The photosensitizer, mono-L-aspartyl chlorin e6 &#40;NPe6&#41;, specifically accumulates in theatheromatous plaque. We detected the fluorescence spectra of NPe6 emitted fromatheromatous plaques on the descending thoracic aorta by an angioscopic approach usingthe animal model of atherosclerosis. We also showed that a fluorescence spectrum peak at675 nm was obtained laparoscopically only in parts of the abdominal aorta with anatheromatous plaque. By a fluorescence endoscope, atheromatous plaques on the carotidartery were recognized as reddish spots from outside the artery. In addition, we visualizedspecifically at the beating heart surface small coronary atherosclerosis using an epifluorescencestereoscope system.We examined the effects of photodynamic treatment with NPe6 on the atheromatousplaque. The change in the elastic framework in the atheromatous plaque after photodynamictreatment was evaluated using scanning electron microscopy. The destruction of thearchitecture of the elastic fiber network in the atheromatous plaque was revealed. We alsostudied the change in the lipid components of the atheromatous plaque using Fouriertransform infrared &#40;FTIR&#41; microspectroscopy. FTIR microspectroscopic analysis showeda dissociation of ester bonds of cholesterol esters in the atheromatous plaque afterphotodynamic treatment. The framework of the atheromatous plaque and the lipidsaccumulated in the plaque could be destroyed following such treatment.

Junichi  Hayashi

Takashi  Saito

Katsuo  Aizawa

Photodynamic Diagnosis and Treatment for Atherosclerosis by an Endoscopic Approach

We have been performing PDT using Excimer Dye Laser &#40;EDL&#41; or YAG-OPO laser, a typeof low power laser, both of which have a considerably higher degree of tissue penetration evenwhen compared to PDT using Argon Dye Laser &#40;ADL&#41;.PDT is a relatively simple procedure without any bleeding and does not require anesthesiasince it causes no pain. PDT is performed 48 h after intravenous injection of 1.5&#8211;2.0 mg&#47;kgof PHE &#40;Photofrin&#174;&#41;. Precise spot irradiation is possible using a colposcope with an optical laser path. We also use a cervical probe which enables photoirradiation of the entire cervical canal.We have performed PDT on 131 cases &#40;95 CIS, 31 dysplasia, 1 vulval dysplasia &#40;VIN&#41;,3 squamous cell carcinoma, microinvasion, and 1 CIS &#43; endocervical adenocarcinoma,microinvasion&#41;. Of these cases, 127 became CR &#40;96.9&#37;&#41;. The first CR case was 10 years agoand no recurrence has been observed yet.PDT is extremely effective to preserve fertility. Except for sensitive reactions to sunlight,there are no noticeable side effects or difficulties related to pregnancy or delivery. We expectthat in the near future PDT will be performed using diode lasers and without hospitalizationdue to new photosensitizers which have shorter retention times.

T.  Muroya

K.  Kawasaki

Y.  Suehiro

T.  Kunugi

K.  Umayahara

T.  Akiya

H.  Iwabuchi

H.  Sakunaga

M.  Sakamoto

T.  Sugishita

 Y.  Tenjin

Application of PDT for Uterine Cervical Cancer

Since 1980, advanced lung carcinomas were treated with palliative laser therapy for thepurpose of opening the endobronchial stenosis and obstruction by either photodynamictherapy &#40;PDT&#41; or Nd-YAG laser treatment at Tokyo Medical University. A total of 258lesions were treated, 81 by PDT and 177 by Nd-YAG laser treatment. PDT achieved effectiveresults in 61 &#40;75&#37;&#41; of 81 lesions. In the Nd-YAG laser group, 143 &#40;81&#37;&#41; of 177 lesions showedeffective results. When the tumor was located in the trachea or main bronchi, effective resultswere obtained in 73&#37; &#40;19 of 26&#41; of cases treated by PDT and in 93&#37; of cases &#40;64 of 69&#41; treatedby Nd-YAG laser. However, in cases in which the tumor was located in lobar or segmentalbronchi, the tumor response was effective in 76&#37; &#40;42 of 55&#41; of PDT-treated patients and 73&#37;&#40;79 of 108&#41; of Nd-YAG laser-treated patients. With a mortality rate of 0&#37;, the greatestadvantage of PDT over Nd-YAG treatment was safety. Considering complications, PDTseems to be useful for obstruction of lobar and segmental bronchus. Nevertheless, whendeciding among alternative therapies, physicians treating patients with advanced lungcarcinoma should give careful consideration to the benefit and complications of both lasertherapies and decide the most suitable modality.

Kinya  Furukawa

Tetsuya  Okunaka

Hideki  Yamamoto

Takaaki  Tsuchida

Jitsuo  Usuda

Hideo  Kumasaka

Junzou  Ishida

Chimori  Konaka

Harubumi  Kato

Effectiveness of Photodynamic Therapy and Nd-YAG Laser Treatment for Obstructed Tracheobronchial Malignancies

Progress of photodynamic therapy &#40;PDT&#41; in gastric cancer and the clinical outcome aredescribed in this paper. &#40;1&#41; We included the whole lesion and a 5 mm margin in the field forirradiation. Marking by injection of India-ink showing the irradiation field was performedbeforehand. &#40;2&#41; We established the standard light dose to be 90 J&#47;cm2 for an argon dyelaser and 60 J&#47;cm2 for a pulse wave laser. &#40;3&#41; The size of cancerous lesion curable by PDTwas expanded from 3 cm in diameter, i.e. 7 cm2 in area to 4 cm in diameter, i.e. 13 cm2 byemploying a new excimer dye laser model, which could emit 4mJ&#47;pulse with 80 Hz pulsefrequency. &#40;4&#41; The depth of cancer invasion which could be treated by PDT was increased fromabout 4 mm, i.e. the superficial part of the submucosal layer &#40;SM-1&#41; to more than 10 mm indepth, i.e. the proper muscular layer. These improvements owe much to the pulse laser, thephotodynamic action induced by which permits deeper penetration than that of a continuouswave laser. &#40;5&#41; We employed a side-viewing fiberscope for gastric PDT to irradiate the lesionfrom an angle of 90&#176;. &#40;6&#41; We designed a simple cut quartz fiber for photoradiation with a spiral spring thickened toward the end. &#40;7&#41; We developed an endoscopic device for photoradiation inPDT which achieves accurate and efficient irradiation. As a result of these improvements ahigher cure rate was obtained even with a lower light dose of irradiation.

Seishiro  Mimura

Hiroyuki  Narahara

Toru  Otani

Shigeru  Okuda

Progress of Photodynamic Therapy in Gastric Cancer

Harubumi Kato

Preface

Laser endoscopic surgery, especially the effectiveness of photodynamic therapy &#40;PDT&#41; usingPhotofrin as a photosensitizer, has now achieved a status as effective treatment modality forlung cancer. Twenty-six lung cancer patients received the preoperative PDT for the purpose ofeither reducing the extent of resection or increasing operability. Bronchoscopical PDT isperformed with topical anesthesia approximately 48 h after the intravenous injection of2.0 mg/kg body weight of Photofrin. Operation was performed 2&#8211;9 weeks after initial PDT. The initial purpose of PDT, i.e. either to reduce the extent of resection or convert inoperabledisease to operable status, was achieved in 22 out of 26 patients treated. The survival rate of T3&#40;main bronchus invasion&#41; cases treated by surgery alone increased significantly from 50.9&#37; to60.0&#37; with the application of preoperative PDT. This remarkable result may imply that thisnew option of PDT as preoperative laser irradiation may contribute to the management ofadvanced lung malignancy.

Toshimitsu  Hiyoshi

Chimori   Konaka

Lung Cancers Treated With Photodynamic Therapy and Surgery

Cancer, when detected at an early stage, has a very good probability of being eradicated by
surgery or radiotherapy. However, less aggressive treatments also tend to provide high rates
of cure without the side effects of radical therapy. We report on the results of our clinical
experience with photodynamic therapy (PDT) for the treatment of early carcinomas in the
upper aerodigestive tract, the esophagus, and the tracheobronchial tree. Sixty-four patients
with 101 squamous cell carcinomas were treated with three different photosensitizers:
hematoporphyrin derivative (HPD), Photofrin II, and tetra (m-hydroxyphenyl)chlorin
(mTHPC). Seventy-seven (76%) tumors showed a complete rsponse with no recurrence
after a mean follow-up period of 27 months. There was no significant difference in terms of
cure rates among the three dyes. However, mTHPC has a stronger phototoxicity and induces
a shorter skin photosensitization than either of the other photosensitizers. There were eight
major complications: three esophagotracheal fistulae after illumination with red light in the
esophagus, two esophageal stenoses following 360° circumferential irradiation, and three
bronchial stenoses. Illumination with the less penetrating green light and the use of a 180° or
240° windowed cylindrical light distributor render the risk of complications in the esophagus
essentially impossible, without reducing the efficacy of the treatment. Therefore, PDT may be
considered as a safe and effective treatment for early carcinomas of the upper aerodigestive
tract, the esophagus, and the tracheobronchial tree.

A. Radu

P. Grosjean

Ch. Fontolliet

G. Wagnieres

A. Woodtli

H. Van Den Bergh

Ph. Monnier

Photodynamic Therapy for 101 Early Cancers of the Upper Aerodigestive Tract, the Esophagus, and the Bronchi: A Single-Institution Experience

Objectives Determine factors affecting survival rates, benefits and complications of patients with obstructive esophageal cancer treated with photodynamic therapy &#40;PDT&#41;. Methods From 1982 to January 1998, we used PDT to treat 140 patients with obstructiveadeno or squamous carcinoma and evaluated survival up to November 1998. All patients had failed, refused, or were ineligible for surgery, ionizing radiation or chemotherapy. The effect of different variables on survival was estimated using multivariate analysis. The Karnofsky Performance Status &#40;KPS&#41;, weight, diet and complications were recorded and biopsies and brushings were taken at each endoscopy. At the beginning and end of each endoscopy the minimal diameter open of the esophagus, and the length, thickness and color of the tumor were recorded. Edema, exudate, bleeding, and mucositis were evaluated and recorded on an ordinal scale.Results The only significant variable affecting survival was the clinical stage. The median survival after PDT for all patients was 6.5 months &#40;mean &#61; 13.9&#41;. Kaplan&#8211;Meier survival after PDT curves were statistically significantly different when stratified by the clinical Stage at the time of PDT &#40;p &#60; 0.0001&#41;. Median survival &#40;months&#41; were for: Stage I &#61; 56; Stage II &#61; 12; Stage III &#61; 6.5; Stage IV &#61; 3.5. Analysis of each individual stage showed the KPS was the only confounding variable with a statistically significant effect on survival after PDT and this was only for Stages III and IV. The most significant effect occurred when the KPS was &#8805; 70. For Stage III the median survival when the KPS was &#8805; 70 was 7.7 months and for a KPS &#60; 70 it was 5.0 months &#40;p &#61; 0.0001&#41;. For Stage IV the median survival when the KPS was &#8805; 70 was 5.5 months and for a KPS &#60; 70 it was 2.5 months &#40;p &#61; 0.0002&#41;. The mean minimum diameter open before PDT was 6.2 mm &#40;median 6.0mm&#41; and at the end of the PDT treatment endoscopy 11.1 mm &#40;median 12.0 mm&#41; for a mean increase in the minimum diameter open of 4.9 mm &#40;median 5.0 mm&#41; This was statistically significant using paired t-tests&#40;p &#60; 0.0001&#41;.Conclusions Photodynamic therapy for esophageal carcinoma caused minimal complicationsand procedure related mortality. Complete obstruction can be relieved by the end of the PDT endoscopy. The length of palliation for &#8220;non-curative&#8221; patients was equal to or better than that reported historically for most other treatment regimens.

James S. McCaughan

Photodynamic Therapy for Obstructive Esophageal Malignancies

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Diagnostic and Therapeutic Endoscopy

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Photodynamic Therapy

Articles

Photodynamic Diagnosis and Treatment for Atherosclerosis by an Endoscopic Approach

Application of PDT for Uterine Cervical Cancer

Effectiveness of Photodynamic Therapy and Nd-YAG Laser Treatment for Obstructed Tracheobronchial Malignancies

Progress of Photodynamic Therapy in Gastric Cancer

Preface

Lung Cancers Treated With Photodynamic Therapy and Surgery

Photodynamic Therapy for 101 Early Cancers of the Upper Aerodigestive Tract, the Esophagus, and the Bronchi: A Single-Institution Experience

Photodynamic Therapy for Obstructive Esophageal Malignancies