According to the numbers of the papers reported in the major world conferences on laser surgery and medicine, the major active research areas are basic research, plastic surgery, PDT, otolaryngology, ophthalmology, biostimulation and laser tissue interactions. As the new medical lasers, Cu and Hg ion, diode, Ho-and Tm-YAG, excimer and free electron lasers are listed up.
As the new frontier areas, PDT & photosensitizers, stereotaxic endoscopic neurosurgery, coronary angioplasty, laser thermia, laparoscopic surgery, transurethral prostatectomy, biostimulation are pointed out.
The most, important subjects in laser medicine will be “How to solve the difficult medical issues of mankind in the 21 century”, that are considered as follows.
1) Treatment for the intractable diseases such as AIDS, cancers, genetic disorders etc. 2) Application to preventive medicine. 3) Contribution to health and welfare promotion. 4) Countermeasure for aging society. 5) Saving of medical resources. 6) Level up of medical standards in the developing countries. 7) International contribution to cope with worldwide accidents and emergency.

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The introduction of Laser technology into medical and surgical fields have been increasing steadily since early 1960. The speaker summarized what have been achieved in 4 periods, namely:
(1) 1960-1970, (2) 1970-1980, (3) 1980-1993 and (4) 1993-2000.
The presentation covered,
On hard-ware development:
(1) Development of Laser System.
(2) Development of Laser Centers.
(3) Miniaturization of the Laser System.
(4) Accessories and Supporting System.
On soft-ware development:
(1) Clinical trial and application in various fields.
(2) Establishment of national, international and regional societies.
(3) Organization of society related with single laser.
(4) Organization of societies related with specialty using laser.
Japan, as one of the industrialized and well educated nations, starting to play active role in the international level since the 1970-1980 period, has developed tremendous works both basically and clinically, especially in the field of endoscopy and PDT. Many laser systems have been developed by companies that meet international standards, and have been highly evaluated.
One of the most important part in spreading the laser technology in medical and surgical fields will be the training program. Japan, as center of Pacific and Asian countries, and with all the exiting powers, will be able to play a very important role as centers for mutual research, and training centers. Some positive ideas were proposed for both NGO and governmental levels to be worked out. These will not only help other developing countries to know how to use the laser properly, but will also help the Japanese laser industries as a whole to survive.

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The rapid growth of research on laser techniques and applications has been considerable during the past 33 years. The 21st century is the golden age of optical technology with laser. For example, Optical communication networks plan to construct around the world by the optical submarine cables with fiber and laser. The medical application of lasers have rapidly expanded to great propotions, and it has become a important division of the laser application fields. Though synchrotron radiation (SR) light is not laser, it will be a useful light source for diagnosis in medicine. The ready-made laser instruments made not sufficiently use the characteristics of wavelength in laser medicine. The living tissues have various absorbabilities with light wavelength at internal organs and parts. So the tunable laser is intensively needed to effective laser therapy. The laser medicine fields are in great hopes of the practical application of the free electron laser (FEL). As is well known, the concept of FEL is different from the ordinary laser.

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By taking advantage of dye laser for the tunability of any wave length from visible to near infrared (IR) spectrum, and by introducing it to endoscopy, new diagnostic and therapeutic methods for early gastric cancer (EGC) were developed in our clinic.
In the diagnostic field, it have been succeeded to observe the autofluorescence of cancer tissue gleamed by the stimulation of argon laser (488nm) in 80% (13/16) of EGC. This method is developing further basically by finding more tumor-affinitive fluorescent substances or utilizing CEA monoclonal antibody labelled by fluorescent dye. Not only on diagnosing the extent of cancerous invasion, but also on diagnosing the depth of cancerous invasion, IR laser (805nm) angiography utilizing the deep permeability of IR beam to the stomach wall and injection of ICG (strong absorbant of IR beam) gave very informative findings of “tumor staining” and “pooling phenomenon” on IR-TV endoscope system. This technique is useful, for differentiation between the mucosal and submucosal cancers to find out the risk of lymph node metastasis.
In the therapeutic field, photodynamic therapy (PDT) using hematoporphyrin derivative (HpD) and irradiation of argon dye laser (630nm, CW) showed complete remission of 88% (21/24) of mucosal gastric cancer in high risk patient for laparotomy. Moreover, PDT using excimer dye laser (630nm, PW) resulted in 100% (15/15) cure in the treatment of EGC including submucosal cancer. PDT was a useful method especially treating ulcerated types of EGC which is difficult to treat by the other endoscopic treatment.
In conclusion, dye laser endoscopy is expectable in establishing the method to diagnose very early cancer and cure it at the same time in the near future.

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To determine the efficacy of Excimer laser coronary angioplasty, experimental studies and clinical results were examined. Histological examination was perfermed using atheromatous lesions of Watanabe Hereditary Hyperlipidemic (WHHL) Rabbit. Catheter tip energy density was 35mJ/mm2 and excimer laser was irradiated in 1 and 3 seconds. Atheromatous plaques were vaporized 1.1+/-0.1mm in diameter and 0.6+/-0.1mm in depth with 1.6mm multifiber laser cathter. Minimal tissue thermal coagulation increased from 47+/-17μm to 66+/-10μm with debulking in 3seconds irradiation (p less than 0.05). However, heavy charring, severe thermal damage and vacuolization were not found. A little residual tissue was found in the bottom of the vaporized crater equivalent to guide wire lumen and laser dead space in catheter. This data suggests that residual tissue can cause intimal flap, thrombs and abrupt closure on long irradiation in the same position.
Operative transluminal laser coronary angioplasty (OTLCA) during aorto-coronary bypass surgery was performed in 4 cases (5 lesions). 4 lesions were successed and one lesion was not crossed by laser catheter because of hard calcification. Post operative angiographic examinations were all satisfied.
Percutaneous transluminal laser coronary angioplasty as an adjunct or alternative to conventional baloon angioplasty was also studied in 34 cases (36 lesions), not ideal for conventional baloon angioplasty. Procedural success was achieved in 34 lesions. Adjunctive balloon angioplasty was perfoermed on 25 lesions. There were no myocardial infarction and no death. This procedure is expected to solve the difficult lesions like type B and type C (AHA / ACC task force).

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Recently we applied surgical lasers to laparoscopic cholecystectomy which promptly became the most common treatment for cholecystolithiasis. From September 1990 to August 1993, 225 patients with cholecystolithiasis underwent this operation and 10 patients of these were complicated choledocholithiasis. KTP laser was used for dissection of the gallbladder bed of the liver in 50 cases, comparing with the group where only electrocautery was used. A quartz fiber was introduced into the abdominal cavity though a lumen of aspiration nozzle or Laser Scalpel which has U-shaped metal tip. The usefulness of KTP laser was investigated from the standpoint of accidental entry to the gallbladder or the liver, ability of hemostasis, and GOT/GPT values in the postoperative period. Pulsed-dye laser was applied to fracture stones in the common bile duct. A quartz fiber was inserted through a working channel of choledochoscope. Inadvertent entry into the gallbladder was occurred in 12.0%(6/50) of the KTP laser group and 18.0%(21/117) of the electrocautery group. Resected specimen revealed that no hepatic parenchyma was found in the KTP laser group but it was recognized in 13.3% of the electrocautery group. Laser Scalpel make manipulation of quartz fiber easier by holding it within the“U”tip. The value of transaminases was lower in the KTP laser group though there was no significant difference. Pulsed-dye laser was used in 5 cases. In only one case, choledocholithiasis cleared at operation. In three cases, small fragments remained but disappeared during postoperative period. In one case, endoscopic sphincterotomy was required to remove the residual stone. Mechanical excoriation by quarts fiber may cause bleeding from the bile duct.
Clinically, surgical lasers are safe and effective in the procedures of laparoscopic cholecystectomy and management of choledocholithiasis through the cystic duct.

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We adopted Carbon Monoxide(CO) laser for thoracoscopic treatment of pulmonary blebs. CO laser (wavelength; 5.4μm) could be delivered by chalcogenide glass(As-S) fiber. A CO laser fiber cable for endoscopic laser therapy was successfully developed. This laser cable contained a As-S infrared fiber covered with a teflon sheath, ZnSe optical window and thermocouple installed at the side of fiber tip. The absorption coefficient of CO laser (10²cm^-1) was equivalent to the thickness of the bleb wall(0.06-0.5mm). The sterilized flexible bronchoscope was inserted through the thoracoscopic outer sheath under local anesthesia. Laser power at the tip was 2-3W and irradiation duration was O.5sec each. Shrinkage of blebs was obtained by non-contact method of CO laser irradiation without perforation of the bleb. The temperature change caused by particle adhesion was easily detected to avoid damage to the fiber tip. Our new technique was found to be safe and effective for less invasive treatment of pulmonary blebs.

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A fiber optic CO₂ laser system made it possible to apply endoscopic treatment. The probe for endoscopic applications is 2.3 mm in diameter and 20 mm in minimum bend radius. The tissue damage of the canine stomach was observed after the CO₂ laser irradiation. It was considered that the optimum condition to radiate on the mucosal lesion was 5 mm distance, 5-10 watts output power and total 5 seconds irradiation time.
On the basis of these results, 38 cases of digestive tract diseases included 13 early gastric cancers have been treated by CO₂ laser, and satisfactory results were obtained.
The endoscopic CO₂ laser treatment is considered to be effective for mucosal cancer of digestive tract.

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A high NA silica fiber has been developed by Mitsubishi Cable Industries Ltd. for the exclusive application to ultrathin fiber scopes and small diameter catheter which are used for various micro diagnosis and therapy in the body. This report describes the detailed study of high density laser power transmission on this high NA silica fiber. Following fibers were utilised for this study
·Ge doped silica glass core-B·F. dope silica glass clad fiber (HiNA/All silica) -0.43NA
·Ge doped silica glass core-polymer clad fiber (HiNA/PCF) -0.53NA
·Pure silica core-B·F dope silica glass fiber (Pure silica core/All silica) -0.20NA
·Pure silica core-polymer clad fiber (Pure silica core/PCF) -0.40NA
·Tapered fiber of both types.
·Core diameter covers 50-500μm
And the laser utilised are,
·50W CW Nd-YAG (λ=1.06μm)
·15W pulse KTP Nd -YAG (λ=1.06, 0.53μm)
·25W Diode laser (λ=0.806μm)
As results
·70% power transmission, 34W out put power and 17.3 KW out put power were achieved for CW Nd-YAG laser and HiNA/All silica fiber having 56μm core diameter.
·Break down thresh old power of HiNA fiber to puls Nd-YAG laser was 1/2~1/10 of that of pure silica fiber.
·On diode laser transmission with a taperd fiber having 400μm core diameter of laser input portion 160μm core diameter of out put portion and 0.53NA, 70% power transmission and 17.5W out put power were achieved.

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Infrared lasers operating in the mid-infrared, such as Er: YAG laser (2.94μm), CO laser (5.3-5.9μm) and CO² laser (10.6μm), received much attention as a medical surgical laser.
IR transmitting fluoride and chalcogenide glass fibers are very promising for applications in power delivery systems of these lasers.
Fluoroaluminate glass fibers with 450μm core diameter and 500μm clad diameter, prepared for Er: YAG laser power delivery have a minimum bending radius of 12mm, high damage thresholds of >8MW/cm2 input power density.
And also, high damage threshold of 210KW/cm2 has been achieved with chalcogenide As-S glass fiber for CO laser power delivery. These fibers are potentially useful for power delivery of Er: YAG laser and CO laser, respectively.
While, chalcogenide Ge-Se-Te glass fibers suffered thermal damage easily with the maximum CO² laser input power density of 40KW/cm2. The absorbance and refractive index increments with temperature of this glass have imposed a limitation on its deliverable power.

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Laser endoscopic surgery has now achieved a status as effective treatment modality for lung cancer. Especially the effectiveness of photodynamic therapy (PDT) using Photofrin as a photosensitizer was demonstrated in our institution in 1980 for the treatment of lung cancers, and increasing attention has been focused on this new treatment technique. In this study, advanced stage lung cancer patients were treated with PDT as a palliative treatment. In advanced lesions, the opening of bronchi obtained by tumor was achieved in 61 of 81 lesions (75%). In this study, effective tumor response was also compared according to the tumor location. Seventy three percent (19/26) of effective was obtained where tumor was located at trachea or main bronchus and 76%(42/55) where tumor was located lobe or segmental bronchus. PDT was also performed preoperatively. Performing PDT made possible to reduce the extent of resection necessary and reserve pulmonary function among 15 advanced lung cancer cases.

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Photodynamic therapy (PDT), which is the endoscopic method using hematoporphyrin derivative (HpD) as the photosensitizer and laser beam as the excitation light source, is regarded as a safe and promising method for treating early gastric cancer, because malignant tissue can be destroyed selectively. However, it was not certain that PDT was curative for early gastric cancer (EGC) with submucosal invasion, because transmissivity of light limits the depth of effectiveness. Then, we newly investigated an excimer dye laser (EDL) instead of an argon dye laser (ADL), because the EDL (specifications: wavelength: 630 nm; pulse energy: 4 mJ; peak power: 400 kW; pulse width: 10 nsec; frequency of repetition: 40 Hz) had higher transmissivity through the tissue, and more effective in photodynamic action than those of ADL. The procedure of PDT was as follows: (1) Two mg/kg of freeze-dried Photofrin II was injected intravenously; (2) About 50 hours later, the entire lesion plus a 5 mm width of marginal mucosa was irradiated with the EDL beam transmitted endoscopically. As a standard, the irradiation was delivered at a total dose of more than 60 joule/cm2; (3) After PDT, the patients were kept in bed with no food and were given continuous i. v. infusion of glucose and saline solution with an H₂-blocker and antibiotics for two days. In this study, from September 1990 until March 1993, eighteen cases of EGC, which consisted of 12 mucosal and 6 submucosal, were treated by PDT with EDL and freeze-dried Photofrin II. These patients could not be treated by operation because of high risk factors or old age. The response was evaluated by endoscopy with biopsy and cytology in the follow-up examinations.The rates of local cure were 100%(12/12) and 83%(5/6) for mucosal and submucosal carcinomas, respectively (Table 1). In the last study, between 1981 and 1990, we treated 37 EGC lesions by PDT with the ADL and Photofrin I/II, and evaluated them in the same standard as in this study. The rates of local cure were 59%(13/22) and 53%(8/15) for mucosal and submucosal carcinomas, respectively (Table 2). The relation between dose (J/cm2) and curability in PDT was examined, comparing EDL with ADL. In EDL, dose of 60J/cm2 was sufficient to obtain local cure in submucosal carcinomas, while in ADL, 90J/cm2 was required at least (Figure 1).

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An effectiveness of photodynamic therapy (PDT) using Hematoporphyrin Derivative (HpD) and Argon-dye or Excimer dye laser for the superficial esophageal carcinoma which cannot be treated by any surgical procedure because of the severe complications was reported.
Laser beam (630nm) has been endoscopically irradiated on the lesions 48 hours after an injecion of HpD with the power of 90-100 joule per 1 cm2.
PDT under this condition has been performed on 17 cases with the superficial esophagealcancer (17 lesions). The esophageal cancer in 12 cases of them has been radically treated in the first PDT, because biopsy specimens obtained endoscopically from the lesions have not proved malignancy more than one year and half. In 2 cases, a local remnant of the cancer was recognized and the remnant cancers were completely removed after the second PDT. Four cases were died from; pneumonia, advanced cancer of the other organ respectively and lymphnode metastasis of the esophageal cancer in 2 cases. In the cases in which the local remnant of the cancer was detected in the biopsy specimens after the first PDT, the size of their lesions was more than 4 cm2. The fetal complications were never observed, but sunburn due to the photosensitive reaction was found after the sun exposure.
Therefore, PDT is considered to be an excellent treatment for the superficial esophageal cancer less than 4 cm2 without lymphnode metastasis in the inoperable cases.

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The incidence of CIS and dysplasia of the uterine cervix is increasing among young women in the recent years. Most of these patients want to preserve their fertility, and some of them are inoperable or refuse surgery. To avoid surgery, high power laser with CO₂ or YAG laser are most often used, but just like the conventional conization, these therapies cause unexpected bleedings and may destroy uterine cervical glands indispensable for pregnancy and delivery. PDT with the use of EDL-a type of pulse laser, has a considerably higher degree of tissue penetration, even compared to the PDT using argon dye laser. It also has a special feature: selective destroying of malignant cells with almost no effect on normal tissue. Furthermore, PDT is performed without anesthesia, since it causes no pain or bleeding.
We studied clinically this method on 39 patients until now. PDT is performed 48 hours after the intravenous injection of photosensitizer Photofrin II (PHE). Out of 24 CIS and 15 dysplasia patients, there were 38 CR (97.4%) and only one NC case. The NC case is thought to be due to the insufficient photo radiation of lesions surrounding the portio. The first CR case was four years ago and no recurrence has been observed yet.
PDT seems to be the most appropriate known method in treating early stages of uterine cervical cancer, as it satisfies our main condition of fertility preservation. With little side effects, no bleeding or pain,and with certain improvements in administration methods, better choice of photosensitizer which would shorten the shading time, PDT promises a brighter future for physicians and their patients in fighting cervical cancer.

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A phase II was conducted between June 1989 and Feburary 1992 to evaluate the activity and toxicity of photodynamic therapy (PDT) with photofrin II in centrally located early-stage lung cancer and to determine the complete response (CR) rate as the primary end point.
Patients and Methods: Patients had histologically proven lung cancer and endoscopically superficial thicking or small protrusions. All lesions were located in subsegmental or larger bronchi. All patients had a performance status (PS) of 0 to 2 and artial oxygen pressure tension (PaO₂) ?60 torr. No lymph node or distant metastases were present. All patients received photofrin II (2 mg/kg) intravenously 48 hours before PDT. Tumor lesions were superficially photoradiated by argon dye laser or excimer dye laser. Results: Of 54 patients with 64 carcinomas, 51 with 61 carcinomas were eligible for toxicity evaluation and 49 with 59 carcinomas were assessable for response. Of the 59 assessable carcinomas, 50 (84.8%; 95% confidence interval, 73.0% to 92.8%) showed a CR after initial PDT. The median duration of CR was 14.0+ months (range, 2.0+ to 32.4+) The multiple regression model indicates that estimated length of longitudinal tumor extent was the only independent prognostic factor for CR (p=0.002). Ten carcinomas that had a CR had a local recurrece between 2 months to 19 months after initial PDT (median recurence time, 6 months). The 16 carcinomas that had a CR duration of 24 months, had no local recumence after initial PDT. Regression model shows that a longitudinal extent of tumor was important factor for local recurrence. Conclusion: PDT with photofrin II has an excellent effect on patients with centrally located early-stage lung cancer who have a longitudinal extent of 1 cm or less.

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Since 1978, our groups have synthesized more than 700 kinds of porphyrin derivatives and studied the mechanism of tumor tissue affinity and photodynamic therapy. Recently our studies suggest that tumor tissue affinity of porphyrin is based on specific physico-chemical properties of porphyrin and lack or imcompleteness of lymphatic system in cancer tissue.
The importance of triplet life time of porphyrins was reported and we can estimate the capacity of singlet oxygen production of each sensitizer. The absorption wave length of future photosensitizer may be 670-700nm. Two photon excitation method is practically expected not to be effective in PDT.

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Laser-hard tissue interaction has been investigated. We studied the irradiation effect of KrF and ArF excimer lasers on teeth enamel and cow thighbone as a hard tissue. The ratio of Ca atoms to P atoms at irradiated surfaces of both samples was measured by using Electron Probe Micro Analysis (EPMA). The ratio Ca/P increased for KrF laser irradiated surface of teeth enamel and for ArF laser irradiated surface of cow thighbone. No change was observed for another case. The results indicate that single photon absorption at the bone surface and two photon absorption at the teeth enamel surface take place for both KrF and ArF laser irradiation.
We tried to improve a bio-compatibility of alumina surface by KrF laser implantation method. Ca and P atoms were implanted into alumina.

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Improvement of laser technology enabled us to treat various kinds of color disorders of the skin. Compared to the other fields of medicine, cutaneous laser surgery has the following advantages; (1) The skin is a organ that exists on the surface of the body, which makes it easy to access from outside. So, the laser delivery system can be simple and easy to make. (2) The target of the skin color disorders is always “color”. So, some laser wavelength can be selected according to the 'color'of the lesion, in order to make the light absorbed selectively and to destroy the abnormal structure selectively. In 1983, Parrish and Anderson developed a new theory called selective photothermolysis. This theory pointed out a possibility to selectively destroy a certain structure within the skin without damaging surrounding structures using a laser light of the following quality; (1) The target structure has a higher absorption rate than the surrounding structures at the wavelength of the laser light. (2) The pulse duration is short enough for avoiding thermal diffusion before the target is completely damaged. Following this new theory, the flashlamp pumped dye laser (585nm/0.45ms) was made for treating cutaneous vascular lesions. We investigated histological responses against this laser and revealed its effectiveness. Although flashlamp pumped dye laser has become the first choice for treating portwine stains, its effectiveness is considered to have its own limitation. A new theory is advocated in which you can understand the histopathological reaction and prognostic diagnosis. Each kind of portwine stain vessels reacts as follows; In case of relatively less energy, coagulated blood dissolute again and the abnormal vessels remain intact (re-canalization). In case of enough energy, some large vessels suffer thermal damage and change to small neo-vessels (re-vascularization) or small vessels turn to be granulation tissue (vanishment). A new histological classification of portwine stain is advocated in which a clinical type is expressed by a combination of three vessel types; subepidermal, papillary and reticular vessels. On magnified inspection, subepidermal vessels look granular, papillary vessels look branching, and reticular vessels look even redness. This theory enables easy analysis for the structure of the portwine stain vessels, and furthermore, easy estimation of the prognosis after flashlamp dye laser exposure. More recently, a new type of lasers called Q-switched lasers was developed for treating dermal pigmented lesions. In near future, every kinds of skin color disorders may be treated by lasers.

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Many lesions in the gastric mucosa have been reported to be caused by change of gastric mucosal blood flow. Several methods have been being used to investigate the mucosal blood flow, but these methods including a laser Doppler methods can merely measure the pin-point area blood flow of the gastric mucosa. Therefore, the experiments have had to be carried out in many different positions to get two-dimensional (2D) information of gastric mucosal blood flow. If the blood flow of broad area of gastric mucosa can be simultaneously measured, further information of the cause of gastric lesions must be available with less effort. The aim of this study is 2D-imaging the gastric mucosal blood flow using a laser speckle method. Using this method, we observed the blood flow in the gastric mucosae of rats and dogs and acquired the 2D-maps of the gastric mucosal blood flow image. Moreover, we have developed an area sensor: it was composed with ten thousand CCD to be able to get rapidly blood flow images without scanning. Using this apparatus, we examined human volunteers and obtained the 2D-map of blood flow in the gastric mucosa under the endoscopy. The blood flow measurement with the apparatus utilized by the laser speckle method has enable us to image the sequential blood flow change in gastric mucosae with any invasion. We suggest that this method of measuring blood flow is extremely useful to investigate gastric lesions.

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Mucosal blood flow is supposed to show a considerable heterogeneity among different sites in organs, however, there has been no good tool for evaluating this. In this study, using rat stomach, we examined the temporal and spacial alteration of blood flow during the development of ischemia-reperfusion-induced gastric damage by using two dimentional laser Doppler perfusion imager. Male Wistar rats 200-250g were used for the experiments. Under pentobarbital anesthesia, stomach was carefully pulled out and exposed under laser Doppler perfusion imager PIM 1.0 (Lisca Development AB) and scanned from the serosal and the mucosal sides. One ml of 0.1N HCl was instilled into the gastric lumen. Systemic arterial pressure was continuously monitored and blood was stepwisely withdrawn from the femoral artery to 80, 60, 40 and 20% of the control pressure. After that the mean systemic pressure was maintained about 20mmHg for 20min. The shed blood was then reinfused and the stomach was removed at 30min later. CV-6209, a PAF receptor antagonist, was intravenously administered at the dose of 0.1mg/kg 30min before the experiment. In control condition, the blood perfusion was uniformly good showing more than 7-8 P. U. throughout the stomach. During the process of gradual decrease in systemic pressure, the blood perfusion of body and antral portion was almost equally decreased, but the perfusion of area along the left gastric artery and prepyloric region was comparatively well preserved. Perfusion detected from mucosal side was more vulnerable to ischemia than the serosal perfusion. After reperfusion, transient hyperemia was observed, and then the hypoperfused area started to appear in the middle body portion of the stomach near the greater curvature, well corresponding to the formation of gastric mucosal damage. CV-6209 well prevented the decreased perfusion as well as the formation of mucosal damage. From these observations, it is concluded that gastric mucosal blood flow shows heterogeneity among different portion of stomach which may closely relate to the occurence of mucosal damage.

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We carried out Laser angioplasty by the metal hot tip contact method with either the Argon laser or Nd-YAG laser and by the pulse laser direct beaming method aided by the Ho-YAG laser. The study was conducted on 69 patients with arteriosclerosis obliterans who had visited our hospital with a chief complaint of intermittent claudication.
The initial success rates were 86% in Argon laser, 90% in Nd-YAG laser, and 87% in Ho-YAG laser. The long-term patency after surgery were 68% in the Argon laser, 64% in the Nd-YAG laser and 84% in the Ho-YAG laser.
Laser angioplasty is an effective technique for the treatment of arteriosclerosis obliterans which can be performed within a short period of time in high risk cases such as those complicated by coronary artery lesions. Combined with bypass surgery, laser angioplasty enabled complete revascularization of the target area.
We proved it possible to obtain a satisfactory initial success rate and favorable long-term patency by carefully selecting the lesion through meticulous observation with the fiberoptic angioscopy.

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Argon laser angioplasty was performed in 74 patients with the occlusive diseases of the peripheral arteries by metal tip probe with thermal feedback control system. Primary clinical success was achieved in 75 (81%) of all 93 lesions. In 65 (88%) of 75 lesions with clinical success, additional dilatation was carried out with a balloon catheter. The clinical success rate was significantly higher (p<0.01) in the lesions (97%) shorter than 10cm than in the lesions (71%) longer than 10cm in 51 femoropopliteal lesions, whereas the clinical success rate was significantly lower (p<0.01) in longer lesions (?5cm) than in shorter lesions (<5cm) in 42 iliac lesions. These were no complications required emergency operation. Reocclusion tended to occur more often in patients with newly dissection by additional balloon dilatation, hypertension or diabetes mellitus, and poor distal runoff. At 68 months of follow up, the cumulative patency rate (CPR) was 90% in 65 cases with clinical success. In the 35 stenotic and 30 occlusive lesions, the CPR were 94% and 85%, respectively. In 37 femoropopliteal lesions, the CPR were 91% In recanalized lesions shorter than 10cm and was 64% in recanalized lesions longer than 10cm. Thus, laser angioplasty was safe and effective to increase the initial success rate for lesions that were difficult to treat by balloon angioplasty. Angioscopy and intravascular ultrasound imaging were useful for the observation of the newly recanalized channel by lasing. These results suggested that laser angioplasty might be a useful treatment for patients with chronic peripheral arterial diseases and improve the long-term patency rate by diminishing restenosis more than conventional balloon angioplasty.

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Percutaneous Transluminal Laser Angioplasty (PTLA) was performed on 132 peripheral arterial lesions (51 occlusions, 81 stenoses ) from March, 1985 through March, 1993. The results and limitations of PTLA were evaluated. The total initial success rate was 90.9% (120/132). Failed cases included six femoropopliteal long lesions and two iliac severe calcified lesions. The cumulative patency rate was 89.7% totally, 91.4% in the iliac lesions, 85.8% in the femoropopliteal lesions and 100% in the below knee lesions. We have no major complications due to laser irradiation. Dissection owing to added balloon PTA may influence long-term patency rate. PTLA has limitation in the case of hard lesion, long lesion, with DM etc. However, it has expanded the indication of PTA and produced a better long-term patency rate. In conclusion, PTLA is a valuable method in treating peripheral arterial occlusion.

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In the recent years endovascular intervention has been widely employed in the field of cardiovascular diseases. We have also applied Argon laser for the peripheral-and the coronary artery diseases.
First of all, relationships between laser energy and the arterial wall, metal tip size and diameter of the artery were experimentally evaluated. Based on our excellent experimental studies, Argon laser was employed for 195 patients with intermittent claudication, or chest pain.
Optimal conditions of laser angioplasty were 6W in output and 3S in irradiation time for the peripheral artery. However, for the coronary arteries which were thin and small 4-5W in output and 1-2S were optimal conditions. In this paper, indications, methods, and results of intraoperative laser coronary angioplasty were reported in detail.

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Excimer laser coronary angioplasty (ELCA) was performed on 36 lesions in 34 patients. The patients consisted of 28 males and 6 females. The mean age was 61±11 years. The lesion was located in the protected left main (1), the left anterior descending artery (28), the left circumflex artery (1), the right coronary artery (3) and saphenous vein bypass graft (3). Nine lesions (25%) were prior angioplasty restenotic lesions. Advanced Interventional Systems Dymer 200+laser system emitting energy at a wavelength of 308nm with a pulse duration of 200 nsec was used. The laser was operated at 20 Hz. Laser energy was delivered through multifiber catheters 1.3, 1.6, or 2.0mm in diameter. Energy fluences at the catheter tip was set at 45 to 60mJ/mm2 per pulse. Laser catheter was advanced into the coronary artery by the over-the-wire technique. Acute laser success was defined as a more than 20% reduction in percent stenosis by laser alone. Procedural success was defined as a final percent stenosis of 50% or less without major complications (death, myocardial infarction and emergency coronary bypass surgery). The reference diameter of treated vessel was 2.7±0.6mm. Seven lesions (19%) were longer than 10mm in length. Seventeen lesions (47%) were calcified lesions. The mean laser operating time was 16±19 seconds. In 19 lesions the laser operating time was less than 10 seconds. The percent stenosis improved from a baseline of 81±10% to 51±20% after ELCA. Acute laser success was achieved in 26 lesions (72%). Adjunctive balloon angioplasty was performed on 25 lesions (69%) in an attempt to obtain an optimal results. The final percent stenosis was 31±13%. The final percent stenosis was less than 50% in 34 lesions (94%) and procedure success was achieved in 33 lesions (92%). Complications included major dissection (8%), transient closure (11%), and side branch occlusion (6%). In one patient transient leakage of contrast media was observed. In this patient emergency coronary bypass surgery was performed to prevent rebleeding. There were no deaths or myocardial infarctions. Our study suggested that ELCA was effective technique especially for lesions not suitable for conventional balloon angioplasty.

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Hyperthermia has been applied to the treatment of human cancer. The heat of more than 42 degree centigrade selectively kills S-phase cells and hypoxic malignant cells. Therefore the hyperthermia for malignant tumor synergistically works with radiotherapy and chemotherapy. Hyperthermia itself has neither painful treatment nor side effect comparing with other cancer treatments. There are many kinds of energy resources for hyperthermia; 1) hot water, 2) electromagnetic energy like RF and microwave, 3) sonic energy, 4) infrared light, and 5) laser energy have been studied and used. The electromagnetic energy is most effective to relatively deeper tumors like esophageal cancer. On the other hand the Nd: YAG laser, which can be transmitted by a flexible optical fiber, is the easiest and the most useful instrument to heat the tumors that locate on the surface of head and neck regions. First, experimental and clinical studies of the interstitial localized hyperthermia using the contact laser probe, namely laserthermia is referred. Secondarily, the clinical application of balloon laserthermia to the paranasal sinus is demonstrated. This new method is that the Nd:YAG laser beam is scattered to all angles through the saline in the balloon and the superficial tumor contacted with balloon surface are easily heated.

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Transoral excision of oropharyngeal carcinoma with CO₂laser was performed for 40 patients during from 1981 to 1992 in our clinic. Most patients were T1, T2 and T3 carcinomas mainly located in lateral, superior or posterior wall. Radiotherapy was combined in most cases, because post-operative histopathological study revealed insufficient safety margin. Five-year cumulative survival rate without intercurrent diseases was 74%. Five-year cumulative local control rate was 75%. The local control rate of laser surgery was significantly higher than that of radiotherapy without surgery. The local recurrence occurred only in 13%of patients with carcinoma of lateral wall, whereas it occurred in 71%of those with carcinoma of posterior or superior wall. The results suggest that T1, T2 and T3 cases of the oropharyngeal carcinoma mainly located in lateral wall are good candidates for transoral laser surgery combined with radiotherapy.

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Since 1986 we have performed laser surgery to more than 200 patients with allergic rhinitis and obtained good result. However, long-term results remain obscure. Lately we conduct a questionnaire on these cases which received laser surgery more than two years ago. The subjects are 70 cases of the 96 cases (80%) for which laser surgery was effective excluding 26 cases whose address was unknown because of removal among 118 cases which received laser surgery between March, 1986 and March, 1991. Of the 70 cases, 50 cases (response rate 71%) responded to the questionnaire. The effectiveness of the therapy continued over the long period of time (26 months at the shortest, 62 months at the longest, 41.7 months on the average) in 38 (76%) out of 50 cases. However, recurrence was noted in 12 cases (24%). Regarding the recurrence, it tended to be seen frequently in the cases which were severe before surgery, but there was no correlation between the recurrence on one hand and the degree of improvement after surgery and age on the other.

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In the ear surgery, laser is generally used on the ossicles with middle ear disease. However the most specific application of the argon laser is thought to be used on the inner ear disease.
The animal study proved that argon laser created localized lesion on the sensory organs of the inner ear without labyrinthine membrane rupture. it showed that the otolithic organe was disappeared with preserving hearing and Caloric response.
A case report of 63-year-old females who complainted vertigo for 6 years was presented. Laser labyrinthectomy was done on the patient. Her hearing and Caloric response was preserved 2 years after the surgery.

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Recently developed KTP laser has been used in the various fields of surgical operations due to its superior performance and easiness of manipulation, however few reports of its application for tracheoesophageal surgery have been made. We have operated over fifty patients with the KTP surgical laser system since March 1992, and found it quite useful. KTP laser has advantages over carbon dioxide laser or YAG laser which have been widely used in otolaryngology, head and neck surgery. First of all, KTP laser has a balanced ability of cutting and hemostasis, so hemostatic cutting can be done easily. Second, Its fiber optic delivery system makes it easy for the operator to manipulate the device. 532 nano meter wavelength of KTP laser is well absorbed into hemoglobin, which makes KTP laser ideal for the treatment of hemangioma. Four representative cases are described in this paper. Two patients had an esophageal stenosis, and the other two had pharyngolaryngeal hemangioma. Hemostatic cutting ability of the KTP laser was useful for three patients and photocoagulation was applied to one of the hemangioma patients. No surgical complications occured and the results of the operations were satisfying.

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As the therapy for benign prostatic hyperplasia(BPH), transurethral resection of the psotate(TURP) is widely accepted as the“gold standard”of surgical therapy. Recently, however, conservative treatment has received more attention. Balloon laserthermia of the prostate by Nd: YAG laser is considered a conservative one.
In this paper, we reported results of 4 different examinations by using balloon laser fiber. 1. Laser prostatectomy. Therapeutic conditions included irradiation at 15W for 20 minutes, while the temperature of 5mm depth below the urethral mucosa was maintained at 60°C without urethral cooling. After 4 weeks, cavity formations in the prostatic urethra were completed. 2. Thermal damage of the prostatic tissues. Muscle damage of the urethral sphincter occurred above 43.2°C for 20 minutes. Protection of urethral sphincter is indispensable. 3. Interstitial temperature measurement during laserthermia. The effect of cooling of the tissue was within 6mm and direct transmission of the laser energy was within 10mm. 4. Urethral compliance after laserthermia. Urethral compliance increased after laserthermia.

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Thity cases of benign prostatic hyperplasia (BPH) were treated with transurethral ultrasound-guided prostatectomy (TULIP) procedure and followed for 1 year. The treatment system (TULIP system) was manufactured by Intra-Sonix, Inc., USA. The device is composed of a 20 F transurethral probe incorporationg laser beam window and ultrasound transducer, a 7.5MHZ, 90°sector ultrasound scanner and a laser generator(Nd-YAG). Under epidural anesthesia, the TULIP probe, covered with a sleeve, was inserted. The probe was fixed in the prostatic urethra by pressurizing the sleeve to 2 atomospheres by distilled water. Then the laser fixed at 40W was applied into the prostate. A single pass consisted of moving the probe along the urethra from the bladder neck to the level of vermontanum under the real-time ultrasound guidance with a speed of 1mm/sec. These passes were applied 9 times from 2 to 10 o'clock. Suprapubic cystostony was inserted.
The evaluation was estimated by symptom score (modified Boyarsky's symptom score), maximum flow rate (MFR), residual urine (RU) and prostate volume (PV). The mean age of the patients was 73.9 years (62-92 years old). The numbers of patients evaluable at 3 months and 1 year were 30 and 26, respectively. Four patients could not be evaluated because of unrelated death (1), frail general conditions (2) and prostatectomy (1). The changes of evaluation parameters(pre→3 months→1 year)were symptom score(24.6→→9.8→6.2), MFR(7.0→> 13.8→14.7), RU(49→18→16), and PV(36.8→> 24.6→32.3). Excepting PV, which regained at 1 year, all the parameters improved at 3 months and remained or even further improved at 1 year

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Animal experiment was performed with seven male dogs weighing between 21 and 25 kg, under general anesthesia, with pentobarbital sodium (25mg/kg). A midline lower abdominal incision was made to expose the urinary bladder. 23Fr conventional cystoscope was introduced into the prostatic urethra via cystostomy. The entire operative procedure was observed under TV monitor. Laser irradiation was begun linearly from proximal to the apex of the prostate using Hercules 5060U^TM and Model 6000^TM Nd: YAG laser (LaserSonics) and UltraLine^TM (LaserSonics) fiber which delivered 50 watts of power for 20, 30, 40 and 60 seconds at 3, 9 o'clock. Animals were killed immediately, and at 2, 4, and 6 weeks after the operation. The bladder, prostate and urethra were carefully examined and removed. Specimens were cut into transverse step-section. As the results, thermal coagulation necrosis and delayed sloughing were observed usually several weeks after the procedure. The prostatic urethral cavity was covered with transitional epithelium in the later stage. Clinically 27 male patients underwent laser operation. Their ages ranged from 53 to 80 years of age. The present study selected the patient with below 15 ml/sec in peak flow rate (uroflometry), above 20 gram prostate volume (transrectal ultrasound) and above 15 points in AUA Symptom Score, and excluded the patient with prostatic cancer and neurogenic bladder. The used instrument was the same as those used in the animal experiment. The laser prostatectomy was carried out with standard lithotomy position under spinal anesthesia. The laser was employed at four radial regions (2,4,8 and 10 o'clock positions), additionally to 3,5,7 and 9 o'clock position, with the fiber being dragged from the bladder neck to the verumontanum. The laser was set at 50 watts power on continuous wave. The drag rate was from 30 to 60 seconds. Clinical efficiency was determined by peak flow rate, residual urine, AUA Symptom Score, prostatic volume and side effect. The total evaluation was divided into 3 grades (useful, slightly useful, not useful). According to the criteria, laser surgery was classified as useful in 11 (68.8%). As the side effect, 13 patients revealed urinary retention and one patient showed acute epididymitis after the operation.

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The goal of our study is to develop a simple and safe laser treatment of the urinary tract stricture without the recurrent stenosis. To select of the therapeutic laser with less probability of the recurrent stenosis after the treatment, we compared between Ho: YAG laser (pulsed waveform) and UV Ar laser (continuous waveform), which have almost equal optical absorption of tissues and the capability of fiber delivery. Although the Ho:,YAG laser ablation efficiency was lower than that by UV Ar laser, histological examination revealed that the thermally damaged layer by Ho:,YAG laser was thinner than that by UV Ar laser. This thermal conduction may cause the lower ablation efficiency and thinner thermally damaged layer comparing to UV Ar laser. The result indicated the usefulness of Ho: YAG laser for the treatment of ureteral stricture. Furthermore, Ho: YAG laser has advantage in low maintenance cost due to solid-state laser and has is commercially available. The fibrotic ureteral stricture was successfully treated using Ho: YAG laser and Multi-fiber catheter. The ureter was kept open for 6 months without indwelled stent catheter. The treatment of Ho: YAG laser through the multi-fiber catheter may be useful for the urinary tract stricture.

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In recently, the confocal reflecting laser microscope (CRLM) has been used in our department for clinical urology, particularly patients with hematuria or male infertility, without requiring fixation and staining. Dysmorphic red blood cells are found in the urine of patients with glomerular bleeding, on the other hand isomorphic red cells characterize non-glomerular or urological bleeding. In this study, urine specimens from 50 patients with hematuria were collected (group A). Thirty three patients had urological disease and 17 had nephritis. The CRLM of the urine specimens showed a marked morphological difference between dysmorphic and isomorphic erythrocytes. The sensitivity and specificity for urological disease by CRLM were 100% and 93.9%, whereas those for nephritis were 100% and 76.5%. Urine specimens from 37 pediatric patients with hematuria (group B) were also observed by the CRLM: 35 had a glomerular disease, and 2 had a non-glomerular origin. Of 35 patients with glomerular disease, only 8 cases (22.9%) were classified as dysmorphic pattern and 11 (31.4%) were diagnosed as mixed pattern. The reason why of this result was supposed that 26 cases were already recieved treatment, and dysmorphism of urinary red cells with glomerular bleeding may be changeable corresponding with the condition of glomerular disease. By the way, semen specimens from 27 fertile men and 14 infertile men were collected. The sperm showed some morphological differences between fertile men and infertile by the CRLM. It was supposed that the good sperm had narrow sperm head, long sperm midpiece and wide acrosomal region of sperm head. From these results, it seems like that the CRLM makes it simpler and easier to evaluate the morphology of the erythrocyte in urine and sperm. The CRLM can be a good assistant diagnostic modality for patients with hematuria and investigative modality for male infertility.

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We performed endoscopic treatment on 182 cases (184 lesions) of early gastric cancer during a period between 1980 and June 1993. Of them 104 cases (106 lesions) were treated by endoscopic mucosal resection (EMR) and 108 cases were by laser irradiation.
On 30 cases of 108 laser irradiation were treated as a additional laser therapies for residual tumors after EMR. We compared the result of additional laser therapy with the result of EMR single therapy and Laser single therapy from the viewpoint of selection of endoscopic methods. Complete resection was possible in 55.7% of all EMR cases, 69.7% for absolute indication group and 20.0% for relative indication group. On 108 cases of laser irradiationi, 41 cases could be folloed-up more than one year after the end of laser single therapy. No residual cancer cell was detected on 31 cases (75.7%).
When these 41 cases were analysed to a indication group, the effectiveness rate was 100% (12/12) for absolute indiaction group, and 65.5% (19/29) for relative indication group. On 30 cases of additional laser therapy 22 cases could be followed-up more than one year. The effectiveness rate was 81.8% (18/22) for all cases, 91.7% (11/12) for absolute indication group and 70.0% (7/10) for relative indication group.
The effectiveness was separately assessed for EMR, which allows histological examination of resected tissue, and for laser irradiation, which dose not allow collection of tissue. Assessment of the effectiveness of laser irradiation requires accumulation of endoscopic and biopsy's data for long period. For the reason of this advantages of EMR, our view as to indications of endoscopic treatment for early gastric cancer is as follows: lesions which belong to absolute indication group are indicated for EMR. In cases where EMR has been incomplete or difficult, additional laser irradiation is given. Lesions which belong to relative indication group are principlly treated by surgical procedures. These group are likely to have lymph node metastasis which cannot be endoscopically treated. For these group endoscopic treatment is limitted to inoperable cases. For these inoperable cases lesions are treated by laser irradiation.

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Recent morphological investigations have revealed that there are severe structural changes in mitochondria after Nd-YAG laserthermia.
The purpose of this study was to evaluate biochemical influences of Nd-YAG laser upon mitochondria. methods The mitochondria was isolated from anesthetized Wister rat liver. Then Nd-YAG laser were irradiated to the suspension at 100, 400, 900mW for 20min. (40, 150, 340J/cm2) respectively. After irradiation respiratory control ratio (RCR: Chance's state3/state4) of each mitochondrial suspension was measured by the oxygraph. And proton Adenosine Triphosphatase (proton ATPase) activity was also measured by fluorometric assay.
To compare the influences of Nd-YAG upon mitochondria with those of the other wavelength laser, Argon ion laser was selected and irradiated at the same condition. results ‹Nd-YAG› Significant decreases of RCR data were observed in Nd-YAG laser groups. But proton ATPase activities were almost preserved in these groups. Especially, after 100mW irradiation, ATPase activity was significantly elevated. It suggests the mitochondrial respiratory activity was photostimulated by low power Nd-YAG laser. ‹Argon ion laser› As regards RCR data, the results were almost similar to Nd-YAG. But according to the increase of laser power, ATPase activities were decreased. During laser irradiation the temperature of the suspension elevated less than 5°C, and they may not cause thermal damage for mitochondria. conclusions The results suggest that Nd-YAG laser light inhibits mitochondrial respiratory activity at 400, 900mW irradiation, but at lower power as 100mW, Nd-YAG laser may cause some acceleration of mitochondrial respiration by photostimulation effect. Also it is recognized different wavelength laser irradiation may cause different effects on mitochondrial respiration.

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Laser therapy for bile duct stones, employing non-contact beam treatment using continuous wave Nd: YAG laser or contact beam treatment using a ceramic rod, has been performed in our institution from 1980. Consequently, the ratio of complete lithotripsy has been increased from 31/47 (66%) to 66/71 (93%).
Recently, we had a oppotunity to use the Lasertripter (Flashlamp excited dye laser), which was devised for urinary stones. It beams pulse wave to crush stones. The effectiveness of with this new laser depends on the kind of the stone,but it is better than a conventional Nd: YAG laser. Furthermore, as this method can be used with a thin fiberscope, it is more effective for peripheral intrahepatic stones than a Nd: YAG laser. The ratio of complete lithotripsyby Flashlamp excited dye laser is 23/23 cases (100%).

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