Rat Liver Measured by Interstitial Laser Doppler Flowmetry

Interstitial laser Doppler flowmetry was used to measure the effect of interstitial laser-induced thermotherapy on local blood perfusion in normal rat liver in the peripheral treatment region elevated to hyperthermic temperatures. The Nd:YAG laser emitting at 1064 nm was utilised as heat generation source. The plane-cut tip of an optical fibre was placed in the middle of the exteriorised left liver lobe. Blood perfusion and temperature were measured in the liver parenchyma 4 mm from the laser fibre. The temperature at the location of the liver temperature sensor was maintained at 41 or 44°C during 30 min by regulating the power of the heating laser. The laser Doppler signal was recorded during and after heat treatment, for a total time of 60 min. At 41°C, a significant increase in perfusion up to 1.3 times the initial value was observed 2–16 min after start of treatment. At 44°C, perfusion decreased continuously during and after treatment, and was significantly different from control 40 min after start of treatment. The results may be valuable in assessing the thermal response of tissues surrounding the target in interstitial laser-induced thermotherapy of liver tumours during conditions of normal blood flow. Paper received 28 September 1998; accepted after revision 24 November 1998.     

Interstitial laser thermotherapy in neurosurgery: A review

Summary One of the most recent laser treatment modalities in neurosurgery is interstitial laser thermotherapy (ILTT). In this review, experimental and clinical studies concerning intracranial ILTT are discussed. Two methods for intra-operative control of the laser induced lesions are described; i.e., computer-controlled power delivery, using a thermocouple that is positioned interstitially at the periphery of the tumour to maintain the desired temperature at that point, and MRI, to visualise the extent of the thermal lesions induced by ILTT. The results show that ILTT using a Nd:YAG laser is easy and relatively effective in the treatment of small deepseated brain tumours with minimal risk and complications. This review is concluded with suggestions for further improvement of this treatment modality.     

Diffusing Fibre Tip for the Minimally Invasive Treatment of Liver Tumours by Interstitial Laser Coagulation (ILC): An Experimental Ex Vivo Study

A newly developed diffusing laser applicator was examined for interstitial laser coagulation (ILC) of liver tumours. The applicator consisted of a matted quartz core and a quartz glass dome, also matted on its inner surface and sealed to the fibre. The applicator provided a homogeneous light intensity distribution over an active length of about 20 mm. Lesions were created in an ex-vivo porcine liver model using a Nd-YAG laser comparing the new diffusing tip with a Ringmode^?-ITT applicator in order to find optimal laser parameters and damage thresholds. The lesions were investigated using macroscopic size measurement, volume calculation and histological examination (H&E, NADPH-dehydrogenase). The damage threshold of the diffusing tip was 6 W at 14 min exposure time whereas the Ringmode^?-ITT applicator had its limit at 5 W and 12 min exposure. Comparing various exposure times showed that treatment over a time of more than 840 s did not significantly increase the lesion volume. At 5 W and 720 s the mean lesion volume was 6.9±1.1 cm³ with the diffusing tip and 6.3±0.6 cm³ with the Ringmode^?-ITT applicator, both having a slight ellipsoidal shape. Hence, the created lesions were not significantly different for both applicators when the same laser parameters were applied. On the other hand, the new diffusing tip had a higher damage threshold and was therefore capable of producing maximal coagulation volumes of up to 7.9±0.5 cm³ at 5 W and 20 min. The experiments showed that lesions with a dimension of 31×22 mm can be achieved with the diffusing applicator which seem suitably sized for treating small human liver metastases in a single laser session. Paper received 25 April 1997; accepted after revision 13 March 1998.     

Coagulation and temperature distribution in Nd: YAG interstitial laser thermotherapy: an in vitro animal study

 Interstitial laser thermotherapy (ILTT) was performed increasingly for local destruction of different tumours. The proposal of the present study was the optimisation of the therapy-relevant ILTT parameters and laser application forms which are a prerequisite for the development of an optimal tumour treatment strategy. Laser-induced temperature changes and coagulation patterns with different laser light applicators (bare fibre, ring mode fibre, side fibre, diffuser fibre) were investigated on liver, spleen and tongue tissues of 26 adult pigs after interstitial thermotherapy with Nd: YAG laser. Analysis of experimental results on ILTT and tissue necrosis showed a dependence on laser exposure time, type of laser fibre and applied laser energy. The most homogeneous and extensive coagulation zone was seen after laser treatment with rather low energy over a longer time period. Received: 18 March 2002 / Accepted: 20 August 2002     

External beam,sapphire tip contact and interstitial Nd-YAG laser therapy at 1.064 μm on a transplanted adenocarcinoma in mice: A comparative study

This study was undertaken to compare three different techniques for treating transplanted tumours in mice with the Nd-YAG laser—no contact (external beam), interstitial and sapphire tip contact therapy. The aspects studied were macroscopic and microscopic tumour necrosis and haemostasis. Forty C_57B1 male mice were transplanted with the adenocarcinoma AC₇₅₅ and divided into four groups—three experimental (one for each treatment technique) and one control. On the 15th day after transplantation tumours were irradiated with an external, no contact beam (Group I), interstitial therapy (Group II) or contact therapy with a sapphire tip (Group III), each with a light dose of 1200 J. Seventy-two hours later all animals (experimental and control) were killed, the tumours excised, weighed and the extent of necrosis measured macroscopically and microscopically and the blood vessels near the zone of necrosis examined. The best results were obtained in Groups I and II (no contact and interstitial) compared with the controls (p<0.001 andp<0.01 for the tumour weight andp<0.01 andp<0.001 for the percentage of necrosis, respectively). Results from contact therapy were poor for each of the parameters chosen with no significant differences between the treated and control animals although marginally better coagulation was observed in this group. It is concluded that sapphire tip therapy has no advantages for tumour destruction but causes slightly better coagulation at the treatment point. Interstitial therapy warrants further investigation.     

Interstitial laser thermotherapy: Comparison between bare fibre and sapphire probe

A sapphire probe and a bare fibre were compared with respect to temperature control and distribution and light fluence in interstitial laser thermotherapy. Experiments were performed in processed liver using an Nd-YAG laser and output power levels of 1–4 W. The temperature was controlled at a distance of 10 mm using a feedback circuit with an automatic thermometry system and thermistor probes. With the sapphire probe, carbonization was rare at power levels of 1–2 W but was observed in half of the experiments at 3 W and in all experiments at 4 W. Using the bare fibre, carbonization was seen in almost all experiments. Absence of carbonization was associated with a moderate decrease in the penetration of light and excellent control of the temperature, whereas carbonization led to rapid impairment of light penetration and temperature control. In addition, the temperature gradient was smaller with the sapphire probe than with the bare fibre or when carbonization was absent. It is concluded that a diffuser tip, such as the sapphire probe, may be preferable to the bare fibre for interstitial laser thermotherapy because it gives a smaller temperature gradient and helps to avoid carbonization which results in preserved light penetration and improved temperature control.     

Synergistic Effect of Interstitial Laser Coagulation and Doxorubicin in a Murine Tumor Recurrence Model of Solitary Colorectal Liver Metastasis

Background Interstitial laser coagulation (ILC) is gaining acceptance for treatment of unresectable colorectal liver metastases. However, local recurrence rates are still high. To overcome this problem, we investigated the potential of additional systemic therapy after ILC in a murine model. Methods Single C26 colon carcinoma nodules (∼1 mm³) expressing firefly luciferase were implanted in the left liver lobe of 32 BALB/c mice. Seven days after implantation, tumors were treated with either ILC alone (neodymium–yttrium aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin intravenously. Controls received either doxorubicin alone or sham treatment. Tumor load was measured by in vivo bioluminescent imaging. Results Solitary colorectal liver metastases developed over 7 days after tumor implantation in the liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0 of 14). Sham treatment or treatment with doxorubicin alone showed an exponential increase in tumor load. Conclusions A murine tumor recurrence model after local ablative treatment of solitary liver metastasis was developed. The combination of ILC and doxorubicin had a strong synergistic effect that led to complete tumor remission in all animals treated.     

Interstitial laser thermotherapy: Developments in the treatment of small deep-seated brain tumors

New technical advances have made feasible the utilization of laser to destroy deep-seated brain tumors under real-time monitoring. Experience with interstitial laser thermotherapy (ILTT) in animal and clinical studies has been obtained. These studies are summarized and the future potential of ILTT in neurosurgery is discussed.     

Interstitial Nd:YAG laser coagulation with a cylindrical diffusing fiber tip in experimental liver metastases

Interstitial laser coagulation as a means of destructing hepatic metastases was investigated. Colon carcinoma CC531 was implanted in the liver of 42 Wag/Rij rats; 20 days later, tumors (5.5±0.2 mm) were exposed to 1,064 nm Nd:YAG laser light at 4 W/cm and either 600, 1,200, 2,400, 3,400, or 4,800 J/cm from a 0.5 cm Helioseal® coated cylindrical diffuser. Temperature and fluence rate were measured at the tumor boundary. Lesions were studied on day 2 and 36 posttreatment by light microscopy. Tumor proliferative activity was assessed by bromodeoxyuridine incorporation. Liver damage and function were determined by serum liver enzymes and antipyrine clearance. Fluence rate increased during laser treatment up to 170%; mean temperature increased logarithmically up to 69.7°C. Short-term light microscopy showed coagulation necrosis of 7–11 mm without charring. Lesion size and liver enzymes increased logarithmically with laser energy applied. No deterioration in liver function was found. At 4,800 J/cm complete tumor remission occurred in three of four animals. This study shows the ability of interstitial laser coagulation to produce selective destruction of colonic tumor within the liver. © 1994 Wiley-Liss, inc.     

Dynamic modeling of photothermal interactions for laser-induced interstitial thermotherapy: parameter sensitivity analysis

A two-dimensional model was developed to model the effects of dynamic changes in the physical properties on tissue temperature and damage to simulate laser-induced interstitial thermotherapy (LITT) treatment procedures with temperature monitoring. A modified Monte Carlo method was used to simulate photon transport in the tissue in the non-uniform optical property field with the finite volume method used to solve the Pennes bioheat equation to calculate the temperature distribution and the Arrhenius equation used to predict the thermal damage extent. The laser light transport and the heat transfer as well as the damage accumulation were calculated iteratively at each time step. The influences of different laser sources, different applicator sizes, and different irradiation modes on the final damage volume were analyzed to optimize the LITT treatment. The numerical results showed that damage volume was the smallest for the 1,064-nm laser, with much larger, similar damage volumes for the 980- and 850-nm lasers at normal blood perfusion rates. The damage volume was the largest for the 1,064-nm laser with significantly smaller, similar damage volumes for the 980- and 850-nm lasers with temporally interrupted blood perfusion. The numerical results also showed that the variations in applicator sizes, laser powers, heating durations and temperature monitoring ranges significantly affected the shapes and sizes of the thermal damage zones. The shapes and sizes of the thermal damage zones can be optimized by selecting different applicator sizes, laser powers, heating duration times, temperature monitoring ranges, etc.     

Indications for biopsy and the current status of focal therapy for renal tumours

The increased detection of small renal masses (SRMs) has focused attention on their uncertain natural history. The development of treatment alternatives and the discovery of biologically targeted drugs have also raised interest. Renal mass biopsies (RMBs) have a crucial role as they provide the pathological, molecular and genetic information needed to classify these lesions and guide clinical management. The improved accuracy has improved our knowledge of the behaviour of different tumour histologies and opened the potential for risk-adapted individualized treatment approaches. To date, studies have demonstrated that percutaneous ablation is an effective therapy with acceptable outcomes and low risk in the appropriate clinical setting. Although partial nephrectomy (PN) is still considered the standard treatment for SRM, percutaneous ablation is increasingly being performed and if long-term efficacy is sustained, it may have a wider application for SRMs after biopsy characterization.     

Interstitial laser photocoagulation and interstitial photodynamic therapy of normal lung parenchyma in the pig

. Interstitial laser photocoagulation (ILP) and interstitial photodynamic therapy (PDT) involve delivery of light to lesions in solid organs using thin fibres passed through needles inserted percutaneously under image guidance. In ILP, the laser energy heats the tissue, whereas in PDT it activates a previously administered photosensitising agent. This study looks at their potential for treating localised, small, peripheral lung cancers in patients unsuitable for surgery. Experiments were undertaken on nine normal pigs, up to four fibres being inserted into the lung parenchyma percutaneously under X-ray guidance (ILP: 2–3 W, 1000 q/fibre, from 805 nm diode laser, PDT, 100–200 J/fibre from 652 nm diode laser at 50–100 W, 3 days after 0.15 mg/kg mTHPC). Animals were killed from 3 days to 3 months later and the treated areas examined macroscopically and microscopically. Both techniques were well tolerated, producing well-defined, localised lesions, typically 3.5×2×2 cm using four fibres. Histology showed thermal coagulative necrosis after ILP and haemorrhagic necrosis after PDT. Early small haematomas and late cavitation were sometimes seen after ILP, but not after PDT. PDT lesions healed with preservation of larger arteries and bronchi in the treated area. A few small pneumothoraces were seen which resolved spontaneously, probably related to the chest wall puncture. It was concluded that ILP and PDT lesions of a size large enough to cover a small tumour can be made safely in the lung parenchyma, although healing was better after PDT. Pilot clinical studies with both techniques are now justified on carefully selected patients. Paper received 6 September 1999; accepted after revision 7 July 2000.     

适形放射治疗后肝损伤的CT表现

目的 对原发性肝癌适形放疗后的患者进行CT平扫或增强扫描，观察肿瘤区周围正常肝组织的影像表现，以发现其特征，为与适形放疗后病灶未控或复发提供鉴别依据。方法 30例单发肝癌患者采用了适形放疗，36—48Gy/8—12次，隔日1次。1-3个月后开始CT复查。结果 肿瘤周围15例平扫表现为低密度；增强扫描：无强化，6例；动脉期为低密度，门脉期或延迟期呈强化状态，2例；早期至延迟期均强化，2例。结论 照射后，高剂量区CT可表现为低密度，可以出现强化，特征为进行性或持续性强化。     

Optical properties of rat liver and tumor at 633 nm and 1064 nm: Photofrin enhances scattering

Predicting the effects of photodynamic therapy (PDT) and Nd: YAG laser coagulation requires knowledge of the light distribution in tumor and surrounding tissue. Therefore, absorption and scattering coefficients and the average cosine of the scattering angle (the anisotropy factor) were measured in rat liver and tumor at 632.8 and 1064 nm. A syngenic colon adenocarcinoma CC531 was implanted subcutaneously in two groups of 7 Wag/Rij rats. In one group Photofrin was administered 5 mg/kg intravenously 48 h before determination of optical properties. Two months after inoculation, samples were taken from tumor and liver and optical properties determined using indirect methods with two integrating spheres. The absorption coefficient was larger in liver than in tumor at 632.8 nm (P < 0.0005), whereas the scattering coefficient was larger in tumor than in liver at 1,064 nm (P < 0.05). Addition of Photofrin increased the scattering coefficient in liver and in tumor at both wavelengths (P < 0.025) and decreased the anisotropy in tumor (P < 0.025), suggesting that for modelling the dosimetry of PDT the optical properties of photosensitized tissue should be used. © 1993 Wiley-Liss, Inc.     

Interstitial Laser Photocoagulation with Four Cylindrical Diffusing Fibre Tips: Importance of Mutual Fibre Distance

. Simultaneous application of multiple fibres could increase the volume of coagulation produced with interstitial laser photocoagulation (ILP) for solid tumours. To take full advantage of the presumed synergistic thermal effect between the fibres, the optimal combination of laser power and distance between the fibres was investigated. Four fibres with a cylindrical diffusing tip of 2 cm length were used, coupled to an optical beamsplitter for Nd:YAG light (four channels, maximal variation 9.5%, transmission >85%). The distance between the fibres was 1, 1.5, 2, 2.5 , 3 or 4 cm with a power output of either 4, 5, 6 or 7 W/fibre; energy per fibre was constant at 1800 J by adjusting exposure time. After laser application, dimensions of the coagulated lesions were measured. The optimal mutual fibre distance was 2 cm ( p<0.01) at all power levels. This resulted in lesions with a mean (SD) volume of 44.5 (2.1) cm³ and a largest diameter of 5.1 (0.4) cm at 7 W/fibre. Smaller distances between the fibres resulted in smaller lesions with central carbonisation, whereas larger distances resulted in four separate zones of coagulation. It was concluded that simultaneous application of four interstitial fibres may result in a considerable increase of volume of coagulation. Fibre position and mutual fibre distance determines whether synergism of the coagulative effect occurs. Paper received 14 July 1998; accepted following revision 18 January 1999     

Nd:YAG laser followed by radiation for treatment of malignant airway lesions

Patients with malignant obstructive airway lesions often present with total or segmental atelectasis of lung. In spite of prompt initiation of palliative external radiation alone, some patients were unable to complete the planned course of radiation therapy. Since May 1983, 17 patients with malignant obstructive endobronchial lesions have been treated by endoscopic Nd:YAG laser vaporization of the tumor. One to seven days later, fractionated external radiation therapy was initiated. Endoscopic use of the laser was repeated as needed during the course of treatment. Fifteen out of 17 patients successfully completed the planned course of therapy. The improved performance status was sustained in 13 of 15 patients for 2-13 months. A control group was selected from among patients with similarly located lesions who underwent external radiation treatment only prior to the availability of the Nd:YAG laser therapy. One patient developed radiation pneumonitis six weeks after completion of a second course of external radiation, another patient developed bronchopleural fistula after laser treatment which healed following closed chest tube drainage. The others had longer palliation of symptoms and improved quality of life. The results indicate that relief of airway obstruction by use of the Nd:YAG laser improved the patients' ability to tolerate subsequent external radiation treatment.