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Editor(s): Gaetano Bandieramonte, Stephen G. Bown, Fausto Chiesa, Jacques Donnez M.D., Herbert J. Geschwind M.D., Gian Francesco Lombard M.D., Gerhard J. Mueller, Hans-Dieter Reidenbach
Gaetano Bandieramonte, Stephen G. Bown, Fausto Chiesa, Jacques Donnez M.D., Herbert J. Geschwind M.D., Gian Francesco Lombard M.D., Gerhard J. Mueller, Hans-Dieter Reidenbach
Experimental results on long-term consequences of laser puncture applied to active points of the projection zones for the reproductive organs in guinea pigs after preliminary exposure to (gamma) -radiation are given. In female guinea pigs, it was shown that combination of external radiation (12.9 mCoul/kg) and incorporated 131I (6.5 mCi/kg) induced morphohistochemical and electron microscopic changes in the ovaries long (6 months) after, which indicated functional tension in the ovarian functioning. Laser biostimulation 3 months after the exposure to (gamma) - radiation induced severe injuries of the ovary, i.e. formation of thin-walled cysts, destruction of interstitial cells of the thecal sheath, by 6 months of the experiment. Functional incompetence of the organ was observed.
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The area of intraepithelial lesions is currently considered to be an important factor in prognosis for the evolution ofthe lesions and for the response to treatment. The association of lesions of different grades within abnormal coiposcopic fmdmgs also makes both the diagnosis and the choice of treatment as well as the evaluation of their results that much more difficult (1 4). To the colposcopic examination is ascribed the important task of diagnosing the topographic extent of the lesions and identifying the histological grade, by means of specific biopsies according to the criteria that constitute colposcopic grading. Colposcopy, considered as a high-responsibility diagnostic test and thus subject to quality control procedures, is therefore a fundamental element in management and therapy protocols (5, 6) that, at the same level of effectiveness, are designed to preserve the organ in terms of: a) sexual and reproductive functions in women with mtraepitheial neoplasia, b) the effectiveness of the cytocolposcopic follow-up. The success rate obtained by different therapy techniques is closely linked to the quality of the original diagnosis as well as the surgical skill arid methods used. The topographic extent of the intraepitheial lesion in the female lower genital tract has, in the literature of the past 1 5 years, always been differentiated according to the organ involved (cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VAIN), vulvar intraepithelial neoplasia (yIN)). The contemporaneous presence and association of the lesions (lower genital tract neoplastic syndrome) (7, 8) requires a further rationalization, in the experience ofthe authors (9, 10), in order for the characteristics of the single therapies to be fully understood and to advance research into treatment that meets the objective of preserving the functions of the organ while ensuring the same level of efficiency in therapy.
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Numerous studies have shown contradictory variable percentages of recurrent HPV lesions, after various therapies. The present study therefore evaluates the effectiveness of CO2 laser vaporization in the treatment of single-site HPV lesions of the lower female genital tract in order to confirm the conviction that physical therapy alone, in agreement with some findings reported in the literature, is capable of guaranteeing a high cure rate in selected patients. From January 1995 to June 1996, seventy- five female patients were treated with CO2 laser vaporization for single-site genital HPV lesions, some of which were associated with low-grade intra-epithelial neoplasia. The success rate after 12 months proved to be 97%. The pre-existing clinical symptoms disappeared in all the patients treated. No complication in the vaporization procedure was encountered.
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Warts lesions of the lower genital tract of women affected by HPV are often characterised by a strong tendency to relapse. This behaviour is undoubtedly influenced by the conditions of the immune system. Prevalence of disease is increased in the 80's due to the spreading of the HIV all over the world. Relapse is probably related to the persistence of the viral genoma in the perilesional area pretreated or to the reinfections by partners HPV positive. The AIDS epidemic continues to spread throughout the world with a frightening power. WHO estimates that 13 million people, including 1 million children who acquired virus perinatally, had been infected by the end of 1994 and that the number may increase by threefold at the end of the century. As heterosexual transmission becomes the primary mode of HIV transmission in western developed countries, the proportion of women of all ages contracting the disease increase steadily. Those at greatest risk are women in their reproductive years, and AIDS is becoming the leading cause of death among the women aged 25-34 in some U.S. urban areas. As more evidence accumulates about HIV infection, new clinical conditions and syndromes emerge. Although relevant data are mosfly anedocted, it seems that certain gynecological problems are more prevalent in HIV-seropositive women. Although a direct effect of HIV infection cannot be ruled out, alterations in the local immune response of the genital tract cause by HIV infection, as well as viral interaction with other infectious agents or known risk factors, probably account for the higher prevalence, recurrence and progression rates of certain gynecological neoplasms. One such phenomenon is the established high rate of HPV and cervical neoplasia reported in HIV-infected women. The mechanism by which immunosuppression increases the incidence of neoplasia is still unclear. The possibility that immunosuppression predisposes to viral infection with HPV or HSV-2 and to subsequent development of neoplastic conditions has been suggested. Animal experiments have shown that immunosuppressive therapy facilitates infection and potentiates the effect of oncogenic viruses. Halpert showed that the rate of HPV infection in immunosuppressed women was nine times and the raste of cervical neoplasia 16 times the rate found in the general population. Siiman reported evidence of HPV infection in all 20 immunosuppressed women with lower genital neoplasia in his study: he furthre demonstrated that HPV infection and neoplasia in these patients rapidly extended to adjacent areas, tended to recur, resisted therapy and frequently progressed to invasive cancer.
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From November 1990 to December 1995 eighty patients were treated with laser conization. They were high grade CIN extending to the endocervical canal and/or with purely ectocervical lesions and patients with low grade endocervical CIN persisting more than one year or cyto- histological discrepancy. Before surgery all the patients had colposcopy, cytology and guided cervical biopsies. Seventy-six out of eighty underwent local anaesthesia and in three cases a general anaesthetic was required although one case was treated without any anaesthesia. Complementary vaporization of the cone bed was performed in every single case. All specimens were judged fully evaluable by the pathologist. The accuracy of the preconization histology as evaluated in 79 patients. Exact agreement or a one degree discrepancy between punch biopsies and cone specimens was found in 96.25%. We did not find any unexpected invasive carcinoma. The apex of the specimen was free of disease in 93.75% of cases. A high grade lesion on the endocervical margin was found in 4 out of 5 cases with an apex involvement. Stenosis of the external cervical os occurred in 7 cases, 3 of which were symptomatic. In our experience laser conization is an effective and safe treatment of CIN with the results comparable to the literature.
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Last decade presented a development in alternative technique for the treatment of cervical dysplasia. Laser or LEEP present advantage and limits. Excissional therapy offers a sample adequate for hystology. Laser therapy is possible to repeat in case of relapse. Indication to laser are esocervical lesions with visible squamocolunnar junction. Endocervical lesions prefer an excissional treatment for hystological specimen. This study compares the therapeutical capacity of laser vaporisation versus LEEP in the treatment of the dysplastic disease of the uterine cervix.
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One of the most successful methods for the treatment of malignant and benign tumors is the thermal denaturation of tissue induced by absorbed light from a laser. Our LITT fiber products are emitting a spherical light profile along the entire length of up to 35 mm. A special spherical laser power meter was designed to measure the integral laser power. An exact coagulation zone can be obtained by varying laser power and application time. For faster treatment a beam splitter is built to apply up to four fibers with one laser unit. This allows the treatment of larger or metastatic tumors. In combination with a stable laser system a maximum of patients safety is obtained and the physical strain is reduced.
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In vitro measurements have been performed to investigate the use of simultaneous multi fiber applications for laser induced interstitial thermotherapy. Because of the complex shape of coagulation zones produced with more than one applicator, a measuring technique was developed to determine the necrotic volume regardless of its form. With this method it was possible to vary the mutual fiber distance for a multi fiber procedure with two scattering applicators. It was found that this method is highly efficient because treatment time is reduced while at the same time necrotic volumes are 2.5-fold larger than those of a comparable single fiber application. It is stated that this kind of procedure shows a critical fiber distance where an overlap of coagulation volumes is not certain and should therefore be avoided. Fiber separation below the critical do not require extremely precise punctures because variations of a few millimeters do not change the necrotic volume significantly.
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Laser-induced interstitial thermotherapy has proven to be an effective method for the treatment of different types of tumors. Until now the attainable coagulation volume was limited by the maximum applicable energy. The limiting factor is the high tissue temperatures around the applicator which may cause applicator damage. Consequently an internally cooled catheter system has been developed in order to reduce the temperature of the applicator surface and therefore enable the application of higher laser powers. The optimal treatment parameters for the Nd:YAG laser were determined on the basis of computer simulations and in vitro studies with porcine liver. Following these experimental studies, 72 patients with liver metastases were treated with the cooled applicator system. The applicator position and the resulting tissue damage were verified using the MRI on- line monitoring system with a FLASH-2D sequence. The optimal treatment parameters were found to be 25 watts for an exposure time of 20 minutes, resulting in coagulated volumes of up to 20 cm3. The experimental and clinical results proved that the combination of a scattering laser applicator with an internally flushed catheter enables a significant increase in the coagulation volume.
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For prediction of the effectiveness of laser-induced thermotherapy of liver metastases and for the understanding and optimal use of laser applications in medicine, especially for dosimetrical questions, the knowledge of the specific optical properties and their thermo-induced changes is important. In our study we were able to evaluate the optical properties of human liver tissue and metastatic tissue. Furthermore, we investigated the dynamic temperature behavior between 45 degree(s)C and 80 degree(s)C at three different exposure times using a double-integrating sphere system. We found significant differences between normal and metastatic tissue resulting in a higher optical penetration depth in the tumorous tissue. During the coagulation the absorption coefficient, anisotropy and optical penetration depth decreased significantly in the temperature range from 45 degree(s)C to 65 degree(s)C, whereas the scattering coefficient increased. Above and below this temperature range the changes of the optical properties were not significant. The coagulation rate differed between the exposure times.
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In addition to the laser, microwave or other energy sources, interstitial thermotherapy with radio-frequency current (RFITT) in bipolar technique has already been shown in vitro to be a safe and economical alternative energy source with a comparable operating performance. The bipolar technique is, from the technical point of view, completely without risk whereas with monopolar devices, where a neutral electrode has to be applied, an uncontrolled current flow passes through the patient's body. The therapeutical application efficiency of these bipolar RF-needle applicators was evaluated using newly designed high performance flushed and cooled probes (qq 3 mm). These can be used to create large coagulation volumes in tissue such as for the palliative treatment of liver metastases or the therapy of the benign prostate hyperplasia. As a result, the achievable lesion size resulting from these flushed and internally cooled RF- probes could be increased by a factor of three compared to a standard bipolar probe. With these bipolar power RF- applicators, coagulation dimensions of 5 cm length and 4 cm diameter with a power input of 40 watt could be achieved within 20 minutes. No carbonization and electrode tissue adherence was found. Investigations in vitro with adapted RFITT-probes using paramagnetic materials such as titanium alloys and high performance plastic have shown that monitoring under MRI (Siemens Magnetom, 1.5 Tesla), allows visualization of the development of the spatial temperature distribution in tissue using an intermittent diagnostic and therapeutical application. This does not lead to a loss in performance compared to continuous application. A ratio of 1:4 (15 s Thermo Flash MRI, 60 s RF-energy) has shown to be feasible.
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A computer simulation has been developed of the temperature and damage distribution during a bipolar RFITT (radio- frequency current induced interstitial thermotherapy) application. The electric field and the heat transfer is calculated by the Finite Difference Method. The model considers the change of tissue parameters due to the heating process and the variation of power during an RFITT procedure. The simulation works on-line with an RF-generator and measures the output power continuously. The electric power density (heat generating term) and the damage distribution can be displayed graphically in real time.
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Christoph-Thomas Germer, Christoph Martin Isbert, Dirk Albrecht, Joerg-Peter Ritz, Andreas Schilling, Andre Roggan, Karl Juergen Wolf, Gerhard J. Mueller, Heinz-Johannes Buhr
Purpose: To evaluate gadolinium-DTPA-enhanced MRI for follow-up monitoring of laser-induced thermotherapy (LITT) and to determine of a useful examination schedule. Materials and Methods: LITT Of the liver was performed in 55 rabbits using a Nd:YAG laser (4 w power output, 840 s exposure time). Gd-DTPA MRI and histological examinations were performed at different times (0 - 168 days). Results: Laser- induced lesions underwent regeneration and volume size reduction (69% after 168 days). The correlation coefficient (MR vs macroscopic analysis) for the mean lesion diameter was r equals 0.96. Histology of lesions comprised the four zones that correlated best with MRI findings. Coagulation necroses immediately after LITT were seen as an area of no enhancement on Gd-DTPA MRI. Circular enhancement was first seen 72 - 96 hours after LITT, which was due to early mesenchymal proliferation. Conclusions: Gd-DTPA MRI is a good monitoring procedure for LITT. MRI should be performed 24 and 96 hours after LITT.
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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.
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Lasersurgery has established itself in the treatment of minor tumors (T1 - T2) of the upper aerodigestive tract. However, advanced carcinomas of the head and neck (T3 - T4) are generally treated with conventional surgical procedures which include pharyngolaryngectomy. The purpose of this study was to evaluate the oncological outcome of endoscopic lasersurgery in advanced head and neck tumors and to compare the results with conventional surgical procedures. Between January 1994 to December 1996, 86 patients with advanced squamous cell carcinomas of the larynx and hypopharynx underwent endoscopic lasersurgery instead of pharyngolaryngectomy as a curative measure. Besides the recurrence and survival rate, the necessity of tracheostomy, postoperative complications and the mean duration of hospitalization were documented. The results showed that the recurrence and survival rate were similar or even better after conventional pharyngolaryngectomy, whereas the patients' postoperative rehabilitation was better after lasersurgery. In this contribution the indication for lasersurgical intervention or pharyngolaryngectomy in advanced carcinomas of the head and neck is discussed.
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Functional results following lasersurgery of minor laryngeal carcinomas were very encouraging. The indication for lasersurgical intervention was then extended to larger carcinomas of the larynx and hypopharynx. The purpose of this study was to assess vocal function and swallowing ability after endoscopic lasersurgery and to compare the results with conventional surgical procedures. From January 1994 to December 1996, 72 patients with advanced squamous cell carcinoma of the larynx and hypopharynx were examined prospectively. The patients underwent endoscopic lasersurgery instead of laryngopharyngectomy. The voice quality was evaluated pre- and postoperatively by subjective assessment, registration of voice parameters and sonegraphic classification. The swallowing ability was judged according to individual scores. The necessity of tracheostomy and nasogastric tube were registered and the duration of hospitalization was documented. The results showed that laryngeal phonation and swallowing ability were significantly better 12 months after lasersurgery compared to the preoperative findings whereas the recurrence rate was similar or even better after conventional pharyngolaryngectomy. Lasersurgery as an alternative surgical procedure to laryngectomy enables patients to retain a sufficient voice function and swallowing ability.
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Laser stapedotomy has now become an established method in the surgical treatment of otosclerosis. Recent experimental studies have demonstrated that, apart from the continuous wave lasers, several pulsed laser systems are also suitable for stapes management. Experiments were performed in guinea pigs to clarify which, if any, of the pulsed lasers used can damage the inner ear on application of the laser parameters required for the stapedotomy. The basal convolution of the guinea-pig cochlea was chosen as the application site. Acoustic evoked potentials (compound action potentials) yielded information on inner-ear function. With the Er:YSGG laser (energy: 85 J/pulse, energy density: 36 J/cm2, total energy: 0.425 J), five applications to the cochlea are necessary for a foot plate perforation of 500 - 600 micrometers . With the Ho:YAG laser, an adequately large perforation can be achieved with at least 10 applications of an energy of 210 mJ per pulse (energy density: 90 J/cm2, total energy: 2.1 J). The aim of this study was: (1) to clarify whether the Er:YSGG and Ho:YAG laser could cause morphological changes in the organ of Corti of the guinea pig on application of the laser parameters required for stapedotomy, and (2) to verify our experimental electrophysiological results and correlate them with the morphological changes detected in the organ of Corti in the guinea pig cochlea by scanning-electron-microscopic examination. It shows that the effective laser parameters (5 X 85 mJ) of the Er:YSGG-laser cause no changes of the guinea pig cochlea. Even with the application of 25 pulses with the same energy the guinea pig cochlea shows normal appearance. The effective laser parameters of the Ho:YAG laser (10 X 210 mJ) show changes in the outer hair cells in the form of stereocilie fusion and giant hair cell formation while the inner hair cells and supporting cells are showing normal appearance. Our results clearly demonstrate a high application safety for the Er:YSGG laser, while the Ho:YAG-laser is not well tolerated in the animal experiment and has only a low application safety. Its application in stapedotomy would be unreliable and dangerous for the inner ear. Our results also clearly show that the electrophysiological data correlate well with the scanning- electron-microscopic data.
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Cardiovascular Diagnostics, Imaging, and Therapies
Under steady flow conditions experiments were conducted to examine the fluid flow regime through a Jellyfish valve inserted into an aortic chamber with sinuses of Valsalva. The diagnostic Laser Doppler Anemometry (LDA) technique was used to determine the instantaneous velocity fields including shear stress distributions downstream of the valve. Maximum turbulent shear stresses were found to be 85 and 277 N/m2 at 0.5 D downstream of the valve under flow rates of 15 and 26 l/min respectively. This values are critical to lethal erythrocyte and platelet damages. Furthermore flow reversal was observed at a location 0.5 D downstream under flow rate of 15 l/min. This may also encourage thrombus formation.
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Coronary artery stenting is known to improve immediate and long-term angiographic result after coronary angioplasty. We report our experience with a new type of stent, the Nir stent, in the treatment of complex lesions.
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We have investigated the use of short pulses of infrared ((lambda) equals 2.09 micrometers ) light from a Ho:YAG laser to photofragment occlusions and restore flow in ventricular shunts, which provide the sole means of maintaining proper intracranial pressure in hydrocephalus patients. These experiments employed model tissues, a polymeric model compound, and patient explants in order to determine appropriate pulse energies and delivery rates for removal of occlusions material. Laser energy doses and rates of occlusion removal were established for these materials. Laser energy doses that do not damage the shunt device or surrounding tissue were identified. Optical fibers (25 ga. or smaller) can be introduced through the dome of current shunt devices and threaded to the occlusion site. Clinical application will require the continued development of an introducer tool for the transcutaneous insertion of the optical fiber into the shunt device and irrigation techniques for removing the occlusion detritus generated by photofragmentation treatment. Using this approach, a minimally invasive and benign procedure for in situ restoration of flow in occluded neurological implant devices becomes possible.
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Results are presented of the study of the cutaneous blood flow in patients with neurological manifestations of lumbar osteochondrosis with the help of a laser specklometer developed by the present authors. Comparative analyses of the present data with the results of IR examination and dermatothermometry has shown a great informative value of speckle-optical indices. Dynamic of the cutaneous blood flow in patients corresponded to the change in the high-frequency fluctuations spectra. In the zones of prevailing innervation of the affected radix a decrease in the average frequency of the spectrogram was observed, which reflects a decrease in the cutaneous blood flow intensity in this region.
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The epicondylitis humeri radialis (EHR) (tennis elbow), is a common disease in elbow joint pain syndromes. We treated patients with chronic pain for at least one year and no improvement with conservative or operative therapies with a new minimal invasive method, the EHR-Laser radiation (EHR- LR). With this method periepicondylar coagulations were applied to the trigger points of the patients. For this the previously established technique of facet joint coagulation with the Nd:Yag-laser was modified. In a follow-up study of between 6 weeks and 2 years all patients reported either a significant pain reduction or were symptom free. EHR-LR is a new method situated between conservative and surgical treatments for minimal invasive therapy of EHR. Several therapeutic rationales were discussed for the resulting pain reduction.
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The laser surgical treatment of carcinomas of the upper aerodigestive tract has become an established treatment modality at many otolaryngology departments throughout the laser years. The oncologic results that can be achieved with this surgical technique are quite as good as the results that can be achieved by conventional surgery, the functional results on the other hand often seem to be superior to conventional surgery. The Nd:YAG laser has so far rarely been used as a cutting device in the head and neck region. The fibertom mode is a new technique, which has been developed to make the employment of the Nd:YAG laser as a laser scalpel feasible. Between December 1995 and May 1997 thirty-five patients with squamous cell carinomas of the oral cavity were treated at the Department of Otolaryngology, Head and Neck Surgery of the University of Kiel with the Nd:YAG laser in fibertom mode (30 - 50 Watt, cw-mode, 600 m bare fiber). The operative approach, intra- and postoperative complications, duration of the operation and of the healing process, as well as functional and oncologic results were documented and compared to the retrospectively raised data of a group of patients (n equals 25), that was treated by CO2 laser surgery. When working with the Nd:YAG laser in fibertom mode fewer hemorrhages during the actual dissection could be observed as opposed to dissection with the CO2 laser. By laser dissection with the Nd:YAG laser in fibertom mode the operation had to be interrupted to a much lesser extent for bipolar cautery, thus resulting in a reduced operation time. Until a complete reepithelialization of the laser wound was achieved an interval of 3 - 4 weeks went by. Following Nd:YAG laser excision the healing process was 7 - 10 days delayed when compared to CO2 laser surgery. The functional and oncologic results were quite satisfactory in both groups and no major difference between the two laser systems could be observed. The fibertom mode renders the use of the Nd:YAG laser for the excision of tumors in highly vascularized regions like e.g. the tongue, the floor of the mouth and the oropharynx. The functional and oncologic results which were achieved with this method in the treatment of carcinomas of the tongue are so convincing that the CO2 laser has been replaced in our department by the Nd:YAG laser for the indications mentioned above. Tumors of the larynx and hypopharynx on the other hand remain to stay a domain of CO2 laser surgery.
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Voluminous vascular anomalies of the head and neck region are still treated with conventional surgery although Neodymium:Yttrium-Aluminum-Garnet (Nd:YAG) laser therapy is an effective treatment method. One hundred thirty give patients with voluminous hemangiomas and vascular malformations were treated with interstitial Nd:YAG laser therapy, partly complemented by a non-contact mode Nd:YAG laser light application. The vascular tumors had a diameter of more than 3 cm in two or all three dimensions. Treatment was carried out under ultrasound and manual control. Nearly 60% of the patients showed a complete clinical regression of the vascular tumor, a third of the patients had a partial regression and were satisfied with the treatment outcome. Four patients were treated unsuccessfully with the laser and three of them subsequently underwent conventional surgery. Only 10 patients showed cosmetic and functional deficits. These results on the interstitial Nd:YAG laser therapy of voluminous hemangiomas and vascular malformations in a large patient group demonstrated the high effectiveness of this novel and innovative therapy modality.
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Patients feel face destruction as the main problem of oncological treatment in maxillofacial area. Finding a compromise between radicality and esthetic point of view is always problematic. Original Czech 1064/1319 nm Nd:YAG laser--U.S. patient pending--is new precise tool which can give new possibilities. Two wavelengths--with different water absorption--give unique chance to control collateral tissue damage. We can combine vaporization, coagulation and hyperthermic therapy special for every part of face and for every tissue. Thanks to that we use this machine in primary treatment and in palliative therapy independently or in combination with classical knife excision. Thanks to the use of fiber we are able to bit not only superficial lesions but we have opportunity of deep hyperthermic therapy with different collateral penetration. After 20 months we can show interesting results.
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