For the purpose of developing a new treatment for human pituitary tumor, the basic study on photodynamic effect of pheophorbide-a (Ph-a) was investigated in cultured rat pituitary tumor cells (G H 3 ).
Ph-a was dissolved in culture medium by alkaline method, and the white cool light was used for irradiation. The following results were obtained.
1) Concentration of Ph-a: under the condition of 120 min. preincubation and 15 min. light exposure, a proportional increase in cytocidal effects was obtained by elevating the concentration of Ph-a. The survival rates of G H 3 with 100, 000 lux irradiation were 54% at 1.25×10^-6 M, 19% at 2.5×10^-6M, and 2% at 5.0×10^-6M. 2) Intensity of light: Effects of photodynamic therapy (PDT) were progressively increased as the intensity of light was increased. The survival rates showed 16% at 50,000 lux, and 2% at 100, 000 lux in 5.0×10^-6M Ph-a concentration. 3) Preincubation time: the survival rates after PDT depended on the preincubation time. In the 2.5×10^-6M Ph-a concentration, the survival rates of GH 3 were 86%, 71% and 54% at preincubation of 60 min., 90 min. and 120 min. respectively. 4) Protective effect of vitamin E: this effect was investigated at 5.0×10^-6M Ph-a concentration, 120 min. preincubation and 50.000 lux irradiation. On “Ph-a+irradiation” group, the survival rate was 18%. but a greater survival rate (35%) was obtained on“Ph-a+Vitamin E (1.0μg/ml) +irradiation” group. Therefore, the administration of vitamin E showed a protective effect a gainst the photocytotoxicity.

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Laser treatment has originally been regarded as a non-contact method, but the so called contact method, in which Quartz fiber is brought into direct contact with the tissue, was developed in 1983. Furthermore, with the introduction of new ceramics (Al₂O₃) into laser treatment in 1985, indications of laser surgery have been remarkably expanded.
Advantages of the contact method are: (1) The depth of tissue destruction can be adjusted according to the objectives of the treatment. (2) Hemostasis in deep tissues is possible. (3) Effects similar to those of the non-contact method can be obtained at a lower power (50%). (4) Good cutting ability. (5) High safety.
Laser treatment has recently been applied to new areas such as laser thermia and photo-dynamic therapy and is considered to be a highly promising medical technique.

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Due to optical fiber to transmit Nd: YAG laser energy and characteristic of wave length 1.06 to penetrate into tissue deeply to be absorbed. Nd: YAG laser used to be accepted mainly by endoscopist to coagulate tissue and stop bleeding.
On the other hand, CO₂ laser played major part of open surgery.
Since 1983, SLT Contact Method with Nd: YAG has enabled either open and endoscopic surgery. Recently cancer treatment based upon Laserthermia and Nd: YAG PDT and Laser angioplasty based upon contact method have been developed.

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Since middle of 1970s, endoscopic laser treatment had been applied hemostasis in the upper GI tract by Frülimorgen P. et al., Dwyer R. M. et al., Kiefhaber P. et al. and so on. At the beginning of 1980s,. Nd: YAG laser endoscopy was applied clinically for the treatment of the GI tumors. From 1984 we have been developing the Nd: YAG laser contact method with several contact probes and a computer-controlled Ncl: YAG laser hyperthermia (Laserthermia) system in cooperation with Surgical Laser Technologies Japan Co.. The experimental studies and technical developments of Nd: YAG laser endoscopy in our hospital were discussed in this paper.
Nd: YAG laser contact method with various kinds of contact probes could treat every type of lesions as endoscopic photocoagulation, vaporization, mucosal cutting, Laserthermia. Actually clinical effects by contact method had been risen about 15-25%, higher than those by the conventional non-contact method. However, it was difficult treating all of the cases concering GI tumors by laser endoscopy alone. Therefore many patterns of the combination therapy of the contact laser methods and the other endoscopic therapeutics and general treatments should be necessary. According to the experimental studies on the ENNG induced gastric tumor in beagle dogs and the transplanted human gastric cancer in nude mice, mucosal GI cancer could be treat by Laserthermia only. On the other hand, the stimulation in the interstitial tissue of the canine stomach and the transplanted human gastric cancer in nude mice as a increase of active collagenase and marked increase of collagen fiber may suggest specific reaction by Laserthermia. We have continuously to study whether these tissue stimulation could be benefit or not in the treatment of GI tumors.^15,16)
The contact method with various contact probes made endoscopic laser therapy easy and safe. Then it is possible to treat endoscopically not only photocoagulation and varporization but also mucosal cutting, interstitial irradiation and Laserthermia. Now we are going to study the Laserthermia by a single channel method using the newly developed Hybrid probe and therapeutic UGI fiberscope (GIF-WT; Olympus).¹⁷⁾

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In 1983 we developed a contact method of Nd: YAG laser irradiation using microprobes made of artificial sapphire. Clinical study of this method has yielded excellent results except in depressed typed early gastric cancer.
We pursued a new method of Nd: YAG laser irradiation for the depressed typed early gastric cancer by applying through an interstitial probe for local hyperthertnia using prolonged, low-powerd contact laser irradiation. Since 1984 we have investigated this method in experimental and clinical studies. We obtained the following results: 1) Initial alteration of cancer tissue after laserthermia treatment observed with light microscopy was dominated by the damage of tumor vessels. 2) Mitochondria may by the primary target in the cell destruction process induced by laserthermia in the electron microscopy. 3) Pathlogical change of the gastric wall after lasertherrnia treatments for 18 preoperative patients indicated the satisfactory penetration and safety of lasertherrnia. 4) Expect for 2 patients with depressed undifferenciated cancer, no local recurrence was found on 13 inoperable patients aiming for complete eradication of cancer cells by lasertherrnia. We propose that laserthermia is the safest and most effective form of treatment for deperssed cancer.

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A comparison of the contact and the noncontact treatment methods has demonstrated the superior advantages of the former: 1) a good field of vision could be maintained due to less smoke, 2) reproducible radiation on the lesion was possible, 3) damage to the blood and mucous membrane by the tip of the fiber was avoidable, 4) pain and abdominal distention was reduced by the use of water delivery instead of gas. In the treatment of early gastric cancers, some portions such as the prepylorus and upper part of the corpus, which were especially difficult to irradiate with the noncontact method, can now be treated with ease. Moreover, the margin of the cancerous lesion can be first irradiated correctly as the marking line by the contact probe because it is most important to recognize the definite margin of the lesion before treatment.
Until now, 83 patients having a total of 89 lesions with early gastric cancer have been treated by laser endoscopic treatment. Of these, 42 lesions were treated by the contact method or the combination of both methods. Especially, effective-rate was 100% for IIa, gastritis-like cancer less than 2cm and focal cancer in adenoma.

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We applied the Nd: YAG laser to 75 patients with advanced cancer in the upper G. I. tract for improving the stricture. In the 75 patients, 27 were treated by the noncontact irradiation method and 48 were by the contact method. For evaluating an effect of the stricture improvement, we studied from two points of view. One was the frequency of the laser treatment until making an endoscope passed through the stricture, and the other was the time occupied for the improvement of diet.
The former in the contact method was lower than that in the non-contact method (P<0.05). The latter in the contact method was more rapid than that in the non-contact method (P<0.05).
The findings resulted from the contact method to be superior to the non-contact in view of as follows: 1) shorter time occupied for the improvement of diet, 2) less difficulty of treatment of the stricture in the pyloric region, that in the post-operative stoma, and linitis plastica type of cardiac region, 3) accuracy in the target irradiation, and 4) occasionally minor bleeding, a field lens little covered with soot, and visual field keeping clear, in the contact method.

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The development of hyperthermia therapy to cancer has been highly reputed by its good results. Effectiveness of fever for a malignant tumor was reported firstly by Dr. W. Busch, 1866. He had experienced a patient with high fever by erysipelas, which caused the disappearance of a sarcoma at the: face.
As well known, hyperthermia therapy combined with radiotherapy for cancer has been performed, clinically. It has been well known that living cancer cell and a cancerous lesion are more fragile to higher temperature as: 42 to 45 degrees than the normal. This principle has been applied to hyperthermia therapy, of which energy ultrasonic wave and radio: frequency have been: adopted.
Recent few years, contact irradiation of Nd: YAG laser using ceramics tip is performing increasingly for treating cancer of GI tract, compared to its non-contact irradiation. The tip can be injected into a cancerous lesion of GI tract and increase its temperature up to 42-45 degree at a lower power: level (3-5w) of Nd: YAG laser irradiation for: 15-30 minutes, causing its destruction. This range of the temperature is controlled by control system using a computer. This effect is called laserthermis, laser hyperthermia or local interstitial laser hyperthermia.
Clinically, laserthermis is able to applied more safely than ordinary laser irradiation, not only to radical treatment of early cancer, but also recanalization of obstruction due to the advanced cancer of GI tract. Balloon laserthermia using Nd: YAG laser has been studied for this purpose. The effect of laserthermia is used to be increased in combination therapy with cancer chemotherapy or radiotherapy. There is one of the significances: of laserthermia in the meaning of the endoscopic treatment for residual carcinoma after the other endoscopic treatments.

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