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Biomedical subjects

K Svanberg

Publications and source records attributed to K Svanberg.

33 records · Page 2Linked to original sources

Detection of adenocarcinoma in Barrett's oesophagus by means of laser induced fluorescence.

PATIENTS: Seven patients with Barrett's metaplastic epithelium and oesophageal adenocarcinoma were investigated by means of laser induced fluorescence after low dose intravenous injection (0.35 mg/kg bw) of Photofrin (QLT, Vancouver, Canada). Laser induced fluorescence measurements were performed immediately after resection of the oesophagus. METHODS: Laser induced fluorescence spectra were recorded from 15-30 locations in each surgical specimen from normal mucosa, Barrett's epithelium, and tumour tissue. Histological examination was performed on each location to correlate the fluorescence spectral characteristics with histological status of the epithelium (normal, metaplastic or malignant). Measurements were also performed during endoscopy in five patients to test the applicability of the method in a clinical setting. Fluorescence spectra were recorded and evaluated at characteristic wavelengths, and biopsy specimens were collected. Fluorescence ratios were calculated as the quotient of Photofrin fluorescence divided by autofluorescence. RESULTS: The mean (SD) fluorescence ratio values were 0.10 (0.058) for normal oesophageal mucosa, 0.16 (0.073) for normal gastric mucosa, 0.205 (0.17) for Barrett's epithelium with moderate dysplasia, 0.79 (0.54) for severe dysplasia, and 0.78 (0.56) for adenocarcinoma. The highest fluorescence ratios were obtained for adenocarcinoma tissue, which could generally be distinguished from all nonmalignant tissue. Metaplastic Barrett's epithelium also yielded higher fluorescence ratios than did normal mucosa. CONCLUSIONS: The results suggest that the technique can be used during endoscopy for real time tissue characterisation in the oesophagus, as an aid in detecting malignant transformation not macroscopically apparent at endoscopy.

Adenocarcinoma↗

Immunotherapy in liver tumors: III. A new experimental model of metastatic liver tumors from colorectal carcinoma for cytokine therapy.

A new model of metastatic liver tumors in Wistar/Furth rats is introduced. A colorectal adenocarcinoma cell line (LDLX40) induced by 1,2-dimethylhydrazine was injected through one of the branches of the ileal mesenteric vein to develop metastatic liver tumors in rats. On day 30 after the inoculation of tumor cells, micrometastases were detected under microscopy in all animals that received tumor inoculation. Macrometastases in 87.7% of animals were found by either the tumor staining test or ultrasonography. No extrahepatic tumor developed in this tumor model. To observe the effects of different treatment strategies on metastatic liver tumors, 35 animals were randomly divided into four groups. Group I served as control. Group II underwent hepatic artery ligation (HAL). Group III received intraportal administration of recombinant interleukin-2 (rIL-2) and interferon-alpha (IFN-alpha). Group IV had intraportal medication of rIL-2 and IFN-alpha + HAL (the IIH protocol). Results indicated that rapid tumor growth was seen in the control tumors. HAL produced little response to metastatic liver tumors as compared to the control group (P > 0.05). The combined application of rIL-2 and IFN-alpha showed an improved result, with 22% of tumor growth inhibition or regression (P < 0.05 compared to the control group). Twenty-eight percent of tumor growth restraint or regression was found in the group treated with the IIH protocol (P < 0.05 compared to the control group). We conclude that this new experimental model of metastatic liver tumors is reproducible, and that the IIH protocol is effective in the treatment of metastatic liver tumors in rats. These beneficial effects from the IIH protocol may be introduced into patients with metastatic liver tumors.

Adenocarcinoma↗

Management of genital warts in women with human leukocyte interferon-alpha vs. podophyllotoxin in cream: a placebo-controlled, double-blind, comparative study.

The purpose of this double-blind, placebo-controlled, comparative study was to evaluate the specific clinical efficacy and tolerance of human leukocyte interferon-alpha (2 x 10(6) IU/g) and podophyllotoxin 0.5% incorporated in a hydrophilic cream to cure genital warts. Preselected Asian women (n = 60) aged 18-40 years (mean 22.9), with a clinical and biopsy-confirmed diagnosis of genital warts, harboring 322 lesions (mean 5.36) were randomly assigned to three parallel groups to receive one of the two test drugs or placebo. Each patient received a precoded tube (40 g) containing either human leukocyte interferon-alpha, podophyllotoxin, or identically appearing placebo cream for 3 days' usage. In addition to written instructions, each subject was shown how to apply a minimal amount of trial medication on their lesions thrice daily for 3 consecutive days per week (maximum nine topical applications per week). Patients were examined on a weekly basis, and a cure was considered to be a biopsy-confirmed, total elimination of a lesion. Moreover, patients cured during the study period were spared further therapy, and were requested to return in 16 weeks to monitor for the occurrence of a relapse. The remaining patients' empty tubes were collected, and similarly precoded replacement tubes were given to continue the treatment; a total of 214 tubes were used. The study was scheduled for 16 weeks with 4 weeks of active treatment. Individuals were excluded from the study due to pregnancy, breast feeding, or the receiving of any type of antiviral therapy during the 4 weeks preceding enrollment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intra-operative laser-induced photodynamic therapy in the treatment of experimental hepatic tumours.

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 rats had two tumours simultaneously inoculated into its liver. The tumour located in the left hepatic lobe 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.

Aminolevulinic Acid↗

Laser-induced fluorescence in malignant and normal tissue in mice injected with two different carotenoporphyrins.

Laser-induced fluorescence (LIF) was used to characterise the localisation of an intravenously administered trimethylated carotenoporphyrin [CP(Me)3] and a trimethoxylated carotenoporphyrin [CP(OMe)3] in an intramuscularly transplanted malignant tumour (MS-2 fibrosarcoma) and healthy muscle in female Balb/c mice, 3, 24, 48 and 96 h post injection. The fluorescence was induced with a dye laser pumped by a nitrogen laser, emitting light at 425 nm. The fluorescence spectra were recorded in the region 455-760 nm using a polychromator equipped with an image-intensified CCD camera. The tumour/peritumoral muscle ratio was about 5:1 for CP(Me)3 and about 6:1 for CP(OMe)3 in terms of the background-free fluorescence intensity, which peaked at about 655 nm. By including the endogenous tissue fluorescence, the contrast was further enhanced by a factor of approximately 2.

Animals↗

Laser-induced fluorescence studies of meso-tetra(hydroxyphenyl)chlorin in malignant and normal tissues in rats.

meso-Tetra(hydroxyphenyl)chlorin (mTHPC) is an attractive second-generation dihydroporphyrin photosensitiser for use in photodynamic therapy. In this study, 1.3 mg kg-1 body weight mTHPC was administered intravenously, and laser-induced fluorescence was used to characterise and compare its localisation and retention in different rat tissues, including an induced experimental adenocarcinoma, 24 h and 48 h post injection. These studies were performed in an attempt to predict the anatomical locations where mTHPC PDT might be most effective and suggest suitable injection--irradiation intervals in each case. Of particular interest were the intra-abdominal and intrathoracic tissues. The fluorescence was induced at 405 nm and the fluorescence spectrum in the region 450-750 nm was analysed. All collected spectra were dominated by the fluorescence signature of mTHPC with its peak at 652 nm, and all values in this study are in terms of background-free drug-specific fluorescence intensity at that wavelength. The photosensitiser accumulated in high concentrations in the tumour and the reticuloendothelial system. Muscular organs, such as the heart and the abdominal wall, were characterised by a low drug fluorescence signature.

Adenocarcinoma↗

Photodynamic therapy of non-melanoma malignant tumours of the skin using topical delta-amino levulinic acid sensitization and laser irradiation.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Clinical fluorescence diagnosis of human bladder carcinoma following low-dose Photofrin injection.

A point-monitoring fluorescence diagnostic system based on a low-energy pulsed laser, fiber transmission optics, and an optical multichannel analyzer was used for diagnosis of patients with bladder malignancies. Twenty-four patients with bladder carcinoma, carcinoma in situ, and/or dysplasia were injected with hematoporphyrin derivative, Photofrin, 0.35 or 0.5 mg/kg body weight, forty-eight hours prior to the investigation. The ratio between the red sensitizer emission and the bluish tissue autofluorescence provided excellent demarcation between papillary tumors and normal bladder wall. Certain cases of dysplasia also could be differentiated from normal mucosa. Benign exophytic lesions such as malakoplakia appeared different from malignant tumors in fluorescence. Flat suspicious bladder mucosa such as seen in infectious diseases or after radiation therapy appeared normal on fluorescence.

Adult↗

Laser-induced fluorescence in malignant and normal tissue of rats injected with benzoporphyrin derivative.

Laser-induced fluorescence was used to characterize the localization of intravenously administered benzoporphyrin derivative-monoacid (BPD-MA) 3 h postinjection in different rat tissue types, including an induced experimental malignant tumor. A comparison of the fluorescence properties and demarcation potential between the newer sensitizer BPD-MA and four other substances, hematoporphyrin (HP), polyhematoporphyrin ester (PHE), tetrasulfonated phthalocyanine (TSPc) and the commercially available Photofrin earlier investigated, is included. The fluorescence light was induced with a nitrogen laser, emitting at 337 nm. The fluorescence spectrum in the region 380-750 nm was analyzed by a polychromator equipped with a diode array detector. The demarcation potential between tumor and surrounding tissue in terms of fluorescence signal for the tumor model used was 2:1 for BPD-MA. In comparison with the other drugs, HP shows about the same demarcation potential, whereas Photofrin and PHE exhibit about 3 times better and TSPc about 1.5 times better demarcation. By also employing the endogenous tissue fluorescence signature the contrast was enhanced by a factor of about 2 for each of the five drugs.

Animals↗

Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and atherosclerotic lesions from normal tissue.

The possibilities of using laser-induced fluorescence for tissue diagnostics are discussed. The tissue types investigated are malignant tumors and atherosclerotic lesions. Studies with natural autofluorescence as well as with fluorescent tumor markers are included in this paper. Fluorescence emission and decay data are presented for some tissue chromophores contributing to tissue autofluorescence. Optical spectroscopic characteristics of fluorescent malignant tumor markers are analyzed and instrumental designs for clinical applications are discussed. Images recorded with a multicolor fluorescence imaging system developed in Lund are presented.

Adenocarcinoma↗

Time-resolved laser-induced fluorescence spectroscopy for enhanced demarcation of human atherosclerotic plaques.

We report on the enhanced demarcation between human atherosclerotic plaques and normal vessel wall obtained using time-resolved detection of laser-induced fluorescence rather than the customary time-integrated monitoring technique. A frequency-doubled mode-locked and cavity-dumped continuous wave dye laser was used for picosecond pulse generation at 320 nm, and photon-counting techniques were employed for the time-resolved signal monitoring from human aorta samples in vitro. Implications for imaging fluorescence angioscopy and spectroscopic guidance in laser ablation of plaque are indicated.

Aorta↗

Fluorescence diagnosis and photochemical treatment of diseased tissue using lasers: Part I.

Lasers are useful in many applications in medicine and biology. Historically, most laser use has involved heat generated in the interaction of the laser beam with the tissue. Today, however, the spectroscopic aspects of this laser use are playing a more dominant role in a number of applications. In this two-part series, Sune Svanberg and co-workers present illustrations of emerging clinical applications from cooperative work performed by the Lund Institute of Technology and the Lund University Hospital. Part I includes a survey of laser techniques for atomic and molecular analyses of samples of medical interest, spectroscopic analysis of the laser-induced plasma obtained when a high-power pulsed laser beam interacts with tissue, and the use of tumor-seeking agents in combination with laser radiation to provide new possibilities for malignant tumor detection and treatment. Part II, which will appear in the January 1, 1990, issue, describes the use of laser-induced fluorescence for tumor and plaque diagnostics. Different lasers have been used, and research efforts increasingly are being focused on excimer lasers and lasers in the IR region for the ablation of atherosclerotic plaques, cell layer by cell layer.

Chromatography, Liquid↗

Fluorescence studies of hematoporphyrin derivative in normal and malignant rat tissue.

Laser-induced fluorescence in rat tissue was studied during the uptake and clearing period of i.v.-injected hematoporphyrin derivative. A malignant rat tumor and normal tissue of 20 different kinds from the tumor-bearing animals were investigated. A pulsed nitrogen laser (337 nm) was used in conjunction with an optical multichannel analyzer system, in which the whole fluorescence light distribution was captured for each laser pulse. Several of the organs exhibited an initial and a delayed intensity peak in the characteristic hematoporphyrin derivative laser-induced fluorescence intensity (630 nm) that might be interpreted as due to intracellular transformations of different chemical components of the hematoporphyrin derivative preparation. By dividing the background-free 630-nm signal by the blue fluorescence intensity, a dimensionless quantity is obtained that could have many advantages in practical endoscopic laser-induced fluorescence work. This ratio was also shown to exhibit a larger contrast between tumor and surrounding tissue. The ratio between the two red fluorescence peaks was also found to be useful for discriminating tumor from normal tissue. A combination of the two ratios was shown to be particularly valuable for tumor discrimination.

Animals↗

Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic therapy and cryotherapy employing laser-Doppler perfusion imaging.

Superficial blood perfusion was monitored using laser-Doppler perfusion imaging in connection with a phase III clinical trial comparing photodynamic therapy, utilizing topically applied delta-aminolevulinic acid, with cryotherapy of basal cell carcinomas. A total of 526 images were recorded before and immediately after the treatment and during the follow-up period. Before treatment, the lesions exhibited a blood perfusion 3+/-2 times that in normal tissue. Both treatment modalities induced an increased blood perfusion inside the lesions, which slowly approached normal values in conjunction with successful treatments. The blood perfusion in successfully treated lesions approached normal values 2 months after photodynamic therapy, and about 1 year after cryotherapy. The tissue perfusion in recurrent lesions did not decrease to normal values after the treatment, suggesting that the laser-Doppler perfusion imaging technique can be used to follow the healing process and discover possible persistent tumour growth.

Adult↗