James H. Kinsey

Photodynamic Therapy for Early Stage Squamous Cell Carcinoma of the Lung

OBJECTIVE To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

Photodynamic therapy with hematoporphyrin derivative in the treatment of superficial transitional-cell carcinoma of the bladder

Photodynamic therapy involves light-induced destruction of tumors containing a photosensitizer such as hematoporphyrin derivative. We conducted a collaborative study to evaluate the efficacy of this form of therapy in treating superficial transitional-cell carcinoma of the bladder. Thirty-seven patients were evaluated and 20 were selected for treatment. A total of 50 papillary tumors and 3 areas of carcinoma in situ were treated. All except two tumors were smaller than 2.5 cm. Assessments for treatment response and toxicity were carried out three months after treatment. The initial diagnosis of one patient was revised after the biopsy material was reviewed, and this patient was not included in the analysis. Complete eradication of all tumors was observed in 9 of 19 patients (47 percent), including those with carcinoma in situ. In the remaining 10 of these 19 patients, 13 tumors could not be eradicated (the overall eradication rate was 37 of 50 tumors [74 percent]), but 9 of the 10 patients had a reduction in tumor size, number, or both of 50 percent or more. We conclude that photodynamic therapy is useful in the treatment of superficial transitional-cell carcinoma of the bladder, but controlled trials will be required to define its place in the treatment of cancer.

Treatment of Transitional Cell Carcinoma of the Bladder with Hematoporphyrin Derivative Phototherapy

The demonstration that intravenously administered hematoporphyrin derivative concentrates preferentially in dysplastic and neoplastic transitional cells in the human bladder prompted a trial of hematoporphyrin derivative phototherapy in patients with transitional cell cancer of the bladder. A dose of 2.5 mg. per kg. was given intravenously 3 to 48 hours before treatment with light of a wavelength of 630 nm. from an argon ion pumped dye laser. Total light dose approximated 150 joules per cm.2. Four patients with resistant carcinoma in situ have been treated and all have had disappearance of the tumors proved by biopsy. Although there are many technical problems we believe that hematoporphyrin derivative phototherapy holds promise as an effective treatment modality, primarily for patients with resistant, recurrent in situ transitional cell carcinoma of the bladder.

Three-dimensional spatial, density, and temporal resolution of the dynamic spatial reconstructor

Spatial, density, and temporal resolution of the dynamic spatial reconstructor (DSR), a multiple X-ray source, high speed, computed tomography scanning system, are evaluated. Hole-pair resolution was evaluated in a stationary phantom surrounded with air, 15 cm of water, or 20 cm of water. Temporal resolution was evaluated by rotation of one of the resolution phantoms during the scan, and with a balloon inflated to a known volume and at a known rate to approximate a typical left ventricular chamber volume and filling rate. These studies confirmed that the spatial resolution is essentially the same in the transverse and axial directions, and that retrospective manipulation of the image data is important for maximization of spatial and density resolution in any structure under examination by obtaining a tradeoff with partial-volume and motion-blurring effects. Maximum spatial resolution in the scanned volume was shown, under ideal conditions, to be greater than five hole pairs per centimeter. Under conditions of intravenous injection of contrast agent, the resolution of blood vessels in an experimental animal approximately 25 kg in weight is expected to be on the order of three hole pairs per centimeter; and in an adult human weighing approximately 60 kg, a resolution of about two hole pairs per centimeter is to be expected.

The DSR: A High-Speed Three-Dimensional X-Ray Computed Tomography System for Dynamic Spatial Reconstruction of the Heart and Circulation

High temporal resolution, full three-dimensional imaging of the heart and circulation is required for accurate basic physiological studies of the structural-to-functional relationships of these organ systems, and for improved diagnostic evaluation and treatment of patients with cardiovascular disorders. A new generation, fully electronic and very rapid whole-body computed tomography system called the Dynamic Spatial Reconstructor (DSR) will provide stop-action (0.01 sec), rapidly sequential (60-per-second), synchronous volume (240 simultaneous transaxial sections) reconstructions and display of the full anatomic extent of the heart throughout successive cardiac cycles, and will permit visualization of the three-dimensional vascular anatomy and circulatory functions in all regions of the body of patients with cardiovascular and other pathological disabilities. The feasibility and potential of a DSR system has been demonstrated by studies using a currently operational single source prototype assembly, the SSDSR, from which full three-dimensional dynamic reconstructions of the thorax and its contents have been obtained.

The Effect of Cooling on the Photodynamic Action of Hematoporphyrin Derivative during Interstitial Phototherapy of Solid Tumors: 1983 Second-Place Resident Research Award: Basic Category*

Hematoporphyrin derivative (HpD), a mixture of compounds chemically prepared from naturally occurring crude hematoporphyrin, is preferentially concentrated in neoplastic cells and produces red fluorescence when irradiated with blue-violet light. In addition, HpD exhibits other photodynamic properties, which, in the presence of oxygen and visible light, result in cytotoxicity. Preliminary reports indicate that early, superficial carcinomas of the upper aerodigestive tract and tracheobronchial tree can be localized and treated successfully with HpD phototherapy (HpD-PT), in which a fiberoptic bundle transmits laser light to the tumors. To assess this modalitys potential for treating solid tumors, the cytotoxic effect of HpD-PT was measured in a murine tumor model. We specifically assessed the effect of cooling on the pure photodynamic action of HpD-PT. Adult female mice with typical mammary tumors received interstitial phototherapy 24 hours after HpD was given intraperitoneally. Light from an argon-dye laser was delivered through an optical fiber, along with simultaneous cooling from a cryosurgical probe, for 15 minutes. After being cooled with a cryosurgical probe, tumors were excised 48 hours after treatment and the necrotic area was measured. The results indicate that cooling enhances the tumoricidal action of HpD-PT.

Physics And Technical Considerations In The Design Of The Dynamic Spatial Reconstructor (DSR)-A High Temporal Resolution Volume Scanner

A. multiple x-ray source high-speed transaxial scanner system (DSR) is about to undergo evaluation. studies. The capH.bility for programmable scanning modes and operator interactive retrospective reconfiguration of scan data makes the DSR a very powerful research tool. The physics and technological basis for system design and selection of several major components of the DSR scanner are discussed.

Some Imaging Characteristics of the Dynamic Spatial Reconstructor X-Ray Scanner System

In late 1979, the Dynamic Spatial Reconstructor (DSR), a multiple x-ray source, stop action, volume scanning imaging device was installed (1, 2). At present, the operational characteristics and biomedical utility of the Dynamic Spatial Reconstructor (DSR) are being evaluated. This research project involves scanning experimental animals and carefully selected patients with cardiovascular and pulmonary pathology. The DSR scanner utilizes a computerized transaxial tomography principle to generate images of transverse slices of the body. As illustrated in Figure 1, 14 x-ray tubes and 14 television cameras (of the 28 for which it is designed) are attached to the scanner. The x-ray tubes are arranged 12° apart along a semicircular array with television cameras positioned opposite each x-ray source. As each x-ray tube is pulsed for 350 microseconds, a 30 cm × 30 cm image is generated on a fluorescent screen. The corresponding television camera is gated on for 762 microseconds and the fluoroscopic image is recorded on the image isocon target for subsequent readout and recording on video disc. The patient or animal scanned is positioned inside the machine at the center of rotation as indicated in the schematic in Figure 1.

High temporal resolution synchronous volumetric scanning tomography: Potential roles in clinical evaluation of ischemic heart disease

Abstract A new quantitative imaging device, the Dynamic Spatial Reconstructor (DSR), is described. Because, unlike commercially available computed tomography scanners, it obtains stop-action (0.01 second) images of a volume rather than a slice at a repetition rate of 60 volumetric scans per second, the DSR is particularly well suited for the study of ischemic heart disease. Its capabilities for recording the transit and dilution of contrast media within the coronary vasculature and all regions of the myocardium simultaneously with regional and global myocardial mechanics are being evaluated as a research tool for physiologic and ultimately clinical investigations.