Fire in an operating room is the most dangerous situation for patient and staff. Besides electrosurgical devices and endoscopic light sources, even surgical lasers can be ignition sources for drapes, gowns and tracheal tubes. This risk was identified very early and several ISO standards for laser proof materials have been published. The medical beam delivery system itself, however, was out of focus. Due to the increasing market on the one hand and necessity for cost reduction in health care on the other hand fibres have come into the market with a risk of self-ignition of the core or cladding material. Furthermore with reinvention of fibre-applicator-systems for contact application or integrated diffusor systems they have an increased risk for self-ignition due to high absorption. So it is important to perform quality requirements for companies suppliers and hospitals. At this time there is no existing work or standard to this topic. This project elaborates reproducible test parameters for medical beam delivery systems.
Because the problem of ignition and damage due to laser transmission is not limited only to medical devices but even e.g. in communication systems and fiber laser system the work was started in close cooperation with WG1 SC9 to avoid any duplication. The presented draft follows the structure, terminology and test procedure the existing standards for surgical drapes ISO11810 and Endotracheal tubes ISO11990 to avoid inconsistency in these standards
Cancer is one of the leading causes for morbidity and mortality worldwide. Therefore, efforts are concentrated on cancer detection in an early stage to enhance survival rates for cancer patients. A certain intraoperative navigation in the tumor border zone is also an essential task to lower the mortality rate after surgical treatment. Molecular spectroscopy methods proved to be powerful tools to differentiate cancerous and healthy tissue. Within our project comparison of different vibration spectroscopy methods were tested to select the better one or to reach synergy from their combination.
One key aspect was in special fiber probe development for each technique. Using fiber optic probes in Raman, MIR and NIR spectroscopy is a very powerful method for non-invasive in vivo applications. Miniaturization of Raman probes was achieved by deposition of dielectric filters directly onto the silica fiber end surfaces. Raman, NIR and MIR spectroscopy were used to analyze samples from kidney tumors. The differentiation between cancer and healthy samples was successfully obtained by multivariate data analysis.
Usually systemic photosensitizers (PS) require a long period of incubation (48-96h) after systemic admission. On the
other hand clearing from healthy skin needs weeks or months. Severe side effects on skin are possible in case of
uncontrolled light exposure. Topical PDT may solve this problem, but deep portions may not be sufficiently sensitized,
resulting in a survival of some tumor cell population after PDT and recurrence. The same problem counts for actinic
keratosis and Bowen's disease, but with even worse consequences as a resulting infiltrating growing squamous cell
carcinoma (SCC) is likely to produce metastatic lesions. Light dosimetry is crucial also. Wavelenght, fluence and total
energy may influence outcome of any PDT substantially.
17 patients with Bowen's disease or BCC where treated using a novel systemic PS (Fotolon®) and 665nm light from a
diode laser. Follow up time ranges between 2.5 and 1 years after treatment. 2 patients received a second PDT, in 15
patients one treatment was efficient. We found a remissions in 1, local control in 2 and no evidence of disease in 14
patients. Significant fluorescence was noted in all lesions. With a light protection protocol for only 48 hours no severe
side effects where seen. One patient developed mild redness of sunlight exposed skin sites 24h after being discharged
from light protection protocol.
In comparison with currently available topical PS Fotolon® offers some important advantages as secure photosenzitation
of deep portions, single treatment, high selectivity combined with a high cure rate. In comparison with currently
available systemic PS Fotolon® offers short incubation time, high selectivity and short time of elimination, while
efficiency was comparable to HPD (hematoporphyrin-derivate) PDT combined with ALA-5 PDT and without need for
additional local PS-application for PDD.
The effect of laser induced thermotherapy (LITT) as palliative method in otherwise pre-treated patients (irradiation, chemotherapy and/or surgery) with local recurrences of breast cancer should be investigated. In 7 women, an interstitial laser application was performed percutaneously into the center of the diseased tissue. The laser used was a Nd:YAG laser with a wavelength of 1064 nm. Heat expansion was controlled digitally and monitored by ultrasound and color coded duplex sonography (CCDS) respectively. This minimal invasive method enabled the precise coagulation of the tumor without destruction of the skin or ulceration, although the areas had been pre-treated by irradiation up to 60 Gy, before. All patients are scheduled in a long-time follow-up. The CCDS-guided interstitial laser therapy is a safe and minimal invasive method for palliative treatment of subcutaneous local recurrences of breast cancer.
In medical diagnosis of superficial lesions at inner or outer surfaces of the human body fluorescence imaging techniques are able to deliver additional information on the metabolic and structural state of the observed tissue. To subtract background fluorescence and to achieve a differential diagnosis a multispectral analysis in several wavelength windows is needed. Additionally, special image algorithms have to be applied which depend on the examined malignancy. For this purpose a multispectral fluorescence imaging device was developed. It can be used both endoscopically and in combination with a standard operational microscope from Carl Zeiss, Germany. In this paper, the device and first clinical results are presented. The device was built to detect superficial lesions like tumors, inflammations, etc. Target chromophores are NADH, Protoporphyrin IX, collagen and other. The measured optical bands are (405 plus or minus 5) nm, (442 plus or minus 5) nm, (458 plus or minus 5) nm, (550 plus or minus 5) nm, (630 plus or minus 5) nm and (690 plus or minus 5) nm. A special UV-source with a liquid light guide is used as the illumination source in two excitation bands of (365 plus or minus 10) nm and (420 plus or minus 20) nm. First clinical investigations of superficial malignancies like squamous cell carcinoma and basalioma are presented.
The standard theories about the mechanisms involved in PDT concern themselves primarily with oxygen-centered species, above all singlet oxygen (1O2) and the hydroxyl radical (OH). The efficacy of the therapy depends very much not only on the photosensitizer used, but also to a great extent on the choice of irradiation parameters, the light source, and the tissue's degree of oxygenation. Both clinical and experimental studies point to the fact that the treatment of hypoxic areas generally results in a disappointing response, and the effects of the changes in perfusion and oxygenation induced by the PDT itself certainly complicate any analysis. The radical nature both of the secondary products generated from singlet oxygen reactions and of the other hypothesized primary products themselves mean that the physical method of choice for research on PDT is electron spin resonance (ESR). The aim of our investigations was the gathering of the particular information that this method could yield in order to make a comparison of the degrees to which various photosensitizers produce both singlet oxygen and hydroxide radicals in vitro. We also dedicated part of our efforts to an investigation into the effects of a simple variation in the partial pressure of the dissolved molecular oxygen.
The pharmacokinetics of 132-hydroxy-bacteriopheophorbid-a methyl ester (132-OH-BPME) and octa-(alpha) -butyloxy-zinc phthalocyanine (8-(alpha) -bo-Zn-Pc) were studied in mice bearing Lewis lung carcinoma. Absorption spectroscopy was used to measure the photosensitizers concentrations. High 132- OH-BPME and 8-(alpha) -bo-Zn-Pc uptakes were recorded in the parenchymatous organs (liver, lung), with 8-(alpha) -bo-Zn-Pc long retention. The malignant tissues accumulated 132-OH- BPME of more than 20 folds than 8-(alpha) -bo-Zn-Pc at all incubation times. 8-(alpha) -bo-Zn-Pc concentrations in the skin and the muscle were lower than 132-OH-BPME concentrations at any interval period, but also, the 8- (alpha) -bo-Zn-Pc retained longer until 168 h. PDT with 132-OH-BPME will be more effective than with 8-(alpha) -bo- Zn-Pc where it has more concentrations in the malignant tissues.
Aim of the study was the comparative investigation of cutaneous and subcutaneous vascular lesions. By means of color coded duplex sonography (CCDS), laser doppler perfusion imaging (LDPI) and infrared thermography (IT) we examined hemangiomas, vascular malformations and portwine stains to get some evidence about depth, perfusion and vascularity. LDI is a helpful method to get an impression of the capillary part of vascular lesions and the course of superficial vessels. CCDS has disadvantages in the superficial perfusion's detection but connections to deeper vascularizations can be examined precisely, in some cases it is the only method for visualizing vascular malformations. IT gives additive hints on low blood flow areas or indicates arterial-venous-shunts. Only the combination of all imaging methods allows a complete assessment, not only for planning but also for controlling the laser treatment of vascular lesions.
KEYWORDS: Laser therapeutics, Skin, Argon ion lasers, Dye lasers, Glasses, In vitro testing, Temperature metrology, Thermal imaging cameras, Cameras, In vivo imaging
The purpose of this study was the evaluation of different combined cooling and compression techniques for the treatment of vascular disorders of the skin and subdermal layers. In combination with flashlamp pumped dye lasers, argon lasers and Nd:YAG-lasers the effectiveness of glass plates, a cooling chamber with a flexible membrane and continuous ice cube cooling were evaluated in vitro by temperature measurements with thermocouples and thermographic camera readings and in vivo by laser doppler flowmetry, color coded duplex sonography and comparison of photographic documents for effectiveness and occurrence of side effects. Experimental and clinical evaluations show excellent results for skin protection, effective treatment depth enhancement and minimalization of side effects as well as for pain perception.
Different laser systems and techniques are used for the treatment of hypertrophic scars, keloids and acne scars. Significant criteria in selecting a suitable laser system are the scar's vascularization, age and diameter. Flashlamp- pumped dye-lasers, CO2-lasers with scanner, Argon and Nd:YAG-lasers are used. Telangiectatic scars respond well to argon lasers, erythematous scars and keloids to dye-laser treatment. Using interstitial Nd:YAG-laser vaporization, scars with a cross-section over 1 cm can generally be reduced. For the treatment of atrophic and acne scars good cosmetic results are achieved with a CO2-laser/scanner system, which allows a precise ablation of the upper dermis with low risk of side-effects.
The two photosensitizers Octa-(alpha) -Butyloxy-Zincphthalocyanine and 132-Hydroxy- Bacteriopheophorbide-a-methylester with the maxima of absorption at wavelengths 735 nm and 750 nm, respectively, are promising candidates for photodynamic therapy (PDT). Photobleaching of these dyes was investigated with a pulsed Titan:Sapphire laser (duration of the pulse: 5 microseconds, repetition rate: 4 Hz) at 750 nm. Different concentrations of the dyes, in each case dissolved in ethanol, were irradiated with this laser. The variation of the bleaching rate (eta) with the total number of pulses at constant irradiation energy per pulse (alteration of the irradiation time at constant pulse duration and repetition rate) as well as with irradiation energy at constant total number of pulses was investigated. The degree of laser- induced bleaching was determined by the decrease of absorption after irradiation. A nearly linear increase of the bleaching rate with the energy per pulse was found for Octa-(alpha) - Butyloxy-Zincphthalocyanine. For 132-Hydroxy-Bacteriopheophorbide-a-methylester at higher concentrations the bleaching rate was smaller (in comparison to Octa-(alpha) - Butyloxy-Zincphthalocyanine) with increasing sensitizer concentration at the same energies. The increase of bleaching rate with energy was approximately linear, again. No saturation effects occurred. The influence of the total number of pulses on the bleaching rate was investigated for Octa-(alpha) -Butyloxy-Zincphthalocyanine at the highest concentration. With longer irradiation times a saturation was observed. No new maxima in the absorption spectrum (monitored region 200 nm less than or equal to lambda less than or equal to 1100 nm) were found after irradiation; so the fragments of the dyes have probably no photoactivity in this range.
The in vivo model of the chorioallantoic membrane of fertilized chicken embryos (CAM) was employed for studying the fluorescence characteristics of tumor tissue in comparison with non tumorous tissue. Tumors were grown from the murine fibrosarcoma cell line SSK II and murine 3T3 fibroblasts (clone A31) were used for cultivating non tumorous tissue. Autofluorescence and xenofluorescence intensities induced by 5-aminolaevulinic acid (5-ALA) were compared. Exogenous administration of 5-ALA, an early precursor in haem synthesis, induces accumulation of endogenous photoactive porphyrins, in particular protoporphyrin IX (PpIX). Fluorescence investigations were performed after 3-4d of incubation, when the tissues had reached macroscopically three dimensional stages of growth. Fluorescences were excited with a HBO-X 100 W lamp (Carl Zeiss) at a wavelength (lambda) equals 405 plus or minus 5 nm. Emissions were detected in the spectral range above 630 nm and visualized by real time digital image processing (Argus 10, HAMAMATSU) using an ICCD camera (HAMAMATSU). After administration of 0.4 mmolar 5-ALA solution to the CAM inoculated tissues the SSK II tumors exhibited higher fluorescence intensities than the 3T3 non tumorous tissues. Autofluorescence intensities of both types of tissues were not distinguishable. Furthermore, the effects of several biochemicals on the xenofluorescence intensities of the fibrosarcoma and fibroblast tissues were investigated.
The phthalocyanines form a continuously growing family of potential photosensitizers. Their chemical and photophysical properties, and therefore their photodynamic activities, are influenced by the type of the central metal ion as well as the type and localization of substituents. Plasma and tissue distribution kinetics are also dependent on the chemical features of a dye molecule. We therefore investigated the pharmacokinetics of newly synthesized octa-(alpha) -butyloxy-zincphthalocyanine (8-(alpha) -bo-ZnPc) on the Lewis lung carcinoma in order to evaluate the application possibilities of this compound in experimental PDT treatments. The zinc complex was chosen on the basis of the known effect of this metal on the photochemical and photophysical properties of phthalocyanines. The pharmacokinetics of octa-(alpha) -butyloxy-zincphthalocyanine were studied on the Lewis lung carcinoma by absorption spectroscopy in mice. Afterwards a regression analysis was performed using the absorption spectroscopic data.
The newly synthesized potential photosensitizer octa-(alpha) -butyloxy-zinc phthalocyanine (8-(alpha) -bo-ZnPc) is characterized by a high absorption coefficient at the far red wavelength 735 nm and a good singlet oxygen quantum yield. The pharmacokinetics of 8- (alpha) -bo-ZnPc were studied on the Lewis lung carcinoma in mice after i.v. administration of 7.8 micrometers ole/kg body weight solubilized in PBS with 1% Tween 80 at 2, 6, 12, 24, 48 and 168 hour incubation intervals. The accumulated dye contents were chemically extracted from selected tissues and the concentrations were measured by absorption spectroscopy. The parenchymatous organs, liver and spleen, showed maximum 8-(alpha) -bo-ZnPc concentrations after 6 h incubation (33 nmole/g liver and 5 nmole/g spleen, respectively). An extensive uptake was detected in the lung where concentrations higher than 90 nmole/g tissue were measured in the 6, 12, 24, and 48 hour extracts. The malignant tissue did not accumulate higher 8-(alpha) -bo-ZnPc concentrations than 0.4 nmole/g tumor during the entire investigation period. The dye contents extracted from muscle, representing normal tumor surrounding tissue, and skin were even lower and never exceeded 0.11 nmole/g muscle (6 h) and 0.21 nmole/g skin (2 h), respectively.
An analysis of injuries and risks using high frequency (HF) and lasers in medicine based on a literature search with MEDLINE was performed. The cases reported in the literature were classified according to the following criteria: (1) Avoidable in an optimal operational procedure. These kind of injuries are caused by a chain of unfortunate incidents. They are in principle avoidable by the 'right action at the right time' which presupposes an appropriate training of the operating team, selection of the optimal parameters for procedure and consideration of all safety instructions. (2) Avoidable, caused by malfunction of the equipment and/or accessories. The injuries classified into this group are avoidable if all safety regulations were fulfilled. This includes a pre-operational check-up and the use of medical lasers and high frequency devices only which meet the international safety standards. (3) Avoidable, caused by misuse/mistake. Injuries of this group were caused by an inappropriate selection of the procedure, wrong medical indication or mistakes during application. (4) Unavoidable, fateful. These injuries can be caused by risks inherent to the type of energy used, malfunction of the equipment and/or accessories though a pre-operational check-up was done. Some risks and complications are common to high frequency and laser application. But whereas these risks can be excluded easily in laser surgery there is often a great expenditure necessary or they are not avoidable if high frequency if used. No unavoidable risks due to laser energy occur.
Since 1984 we use the interstitial application of laser induced thermotherapy (LITT) for the treatment of congenital vascular disorders (CVD) such as hemangiomas and vascular malformations. In most of the procedures a 600 micron core bare fiber is used to deliver the radiation of a cw Nd:YAG laser emitting at 1064 nm into the diseased tissue. As most of the CVD treated this way are located subcutaneously, the localization of the fiber and the interstitial laser coagulation (ILC) is controlled by transillumination and palpitation of the heat expansion of the skin surface, this way a crepitation can also be detected during the ILC. As the ILC in deeper body structures cannot be controlled directly we use color coded duplex sonography (CCDS), both for diagnostic and treatment control. In the procedures where we use the B-scan image for puncture control, a color signal is displayed representing tissue movements. These movements caused by degasification and vapor are those detectable as crepitations when using direct control. The color signal starts, changes, and moves in a reproducible pattern following the heat distribution and the subsequently occurring degasification in the tissue. Also the changes in perfusion are detectable by the means of CCDS. The precise extent of the coagulation is visible in the B-scan several minutes after laser exposure. The clinical experience and an extensive experimental evaluation has proven that CCDS is a valuable real time method to monitor the tissue reaction in ILC-procedures. For two years we have performed ILC-procedures with CCDS control in patients with CVD (n equals 65) successfully. Because of its reliable imaging and the clinical advantages recently we applied this type of ILC-control to the palliative treatment of nonresectable primary and secondary liver tumors (n equals 3) and subcutaneous metastases of mamma carcinoma. (n equals 6).
A variable application-set was developed to enable a safe and effective LITT treatment. The set consists of various laser applicators, a protecting catheter and an introducing equipment. The laser applicator was developed with different radiation patterns to match the topological conditions of the diseased area. For MRI-controlled LITT treatments a special marker is mounted at the distal end of the glass fiber which facilitates its localization. To increase the patient's safety a special protecting catheter was designed which is temperature stable up to 250 degree(s)C and transparent for NIR-radiation. The catheter can be placed into the diseased area using the introducing equipment which consists of modified parts of standard interventional radiology equipment. The laser applicator is finally guided through the protecting catheter so that there is no direct contact between applicator and tissue. The system can be used both for intraoperative and for percutaneous treatments.
During the period of January 1984 - July 1993, we have treated 611 children with more than 2000 lesions of congenital vascular disorders (CVD) such as hemangiomas and vascular malformations. This number does not include the patients with port wine stains, which also have been treated by means of laser. Most of the CVD patients (n equals 467) presented hemangiomas of the face, the anogenital region, and the extremities, some were located in the trachea or mouth or in the urogenital tract. All of these hemangiomas were growing prior to intervention or showed complications such as bleeding, ulceration, superinfection, or obstruction. Nearly a quarter (n equals 144) of the patients presented vascular malformations, either of singular vessel type involvement or of mixed vascular genesis (venous, arterio- venous, veno-lymphatic or lymphatic) with various complications like tracheal obstruction or recurrent thrombophlebitis. According to our step program, which is based on a clinical classification, the hemangiomas were treated as early as possible, while the vascular malformations were only treated with laser when no other therapeutic technique (embolization, resection) was suitable. All patients were referred for laser treatment from other centers. The lasers used were Nd:YAG and Argon lasers with transcutaneous application with or without continuous ice-cube surface cooling or interstitial laser application. The treatments were performed either on in- or outpatient basis according to age, localization and with good to excellent results in most cases and a complication rate of less than 2%.
The aim of our experimental and clinical studies was to investigate the suitability of Color- Coded Duplex Sonography (CCDS) for on-line monitoring of the Laser-Induced Thermotherapy procedures. Both the changes in the CCDS imaging during irradiation as well as the thresholds at which a `color bruit' occurs were investigated. Furthermore we have evaluated the correlation between the B-scan imaging of the damaged area and the size of coagulation in pathology measurements.
The pharmacokinetics of 132-hydroxy-bacteriopheophorbide a methyl ester (OH-BPME) was studied on Lewis lung carcinoma bearing mice by fluorescence spectroscopy. The sensitizer distribution in different organs and in the tumor was investigated in dependence on the incubation time. A very fast cleaning of the blood and the skin was observed. The results of our investigations suggest that PDT using OH-BPME could be effective at sensitizer incubation times of about 12 h.
Because of the different step programs concerning the preoperative diagnostic and the onset of therapy for the various types of congenital vascular disorders (CVD) a clear classification is important. One has to discern the vascular malformations, including the port wine stain, from the real hemangiomas which are vascular tumors. As former classification, mostly based on histological findings, showed little evidence to a clinical step program, we developed a descriptive classification which allows an early differentiation between the two groups of CVD. In most cases this can be done by a precise medical history of the onset and development of the disorder, a close look to the clinical signs and by Duplex-Ultrasound and MRI-diagnostic. With this protocol and the case adapted use of different lasers and laser techniques we have not seen any severe complications as skin necrosis or nerve lesions.
Fiber optics are used in medicine in power transmission for therapeutic use as well as in signal transmission for diagnostics. Fibers are the key component of the applicators which find a wide and varied use. Applicators with optical fibers are part of the standard equipment used with the various continuous and pulsed medical laser systems. Recently, optical fiber applicators for the Er:YAG, CO, and CO2 laser have become available. A combination of therapeutic and diagnostic fibers promises, for example in lithotripsy and angioplasty, not only to improve the safety level, but also to ensure the accuracy of the dosage and the precision of the laser energy applied. For the design of commercial fiber optic components a practical definition of the engineering damage threshold including a reasonable safety factor is given. With respect to this engineering damage threshold an overview of existing fiber technology with respect to the fields of application is presented and two examples of feedback systems to increase safety are discussed.
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