Laser medicine is one of the earliest developed and most prominent branch of applications of laser technology. Since the first appearance of the ruby laser in 1960 it took only one year for the ruby laser retina coagulation machine to be found in the market. Accompanying the development of various species of new lasers, together with the development of fiber techniques and applications of electronics, tremendous progress has taken place on laser applications to biological and medical basic research as well as to laser medical treatment and diagnostics. Indeed, laser medicine is a multi-disciplined new technology and profession, and much more important developments are expected.

We received our first CO₂ laser at Baylor University Medical Center in December 1974, following a trip to Israel in January of that year. Discussion with the customs office of the propriety of charging an 18% import tax lasted for nine months. We lost that argument. Baylor has been using lasers of many types for many procedures since that time. About ten years ago, through the kindness of Tom Dougherty and Roswell Park, we started working with photodynamic therapy, first with hematoporphyrin I and later with dihematoporphyrin ether (II). In February 1984, we were invited to a conference at Los Alamos, New Mexico, U.S.A. on medical applications of the free electron laser as part of the Star Wars Program. A grant application from Baylor was approved that November, but funding did not start for many months. This funding contributed to the development of a new research center as part of Baylor Research Institute. Many of the projects investigated at Baylor dealt with applications of the free electron laser (FEL), after it became available. A staff was assembled and many projects are still ongoing. I would like to outline those which are in some way related to photodynamic therapy.

Although the laser has been in existence for abut 30 years, its application in heart disease has only been examined in the past decade. Much attention has been given its exciting potential in treating coronary artery disease. Transmitted through a catheter comprised of one or more thin optical fibers which can be threaded nonsurgically into the coronary artery, the laser can ablate atherosclerotic plaque that obstructs the artery and diminishes blood flow to the myocardium. In clinical studies, the laser can treat some obstructive lesions that are not suitable for balloon angioplasty (i.e., long and diffuse lesions, very tight stenoses, ostial lesions, calcified lesions). In patients who failed balloon angioplasty due to severe dissection or abrupt closure, the laser may seal up the dissections and restore antegrade blood flow. In addition, the laser may have other applications and treatment modalities that are still under investigation. It may ablate ectopic ventricular foci, or terminate supraventricular tachyrhythmia by destroying the heart's abnormal conduction pathways. It can cut the hypertrophied septum that is associated with left ventricular outflow tract obstruction, or create a channel in the atrial septum as a palliative procedure in newborns with transposition of the great vessels. It may provide a wider orifice for blood flow within the heart in infants with pulmonary outflow obstruction and in adults with aortic valvular stenosis. It is also capable of fusing small thin-walled blood vessels together. Further, a more intriguing possibility is its use to bore several tiny channels in the myocardium to allow oxygenated blood from within the ventricular chamber to perfuse the ischemic heart tissue.

After the pioneering work of photodynamic therapy of malignant tumors had been reported by Dr. Dougherty and his colleagues, applications of hematoporphyrin derivative for the diagnosis and treatment of human cancers has been reported by Professor Hayata et al. Chinese HpD was first made by Shi-Lin Xu, an engineer of Beijing Institute of Pharmaceutical Industry in 1980. The first patient to receive the PDT in China was a case of basal cell carcinoma of the lower eyelid, treated in 1981 by Dr. Ping Zhu a physician in Tong Ren Hospital in Beijing using a Chinese made laser. In 1982, research groups of PDT were established under the sponsorships of the State Science and Technology Commission of China, Beijing Commission for Science and Technology, etc. Physics, chemistry, preclinical and clinical research studies of PDT were then started widely.

It is no exaggeration to state, no single specialty of medicine has so thoroughly investigated the different possibilities of laser systems as urology. Twenty years of experimental and clinical use of laser technology has led to a number of standard procedures.

Photodynamic therapy (PDT) utilizes a tumor-localizing photo-sensitive substance which, when activated by light of an appropriate wavelength, releases cytotoxic substances causing destruction of the malignant tumor with preservation of surrounding normal tissues. In this technique the only drug/light combination which has been used regularly is that of hematoporphyrin derivative (HPD) and red light at a wavelength of 630 nanometers usually produced by a dye or gold vapor laser. This paper describes the results of a pilot/feasibility study using this technique to treat superficial tumors of the skin and head and neck carried out in Southampton between 1983 and 1989. Ethical permission was obtained to treat only patients who had failed all other appropriate treatment modalities and for whom there was no practical alternative therapy. It became apparent that, particularly in the treatment of tumors of the head and neck, PDT would be used as one of the arms in multi-modality treatment programs replacing chemotherapy in established protocols. It was considered essential, therefore, to undertake an experimental study to determine the interrelationship between photodynamic therapy and ionizing radiation and particularly to show that PDT does not have any adverse effects on the healing following radiation therapy.

To compare the safety and efficacy of PDT plus XRT versus XRT alone in patients with obstructive endobronchial tumors, 41 patients with inoperable non-small cell bronchogenic carcinoma obstructing a central airway were randomized into either XRT alone or PDT followed by XRT. The most proximal site of obstruction was in a main stem bronchus (32) or a lobar bronchus (9). The histology was squamous cell carcinoma in 34, large cell carcinoma in 4, and adenocarcinoma in 3. The age, location of tumor, degree of endobronchial obstruction, and Karnofsky rating were similar between the two groups. The radiation dose was 3000 cGy in 10 fractions over two weeks using a parallel pair technique. The patients were reassessed 4, 8, and 12 weeks after completion of XRT and then quarterly thereafter. Response to treatment was assessed by changes in respiratory symptoms, bronchoscopy, spirometric measurements and arterial blood gas sampling. All 20 patients improved symptomatically after PDT and XRT. Four out of 21 patients failed to respond after XRT alone. The median interval between treatment and local recurrence was two times longer in the PDT and XRT group (233 days versus 107 days, p equals 0.005). Our results suggest that the addition of PDT prior to XRT provides significantly better and longer lasting local control than XRT alone.

Ultrasound is being used in directing therapy in all branches of surgery. We report on our experience using the combo laser and rectal ultrasound probe for inoperable cancer of the sigmoid colon.

The rationale of photodynamic therapy is based on the cytotoxic action of products generated by excited photosensitizers. Recent development has brought forward a series of promising photosensitizers ranging from hematoporphyrin derivative, various kinds of phthalocyanines and chlorins, to (delta) -aminolevulinic acid. The therapeutic efficacy is dependent on parameters such as tissue oxygenation, sensitizer distribution, drug clearance, optical irradiation, and exposure time. The general outline of a dosimetry model, which enables all these effects to be taken into account, is discussed.

Patients with recurrent gynecological carcinomas have a poor prognosis with a median survival time of 3 - 6 months. Four patients with recurrent vulva carcinomas, one patient with a recurrent breast cancer, and one with a recurrent cervical carcinoma underwent PDT after parenteral or topical sensitization with Photosan 3. Of those patients two women made a complete recovery with no evidence of disease 27 and 24 months after. One patient responded partially with two recurrences which were retreated twice after topical sensitization, she has survived 16 months. The remaining patients showed partial response and died 3 and 8 months after PDT. The energy delivered by an argon-dye-laser ranged between 225 and 750 J/cm². Photosan 3 was given intravenously at a dose of 2.5 mg/kg body weight and was tolerated without any allergic reaction. A response rate of nearly 50% in recurrent gynecological malignancies encourages us to pursue PDT in gynecological diseases.

During a 3 year period, 20 patients with morphologically proven squamous cell carcinoma of the trachea or bronchi have been treated by photoradiation therapy (PRT). A Bulgarian gold vapor laser and hematoporphyrin of `Jacopo Monico,' Italy were used. The photosensitizer was applied intravenously 24 - 48 h prior to PDT. The median realized energy dose was 410 J/cm² for each patient with a middle power of 180 mW. In 5 of all the cases we performed two sessions. The obtained therapeutic results are as follows: CR -- one case (5%), SR -- 10 cases (50%), NR -- 3 cases (15%). The median survival of the patients with advanced cancer was 13.3 months. At the end of 1990 three patients were alive. Our experience shows that PRT is a promising palliative method in cases of advanced carcinoma for the recanalization of airways.

Brain tumors of various histologies were subjected to an in-vitro photodynamic-sensitivity test. The studies were performed on primary cultures of human glioblastomas, meningiomas, and ependymomas, which were exposed to increasing concentrations of hematoporphyrin derivative and 60 J/cm² delivered by an argon-dye laser at 632 nm. A growth inhibition of 75% was demonstrated at a concentration of 25 (mu) g and 10 (mu) g HPD/ml medium for two different glioblastomas, respectively. A growth inhibition of 75% was observed in the ependymoma line at 10 and 50 (mu) g HPD/ml with and without light, respectively. The meningioma demonstrated a 75% inhibition already at (mu) g and 75 (mu) g/ml medium with and without light, respectively. These results demonstrate a significant difference in the response of brain tumors to photodynamic treatment (PDT). In vitro-PDT-assay should be taken into account if clinical application of PDT is considered.

Normal mice received hematoporphyrin derivative (10 mg/kg iv) immediately, 24 or 48 hrs prior to red light irradiation. The blood was collected and the platelet-rich plasma was irradiated by red light (100 J/cm²). The platelets were fixed immediately, 8 or 16 hrs after irradiation, and processed for EM examination. In comparison with those of control mice, the platelets of all experimental mice showed structural changes: 16 hrs after irradiation all platelets were necrotized; 8 hrs after irradiation almost one fourth of the platelets were necrotized and the remaining were considerably damaged; immediately after irradiation a small number of platelets became necrotic and most other platelets were swollen and deformed, often with many cytoplasmic projections and considerable dilatation of the canalicular membrane system. Our findings provided a clear evidence that platelets are highly sensitive to PDT action and can be directly and rapidly injured by PDT even in the absence of vascular endothelial cells. Our results give firm support to the hypothesis that both endothelial cells and platelets may play an important role in the initiation of early vascular damage and microcirculatory alterations induced by PDT in vivo.

Two principal aspects of interlinkage of the immune system with photodynamic therapy (PDT) treatment are discussed in detail: (1) participation of tumor associated macrophages (TAM) in tumor localization of photosensitizers, and (2) induction of an inflammatory immune response by phototoxic effects in endothelial cells, TAM and other cells in the tumor, leading to necrosis of the tumor tissue. It is illustrated how Photofrin levels in TAM, and consequently in the tumor as a whole, can be altered (increased or decreased) by specific agents that stimulate or impair physiological processes in TAM. It is suggested that the selectivity of tumor localization of some photosensitizers can be augmented by TAM targeted immunotherapy with agents that enhance the rate of tumor infiltration of these cells and stimulate their phagocytic activity. Preliminary results of ongoing studies suggest that PDT induces a massive infiltration of immune cells into the treated tumor. It is hypothesized that by combining PDT with an appropriate type of immunotherapy the immune reaction can be potentiated and directed against the surviving tumor cells. As as an example, it is shown that much better control of SCCVII tumor is achieved by combining PDT with the treatment by the immunoactivator SPG compared to PDT alone.

Sulfonated chloroaluminum phthalocyanine (AlClPCS) has been considered in recent years as a new photosensitizer with promising use in photodynamic therapy (PDT) of cancer. In this work, its biological effects were studied in mice bearing S180 tumors. It was found in tissue distribution measurements that AlClPCS can be selectively accumulated in the tumor, the peak tumor concentration of AlClPCS occurs 36 h after administration, with a tumor:skin ratio of 3:1. The spectral transmittance measurement in the tumor, carried out in vivo at 48 h after administration of AlClPCS at 10 mg/kg, showed that AlClPCS accumulation in the tumor affects the light penetration to some extent at its 675 nm main absorption peak, but the transmittance at 675 nm is still comparable to that at 630 nm, the absorption peak of HPD. The temperature measurement in the tumor showed that the temperature increase is minimal under 100 mw/cm² irradiation. The tumor response to AlClPCS photodynamic therapy was encouraging. The cure rate of tumors (20 mice) reached 60% under conditions where the irradiation dose of red light was 180 J/cm² and the dose of AlClPCS administration was 10 mg/kg, showing AlClPCS has the potential to become a candidate for clinical photodynamic therapy.

The role of non-skin phototoxic dose of Photofrin in the detection of dysplasia and carcinoma in situ was assessed in a small animal model of oral squamous cell cancer (SCC). Nine,10-dimethyl 1,2-benzanthracene (DMBA) impregnated cotton sutures, covered with a silicone sheath, were sewn into the hamster cheek pouch to produce dysplasia, carcinoma in situ, and invasive cancer. The yield of SCC was 83% by 20 weeks. Fluorescence imaging was performed using a specially designed device that exploits differences of fluorescence properties of normal, precancerous, and cancerous tissues with and without Photofrin. The fluorescence was induced by a helium-cadmium laser (442 nm) and then measured at two different wavelengths by an image intensified camera. Computed images using a mathematical transformation of fluorescence data were then displayed on a video monitor. Areas with dysplasia and both in situ and invasive cancers could be clearly delineated from the adjacent normal tissues. Lesions as small as 2 mm in diameter could be identified. Because of the presence of endogenous porphyrins, the addition of a non-skin phototoxic dose of Photofrin (0.25 mg/kg iv) did not enhance the signal to noise ratio. Our results suggest that fluorescence imaging can accurately detect both precancerous and cancerous lesions in the oral mucosa without exogenous porphyrins. It may have an important role as a non-invasive, clinical diagnostic tool in oropharyngeal cancer.

Since 1981, we have been employing endoscopic Nd:YAG laser irradiation for treatment of early gastric cancer. However, the therapeutic results have not always been satisfactory. Therefore, we have developed a new Nd:YAG laser-irradiation method which uses an endoscope fitted with a transparent thin-membrane balloon at its tip. Basic studies on this balloon method confirmed that the balloon did not affect the tissue-destructive effect of the laser. In clinical studies, the balloon method was used to treat 20 lesions. The degree of efficacy (effective: negative against cancer for at least one year after treatment) was 90%. Thus, in comparison with the conventional method, the balloon method produced clearly better therapeutic results.

In 2 years 53 patients with tumors of the tracheobronchial tree have been treated by photocoagulation therapy. Forty cases of them were with different types of cancer and 13 cases with benign lesions of the trachea or bronchi. As a laser source we used an Nd:YAG laser, MBB, Germany. At first the tumor was irradiated with a power of 25 - 30 W, following power up to 90 W. The median energy dose was 3,500 J/sq cm for each patient. The treatment was executed under local anesthesia with a rigid or flexible bronchoscope. In all of the cases with benign tumors we obtained a stable positive effect. In 15 cases of carcinoma we attained a recanalization and restoration of the ventilation to the treated area -- 37.5%. The only complication due to the procedure was the death of one patient with a tracheal cancer and myasthenia gravis. Photocoagulation therapy is an effective method for benign tumors. In cases with carcinoma this therapy is used with palliative purpose -- recanalization of the bronchus. Laser endobronchial therapy shows an immediate positive effect in the treatment of airway obstruction.

Photodynamic therapy (PDT) utilizing Photofrin II is proving to be an effective modality in the treatment of early stage lung cancer. However, wider clinical application of Photofrin II as a photosensitizer for various cancers is hampered by the potentially serious and prolonged skin photosensitivity. To prevent these side effects and reduce the inpatient period, we recently tried to give reduced doses of Photofrin II by bronchial artery infusion (BAI). Six patients with endoscopically evaluated early stage carcinoma of the lung were given 0.7 mg/kg of Photofrin II by BAI 48 hours before PDT. Complete remission was obtained in all 6 cases, and there was no evidence of skin photosensitivity when exposed to outside light under careful surveillance at one week after PDT.

Whole bladder wall photodynamic therapy using hematoporphyrin derivative and argon-dye laser light 630 nm was performed on 40 patients with mainly carcinoma in situ of the bladder. Two types of laser light scattering diffuser developed at our department were used: motor-driven and endoscope-modified laser light scattering diffusers. The total energy density used was 10 to 30 Joules/cm². Of the 40 patients, 29 (72.5%) achieved complete response and 5 (12.5%) partial response at 3 months follow-up. In 9 of the 40 patients there was no recurrence and average tumor-free time was 27.1 months, ranging from 12 to 84 months.

Photodynamic therapy has attracted attention by its potential for selective tumor destruction. However, selectivity is limited by unsatisfactory accumulation of porphyrin derivatives in tumors. Porphyrins injected intravenously are rapidly cleared from circulation by the liver. We examined the possibility of inhibiting the liver uptake of porphyrins by using the non-phototoxic hemin to compete for liver accumulation. The tumor model was an ovarian carcinoma (O-342, Zeller) transplanted in the muscle of the left hind leg of BDIX rats. To monitor the biodistribution of the photosensitizer various porphyrins were labelled with ¹¹¹Indium. The distribution of the radioactivity was imaged by a gamma camera (Phogamma IV; Searle/Siemens) and biopsies measured in a gamma counter (Berthold, Freiburg). An injection of 5 mg/kg hemin prior to introduction of the porphyrin caused competition for uptake of the photosensitizer by the liver. Consequently, the plasma half-life for all ¹¹¹Indium-porphyrins investigated was increased by 30 - 50%. The liver competition was possible both by preinjection of 5 mg/kg hemin 5 minutes before administration of the photosensitizer or by injection of hemin within 15 minutes post injection of the photosensitizer. This saturable process suggests distinct binding sites for hematoporphyrin in the liver. However, tumor uptake of the radio-labelled porphyrins was not blocked by hemin. Tumor accumulation of the porphyrins demonstrated a positive correlation to plasma retention time. Preinjection of hemin induced higher tumor uptake rates, up to a factor of 5 within 24 hours post injection. Pretreatment of the animals with hemin caused better therapeutic ratios for all porphyrins. The tumor to skin ratio of Photofrin II was raised from 4:1 to 7:1 by preinjection of hemin. This effect may be useful to reduce skin phototoxicity of PDT in man by dose reduction of the applied photosensitizers.

The possible value of adjuvant PDT of the open surgical wound after tumor resection in a clinical situation was the goal of our study. Nude mice allow heterotransplantation of human oral cancer material. Such tumor particles show an individual take and growth rate and possibly variable reaction to PDT.

The photosensitizer of choice in photodynamic therapy (PDT) is the hematoporphyrin derivative (Hpd). However, Hpd has many characteristics which make it less than an ideal photosensitizer. The sulfonated phthalocyanines represent a new group of interesting compounds that have a strong absorption in the red part of the spectrum at 675 nm. In our laboratory we compare the efficacy of two phthalocyanines, the zincum tetrasulfonated (ZnS₄Pc) and the aluminum disulfonated (AlS₂Pc), on a murine tumor. Mice bearing MS-2 fibrosarcoma were treated with 5 or 25 mg/kg of ZnS₄Pc or AlS₂Pc and then the tumor mass was exposed to a laser light (100 mW for 10'). The results show that the treatment with AlS₂Pc is significantly more therapeutically active in respect to the treatment with the same dose of ZnS₄Pc. Moreover, resistance to rechallenge with the MS-2 tumor was evidenced by surviving animals. Studies are in progress with other murine tumors with different biological properties.

Three samples of sulphonated aluminum phthalocyanine with predominance of different sulphonated degree (AlPcSn) were investigated in vivo in comparison with different commercial samples of HpD. The criterium of primary biological assessment of photodynamic activity was the field of necrosis spot upon the liver tissue of mice under the same parameters of influence combination. The preliminary experimental and morphological study of antitumor activity demonstrates different mechanisms of photodynamic activity when we use for PDT more effective di- and trisulphonated phthalocyanine Al and most effective from HpD - Photofrin II.

One-hundred-ten cases with esophagus-cardiac carcinoma treated by YAG laser gasifying together with irradiation of hemoporphyrin derivatives is reported. Here complete remission is seen in 28% of the patients, the total effective rate was 87%. The treatment method is simple and convenient, therefore, it is useful for the treatment of esophaguscardiac, carcinoma in a different stage.

Toxicity, pharmacokinetics, and the tumor damage effect of chlorin e₆ after light irradiation were studied. The results show that chlorin e₆ LD50 value in C57Bl mice was 189 +/- 10 mg/kg, in non-inbred white rats it was 99 +/- 14 mg/kg 14 days after the agent iv injection. The concentration of chlorin e₆ in blood, liver, kidney, spleen, and tumors (sarcoma M-1 and sarcoma 45) of the rats was determined by the fluorescence method 3, 6, 12, 18, 24, 48, and 72 hours after the agent iv injection at the dose of 10 mg/kg. For this purpose chlorin e₆ was extracted from tissues by detergent triton X-100. The depth of necrosis spreading in tumor tissue was evaluated after chlorin e₆ injection at the doses of 1 - 10 mg/kg and subsequent irradiation by a krypton laser with light energy density of 90 J/cm², using the method of vital staining with Evans blue. It was found that depending on the agent dose and time interval between chlorin e₆ injection and photoradiation, the depth of tumor necrosis varied from 4.0 to 16.6 mm in sarcoma M-1 and from 5.0 to 15.0 in sarcoma 45.

With hematoporphyrin derivative (HpD), the glass-type gold vapor pulsed laser was used in laser-induced photodynamic therapy (PDT) in the treatment of 36 cases of malignant tumors. All the cases were confirmed by the pathological and cytological diagnosis. The follow-up revealed that the total effective rate was 88.9%. The shallow-surface malignant tumors of the early stage can be cured completely, while the malignant tumors of the middle or late stage can be palliatively treated with satisfaction. The glass-type gold vapor pulsed laser is a newly developed approach for treatment of malignant tumors in recent years. Here we report the results of HpD and laser-induced PDT in the treatment of 36 cases of malignant tumors.

It has been proven that the hematoporphyrin derivatives (HPD) could be accumulated and retained in malignant tissues for a long time. Using a newly established procedure, we labelled HPD with radioactive isotope 99mTc. These studies suggest that: 99mTc-HPD can be used to study the in vivo distribution and metabolism of the HPD; that the accumulation and retention of 99mTc-HPD in tumor tissues is not highly specific; that the 99mTc-HPD radio-imaging can be used to study the distribution and metabolism of HPD in the human body; and that, if the radioactive ratio of tumor to surrounding tissues is high enough, it can be used to localize the tumor qualitatively. In this article the desirable time for imaging, the diagnostic criteria, and the correlation between the sensitivity and the pathologic grade, stage, and size of the bladder tumor are discussed.

The paper presents a new method for malignant tumor diagnosis by rapidly detecting the argon laser induced autofluorescence spectra. The diagnostic system consists of an argon laser and an optical multichannel analyzer. With a special processing program, the spectral signal acquisition and the specific index I_s/I analyzing could be done simultaneously in real time by a micro-computer. The system can not only be used for spectral measurement of separate points individually, but applied to continuous I_sI scanning of entire suspicious areas as well. By this technique, the Lewis lung tumors less than 1 mm were identified in in-vivo experiments, and the human cancer of 2 mm was found in clinical detections.

Vhe paper reports that 149 bladder tumors in 40 patients were treated by gold vapor laser photodynamic therapy in the period from June 1989 to August 1991. The light fiber output power of gold vapor laser is more than 2 W, that spread through a spherical diffuse light leading fiber. Focusing the irradiation on the tumor and the whole bladder the power density was 70.77 mw/cm² to approximately 509.55 mw/cm². After a follow-up of 4 to 24 months we found the following results: cured 28 cases (70%); good effect in 11 cases (27.5%); improved 1 case (2.5%); and regenerated 4 (10%).

We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 10⁶ of C⁶ type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm², which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

Our early observations have confirmed that laser hyperthermia or PDT alone does not promote the tumor metastasis. In order to evaluate the combined effect of local tumor laser hyperthermia on the distant metastasis, transplantable forestomach carcinoma (Fc) in 615 line mice was treated by Nd:YAG laser hyperthermia (45 degree(s)C/20 min) combined with PDT (HpD 5 mg/kg, 480 J/cm², 20 min), chemotherapy (Cyclophosphamide 28.8 mg/kg) and excision, respectively. The results show that (1) the tumor growth inhibition by various treatment was significant compared with a control group; (2) no statistics different in metastasis rate were observed in laser hyperthermia combined with PDT, chemotherapy, or scalpel excision separately. It is suggested that laser hyperthermia combined with PDT, chemotherapy, or excision does not increase the incidence of the tumor metastasis.

Interstitial photodynamic therapy, in which the straight cut optical fiber was directly inserted into tumors and the insertion points were rationally arranged on an entire lesion area, was performed on 31 oral cancers, 6 skin cancers, and 4 cervix cancers in 41 patients. A highly satisfactory rate of complete response (90%) was obtained via only one treatment. And no severe complication occurred in any of the treatments. The follow-up record for 33 cases with a CR curative effect shows 12 cases have survived free of tumor more than 4 years and only 5 cases relapsed within a year. In this paper, the factors affecting therapeutic effectiveness and the selection of indication are discussed.

One-hundred-twenty cases of malignant tumors treated by endoscopic photodynamic therapy with hematoporphyrin derivative from August 1982 - July 1990 are reported. Of the 120 cases, including 97 males and 23 females ages varying from 39 to 77 years old, 40 cases were primary tumors and 80 cases were local residual or recurrent after surgery or radiotherapy or chemotherapy. All cases were confirmed in pathological biopsy, including 58 squamous cell carcinoma, 28 various adenocarcinoma, and 34 transitional cell carcinoma. Twenty-four, 48 and/or 72 hours after intravenous injection of HpD 2.0 - 3.0 mg/kg, or DHE 1.5 - 2.0 mg/kg, or Y-HpD 5.0 mg/kg, the tumor was irradiated with 630 nm wavelength of argon dye laser via a quartz light fiber inserted through the forceps channel of the endoscope. Of the 120 cases treated, CR was obtained in 38 cases, PR in 25 cases, MR in 52 cases, and NR in 5 cases. Total response rate was 95.8%; significant response rate 52.5%; and tumor eradicated rate 31.7%. The 38 cases included: 14 cases of early esophageal carcinoma, 3 cases of early cardiac carcinoma, 1 case of early lung cancer, 1 case of early gastric carcinoma, 15 cases of superficial bladder carcinoma, 3 cases of local residual recurrent micro lung cancer, and 1 case of cardiac carcinoma. The longest cancer-free survival was over eight years. Endoscopic photodynamic therapy is, therefore, curative effective in the treatment of early and superficial carcinoma, and palliative effective in the treatment of advanced carcinoma. Standardized and controlled trials are required to assess its place in combined treatment of malignant tumors.

Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

Photodynamic therapy (PDT) was performed on 11 cases of recurrent cerebral glioma, including 3 cases of recurrent glioblastoma, 7 of recurrent anaplastic astrocytoma, and 1 recurrent ependymoma. Hematoporphyrin derivative (HPD) was administered intravenously at a dose of 4 - 7 mg/kg 5 - 24 hours before the operation. All patients underwent a craniotomy with a nearly radical excision of the tumor following which the tumor bed was irradiated with 630 nm laser light emitting either an argon pumped dye laser or frequency double YAG pumped dye laser for 30 to 80 minutes with a total dose of 50 J/cm² (n equals 1), 100 J/cm² (n equals 2), 200 J/cm² (n equals 7), and 300 J/cm² (n equals 1). The temperature was kept below 37 degree(s)C by irrigation. Two patients underwent postoperative radiotherapy. There was no evidence of increased cerebral edema, and no other toxicity by the therapy. All patients were discharged from the hospital within 15 days after surgery. We conclude that PDT using 4 - 7 mg/kg of HPD and 630 nm light with a dose of up to 300 J/cm² can be used as an adjuvant therapy with no additional complications. Adjuvant PDT in the treatment of recurrent glioma is better than simple surgery.

The authors report that 41 patients with cancer of the urinary bladder were treated with YAG, hematoporphyrin derivative (HPD) photodynamic combination therapy (combination group) and simple YAG laser (simple group). Forty-one cases were divided into 2 groups: 20 cases in the combination group (31 tumors) and 21 cases in the simple group (26 tumors). A follow-up survey was made for 12 - 36 months after treatment. In the combination group 2 cases in 12 months and another 2 cases in 24 months showed no recurrence. Sixteen cases were followed up for 29 to 36 months with 2 recurrent cases. The 36-month recurrence rate in the combination group was 12.5%. In the simple group recurrences took place in 2 out of 6 cases during the follow-up of 13 to 16 months after treatment. The 24-month recurrence rate was 33.3%. Recurrences were observed in 8 out of 15 cases followed up for 31 - 36 months. The 36-month recurrence rate in the simple group was 53.3%. There was significant difference in the 36-month recurrence rate. The results indicate that the combination group is highly superior to the simple group for a long-lasting therapeutic effect on bladder cancer. The follow up is reported in this paper.

Fifty-seven patients suffering from alimentary tract cancer or precancerous gastric diseases were treated in three years. Forty-five were males and 12 were females, ages 41 to 83. The argon laser used had a wavelength of 5145 ampere degree(s), a power output of 100 J/cm². The validity of diagnosis by fluorescence against pathological diagnosis in regard to 22 of the 57 patients was 86.4%. The full spectrum argon laser and pump dye laser had a wavelength of 6300 ampere degree(s) and a power output of 200 - 400 J/cm². The total validity was 93%. The survival rate for a half year was 92.3%; for one year, 86.5%; and for two years, 68.3%. Selective function of PDT on cancerous tissues is harmless to normal ones and without side effects. PDT may have palliative effects on advanced alimentary tract cancer. It is very effective in treating the second and third degree untypical hyperplasia of precancerous gastric diseases.

Forty-one cases of recurrent cancer in the maxillary sinus and ethmoid sinus were treated by Nd:YAG laser, CO₂ laser, PDT, and operation. The partial skull fundus invaded by the advanced carcinoma in the maxillary sinus and ethmoid sinus was resected with laser through the cranial facial section. The cancer in the maxillary sinus is the most common in primary paranasal carcinoma, accounting for 80 percent. The malignant tumors in the ethmoid sinus are minor. Radiation and operation are usually performed in them, but it is easy for the cancer to recur after treatment. To save and continue life, 41 cases of recurrent carcinoma in the paranasal sinuses were cured by laser and PDT from 1979 to 1991.

We report 117 cases of clinical data of photodynamic treatment of bladder cancer and confirm that treatment of the bladder cancer between 1 cm to 2 cm in diameter should get better results. That of 2 - 4 cm diameter needs increased energy density and repeated exposures. If the cancer is larger than 4 cm diameter or includes invasion of the deep muscle and the cervix of the bladder, the results of treatment would not be satisfactory. The elimination rate of cancers in this group of patients was 94%. The total recurrence rate reduced to 30.1% after the survey of patients in 8 years. By the way, we also discuss and investigate the results, the mechanism, and the cause which decreased the rate of recurrence in photodynamic treatment of bladder cancer.

Hematoporphyrin derivatives (HPD) argon laser phototherapy has been carried out since 1986 for 37 cases of superficial transitional cell bladder tumor. A modified high power interstitial (contact) irradiation of argon ion laser was employed to destroy the visible tumor and a cylindrical optical fiber was used for whole bladder mucosal irradiation to lessen recurrence. Follow up cystoscopic examination 1 - 3 years after treatment revealed complete remission of the growth in all the patients. Recurrence was found by cystoscopy in 9 cases (24.4%). The procedure was claimed to be a simple, safe, and effective new means for the management of superficial transitional cell tumors of the bladder. Satisfactory results have been achieved.

The computer diagnosis apparatus for human diseases is used to detect the curative effect of photodynamic therapy (PDT). It directly takes the electric signals from auricular acupuncture points of patients turns the signals into data and displays the data on the screen. Comparing the data with the critical point, it gives out the diagnosis of the condition of the disease. If the signals are detected many times in the period of the photodynamic therapy, the change of the condition and the effect will be perceived. This provides scientific data for doctors' clinical diagnoses. The apparatus, combining computer and laser technology with Chinese traditional auricular diagnosis, has many advantages: quickness, preciseness, no injury, no pain, and no side effect. It can also store and print out cases. It's an ideal detector in the field of auricular acupuncture point diagnosis.

Hematoporphyrin photodynamic therapy (HpD-PDT) was used to treat 50 patients (51 lesions) with skin cancers or precancerous lesions. The preliminary results were satisfactory, with 44 cases (45 lesions) obtaining excellent results, 4 cases good, 1 case fair, and 1 case poor. The effective rate was 98%, the significant remission rate 96%, and the complete remission rate 88.2%. Exposure to sunlight should be avoided after HpD injection, since it produces photosensitivity. A follow-up for 1 to 3 years confirmed that HpD-PDT is a good new adjuvant therapy for selected cases. It brings a hopeful future to the treatment of skin cancers.

This 60-case report deals with the application of photodynamic therapy in the treatment and diagnosis of cancer. The application of photodynamic therapy in the treatment and diagnosis of cancer is a development from the late seventies. Since March 1989, we have diagnosed and treated 60 cancer patients with this therapy. Our results show that the positive rate in diagnosis is 100 percent, the effective rate in treatment is 75 percent.

The dye laser pumped by copper vapor pulsed laser was used in the diagnosis and treatment of 110 cases of malignant tumors. The total effective rate was 83.6%. Photodynamic therapy in the diagnosis and treatment of cancers has been a new technology developed in recent years. We've used it to diagnose and treat 110 cases of cancers from Nov. 1989 to Aug. 1990. Here we report the results.

Sixty-nine patients with various malignant tumors were treated with different regimens of radiotherapy or chemotherapy combined with HpD. The immediate response showed that the over-all response rate was 94.2% and complete response rate was 60.9%. The present study suggests that HpD be used as a radiosensitizer with mild side effects but no drug resistance on repeated administrations. Special effects of HpD on radio-resistant tumors, such as malignant melanoma, were observed. It may render radiation effective in advanced or recurrent lesions. Mechanism of radiosensitization of HpD is discussed. Tentative ideas for further investigations are put forward.

Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T₁, 5 cases of T₂, and 35 cases of T₂ - T₃. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ₃ showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

A quantitative comparison of the photodynamic effect of pulsed (copper vapor-pumped dye laser), continuous-wave laser (He-Ne laser), and non-coherent red light (filtered from a halogen lamp) to the liver in normal mice has been carried out. The mice (each group containing 18 - 20 mice) received hematoporphyrin derivative in a dose of 10 mg/kg iv 24 hours prior to light irradiation. The mouse livers were directly irradiated with different red light in a dose of 5, 10, 25, 50, or 100 J/cm², respectively. Forty-eight hours later the mice were killed, and the depth of liver necrosis was measured using a computer image-analysis system. No necrosis was found in the control liver irradiated with 500 J/cm² alone. The depth of photodynamic necrosis showed a light dose-dependent response. The mean depth of necrosis of all groups were compared statistically. The Cu-dye laser showed the best effect while the non-coherent light showed the poorest. There were significant differences between non-coherent light and laser irradiated groups, but not between Cu-dye and He-Ne laser groups. The results indicate that among the examined light sources, the Cu-dye laser is most suitable to photodynamic therapy (PDT) of tumors. However, the halogen lamp with a special filter device may still be occasionally used as a light source in PDT if needed.

An optical phantom of tissue has been devised to simulate the optical properties of typical tissues for research in photodynamic therapy (PDT). The phantom consists of a scatterer (polystyrene-divinylbenzene microspheres) and an absorber (india ink) in distilled water. A set of relevant data for the microscopic optical properties and macroscopic optical parameter of the phantom was found. The results obtained approximate the optical properties of typical tissues. This optical phantom may duplicate the spatial variation of the radiant energy fluence of typical human tissues at 630 nm wavelength in PDT.

Beta-carotene 100 mg/kg per day or vitamin C 50 mg/kg per day was administered orally for two days and did not prevent mouse skin photosensitization caused by hematoporphyrin derivative (HpD). However, (beta) -carotene 100 mg/kg per day administered intramuscularly for two days prevented mouse skin reaction. Cimetidine and benadryl 10 mg/kg per day, P.O.X 2, effectively prevented mouse skin reaction. This suggests histamine may be involved in skin photoreaction induced by HpD.

Mouse hepatoma cells, mitochondria, and lysosomes of rat liver cells after incubation with hematoporphyrin derivative (HPD) were treated by ascorbate and exposed to light. The product of membrane lipid peroxidation -- malondialdehyde (MDA) -- was determined. The MDA level increased with the increase of ascorbate content (in a range of certain concentrations) and irradiation time. Thiourea, an inhibitor of hydroxyl free radical, showed an inhibiting effect to the production of MDA in the experimental groups. The MDA level decreased with the increase of thiourea concentration. Ear index, a parameter to evaluate photosensitive reaction of mouse skin by HPD plus light was determined. The value of ear index of mice treated with ascorbate was greater than that of mice without ascorbate treatment. Those results suggest that hydroxyl free radical produced by HPD and ascorbate after light irradiation could oxidize membrane lipids, and showed that ascorbate may enhance porphyrin photosensitization of tumor cells.

The mechanism of photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPC) studied with the human hepatocellular carcinoma cell line in culture is reported herein. Photofrin II (PII) was chosen as the control photosensitizer of AlSPC. Deuterium oxide (D₂O), an enhancer of singlet oxygen (¹O₂); 1,3-diphenylisobenzofuran (DPBF), a quencher of ¹O₂: glycerol, a quencher of OH radical (OH(DOT)); superoxide dismutase (SOD), a quencher of O₂^- radical (O₂^-(DOT)); diethyldithiocarbamate (DDC), an inhibitor of SOD and glutathione peroxidase; were introduced into both the processes of photodynamic inactivation of human liver cancer cells in culture with AlSPC (AlSPC-PDT) and with PII (PII-PDT). The results suggest that: ¹O₂ is dominantly involved in both PII-PDT and AlSPC-PDT; O₂^-(DOT) is involved in AlSPC-PDT in a lower degree than ¹O₂, while almost not involved in PII-PDT; OH(DOT) is involved in PII-PDT in a lower degree than ¹O₂, while almost not involved in AlSPC-PDT.

Using hepatocarcinoma transplanted rats, the present study made consecutive observation for the color change and indocyanine green (ICG) absorption peak of the normal liver and tumor tissues after intravenous injection of ICG. The normal liver tissue of the rat was found to turn violet-green soon after ICG injection and the optic density (OD) of ICG-characteristic spectral peak of the tissue homogenate reached its maximum value at 35 minutes post-injection, while neither color change nor OD value increase was noticed in the tissue of transplanted hepatocarcinoma, suggesting that there is a specific absorption of ICG by the normal liver tissue. Chemiluminescentoassay revealed inhibited luminal chemiluminescence by ICG, indicating the depression of singlet oxygen and reactive oxygen species (ROS) oxidation during HPD photosensitization by ICG. In PDT of the hepatocarcinoma, the irradiated area was examined under microscope and auto-microimage analysis system after ICG administration. For tumor-free tissue, the photosensitization induced necrotic area was found smaller in those with than those without ICG administration, whereas the tumor killing effect was almost the same of the two. It is suggested that ICG may offer selective protection for healthy hepatocytes without diminishing the destruction of tumor cells. The protection of healthy hepatocytes by ICG is thought to be in accordance with the amount of ICG in the cell and the distribution of light energy.

The immunophotosensitizer was prepared by conjugating hematoporphyrin (HP) with anti-CEA and anti-colonic cancer monoclonal antibody (McAb), respectively. In vitro, the anti-CEA McAb-HP conjugate showed cytotoxicity for human colonic cancer cell line SW1116 which was CEA positive, but no cytotoxicity for the CEA-negative Hep-2 cell line. The cytotoxicity of immunophotosensitizer was much higher than the McAb alone, the HP alone, or the mixture of McAb and HP. In vivo experiments, the nude mice bearing the xenografted human colonic cancer were used to test the activity of the anti-colonic cancer McAb-HP conjugate. The results demonstrated that the tumor necrotic areas of the conjugate-treated animals were notably larger than those of the free HP-treated animals. The specificity offered by the McAb permits increase of the aggregation of the drug at the tumor site. This property makes it possible to use a lower effective dosage of the drug, which minimizes undesired side effects. Further experiments are now in progress.

Can-sha photosensitizer (CPS) extracted from the silkworm excreta (a Chinese herb) was administered to tumor bearing mice by iv or the intragastrointestinal route in dosages of 50 mg/kg and 550 mg/kg, respectively. Six to ten hours later the tumorous site was irradiated with light. The results showed that the tumor inhibition rates were 69 - 98% by iv and 62 - 79% by intraduodenal (id) injection, but no photodynamic effect was found in the tumors of mice after administering CPD by p.o. ³H-TdR or ³-uR incorporation ability of the tumor cells pretreated with the drug and light was significantly inhibited.

Hypocrellin A (HC-A) isolated from Hypocrella Membrane Sacc, a derivative of 3,10-dihydroxy-4, 9-peryleneguinone, is a new effective photosensitizer. Treatment of the CESS cell with 20 (mu) g per ml of HC-A plus laser (532 nm) radiation led to the formation of DNA single strand break. The number of single strand breaks for cell membrane DNA was approximately 2.5 times that of nuclear DNA. Treatment of the CESS cell with HC-A plus laser radiation reduced the cell DNA binding capacity by 59%. It is shown that cell membrane DNA is also a target for HC-A photosensitization.

Gold-vapor laser glass type is a new laser for photodynamic therapy (PDT). Its chief characteristics are pulse type, 6000 - 7000 Hz of frequency, 627.8 nm in wavelength, 3 - 4 watts output, etc. By changing laser energy density, we noticed changes of necrosis depth and surface temperature. The results show that the depth of groups of 500, 1000, 1500, and 2000 Jol/cm² were 0.62 +/- 0.21, 0.72 +/- 0.05, 0.97 +/- 0.10, and 1.56 +/- 0.13 cm (p < 0.05), respectively. This study indicates that the pulse laser energy density should be larger than that of a continuant one in PDT, thus photodynamic effect may be improved in the clinic. The surface tumor temperature was changed during the treatment, reaching as high as 39.13 degree(s)C, 43.78 degree(s)C, 44.16 degree(s)C, and 43.5 degree(s)C in different groups. This paper also discusses the coordinated effects of hyperthermia and photodynamic therapy.

The ability of photosensitized generation of singlet oxygen by phthalocyanines has been evaluated using diphenylisobenzofuran as a chemical trap and arranged in the following decreasing order: ZnDSPC > ClGaTSPC > H₂TSPC > ClAlTSPC. The efficiency of photogeneration of superoxide anion radical has also been estimated using 5,5-dimethyl-1-pyrroline-1-oxide DMPO as a spin trap and identified by ESR. The ability of photochemical generation of O₂^- is arranged in the decreasing order: ClGaTSPC > ClAlTSPC > CuDSPC > ZnDSPC. The interaction of phthalocyanines with amino acids has been studied by laser flash photolysis. The results show that the excited states of phthalocyanines interact with tyrosine and tryptophan via electron transfer but not with cysteine. It is thus concluded that photo-oxidation of cysteine sensitized by phthalocyanines is mediated solely by Type II (O₂^- involving) mechanism while photo-oxidation of tyrosine and tryptophan proceeds via Type I (electron transfer) and Type II mechanism depending on the structure of the sensitizer and substrate as well as the environment.

Photocarcinorin (PsD-007), a new porphyrin preparation for tumor-photolocalization and photodynamic therapy, was prepared. It differs from the commonly used photosensitizer HpD both in chemical composition and spectral properties. PsD-007 is composed of 7 different porphyrins, structures of which were shown through chromatographic separation in combination with spectroscopic determinations and confirmed by comparative analyses with those of their corresponding synthetic authentic porphyrin samples. Three out of these porphyrins i.e., 3(or 8)-(1-methoxyethyl)-8(or 3)-(1-hydroxyethyl) deuteroporphyrin IX, (MHD)3, 8-di (1-methoxyethyl)-deuteroporphyrin IX (DMD) and 3(or 8)-(1-methoxyethyl)-8(or 3)-vinyl-deuteroporphyrin IX (MVD) were shown to be the major tumor-photobiological active components of this porphyrin preparation, based on the data obtained from the determinations of photosensitizing ability in a cell-free system, photoinactivation of human cancer cells in vitro and efficacy of photodynamic therapy for transplanted animal tumors of them.

In the present study, the effects of a newly developed photosensitizer chrolophyll derivative (CPD4) from Chinese Medicine Cansha (silkworm excrement) with pulsed copper vapor laser and pumped-dye laser (510, 578, 630, and 670 nm wavelength) on human rectal cancer cell line HR8348 was investigated. Hematoporphyrin derivative (YHPD) was used as a positive control. The relationship between CPD4 dose, the laser wavelength, and laser energy was explored. The MTT rapid colorimetric assay was used as a measuring indicator of photodynamic cytotoxicity and compared with ³H-thymidine incorporation assay and colony-forming assay. The photodynamic sensitivity of different cell lines was observed. The results showed that CPD4-induced HR8348 cells irradiated with pulsed copper vapor laser displayed a markedly photodynamic effect.

The antitumor effect of photodynamic treatment with chlorin e₆ was studied. A transplantable rat tumor (sarcoma M-1) was irradiated by krypton ion laser light after chlorin e₆ injection at different doses of photoradiation (22.5 - 180 J/cm²) and photosensitizer (1 - 10 mg/kg). The time interval between chlorin e₆ intravenous injection and photoradiation was varied from 15 min to 72 hours. Tumor growth inhibition coefficient (TGIC), tumor regression rate, and cure of animals were used as antitumor criteria of photodynamic treatment. It was found that the antitumor effect of photodynamic therapy was in direct relationship to the chlorin e₆ dose and light energy exposure value and in the inverse one to the time interval between photosensitizer injection and photoradiation.

Pathologic changes were observed in S₁₈₀ fibrosarcoma transplanted in white mice of Kunming line and in human hepatocellular carcinoma transplanted in balb/c nu/nu nude mice after photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPC). The experimental tumors in mice were chosen with diameters in the range of 0.5 - 0.8 cm. A dose of 10 mg/kg AlSPC was given (iv). The dose of light (600 - 750 nm) was 180 J/cm². Degeneration of tumor cells, microvascular hyperemia, stroma edema, and hemorrhage were found soon after PDT under the microscope and the hyperemia and hemorrhage in hepatocellular carcinoma seems more obvious than in S₁₈₀ sarcoma. Heave hyperemia and hemorrhage can not always be seen in the degenerative and necrotic area in S₁₈₀ sarcoma. With transmission electron microscopic technique, the most significant early changes are apparent degeneration of the mitochondria, slight dilation of rough endoplasmic reticula, a little increase of lysosmes (both in tumor cells and in endathelia), collagen fiber degeneration in the subendothelial zone of the capillary wall and in other connective collagen fibers, and slight edema in intercellular space and in the interstitial tissue surrounding capillaries immediately after completion of 30 min PDT. Additionally, the results were discussed in combination with our other study of histochemistry on seven kinds of tissue enzymes in hepatocellular carcinoma which shows the activities of these enzymes reduced to be inconsiderable from within 30 min to within 6 h after AlSPC-PDT, in which the activity of SDHase reduced most quickly. The pathologic study suggested the cellular membrane system, especially the mitochondria, was probably one of the main reaction targets of AlSPC-PDT though what is the most important primary target (the tumor cell's and endothelium's mitochondria or subendothelial zone, or some other structure) further study is required to answer.

Photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPC), i.e., AlSPC-PDT, in two murine tumor models is reported here. The encouraging therapy results were observed in S₁₈₀ fibrosarcoma transplanted in white mice of the Kunming line and in human hepatocellular carcinoma transplanted in balb/c nu/nu nude mice. The experimental tumors in the mice were chosen of those 0.5 - 0.8 cm in diameter and 0.4 - 0.7 cm in thickness. Photofrin II (PII) and Photosensitizing drug-007 (PSD-007), two kinds of porphyrin derivative dyes, were chosen as the contrast photosensitizers of AlSPC. A dose of 10 mg/kg AlSPC or PII or PSD-007 was given (iv). The dose of light (600 - 750 nm) was 180 J/cm². `Cure (short-term)' was defined as regression of neoplastic tissue to a non-palpable tumor within 14 days after PDT. `Cure (long-term)' was defined as absence of local tumor tissue and tumor metastasis on gross and microscopic examinations within 107 days after PDT. The curative results suggest that AlSPC may be a more effective sensitizer than both PII and PSD-007.

In view of explaining the results that AlSPC-PDT was more effective than HPD-PDT in destroying S₁₈₀ fibrosarcoma (diameter: 0.5 - 0.8 cm; thickness: 0.4 - 0.7 cm) transplanted in white mice, the depth of necrosis of S₁₈₀ sarcoma in mice in AlSPC-PDT was studied, compared with it in HPD-PDT. Two kinds of HPD were chosen as the control photosensitizers of AlSPC: Photofrin I (PI), and Photosensitizing drug-007 (PSD-007). The experimental tumors in mice were chosen with longitudinal diameters in the range of 0.8 - 1.0 cm and thickness in the range of 0.7 - 1.0 cm. A photosensitizer dose of 10 mg/kg was given (iv) for PI-PDT, PSD-007-PDT, and AlSPC-PDT. The dose of exposure light (600 - 750 nm) was 180 J/cm². The experimental mice were killed 48 h after PDT to get the tumor necrotic depth. The depth was 0.55 +/- 0.14 cm (0.30 - 0.85 cm) in the AlSPC-PDT group, 0.35 +/- 0.12 cm (0.20 - 0.55 cm) in the PI-PDT group, and 0.36 +/- 0.11 cm (0.20 - 0.50 cm) in the PSD-007-PDT group. These differences may be due to the differences of the dyes' light absorbance spectra. AlSPC's main absorbance peak is at 675 nm and HPD's is around 400 nm with a smaller peak at 630 nm. The penetration of 675 nm light through biologic tissue is deeper than that of 400 nm light and 630 nm light.

Intraperitoneal injection of hematoporphyrin derivative (50 mg/kg) was given to mice with S180 and M16-MB. Seventy-two hours after injection, the tumor was radiated by 510.6 nm wavelength copper vapor laser. Power density was 330 - 660 mw/cm². Energy density was 200 - 270 J/cm². After the irradiation, the volume and weight of the tumors were decreased significantly compared with that of the other four groups. Necrosis was seen in the center of the irradiated tumor by pathological examination. The depth of necrosis ranged from 5.5 - 8.8 mm with an average of about 7 mm. Swollen mitochondria, dilated rough endoplasmic reticulum, and broken plasma membrane could be seen in cancer cells by electrical microscope. Experimental results showed that copper vapor laser could be used as the light source of photodynamic therapy (PDT) for the treatment of superficial cancer. The killing effect and cause of cancer recurrence in PDT treatment of cancer is discussed.

The effect of sulfonation degree on aggregation and photophysical properties of metal phthalocyanines was studied. Absorption and fluorescence spectra showed that association was decreased with the increasing of the sulfonation degree in aqueous solution. Little change was observed for fluorescence quantum yields and lifetime; triplet-triplet absorption and triplet lifetime for phthalocyanines with different degrees of sulfonation. However, the measurement of absolute yields of singlet oxygen in DMSO showed that the degree of sulfonation has a dramatic influence on the ability of photochemical generation of singlet oxygen. Irradiation of oxygenated aqueous solutions (PH10) of tryptophan containing 10 (mu) M sulfonated zinc phthalocyanine and/or specific quenchers of the possible reactive intermediates suggested that photo-oxidation of amino acid was largely proceeded by Type-II mechanism.

The distribution, contents, and cellular uptake processes of various photosensitizers have been measured by scanning microspectrophotometry for single living cells of squamous epithelium carcinoma.

Through He-NE laser stimulation of acupuncture points, we treated and observed 50 cases of Temporomandibular Joint Dysfunction Syndrome (TMJDS). The results proved that this treatment was very effective for relieving the patient's pain. In cases which had structural disturbances and organic damage such as limitation of mouth-opening and joint clink, there was less improvement of symptoms and no relief for joint clink.

Forty to eighty percent of the patients with accessory pathways (APs) manifest themselves by tachyarrhythmias. Many of these patients needed either life-long medical therapy or surgery. In order to avoid the discomfort and expenses in surgical procedures, closed chest percutaneous catheter ablation of APs became a potentially desirable therapeutic approach. Many investigations indicated that ablation of right APs by transcatheter direct current (dc) shock could cause life-threatening arrhythmias, right coronary arterical (RCA) spasm, etc. With the development of transcatheter laser technique, it has been used in drug-incurable arrhythmias. The results show that laser ablation is much safer than surgery and electric shock therapy. The purpose of this study is to explore the effectiveness, advantages, and complications with transcatheter Nd:YAG laser and dc shock in the ablation of right atrioventricular accessory pathways in the atrium near the tricuspid annulus (TA) in 20 dogs.

The coronary lesions are usually diffuse, so bypass and PTCA are indicated in only a limited proportion of coronary patients. Revascularization with laser was studied in our laboratory. Fifteen dogs with mimic myocardial ischemia by multiple coronary artery ligation were divided into two groups, five acting as a control group. In 10, CO₂ laser was adopted in making a series of channels in the myocardium. We aimed to evaluate the effect of laser in revascularization, and to document long-term follow up. Our experiment demonstrated that laser-producing channels protect myocardium from ischemic events. Postoperative improvement of ventricular function and increased regional myocardial perfusion were observed. Microscopic and SEM examination at intervals of 3 days to 3 months showed the patency of channels and development of collateral circulation.

From May 1982 to December 1990, 50 patients with upper gastrointestinal cancer were treated by photodynamic therapy (PDT) in our hospital. The clinical effect was good, the results of treatment are reported.

In this paper, 30 cases of extracapsular cataract extractions with the assistance of an Nd:YAG laser are reported. Myosis phenomenon in laser operation is observed and its producing mechanism is discussed. Laser ophthalmology was the earliest field in laser application research, and pulse Nd:YAG laser ophthalmic instruments have been developed rapidly because of unique advantages in the anterior and posterior capsulotomy and trabecula shaping method.

An Nd:YAG Sapphire laser blade was used for performing hepatectomy and splenectomy in dogs. The results suggest that a laser blade provides a new way to reduce intraoperative bleeding and to minimize tissue damage. In recent years, there have been some reports on performing surgical procedures using a contact Nd:YAG Sapphire laser system. The current animal study was conducted in order to explore the capability of incision and excision of the laser tip, the damage to the tissue, and the recovery course.

The effect of He-Ne laser intermittent irradiation on the bone marrow cell suspension of donor mice is presented in this paper. The recipient mice, irradiated with 8.5 GY CO⁶⁰-(gamma) ray, were then infused, and they were killed different days (1, 3, 5, 7, 9, and 11 days post injection). Spleens were removed and fixed in Bouin's solution for 24 hours, and then the numbers of protruding splenic nodules visible on the surface of the spleens were counted. According to statistics, the number of the splenic nodules increased with laser exposure over the control group.

A comparative experimental study was performed in 105 Wistar rats for micro-arterial anastomosis between CO₂ laser welding and traditional hand suture. The advantages of laser welding of small arteries were: (1) It's easier, more accurate, and faster. (2) More rapid, smooth healing and less inflammatory reaction. (3) The diameter of anastomotic stoma increased corresponding with the growth of the animals. Compared with hand suture, the tensile strength of anastomotic stoma with laser welding was weaker during the early postoperative period, and there was a certain percentage of aneurysm formation at the stoma.

As research and the application of lasers by the various professional bodies continues growing, one question on this issue still remains unanswered: to what extent are the harmful effects of low power laser light detrimental to the human eye? This paper analyzes the result of permanent impairment to the eyes of those who have worked with laser for a long time; advances an argument that harmful effects, resulting from low power lasers, can be both accumulative and irreversible. This argument is supported and verified by clinical comparison. In view of the evidence, it is recommended that physical protections be provided with particular attention to those who are working with lasers and methods for adoption are also put forward by the researchers engaged in this paper.

Human platelet-rich plasma (PRP) was irradiated in vitro with a fiberoptic Nd:YAG laser-heated metal cap to study its effects on platelets. The energy of the laser was 5 and 10 watts with an irradiation time of 0, 3, 6, and 9 seconds and 14 watts with an irradiation time of 0, 3, 4, and 5 seconds, respectively. The irradiated PRPs were analyzed for platelet count, aggregation reaction, thromboxane (TX)B2 measurement and electron microscopy. Various degrees of decrease in platelet count were observed in all groups. Except the 5Wx3S group, the other groups showed an increase in the maximum aggregation rate of platelets, which corresponded to the enhancement of TXB2 formation. It was also demonstrated by a transmission electron microscopy in 10Wx3S, 10Wx6S, 10Wx9S, 14Wx3S, 14Wx4S, and 14Wx5S energy groups that alpha- and dense-particles in irradiated platelets became sparse in number or even disappeared, less electron density, irregularity in size and shape, and a tendency for these particles to cluster around platelet membranes and open canalicular systems, which dilated apparently. Furthermore, scanning electron microscopy depicted the appearance of short and thick pseudopods on the surfaces of some irradiated platelets and an increase in the axis rate in most of the irradiated platelets.

Since 1988, 30 pieces of gastric polyps (25 cases) and 184 pieces of colonic polyps (73 cases) were diagnosed by endoscopy and pathology and removed with laser treatment in our department. No serious complications happened during and after polypectomies. In this group, the polyps were destroyed and disappeared through tissue carbonization and vaporization by using the high heat efficiency of endoscopic YAG laser. Follow-up endoscopy after 3 - 4 weeks showed the complete disappearance of polyps and the normal growth of mucosa of the wounds.

Laser, being intensely bright, highly directional, monochromatic, and coherent, has a wide application in the future of bio-medical science. As a new therapy, laser in clinical practice is mainly used for certain curing effects through its heat and photochemical effects, respectively, obtained from its four properties acting on human organisms to produce certain desired changes. Laser therapy, according to its bio-chemical effects, can be roughly divided into three categories: laser vaporization, laser solidification, and laser stimulation. Clinical practice has proven that each category has its appropriate symptom in all kinds of diseases. Laser therapy is playing a unique part in clinical practice.

In order to find an objective criteria to determine ischemic intestinal necrosis and present the proof for intestinectomy by surgeons, the fluorescence spectrum on the normal and ischemic intestine, which were stimulated by N₂-laser, was obtained. The intestine ischemic model was established in dogs by ligaturing the blood vessel of mesentery. The fluorescence spectrum was painted by enlarging its signals and inputing them into a computer control system. There is significant difference between normal and pathological tissue: the longer the ischemic duration of the intestine, the more severe its pathological changes and the lower its fluorescence peak. After 6 - 8 hours of ischemic duration going on and complete intestinal necrosis occurred, its fluorescence peak decreased from normal 1.96 - 2.41 to pathological 1. It seems that the laser fluorescence is a simple, quick, accurate, and non-invasive method which can be used in determinations of the ischemic intestinal necrosis.

The treatment effects of 7 cases of choroid hemangioma are reported. Of them, 4 cases were men and 3 cases were women. Ages varied from 34 to 52 years. The mean age was 43 years. All of their eyesight was between 0.01 and 0.4. Six of the seven cases were solitary hemangioma, the other one was Sturge-Weber syndrome. After treatment photography, the color of the hemangioma body gradually got weak and the local presented pigmentation. The results of the fluorescein fundus angiography indicated that the hemangioma body reduced, then got atrophy and fibrosis. In five cases eyesight increased, and it didn't in the other two cases.

This paper reports that cellular immune function was observed when He-Ne laser was used to irradiate `zusanli' point in rats using various power, time, and periods. The indicator was a lymphocyte transformation test (LTT) by MTT colorimetric analysis. The best irradiating condition was determined, the effect and both virtues and defects of the laser were compared with those of electropuncture. The results show (1) LTT was enhanced in the group of laser irradiating point, but LTT was not enhanced in non-point (t' test, P < 0.01). (2) Lower power -- 2 mW or 5 mW of irradiating for 15 - 20 min, was better; 10 mW or 20 mW of irradiating for 10 - 15 min was suitable. Prolonged irradiating time did not enhance the immune function of the rats. On the contrary, immune function was inhibited. (3) A 7-day period of irradiating was best (once a day, 10 mW for 10 min). Enhanced LTT was not seen when irradiation days were added (SNK, P > 0.05). (4) Laser irradiation point and electropuncture were compared with vehicle control, LTT in the former two groups was enhanced significantly (ANOVA, P < 0.01), and laser irradiating point and electropuncture had the same effect (SNK, P > 0.05). The data suggest that laser irradiating point was able to enhance cell immunity and the enhancement of LTT had a point specific characteristic. The best condition of laser irradiating point was 2 mW for 15 - 20 min, and 10 mW or 20 mW for 10 - 15 min. The best period was 7-day irradiation. The results show laser irradiating the point may activate the main and collateral channels system, then modify the immune function of the body. Our observations provide experimental evidence for proper clinical application of laser irradiating points. The paper theoretically discusses and analyzes the experiment results in detail.

Eight-hundred-sixty cases of circumcision using CO₂ laser are reported. The age of patients ranged from 9 - 65 years, with a mean age of 23.8 years. The technique was simple and can be quickly accomplished by a single operator. After local anesthesia the glans penis was protected by a protector. Then, circumcision was performed with a CO₂ laser -- HeNe laser combined machine. There was an HeNe laser aiming system in this machine thus the surgeon had a three-dimensional visible indicator of the incision. The focusing CO₂ laser beam was used for cutting the prepuce during the operation. There was almost no operative bleeding. All the patients needed no antibiotic postoperatively. Complications were minimal and satisfactory results were achieved.

Forty-seven patients with tinea unguium and 110 tinea unguium, proven bacteriologically and pathologically, were treated with an Nd:YAG laser and Chinese herbal medicine, after which they were analyzed. All patients were adult men and women. The duration of illness varied from 1 to 10 years. The patients were treated with Nd:YAG laser wavelength 1.06 micrometers and the ending output power 500 w/cm². The diseased nail was removed by laser scanning or cauterization, charring, gasification and coagulation layer by layer until the nail matrix was exposed, and then it was bandaged with a small amount of Chinese herbal medicine. The cure rate is 80.0%. The tinea unguium infection rate of pars super finialis is very high in cities, accounting for more than 80% of the cases among the population. It influences patients' lives and finger appearance. However, removal of tinea unguium with Nd:YAG laser cauterization and coagulation is simple, painless, and does not require disinfection. Also, the reoccurrence rate is low. Treatment of tinea unguium is intractable. Oral administration of griseofulvin and ketoconazole are not completely satisfactory and hardly persist for a long-term treatment course. Moreover, long-term administration of these drugs might produce serious side effects such as renal injuries, leukopenia, psychosis, etc. Thus, we conclude from this data that Nd:YAG laser and Chinese herbal medicine are an effective treatment for hypertrophic scarand kiloid and valuable for further investigations.

The treatment of 65 patients with cholelithiasis by low power helium-neon laser irradiation on acu-points was studied. The results show that 51 of them started to discharge the gallstones within the duration of 6 to 15 laser irradiations, and 11 patients after more than 15 treatments. Two patients (3.1%) were fully cured, 42 (64.6%) markedly effective, 18 (27.7%) effective, and 3 (4.6%) failed. The total effective rate was 95.4%. By chemical analysis, the discharged gallstones were identified as calcium bilirubinate or mixed stones. Patients with stones smaller than 1 cm in diameter or stones made of calcium bilirubinate were more effectively treated than others. The He-Ne laser seems to be a useful treatment for some patients with cholelithiasis without surgical operation.

Here is a report on resecting a huge lipoma which was 4 X 5 cm² using an Nd:YAG laser through a small incision. The lipoma is a kind of benign tumor-poly lipomata usually appearing subcutaneously. Normally, the larger the lipoma is the longer the incision is and also the longer the cicatrix is. Hence, the Nd:YAG laser was used to incise a 0.5 cm long incision in the middle of the lipoma, then put the light fiber through the incision into the lipoma to resect the tissue of the lipoma step by step. Some of the tissue of the lipoma affected by the heat of the laser was turned into liquid. The liquidized adipose tissue may be eliminated through the incision by pressing around the position of the tumor, or sucked out by a ribbon gauss. The whole operation was done easily and simply. There was no need to suture and the recovery after operation was satisfactory. It is actually an efficient way to treat this kind of lipoma.

This paper introduces the potential harm of lasers to human beings. In order to ensure the health of the operator, the inside wall of the laser operating room needs a coating that can strongly absorb laser. The coating is composed of the laser absorbefacient, making membrane substance, additive and solvent, according to the proportion mixed. It can be prepared in all kinds of colors, brushing on the wall and clearing easily. According to need, it can be made to the protection coats of the single laser waveband or some other laser wavebands.

The key to the treatment of anal fistula lies in scavenging the infected anal gland thoroughly, which is the source of anal fistula infection. The fistula tract at the internal orifice of the anal fistula is cut 1 cm using laser with the infectious source completely degenerated and the wound gassified and scanned. The residual distal fistula softens and disappears upon the action of organic fibrinolysin.

Bartholin's cyst is a common disease of gynecology. It is cystic expansion of the gland tubes, which is caused by scar and infection. Forty years ago this disease was completely cut away by operation. In 1966, someone thought that cystostomy was a certain treatment method. Although there are many therapies used to treat this disease, e.g., incision drainage, excision, puncture, etc., they all have a better or worse side. In the past two years we used CO₂ laser to treat patients in our hospital. Comparing outpatients with inpatients, the writer thinks that inpatients treated with laser (CO₂) have less bleeding, less pain, faster recovery, and a higher success rate. This operation is done in the clinic and its both convenient and cheap. This method is one of the valuable methods which is worth spreading. From April 1989 to April 1991, 74 patients were treated with traditional operation and drug treatment. Another 38 patients were treated with the laser in the clinic. Clinical treatment results are contained here.

Chronic rhinitis is a common disease. The patients feel troubled by nose obstruction and discharge. One-hundred-fifty cases were treated by an He-Ne laser from 1982 to 1991. Entire recovery was achieved in 16 cases; improvement was seen in 52 cases in which symptoms and signs notably declined; 41 cases were helped; and inefficacy was seen in 40 cases. The total effect rate was 73.3 percent. To study the mechanism of the disease cured with an He-Ne laser illumination experiments were performed by taking temperature, examination of blood, change of the hemostreamgraph in the brain and attenuated bacteria.

This study was undertaken to compare, objectively, healing rates (in dogs) of wounds caused by CO₂ laser with those caused by a scalpel. The rates of contraction and epithelialization of standard wounds were determined with daily measurement of the wound area from the time of wounding until the wound had healed. Results demonstrate significant delays in both wound contraction (p equals 0.0001) and epithelialization (p equals 0.0001) for CO₂ laser-created wounds when compared to those seen in scalpel-created wounds. The appearance of the healed areas appeared comparable for both modalities.

This article is about 203 examples and 14 types of pathological illnesses in the nose, pharynx, and trachea. All these are effectively treated under fiber endoscope with YAG laser, except one example of adenocarcinoma in the nose and pharynx which has relapsed after three times of treatment with rays. The other 202 examples needed only one time of treatment with the rays. The results of the experiment in one to three years is satisfactory.

The writer has analyzed treatment of 299 cases of condylomatous acuminata. The best results were in 165 cases treated with carbon dioxide laser, cure rate was 98.18%. Cure rate with freezing was 62.1% or less, cure rate with 5-FU was 56.4%, cure rate with laser for only one application was 81.2%. For 1 - 6 months of follow up we did not see recurrence of the disease. The creative effect was very satisfying. Baggish thought laser cure rates in foreign countries were about 95% while the writer reports a laser cure rate of 98.18%. It is better than the foreign report.

This paper describes the effective result of carbon dioxide laser on type I and II internal hemorrhoids, mixed hemorrhoids, anal fissure or fistula, etc. At present, simple hemorrhoidectomy is less acceptable to patients for its excessive bleeding and severe pain during and after the operation. Therefore, the results of 71 anorectal cases of hemorrhoidectomy using carbon dioxide laser have been observed in our hospital. The rates of effective treatment and cure were 100% and 94.3%, respectively.

A three-layered model of Monte Carlo simulation for photon flux in the epidermal, dermal, and subcutaneous tissues of skin is presented to simulate laser Doppler velocimetry of blood flow assuming that the skin is illuminated by a collimated laser beam (630 nm).

The treatment of this disease with laser such as He-Ne laser, Nd:YAG laser, and CO₂ laser, etc., has been applied in our country, but application of the semiconductor laser therapy has received few reports. It has many advantages, such as ting volume, steady function, simple operation (the patient can operate it by himself), no side effects, remarkable results, and it is very convenient. So the semiconductor laser can be used to treat the chronic pharyngitis with irradiation on acupunctural points. One-hundred-twenty chronic pharyngitis patients were divided into 2 groups, a laser group and a medicine group, 60 cases for each. The effective rate is 91.6% and 66.6%, respectively. Obviously the treatment of chronic pharyngitis with semiconductor laser is valuable for widespread use. The principle of the laser therapy is discussed in the last part of this paper.

A treatment for eleven eyes on posterior capsular opacifications after artificial intraocular lens (IOL) implantations with an Nd:YAG laser is reported, and a secure range of laser energy under which IOLs are not injured in the operations is given in this paper.

This paper presents the results of 280 cases concerning the use of laser irradiation at Ashih Point and Hoku Point for anesthesia in drawing a tooth. It shows that the percentage of excellent and good results is 78.8% for permanent teeth and 93.3% for milk teeth. This method has been proven to be practical, effective, and easy to master in clinical practice. The limitation of this method is also discussed in this paper.

The results of treating hemorrhoids in 700 cases with a YAG laser knife is reported. Since 1988, the author introduced the YAG laser into the treatment of various kinds of hemorrhoids. The satisfactory results were achieved with 100% cure rate. Some related problems also are discussed in this paper. Hemorrhoid is a kind of common disease. It usually appears in the superior or inferior rectal venous plexus covered with mucosa. The hemorrhoids are divided into internal, external, and mixed types according to their location and origination. The internal hemorrhoid is superior to the dentate line and caused by varicosity of superior rectal venous plexus covered with mucosa, the most common presentation is a bleeding and prolapse mass out of the anus. The external hemorrhoid arises from varicosity of inferior rectal venous plexus, the most important clinical finding is a painful mass covered with skin of the anal canal. The characteristics of mixed type are the combination of the two types as mentioned above.

A new technique of treating hircus with YAG laser is described in this paper. One-hundred-fifty patients have been treated and 100% cure rate has been achieved with few complications. Some related problems are discussed. Hircus as a common disease can be treated by many surgical procedures, but none of them can be considered as a perfect one. Some of them may cause pain during operation and other problems postoperatively. Since 1988, 150 patients with hirci have been treated with YAG laser and satisfactory results have been obtained.

The method of treating anal fistula with YAG laser technique is described in this essay. One-hundred-twenty patients have been treated successfully with this method and no recurrence was found in our series. Anal fistula is a common disorder in the anus and rectum. The tunnel of fistula zigzags around the external or internal sphincters. If the drainage is poor, and the skin around the external opening grows rapidly, false healing may occur and cause recurrent abscess. In this case, a fistula can not be cured except by operation.

By using laser radiation on rats which had body surface malignant tumors, we observed the pathological changes in these tests and took further steps to research the influence of photodynamic effects on remaining cancer cells. We observed that the PDT treatment provided maximum security in these malignant tumor treatments. It enhanced the killing ability on the tumor tissues and retained the normal tissues in the greatest limitation. But it may be dangerous to kill the remaining cancer cells in peri-carcinoma tissue when using Nd:YAG laser for continuing illumination. Our research confirms that the effects of combined use of the HPD and continued illumination are better.

In recent years, there has been great development in the area of applying laser technique in the field of otorhinolaryngology. The application of Nd;YAG operating apparatus, the fiber that carries light, has opened up a new dimension of treating some diseases of the ear, nose, and throat. YAG laser is especially suitable for use in deep canal or cavity of the ear, nose, and throat because of the following features: good heat conductivity, easy power adjustment, highly concentrated energy, strong penetrating ability, good hemostasis, excellent coagulation and vaporization. YAG laser can be combined with the use of rhinolaryngeal fiberscope because the fiber optics are flexible due to their very small fibers. We treated 501 cases of nose and throat diseases using YAG laser from 1988 - 1990, and the results were satisfactory. The applicance of laser in rhinolaryngology is discussed.

Based on laser irradiation experiments on isolated lung specimens of animals done in 1989, 8 patients with central type lung cancer were treated with Nd:YAG laser irradiation via fiberoptic bronchoscope from January 1990 to August 1991 in our hospital. The patients recruited were all diagnosed by fiberoptic bronchoscopy and histology as having central type bronchopulmonary cancer without distal metastasis. All patients were male with a mean age of 64 (range 57 - 72). Of 8 patients, 4 had squamous cell carcinoma, 3 adenocarcinoma, and 1 undifferentiated small cell carcinoma, all being stage TUM 3. After laser treatment, 6 cases had a result of significant response and 2 had minor response. Among 6 cases of atelectasis, 4 were completely cured or partially improved and 4 recovered from their hemoptysis. The subjective symptoms in all cases remitted. A combined chemotherapy was carried out accompanying laser therapy for all, 6 of whom had a shrink of focus over 25%. Six cases were re-examined with fiberoptic bronchoscopy, showing a distinct reduction of the tumor. Four cases expectorated black charring tissues and residual tumorous tissues persistently as an outcome. Two typical cases are reported, the characteristics, indications, techniques, and side effects of laser therapy are analyzed and factors affecting efficacy discussed, indicating that the technique has such advantages as easy operation, accurate orientation, and safe outcome. The procedure is really an effective one for treating central type lung cancer in intermediate or late stage.

This paper reports the results of non-operative therapy for cholelithiasis in 105 cases using He-Ne laser lithotripsy and a high fat diet, as well as Chinese and Western medicine. There were 32 male and 73 female patients ages 11 - 67 years (with an average of 41.2 years). All cases were confirmed by either B mode sonography or cholangiography. This paper presents the technique of treatment, its indications, contraindications, and therapeutic results. The results reveal a cure rate of 20% (21/105), satisfactory in 72.4% (76/105), and failed in 7.6% (8/105). Successful passage of gallstones was found in 92.4% and 52 samples of gallstones were examined qualitatively. The results show that He-Ne laser irradiation in the treatment of cholelithiasis is associated with neither pain, side-effect, nor cross infection, and is readily accepted by the patients.

This study investigates the effectiveness of Nd:YAG laser irradiation in treating dentin hypersensitiveness. Among 58 patients, Nd:YAG laser was used in 241 teeth, Naf was applied to the other 130 teeth. The immediate effectiveness and effectiveness 3 months after the treatment was evaluated. Of the treated group pain disappeared immediately after the treatment in 211 teeth (87.6%), while in the control group pain disappeared immediately in 98 teeth (75.4%, p < 0.05). Three months after the treatment, 204 teeth recovered completely in the treatment group, while in the control group only 59 teeth were cured (p < 0.01). This study suggests that using Nd:YAG laser in treating dentin hypersensitiveness is fairly effective.

For most of the patients with chronic hepatitis B the immunologic function is deficient. Immunopotentiation and immunoregulation can be used as effective treatments. Laser irradiation can potentiate the cellular immune function of the human body and has good effects on improving clinical symptoms, cutting short the process of diseases, and promoting HBsAg negative change. Thereby we have a randomized opportunity to study the effect of He-Ne laser acupoint irradiation on serological HBV markers (HBVM) in chronic hepatitis B (CHB).

The incessant development of laser medical technology has created the higher requirement that a laser diagnostic and cure instrument be applied comprehensively into clinical medicine. That is, it can be used to diagnose tumors in clinical medicine, and especially that it can be adapted to multifold application of medical items in clinical medicine. With this objective, we designed and successfully manufactured the tri-wavelength laser diagnostic and cure instrument (red color light 625 nm, orange color light 570 nm, green color light 532 nm). It actually is a new development of laser pumping source to diagnose and cure cancer. We synthesized the diagnostic and cure application circumstances of HPD-PDT in domestic clinical medicine and manufactured this tri-wavelength laser diagnostic and cure instrument. We use YAG frequency multiplied laser in place of argon laser, which is the cure light (power adjustable) as well as the diagnostic light. Also, we produced a pump of dye laser which has some definite merits.

This paper describes 120 cases with benign lesions of the vocal cord, such as the polyp and the nodule, treated by laser irradiation and application of Nd:YAG laser and optical fiber carried out through fiber laryngoscope under surface anaesthesia. One-hundred-eleven of the cases were cured, 9 improved, and 0 failed. This method is superior to other methods and has the following features: accuracy, rapidity, non-bleeding, painlessness, easy operation, rare complication, and good effect.

Nonspecific edema is a syndrome which is caused by a metabolism disorder of sodium and water. The people who suffer with this are mostly women about 25 - 50 years old. When it happens periodic edema, abdominal distension acratia, and obesity accompany the disease. Through several means of examination, no organic disease was found in the heart, liver, or kidney. Now 16 edema cases have been irradiated with laser and the result is satisfactory. The results are reported in this paper.

Despite extensive research into the biology of tendon healing, predictably restoring normal function to a digit after a flexor tendon laceration remains one of the most difficult problems facing the hand surgeon. The challenge of simultaneously achieving tendon healing while minimizing the peritendinous scar formation, which limits tendon gliding, has captured the attention of investigators for many years. It has been said that low-power density helium-neon laser radiation had effects on anti-inflammation, detumescence, progressive wound healing, and reducing intestinal adhesions. This experimental study aims at whether helium-neon laser can reduce injured tendon adhesions and improve functional recovery of the injured tendon. Fifty white Leghorn hens were used. Ten were randomly assigned as a normal control group, the other forty were used in the operation. After anesthetizing them with Amytal, a half of the profundus tendons of the second and third foretoes on both sides of the feet were cut. Postoperatively, the hens moved freely in the cages. One side of the toes operated on were randomly chosen as a treatment group, the other side served as an untreated control group. The injured tendon toes in the treatment group were irradiated for twenty minutes daily with a fiber light needle of helium-neon laser therapeutic apparatus (wavelength, 6328 angstroms) at a constant power density of 12.74 mW/cm², the first exposure taking place 24 hours after the operation. The longest course of treatment was 3 weeks. The control group was not irradiated. At 3 days, 1, 2, 3, and 5 weeks after surgery, 8 hens were sacrificed and their tendons were examined. The experimental results: (1) active, passive flexion and tendon gliding functional recovery were significantly better in the treatment group (p < 0.01); (2) width and thickness of the tendon at the cut site were significantly smaller in the treatment group (p < 0.01); (3) degrees of tendon adhesions were significantly lighter in the treatment group (p < 0.05). The experimental results demonstrate helium-neon laser radiation had significant effects on anti-inflammation, detumescence, progressive hematoma absorbing, inhibiting the tendon extrinsic healing, reducing tendon adhesions, improving the tendon intrinsic healing, i.e., stimulating epitenon and endotenon cells proliferation and migrating into the gap, stimulating collagen synthesis in the tendon gap, and enhancing the late remodeling of fibrous peritendonous adhesion.

This article emphasizes the treatment of endometriosis by using laser acupuncture and moxibustion which belongs to Shi Zhen. The major pathophysiology is that the circulation of the Qi and blood is obstructed. The obstruction of Qi leads to a block of blood and poor circulation which causes pain. The treatment should be introduced mainly by adjusting Qi and blood. We used an He-Ne low level laser instrument. Its export function is >= 20 mw, wavelength 6328 angstroms with a single-red light. By using a double tube fiber bundle it strikes directly on Liv. 3, Ren. 6, SP. 8. Each of the three points needs to be struck for five to ten minutes once a day. One therapy phase requires seven applications continually. This treatment results in cleaning the liver, adjusting the oxygen, and disencumbering the piles and the pain. When it makes the circulation of Qi free, the blood is normally transported and the pain disappears. After one or two phases of therapy, clinical re-examination indicated the disappearance of scleromata in the uterus. Five patients treated and continually re-checked recovered. Finally, their menses turned normal and clinical symptoms vanished within six months.

Cases of various kinds of warts, nevi, papillomas, skin angiomas, ephilises, skin vegetation, scars and brandy noses were vaporized and solidified with a 2.5 - 8 W low power CO₂ laser with an overall satisfaction rate up to 99.8% and the satisfaction rate for one time 92%.

We announce with satisfaction that combined treatment on 70 inpatients who suffered esophageal cancer in its middle or late course is perfectly successful. The combined methods include phototherapy, microwave therapy, and anticarcinogen local injection. The results are as follows: CR 3 cases, holds 4.3% of the total inpatients; PR 36 cases, 51.4%; MR 24 cases, 34.3%; NR 7 cases, 10%; the total effective rate 90%. Splendid results of treatment on enlarging the canal, improving dysphagia, and releasing obstruction have been obtained. The dysphagic grade increased from 66 to 148, the grade of esophagostenosis from 64 to 147, and the obstruction releasing rate is 69 out of 70 (that is 98.6%). The histological observation after treatment shows that 59/62 inpatients being reported as having cancer cells appear to have retrogression accompanied with a few or large quantities of necrotic cancer cells, and 3 inpatients were changed to negative reaction. No obvious poisoning or side effects arose. The combined treatment is more advantageous on those of old age or the physically weak and those who cannot stand for an operation, radiotherapy, or normal chemotherapy.

We treated 102 cases of polyps of the nasal cavity and nasal sinuses with Nd:YAG laser surgery or routine surgical removal between January 1987 and August 1988. During a follow up period of 18 - 36 months, the postoperative recurrent rates were 40.6% (24/54) and 66.6% (32/48), respectively, for the laser surgery group and the routine surgical removal group. Laser therapy of nasal polyps has the advantage of less bleeding, no postoperative packing of the nose needed, and lower postoperative recurrence rates. It seems laser surgery may be better than surgical removal alone in the treatment of nasal polyps.

Laser acupuncture -- a woundless therapy proven by clinical application features quick-action, painlessness, and safety. Thus it is well received by broad masses of medical workers and patients.

The application of laser technique is an extremely important subject in the medical field in this century. It is used more and more extensively in every respect, such as basic medial research, clinical diagnosis, treatment, etc. It shows good effects and inestimable prospects. It demonstrates its superiority, especially in the dermopathic therapy and cosmetic respect. We have achieved good effects by treating 500 dermopathic cases with laser therapeutic equipment for many years. We observed partial patients' microcirculation of the nail fold before and after the treatment for further evaluating the effect and mechanism of laser.

We made the experiment of sterilization by using neodymium yttrium aluminum garnet (Nd:YAG) laser (wavelength 1.06 micrometers ) to penetrate vas deferens in 30 male goats. The results of the experiment show that among the 50 vas deferens, there were 29 occurrences of seminal cysts (58%), but not any occurrences of hematoma. Both low-power, long-time (3 - 6 w, 20 - 40 s) and high-power, short-time (8 - 20 w, 5 - 20 s) penetrations were effective to occlude the vas deferens.

Sixty-six cases of hemangioma were treated with CO₂ laser alone (22 cases as a control group), or CO₂ laser supplemented with He-Ne laser (44 cases of the treated group). Optimum power dosage was first sought on normal volunteers. Arteriolar vasculature and lymphatics were blocked 3 - 5 times with procaine hydrochloride (5:1) to minimize local blood congestion. Results show that the healing rate of the treated group was significantly higher than that of the control group (X³ equals 3.92, P < 0.05). Eleven cases (50%) were complicated with exudation in the control as compared with 3 cases (6.8%) in the treated group (P < 0.01). Of the 18 cases completely cured in the control group, the number of treatments averaged at 11.4 times, while of the 39 cases completely cured in the treated group, the average number of treatments was 5.9 times, which is also statistically significant (P < 0.01). It is considered that CO₂ laser supplemented with He-Ne laser is superior than CO₂ laser alone for the treatment of hemangioma. Furthermore, it is also proposed that the supplement of copper and Chinese herbal medicines may prevent the incidence of recurrence. Laser was used for the treatment of hemangioma in our country during the 1980s. In foreign literature, there were several reports using Nd:YAG and copper vapor laser for the treatment of agniomasimplex and nevus flammeus. Ar⁺ laser agglomeration was commonly used for the treatment of angioma conjunctive in our country, but the use of CO₂ laser for the treatment of angioma epiderma is not well documented. We wish to report the use of CO₂ laser supplemented with He-Ne laser for the treatment of hemangioma in our hospital from April 1988 to December 1989.

In the basic research of laser surgery in our laboratory, a fresh, isolated canine liver irradiated by Nd:YAG laser was histologically observed. The results are presented.

A pulsed laser acupuncture was used to irradiate mice and the changes of blood velocity and flow. The diameter and section area of blood vessel in the region of the mouse legs after irradiation were observed. It was found that locally irradiating mice by YAG laser causes expansion of micro-circulation blood vessels and increase of blood flow, thereby adjusting micro-circulation function. The changes of the local skin temperature and weight of the mice after irradiation were also observed. The results are described.

Seventy-six patients were treated by low power He-Ne laser irradiation on Yangbai, Sibai, and other related acupoints. The other 77 cases were treated by Galvan-acupuncture with infrared radiation on the same acupoints. There was little difference between the therapeutic effects of these two groups (P > 0.05). However, the laser group had a much shorter treatment time than the other group. According to the theory of traditional Chinese medicine, circumferential facial paralysis is caused by exposure to cold which blocks the channel of vital energy resulting in the damage of bodily function. Acupuncture and moxibustion on certain acupoints can warm up the channels and remove the stasis allowing vital energy to pass through their passages to regulate bodily functions. Laser can do the same effectively with much less time. The laser therapy also features painlessness, safeness, and is free of bacteria. Circumferential facial paralysis is a common disease, which is clinically treated by acupuncture with reliable results. However, acupuncture is not fit for children who are not cooperative and those patients who are afraid of the pain accompanied with acupuncture. So we applied low power laser irradiation in the treatment of circumferential facial paralysis starting in 1985. The results were favorable. And the treatment time was shortened. The treatment procedures are reported.

GaAs semiconductor laser was used to treat trigeminal neuralgia with an effective rate of 91.1%, and no side effects were found in 67 cases. Changes in and the recovery of the trigeminal nerve cell were studied with light and electromicroscope. Discussed in this article are the time length and quantity of laser treatment with low power. Experimental study and clinical application of the GaAs semiconductor laser have been carried out in our department since 1987. One-hundred-fifteen patients with various diseases in the maxillofacial region (including 67 cases of trigeminal neuralgia) have been treated with satisfactory effects and without any side-effects. The wavelength of the laser is 904 mu, the largest pulse length is 200 mu, and the average power is 2000 HZ.

This article reports a satisfactory result through the observation of 42 cases of soft tissue inflammation treated by nitrogen molecular laser including 22 cases that failed under treatment of antibiotic and ultraviolet ray. Of the 42 cases reviewed, 34 patients recovered. The average of recovery days was 13.8 days; 8 patients made obvious progress in recovering. Compared with the therapeutic results of ultraviolet ray, nitrogen molecular laser could get the same results with ultraviolet ray in an acute stage of inflammation, and it could shorten the course of disease and raise the cure rate for chronic soft tissue inflammation and delay in wound healing. The following is a brief introduction of the comparison between nitrogen molecular laser and the antibiotic and ultraviolet ray.

The damaged areas in the cerebral tissue exposed to CO₂ laser irradiation in experimental animals and human cerebral tumors were investigated with light and electron-microscopy (LM & EM). After CO₂ laser irradiation, a damaged area composed of a charred zone, a coagulation zone, and an edematous zone was observed under LM. However, at the ultrastructural level another zone 60 - 100 micrometers in width surrounding the edematous zone was found. Mitochondria swelling, dilatation of rough endoplasmic reticuli, and degeneration of synapses appeared in that zone which we named `periedema zone.'

By using He-Ne laser treatment, 84.7 - 91.1% of patients with menorrhagia, a common symptom of multiple gynecological diseases, are treated effectively. After laser irradiation, the amount of vaginal bleeding was reduced 47.1% on average. It has been proven that low-energy laser is an effective non-traumatic, painless, and easily acceptable new physical method in patients with menorrhagia. To study the mechanisms of efficiency, the quantitative determination of PGE₂, PGF_2(alpha ), 6-Keto-PGF_1(alpha ), TXB₂ in endometrium and blood flow before and after treatment were carried out. The results suggest that the effectiveness may be due to the recovery regulation of local uterine PGS level.