Lasers in surgery and medicine reviewers. November 1, 1992 through October 31, 1993

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active dye employed in photodynamic therapy (PDT). CASPc is a potent generator of singlet oxygen when irradiated with 675 nm light and is also capable of fluorescence, allowing visualization of the dye in tissues. We devised an angiography system using CASPc fluorescence to determine its localization in experimental choroidal neovascularization in monkeys and then investigated the ability of CASPc to produce photochemical closure of neovascularization upon irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc localized angio-graphically in areas of neovascularization for at least 24 hours. Irradiation with 675 nm laser light 5–30 minutes after CASPc injection produced complete closure of choroidal neovascularization with minimal damage to overlying retina. We conclude that CASPc localizes in neovascular choroidal vessels and that CASPc photodynamic therapy can produce closure of these choroidal vessels. © 1994 Wiley-Liss, Inc.     

Scanning laser system for photodynamic therapy of choroidal neovascularization

BACKGROUND AND OBJECTIVES: In order to improve selectivity of photodynamic therapy (PDT) to choroidal neovascularization (CNV) associated with age-related macular degeneration, a laser scanning technique was applied to perform focal laser irradiation to the retina, and the occlusion effects of a new device to the choriocapillaris were evaluated in primate eyes. STUDY DESIGN/MATERIALS AND METHODS: The device contains lasers for fundus observation of 785 nm and for PDT of 670 nm, matching the absorption peak of a photosensitizer, ATX-S10(Na). The laser irradiated the shape on the retina specified before treatment and shut off automatically when the predetermined treatment was achieved. The occlusion of the choriocapillaris after PDT was documented by fluorescein and indocyanine green angiography and histology. RESULTS: The area designated for PDT was easily drawn on the touch-screen monitor, and occlusion of the choriocapillaris was achieved precisely in the area pre-selected for treatment with 5 J/cm(2) or more of radiance following administration of 8 mg/kg ATX-S10(Na). CONCLUSIONS: This device is useful for irradiating CNV of any shape, sparing the surrounding retina. Since our previous studies suggested that selective occlusion of CNV would decrease not only the functional disturbance caused by PDT, but also the recurrence of CNV, the present device may allow more effective PDT than the slit-lamp system presently used.     

A comparison of gold-vapour and dye lasers for photodynamic therapy

This paper compares the relative merits of the continuous wave argon-pumped dye laser and the pulsed gold-vapour laser as used clinically for photodynamic therapy. At comparable power and energy outputs, the biological effect of the two appears to be the same. However, for 1 W output (a suitable level for clinical use), the gold laser is simpler and easier to install and run, although it requires a larger diameter fibre for light delivery (0.6 mm v. 0.2 mm). The wavelength of the dye laser is tunable, whereas that of the gold is not, although the gold laser can be easily converted to a copper-vapour laser which can pump a tunable dye laser.     

Immediate changes in subcellular structures of transplanted tumors following photodynamic and laser hyperthermic therapy

Background and Objective: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. Study Design/Materials and Methods: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. Results: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. Conclusion: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH.     

Laser light application and light monitoring for photodynamic therapy in hollow organs

Photodynamic therapy (PDT) of tumours in hollow organs requires light application devices which enable homogeneous illumination of the tissue surface in hollow organs. This paper presents two laser light application systems generating a homogeneous light distribution and one monitoring unit which detects variations in the applied laser light intensity during treatment. A cylindrical light diffuser has been developed for PDT of cylindrical organs (e.g. bronchus, oesophagus). This system guarantees a defined homogeneity of the laser light intensity. An exact positioning to a defined treatment area is possible. Adjacent tissue is prevented from laser light irradiation. A special lens system has been developed for the irradiation of flat surfaces (e.g. skin, carina, organ wall of the large bowel and the stomach). The illumination area is defined by the distance to the tissue and the large aperture. The size of the system allows for it to pass through the biopsy channel of conventional endoscopes. A monitoring device recently developed helps to detects of the fibre, changes in the medium around the fibre tip, and variations of the laser output power during laser treatment. All devices serve for evaluating an accurate light dosimetry in clinical PDT.     

ALA光动力疗法治疗皮肤鳞状细胞癌的临床研究

目的:观察5-氨基酮戊酸光动力疗法(ALA-PDT)治疗皮肤鳞状细胞癌的临床疗效和复发率.方法:对30例经组织病理学确诊的皮肤鳞状细胞癌进行了4～11次ALA-PDT治疗,并与经手术治疗的30例患者进行复发率的比较.结果:治疗组29例患者获完全缓解,临床治愈.经6～12月随访后,4例复发;对照组5例复发,统计学处理无显著性差异(P＞0.05).但光动力组美容效果满意.结论:对皮肤鳞状细胞癌尤其老年患者,ALA-PDT疗法损伤小、美容效果好,复发率与手术方法相当(P＞0.05).     

Evaluation of photodynamic therapy in gastric cancer

Twenty-eight patients with gastric cancer were treated by photodynamic therapy. Haematoporphyrin derivative was used as a photosensitizer and an argon dye laser as a light source. Histologically, all tumours were adenocarcinomas. On the basis of endoscopy, 17 cases were categorized as early-stage cancer and were classified as type IIc (10 lesions), Ha (three lesions), combined type IIc and type III (three lesions) and type I (two lesions). In 11 patients with advanced-stage cancer, endoscopy showed one case of Borrmann I, three of Borrmann II, six of Borrmann III and a single case of Borrmann IV. In the 17 patients with early-stage cancers (18 lesions), complete remission was obtained in 10 patients (11 lesions). Of 13 resected cancers complete remission was confirmed in six lesions on the basis of detailed histological examination of resected specimens. In the advanced stage tumours all 11 patients showed incomplete remissions. It is considered that an incomplete response in the early-stage cancers is due to insufficient light dosage because of the wide area of tumour, because the site of the lesion is anatomically difficult to photoradiate and because the invasion extends to the muscular layer and serosa.     

δ氨基酮戊酸光动力法治疗颜面部原发性皮肤癌

目的 探讨δ氨基酮戊酸光动力学疗法(δ-aminolae vulinic acid-photodynamic thera-PY,ALA-PDT)治疗颜面部原发性皮肤癌的疗效.方法 对14例鳞状细胞癌(squamous cell carcino-ma,SCC)、38例基底细胞癌(basal cell carcinoma,BCC)、5例Bowen病患者进行ALA-PDT治疗,依据肿瘤部位及形态大小,每位患者分别接受治疗4～8次.结果 57例患者接受治疗后,分别有10例(71.4%)SCC、34例(89.5%)BCC及5例(100%)Bowen病患者获得治愈,其余患者病情皆示显效.治疗结束后,肿瘤周边正常组织基本得以保留,无瘢痕形成.末次治疗结束6个月时,上述SCC、BCC及Bowen病痊愈患者分别有1例(10.0%)、4例(11.8%)及0例(0%)复发.结论 ALA-PDT适用于颜面部位的局限性、原发性皮肤癌的治疗,是一种疗效好、副作用少且对容貌损害较轻的新疗法.     

光动力疗法联合手术治疗面部皮肤肿瘤的临床观察

目的：观察5-氨基酮戊酸光动力疗法（ALA—PDT）联合手术治疗面部皮肤肿瘤的临床疗效。方法：对16例老年面部基底细胞癌、鳞状细胞癌、Bowen病分别先接受ALA—PDT后行手术治疗或经手术治疗后再进行PDT。结果：无论先接受ALA-PDT后行手术治疗还是手术治疗后再进行PDT的面部基底细胞癌（5／16）、鳞状细胞癌（10／16）、Bowen病（1／16）均获得满意效果。结论：对老年面部皮肤恶性肿瘤,ALA-PDT联合手术治疗是一种损伤小、患者可选择接受的方法之一。     

In vitro and in vivo effects of photodynamic therapy on murine malignant melanoma

Background: The role of photodynamic therapy (PDT) in the treatment of malignant melanoma is not well defined, nor is it known whether the dark melanoma cells absorb the light used in PDT. Methods: In vitro studies: 2×10⁵ B16 murine melanoma cells were incubated with aluminum phthalocyanine (AlpcS₄, 2.5 mg/kg) and were then subjected to photoradiation (50, 100 or 200 J/cm²). Viability was then assessed.In vivo studies: Histology: C57/B1 mice received 2×10⁵ B16 cells subcutaneously and were randomized into study (PDT) and three control groups. AlpcS₄ 2.5 mg/kg was injected intraperitoneally and the mice were exposed to light (100 J/cm²). After 24 hours they were sacrificed and underwent autopsies. Survival: 40 mice were randomized into PDT (40 J/cm²) and control groups and were monitored for 50 days. Tumor growth: 40 mice were randomized into one control and three treatment groups (PDT on day 3, 6, or 12 after injection with B16 cells), and were monitored for 50 days. Temperature: Tumor temperatures before and at the end of PDT were recorded. Results: In vitro studies: PDT caused a decrease in cell viability to 15.5±0.7%, 11.5±2.1%, and 1.5±0.7% (at 50, 100, and 200 J/cm², respectively;P<.001). A significant reduction in thymidine incorporation was noted at all energy levels.In vivo studies: Histology: PDT caused massive tumor necrosis. Survival: PDT prolonged the survival of mice (41±13.4 days) compared to controls (15.8±3.8 days,P<.001). Tumor growth: 31 days after injection with B16 cells, the tumor size was 2.6±0.3 cm in the control group and 1.6±0.2, 0.9±0.3, and 1.0±0.4 cm in the PDT groups (days 3, 6 and 12, respectively;P<.01). Temperature: PDT increased skin temperature to 42.8°C±1.3°C, 45.3°C±3.5°C, and 51.7°C±2.7°C at 40, 60, and 100 J/cm², respectively (P<.01). Conclusions: Photodynamic therapy was found to have significant effects in experimental melanoma in mice. The role of PDT in human melanoma remains to be studied.Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Phthalocyanine mediated photodynamic thrombosis of experimental corneal neovascularization: Effect of phthalocyanine dose and irradiation onset time on vascular occlusion rate

The aim of this study was to evaluate the possible influence of phthalocyanine dose and of time interval between phthalocyanine injection and irradiation commencement on the rate of experimental corneal neovascularization photodynamic thrombosis in albino rabbits. New corneal vessels were irradiated with a diode laser (670 nm, 2 mW) after the intravenous injection of chloroaluminum sulfonated phthalocyanine. Different animals were irradiated either 5 min after the injection of different phthalocyanine doses (3, 6, 8, 12, or 14 mg/kg), or at different times (5 min, 24 h, or 58 h) after a standard phthalocyanine dose (3 mg/kg) injection. Irradiation time necessary for vascular occlusion was recorded. Decrease of phthalocyanine dose as well as delay of irradiation onset resulted in a statistically significant increase of irradiation time. Electron and light histological examination revealed platelet thrombi inside irradiated corneal new vessels. Damage in the vascular endothelial cell membrane and in intercellular contact structure was noted, leading to disorganization of the endothelial cells layer and death of most endothelial cells. These results indicate that both early commencement of irradiation after phthalocyanine injection and phthalocyanine dose increase accelerate the rate of phthalocyanine mediated corneal neovascularization photodynamic thrombosis. Thrombosis seems to result from photochemically induced vascular endothelial cell damage. © 1994 Wiley-Liss, Inc.     

Basic studies of photodynamic therapy in experimentally induced canine gastric cancer

Photodynamic therapy (PDT) was used in two cases of experimental canine gastric cancer produced by the oral administration ofN-ethyl-N′-nitro-N-nitrosoguanidine (ENNG). Endoscopic examination and biospy showed the development of cancer in the gastric antrum. The cancerous lesions, a polypoid lesion and the normal epithelium were photoradiated superficially by an argon dye laser with a power of 300 to 400 mW for five to ten 30-s periods, 48 h after the intravenous injection of 3.0 mg/kg body weight of haematoporphyrin derivative (HPD). Dog 1 was killed three days after PDT, and was examined histologically. The tumour cells showed vacuolar degenerative changes in the mucosa, and the irradiated normal epithelium was less damaged. Dog 2 was followed up periodically by means of gastrofibrescope and biopsy. A wider and deeper ulcerative lesion was observed three days after PDT and it was healed by day 40. But the recurrence of a cancerous lesion was shown on day 80. The remnant of a small cancer nest was revealed histologically by means of biopsy and autopsy. The results show that PDT is suitable for superficial gastric cancer and that long-term follow-up observation is necessary for the evaluation of PDT.