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1.
  • Pålsson, Sara, et al. (författare)
  • Methods for detailed histopathological investigation and localization of biopsies from cervix uteri to improve the interpretation of auto fluorescence data
  • 2006
  • Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 25:1-2, s. 321-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Fluorescence spectroscopy is one of many optical methods that are potentially clinically useful for noninvasive detection and characterization of disorders on the cervical part of uterus, including precancerous lesions. The cervix uteri exhibits a biologically complex tissue and the morphology of a biopsy is generally not homogenous. The standard histopathological protocol accounts only for the most severe condition found within the biopsy and no information is given on other constituents potentially influencing the recorded fluorescence spectra. Spectra are usually correlated, using multivariate techniques, to the histopathological diagnosis of the biopsies. Since the probe volume of fluorescence spectroscopy is considerably smaller than the extension of the biopsy, this can cause problems in the search for correlation between the fluorescence signals and the pathological structures. In addition, the orientation and location of the biopsies are normally not recorded. We now report on the first detailed histopathological protocol where numerous tissue parameters, such as thickness and type of the epithelium and the number of blood vessels, glands, and inflammatory cells, are tabulated and the orientation and location of the biopsy are recorded as precisely as possible. Hopefully, the use of this protocol together with sophisticated mathematical methods will increase the probability to classify cervical disorders of the uterus, including precancerous lesions, with high sensitivity and specificity.
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  • Andersson-Engels, Stefan, et al. (författare)
  • Laser-induced fluorescence used in localizing atherosclerotic lesions
  • 1989
  • Ingår i: Lasers in Medical Science. - 0268-8921. ; 4:3, s. 171-181
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated laser-induced fluorescence frompost mortem human arteries in order to find spectroscopic properties allowing discrimination between normal and atherosclerotic vessel wall. A pulsed nitrogen laser emitting light at a wavelength of 337.1 nm was used as an excitation source. The fluorescence spectrum from 370 to 700 nm was captured and analysed by an optical multichannel analyser. Dimensionless contrast functions were formed by using characteristic spectral features at 390, 415, 480, 580 and 600 nm. All samples were investigated in scans across a region where normal as well as diseased vessel wall appeared. The types of plaque were histopathologically divided into four groups, of which three could be singled out using one or more of our spectroscopic criteria. We also investigated the different layers of the normal and diseased vessel wall in order to determine the various contributions to the fluorescence signal. Furthermore, plasma emission spectra were recorded while ablating the normal as well as the diseased vessel wall with an excimer laser, emitting radiation at 308 nm, thus detecting the change in spectral characteristics during the ablation process down into deeper layers.
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4.
  • Andersson-Engels, Stefan, et al. (författare)
  • Malignant-tumor and Atherosclerotic Plaque Diagnosis Using Laser-induced Fluorescence
  • 1990
  • Ingår i: IEEE Journal of Quantum Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9197. ; 26:12, s. 2207-2217
  • Tidskriftsartikel (refereegranskat)abstract
    • A review of tissue diagnostics using laser-induced fluorescence is given with illustrations chosen from work performed by the Lund group. Two major topics are considered: the demarcation of malignant tumors from normal surrounding tissue and the identification of atherosclerotic regions in arteries. Specific fluorescence from injected agents as well as tissue natural autofluorescence is discussed. Steady-state, as well as time-resolved fluorescence can be utilized. Furthurmore, original data showing immunity to blood interference in artery monitoring are presented. Finally, imaging techniques for diseased tissue real-time visualization are discussed and illustrated.
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  • Andersson-Engels, S., et al. (författare)
  • Tissue diagnostics using laser-induced fluorescence
  • 1989
  • Ingår i: Berichte der Bunsengesellschaft für Physikalische Chemie. - : Wiley. - 0005-9021. ; 93:3, s. 335-342
  • Tidskriftsartikel (refereegranskat)abstract
    • We have performed extensive investigations of laser-induced fluorescence in animal and human tissue aimed at instant tissue characterization. Autofluorescence, as well as specific fluorescence from HPD/DHE and other photosensitizers, has been utilized. The studies have been focused on the demarcation of malignant tumours and atheroscleortic plaques. A nitrogen laser or an excimer-pumped dye laser was used to induce fluorescence, which was analysed with an intensified optical multichannel system. A fibre-optic sensor system was developed for the clinical work. Multi-colour fluorescence imaging has also been demonstrated along a line and equipment for two-dimensional imaging is being constructed. Dimensionless spectroscopic functions, which are not affected by factors that are clinically uncontrollable have been employed for optimum tissue discrimination. The investigations have so far been performed in a time-integrated mode, but time-resolved studies are now being initiated to fully exploit the diagnostic power of tissue laser-induced fluorescence. In addition to a presentation of our own work a brief review of tissue fluorescence studies performed by other groups is also given.
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10.
  • Liu, D. L, et al. (författare)
  • Beneficial-effects of Platelet-activating-factor Receptor Antagonist Web-2170 On 90-minute Hepatic Inflow Interruption
  • 1994
  • Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 6:11, s. 1015-1022
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study the effects of different doses of platelet activating factor receptor antagonist WEB 2170 on animal survival, haemodynamics, reperfusion and ultrastructural changes in the ischaemic liver in rats undergoing 90-min total hepatic inflow interruption (THII). Design: Sixty-five rats were divided into five groups. All animals underwent 90-min THII. Group 1 served as controls. Group 2 underwent THII alone. Group 3 received an intravenous injection of 1 mg/kg WEB 2170 prior to THII. Group 4 received a bolus injection of 3 mg/kg WEB 2170 before THII. Group 4 received a bolus injection of 3 mg/kg WEB 2170 before THII. Group 5 received 3 mg/kg WEB 2170 before, during and after THII. The liver reperfusion index using laser Doppler flowmetry, the time of ischaemic liver initiative reperfusion, and scanning electron microscopy were performed to evaluate the results of different dose schedules. Setting: Lund University Hospital, Lund, Sweden. Results: Animal survival rate, liver reperfusion index, the time of ischaemic liver initiative reperfusion and ultrastructural damage of the ischaemic liver were markedly improved in the groups treated with WEB 2170 compared with the non-treated 90-min THII group. The best result was obtained in the group receiving the three separate doses. Conclusion: In the 90-min THII model, WEB 2170 protects the liver from ischaemia-reperfusion injury and the spread of damage to the post-stasis splanchnic organs. These beneficial effects may be extended to hepatic transplantation or major resections of the liver.
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11.
  • Liu, D. L, et al. (författare)
  • Intra-operative laser-induced photodynamic therapy in the treatment of experimental hepatic tumours
  • 1995
  • Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 7:11, s. 1073-1080
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine the effect of photodynamic therapy (PDT) on experimental liver tumours in rats. Design: An experimental liver tumour model was used. Each of a group of Fats had two tumours simultaneously inoculated into its liver. The tumour located in the left hepatic robe was used for PDT, and the other one, in the median lobe, as a control. The haem precursor delta-amino laevulinic acid (ALA), at a dose of 30 mg/kg body weight, was injected 60 min before laser irradiation. Rats in group I received ALA through a femoral vein. Those in group II received ALA through the portal vein. Group III had an injection of ALA solution through the portal vein plus hepatic inflow occlusion. Three and 6 days after the treatment, the rats were killed, and the tumours were measured, and ultrastructural changes were examined using scanning electron microscopy. Setting: Lund University Medical Laser Centre, Lund, Sweden. Results: The mean tumour volume of the treated tumours increased by factors of 1.9, 1.5 and 1.7 in groups I, II and III, respectively, compared with the pretreatment baseline value. However, the mean tumour volume in the control tumours increased by factors of 9.5, 4.3 and 4.8 in the respective groups. Under the light microscope, marked necrosis of the treated tumour and the surrounding liver tissue was observed. Scanning electron microscopy revealed heavy damage to the cells and vessels in the treated tumour. Conclusion: PDT with ALA is an effective treatment modality for rat liver tumours.
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14.
  • Möller, P. H., et al. (författare)
  • Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver
  • 1998
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 77:11, s. 1884-1892
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare interstitial laser thermotherapy with excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was transplanted (implanted if not stated otherwise) into the left lateral lobe of the rat liver, and treatment was performed 8 days later. In the main experiment, rats were treated with resection of the tumour-bearing robe or underwent interstitial laser thermotherapy, which was performed at a steady-state temperature of 46°C for 30 min, 3 mm from the tumour margin. The incidence and extent of intraperitoneal spread was smaller after laser thermotherapy than after resection of the tumour-bearing lobe, with no difference in local control. Metastatic spread after resection of the median liver robe was similar to that observed after sham procedures for thermotherapy or resection, suggesting that the advantage of thermotherapy was not due to a difference in surgical trauma. Additional studies showed that laser thermotherapy reduced intraperitoneal spread when treatment was suboptimal or in a tumour inoculation model and suggested that immunological mechanisms might be involved. It is concluded that interstitial laser thermotherapy reduces spread of liver tumour compared with resection.
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15.
  • Naredi, Peter, 1955, et al. (författare)
  • The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma.
  • 1993
  • Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 54:4, s. 645-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of TNF alpha on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF alpha on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF-alpha exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF alpha was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF-alpha administration with the 133Xe-washout technique. The passage of microspheres through the tumour vascular bed (non-entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF-alpha administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF alpha in vitro was tested. A reduction of tumour blood flow was observed in TNF-alpha-treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF-alpha groups as compared with controls. There was no significant change in non-entrapment for the TNF-alpha-treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF alpha had no effect on the viability of the cloned hepatoma cell line in vitro.
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16.
  • Ohlsson, B., et al. (författare)
  • Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours
  • 2002
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 89:6, s. 757-762
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of the study was to investigate the value of percutaneous fine-needle aspiration cytology (FNAC) in the diagnosis and management of liver tumours. METHODS: FNAC followed by histopathological examination was carried out in 216 patients with suspected liver tumours. The final diagnosis was primary liver cancer in 106, colorectal metastases in 51, non-colorectal metastases in 46, benign tumour in nine and no tumour in four patients. RESULTS: Cytology resulted in correct classification of the lesion as benign or malignant in 87 per cent of patients, correct discrimination between primary and secondary malignancy in half of the patients, and a correct diagnosis of tumour type in one-third of patients. The tumour was erroneously classified as benign or malignant in 22 patients (11 per cent) and four patients (2 per cent) respectively. When FNAC showed malignancy, the predictive value was 98 per cent, whereas the predictive value was 27 per cent when it did not. FNAC guided investigations and treatment in one-quarter of patients. Implantation metastases were recorded in seven patients (3 per cent), including five (10 per cent) of 51 patients with colorectal liver metastases, and caused major local problems and death in four patients. CONCLUSION: FNAC was valuable in about a quarter of patients with liver tumour. The risks of implantation metastases and a false-negative finding do not justify its use in candidates for curative therapy of liver tumours.
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17.
  • Soto Thompson, Marcelo, et al. (författare)
  • Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery
  • 2006
  • Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 25:1-2, s. 411-424
  • Tidskriftsartikel (refereegranskat)abstract
    • To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.
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18.
  • Stenberg, M, et al. (författare)
  • Interstitial photodynamic therapy - diagnostic measurements and treatment in rat malignant experimental tumours
  • 2000
  • Ingår i: OPTICAL BIOPSY AND TISSUE OPTICS. - : SPIE. - 1996-756X .- 0277-786X. - 0819438170 ; 4161:32, s. 151-157
  • Konferensbidrag (refereegranskat)abstract
    • A recently developed multiple fibre system for treating malignant tumours with interstitial photodynamic therapy was used in studies on rats with colon adenocarcinoma inoculated into the muscles of the hind legs. The animals were intraperitonially administrated delta -aminolevulinic acid (ALA), which is metabolised to protoporphyrin IX (PpIX) in the tissue. The treatment system consists of a laser light source, a beam-splitting system dividing the light into three or six output fibres and a dosimetry programme calculating the optimal fibre position within the tumour as well as the treatment time needed to obtain a given threshold value of the light dose. One aim of the study was to compare the treatment outcome with the modelled dosimetry predictions. Tumour reduction was examined three days post treatment. A volume decrease was found in 85\% of the treated tumours. The mean volume reduction was 44\%, with one tumour completely disappearing. Histopathological examination three days post treatment showed substantial necrotic parts which, however, to a smaller extent were present also for non-treated tumours. These results indicated that the tumours have been under treated and the light dose has to be increased. Measurements of the build-up and photo-induced bleaching of PpIX using laser-induced fluorescence were also performed during the experiments.
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21.
  • Sturesson, C, et al. (författare)
  • Hepatic inflow occlusion increases the efficacy of interstitial laser-induced thermotherapy in rat
  • 1997
  • Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 71:1, s. 67-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Interstitial laser-induced thermotherapy (ILT) destroys tumors thermally, ILT was performed for treatment of liver tumors in rats to investigate the effect of hepatic inflow occlusion on temperature distribution and lesion size. Tumors were irradiated for 20 min with near-infrared light from a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, The laser light at a power of 1.5 W was delivered through a plane-cut optical fiber, the tip of which was placed in the tumor. Rats in group I received ILT without interruption of hepatic blood flow. Those in group II received ILT during hepatic inflow occlusion. Liver temperatures were measured during treatment. After 3 days the animals were sacrificed and the size of the lesions was measured. Occlusion of the hepatic inflow during ILT increased the maximum lesion diameter, as measured at the liver surface, by 47%. Linear interpolation between the temperatures measured at 6 and 12 mm distance from the fiber tip revealed that the temperature at the necrotic border just before the end of treatment was approximately 45 degrees C in both the occluded and nonoccluded groups, indicating that the hepatic inflow occlusion caused no increase in tissue thermal sensitivity, This study shows that occlusion of the hepatic in-flow during interstitial laser-induced thermotherapy causes a significant increase in lesion size, which could have implications for the treatment of hepatic tumors. (C) 1997 Academic Press.
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22.
  • Svanberg, Katarina, et al. (författare)
  • Photodynamic Therapy of Nonmelanoma Malignant-tumors of the Skin Using Topical Delta-amino Levulinic Acid Sensitization and Laser Irradiation
  • 1994
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 130:6, s. 743-751
  • Tidskriftsartikel (refereegranskat)abstract
    • Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor delta-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10-20 mm beyond the visible tumour border, 4-6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LIF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp-IX distribution demonstrated by LIF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas. Laser light from a pulsed frequency-doubled Nd:YAG laser pumping a dye laser with light emission at 630 nn was used for the therapy. The power density in the irradiation was kept below 110 mW/cm(2), in order to avoid hyperthermal effects. A total energy of 60 J/cm(2) was delivered for 10-20 min, depending on the tumour size. A complete response rate of 100% in superficial BCCs and 64% in nodular BCCs occurred after a single laser treatment, and a response rate of 100% was achieved after one additional. treatment in the nodular BCCs. in the Bowen's disease lesions a complete response of 90% was obtained with a single treatment. Two of the four T-cell lymphomas resolved completely. The follow-up time was between 6 and 14 months.
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23.
  • Svanberg, Katarina, et al. (författare)
  • Photodynamic therapy using intravenous delta-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats
  • 1996
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 74:10, s. 1526-1533
  • Tidskriftsartikel (refereegranskat)abstract
    • The efficacy of photodynamic therapy (PDT) using delta-aminolaevulinic acid (ALA)-induced protoporphyrin M. (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour cells through the portal vein in rats. ALA at a dose of 60 mg kg(-1) b.w. was intravenously administered 60 min before PDT. PpIX accumulation in tumour, normal liver and abdominal wall muscle was detected by means of laser-induced fluorescence (LIF). Laser Doppler imaging (LDI) was used to determine changes in the superficial blood how in connection with PDT. Histopathological examinations were performed to evaluate the PDT effects on the tumour and the surrounding liver tissue, including pathological features in the microvascular system. The accumulation of PpIX, as monitored by LIF, showed high fluorescence intensities at about 635 nm in both the hepatic tumour tissue and normal liver and low values in the abdominal wall. LDI demonstrated that the blood how in the treated tumour and its surrounding normal liver tissue decreased immediately after the PDT, indicating an effect on the vascular system. A large number of thrombi in the irradiated tumour were found microscopically 3 h after the PDT. The tumour growth rate showed a marked decrease when evaluated 3 and 6 days after the treatment. These results show that the ALA-PDT is effective in the inhibition of growth of experimental hepatic tumours.
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25.
  • Tranberg, K G, et al. (författare)
  • Interstitial laser thermotherapy of a rat liver adenocarcinoma
  • 2002
  • Ingår i: Journal of X-Ray Science and Technology. - 0895-3996. ; 10:3, s. 177-185
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare interstitial laser thermotherapy with excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was implanted into the left lateral lobe of the rat liver, and treatment was performed 8 days later. Rats were treated with resection of the tumour-bearing lobe or underwent interstitial laser thermotherapy, which was performed at a steady-state temperature of 46°C for 30 min, 3 mm from the tumour margin. The incidence and extent of intraperitoneal spread was smaller after laser thermotherapy than after resection, with no difference in local control. Using inoculation of tumour cell suspensions into the lateral and the median lobes of the liver simultaneously and treating the lateral lobe tumour only, we found that laser thermotherapy reduced take and growth of the untreated tumour in the median lobe indicating that laser thermotherapy may induce immunologic effects. It is concluded that interstitial laser thermotherapy reduces spread of liver tumour as compared to resection. It is suggested that this can be at least partly explained by a laser-induced immunologic effect.
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26.
  • Tranberg, K. G., et al. (författare)
  • Interstitial laser treatment of malignant tumours : Initial experience
  • 1996
  • Ingår i: European Journal of Surgical Oncology. - 0748-7983. ; 22:1, s. 47-54
  • Tidskriftsartikel (refereegranskat)abstract
    • This is a prospective pilot investigation of interstitial laser treatment. Twelve patients were treated at 13 sites: seven patients had metastatic or primary liver cancer (with a total of 21 tumour nodules), two had pancreatic carcinoma and four patients had disease at other sites. Treatments mere performed with an Nd-YAG laser, using a high power (6 or 10 W), short-time (5 min) technique or a feedback system for temperature regulation at low power (3 W) for 12-16 min. Treatment with high power invariably resulted in rapid carbonization of tissue, which may have contributed to the postoperative death in one patient. The local effect of treatment could be evaluated in 13 hepatic tumours (1.0-10 cm in diameter): 100% necrosis was seen in five and > 50% necrosis in the remaining eight. Two tumours were eradicated, five became smaller, and six remained unchanged in size or showed continued growth. Treatment removed or alleviated symptoms in 7/8 symptomatic patients. The feedback system made it possible to avoid carbonization and allowed better control of the tissue temperature. The main problem with either method was to monitor tissue changes in real time, and ultrasonography was found to be of little help in this respect. It is concluded that interstitial laser treatment is a promising method for treatment of tumours. Further development should focus on real-time monitoring and increased volume effect without carbonization.
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