Jutaro Ono

Fiberoptic bronchoscopic photoradiation in experimentally induced canine lung cancer

The potential of diagnostic and therapeutic applications of a system using hematoporphyrin derivative (HpD) and laser photoradiation for the localization and treatment of canine lung cancer experimentally induced in the bronchi was studied. Seven cases of canine invasive squamous cell carcinoma were used in this experiment. A dose of 2.5‐3.0 mg/kg body weight HpD was administered intravenously in each dog forty‐eight hours prior to examination for fluorescence. The violet light source was a krypton ion laser beam. The beam was transmitted via a quartz fiber inserted through the fiberoptic bronchoscope, and an image intensifier was used to detect the fluorescence from the bronchial foci. An argon dye laser was used for treatment of the foci with red light. Six of seven dogs with squamous cell carcinoma revealed fluorescence at the foci. Conversely, the bronchi of controls, consisting of normal dogs, showed no fluorescence. Three dogs with squamous cell carcinoma received treatment. The therapeutic system consisted of photoradiation with an argon dye laser beam also transmitted via a quartz fiber inserted through the fiberoptic bronchoscope and a dose of 2.5‐3.0 mg/kg body weight HpD was administered intravenously 72 hours before the procedure. All carcinoma cases showed complete responses.

Effectiveness of HPD and Radiation Therapy in Lung Cancer

The diagnostic rate of lung cancer has been improved by the development of the fiberoptic bronchoscope and this instrument has particularly promoted the detection of early stage of central type lung cancer. But therapeutic results have been unsatisfactory, partly because of difficulties in resecting cases with poor pulmonary function. On the other hand, chemotherapy and radiation therapy can have serious side effects. New therapeutic modalities are therefore required for treatment of early stage inoperable lung cancer cases.

Reversibility of 20-methylcholanthrene-induced bronchial cell atypia in dogs

The sequence of cellular alterations in the bronchial epithelium of individual dogs was studied by means of combined morphologic and cytochemical techniques during a period of exposure to 20‐methylcholanthrene (20‐MC) and during a subsequent period without treatment. In agreement with earlier observations, 20‐MC was found to induce progressive cellular changes which in four of seven dogs resulted in the occurrence of cells morphologically diagnosed as cancer cells. When the 20‐MC treatment was stopped these cellular alterations were found to regress in three of the four dogs. Only in one dog did the advanced cellular atypia persist and cause the death of the animal. The results indicate that cells exhibiting cytomorphologic and cytochemical characteristics of cancer cells may reflect reversible lesions which regress on withdrawal of the carcinogen.

Photoradiation Therapy in Early Stage Cancer Cases of the Lung, Esophagus and Stomach

Photoradiation therapy (PRT) was performed in clinical cancer cases ascertaining the therapeutic effectiveness and safety of this new modality in experimentally induced canine central type lung cancer. In the canine experiments, weekly submucosal injections of the carcinogen 20-methylcholanthrene were made at the bifurcation of the right apical and cardiac lobe bronchi in beagles and mongrel dogs1. This is one of only a very few successful dog lung cancer models in the world.

Photoradiation Therapy with Hematoporphyrin Derivative and an Argon Dye Laser of Bladder Carcinoma

Hematoporphyrin Derivative (HpD) which has an affinity for malignant tumors is excited by light exposure and reacts photodynamically in tumor tissue. Therefore it is possible to treat malignant tumor selectively without any damage to surrounding normal tissues. HpD is excited by a light in the spectrum from ultraviolet to visible red. Previously arc lamps and slide projectors were used for excitation of HpD but laser beams which facilitate photoradiation via endoscopes has been used recently. Much of the early basic and clinical studies on HpD and light photoradiation therapy was performed by Dougherty and his coworkers1. Hayata et al. investigated photoradiation therapy using an argon dye laser following an intravenous HpD administration in mice, and on cultured human lung cancer cells2, and in experimentally induced canine lung cancer and demonstrated its therapeutic effectiveness3. Malignant bladder tumor were treated by this new technique in this study.

Effects of Photodynamic Therapy in Lung Cancer with Particular Reference to Early Stage Cases

In Lung Cancer 1982 [1] we described the technique of photodynamic therapy (PDT) with hematoporphyrin derivative (HPD) and reported the possibility of curative effect in early stage central type cases, possible prophylactic treatment in precancerous lesions and preoperative PDT in advanced cases to reduce the extent of resection or to widen the indications of surgery of the method. Since then 100 cases of lung cancer have been treated with PDT at the Department of Surgery, Tokyo Medical College. Here we present the therapeutic effectiveness of PDT in early stage central type lung cancer with especial reference to cases in which complete tumor remission was not obtained with PDT.

Photodynamic Therapy in Early Stage Carcinoma

While attempts to employ hematoporphyrin with light in malignant disease extend for over half a century, the first studies with practical import were published in the early 1960’s by Lipson, Olsen and their colleagues (1). They developed a derivative of hematoporphyrin (HPD) which reduced the side effects. Also, they showed that the material was retained at higher levels by malignant tissue than by normal tissue and that the fluorescence of the material emitted upon excitation by light could be employed for diagnostic applications. In the early 1970’s, Dougherty, Weishaupt and their colleagues demonstrated that the cytocidal effect is of HPD upon stimulation by light had potential in the treatment of malignant tumors and metastatic lesions of advanced cancer (2–4). They also explored the applications of laser light in combination with HPD in advanced cases (5–8). Their studies and those of other investigators showed that this modality could obtain regression of malignant lesions (9–29).

CYTOMORPHOLOGICAL CHANGES CAUSED BY PHOTODYNAMIC THERAPY WITH HpD

Laser photodynamic therapy (PDT) with homatoporphyrin derivertive has been given increase attation. Many investgators have recognized that PDT is an effective local treatment of eraly stage cancer. To clarify experimental and clinical effectiveness due to PDT, a bronchofiberscopic brushing cytology was performed chronologically. The change of cellular components were studied by means of a phase contrast microscopic system and electron microscopy. The initial changes, halting of cellular movement, the degeneration of mitochondria, endoplasmic reticulum, and decrease of free ribosome. were recoanized.