Sugandh D. Shetty

Changes in In Vivo Optical Properties and Light Distributions in Normal Canine Prostate during Photodynamic Therapy

The optical absorption and transport scattering coefficients of normal prostate tissue have been measured in vivo in dogs. The measurements were made at 630 nm before and during treatment by Photofin photodynamic therapy using interstitial optical fiber fluence-rate detectors. Corresponding measurements were made ex vivo, at 1 week after treatment, in the contralateral lobe. The optical properties were derived by applying a diffusion theory model to the fluence rates measured at two different source-detector fiber distances. While the in vivo pretreatment and in vivo contralateral post-treatment absorption and scattering values are self-consistent and in agreement with published data, significant changes were observed in the light fluence rates, and hence in the derived optical properties, during light irradiation. The possible causes of such changes are considered, and the implications for light dosimetry in photodynamic therapy are discussed.

Management of partial segmental priapism

We report the cases of 2 patients with partial segmental priapism. The patients presented with pain, a perineal mass, and proximal segmental corporal thrombosis. Treatment consisted of a proximal corpus cavernosal-spongiosum shunt. Diagnostic considerations, literature review, and treatment options are discussed.

Tumor Necrosis Factor Alpha Production in Schistosomiasis with Carcinoma of Urinary Bladder

Schistosomiasis parasitic infection (Schistosoma haematobium) is associated in some patients with bladder cancer. The production of cytokines such as tumor necrosis factor alpha (TNFα) is a key event of inflammation in human infectious disease and malignancy. TNFα has not been previously investigated from schistosomiasis infection and bladder malignancy. In this report we demonstrate that serum levels of TNFα are highly elevated in patients with schistosomiasis of urinary bladder (SB), schistosomiasis with carcinoma of urinary bladder (SCB), and carcinoma of urinary bladder without schistosomiasis (CB). Purified monocytes from bladder malignancy (SCB and CB) cultured without exogeneous stimuli release TNFα in the culture supernatants. However, lipopolysaccharides and concanavalin A stimulation of monocytes from these patients produced highly elevated levels of TNFα compared with normal controls. The findings that monocytes are the potent producers of TNFα in this malignancy may be a key observation implicating these cells in the pathophysiology of this disease. Furthermore, it was shown that serum TNFα levels correlated with the clinical staging of disease in both SCB and CB, with higher levels in T3 and T4 advanced-stage patients and low levels in T1 and T2 early-stage patients. These results suggest that monocyte abnormality and serum TNFα levels might be one of the factors contributing to the progression of disease.

Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

Evaluation of prostatic optical properties and tissue response to photodynamic therapy in a canine model

A new modality of interstitial therapy to treat prostate cancer using photodynamic principles has been studied in a canine model. The effect of interstitial application of monochromatic light from an argon pumped dye laser at 630 nm was studied in a canine model. No significant hyperthermia was seen during the treatment. A concentric zone around the treatment fiber was seen during the treatment. A concentric zone around the treatment fiber was seen in PDT treated dogs and the maximum size was 18 mm. The data suggests that PDT may be clinically applicable in achieving tissue necrosis using interstitial light application in a solid organ like prostate.

Interstitial photodynamic therapy for the prostate: a canine feasibility study

Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.

Photodynamic therapy of normal canine prostate

To provide basic scientific information for utilizing photodynamic therapy to treat prostatic carcinoma, PDT dosimetry and effective treatment volume were investigated using canine prostate as an in vivo animal model. The prostate glands were surgically exposed. Isotropic tip fibers were inserted into the gland for either light irradiation or detection. PDT doses of 400 J and 1, 3 or 5 mg/kg Photofrin were used for single fiber irradiation treatments. All animals were terminated at 1 week and the prostates evaluated histopathologically. The results show that the lesion size was dependent on the treatment dose. The maximum lesion dimension was approximately 1.6 cm. The data acquired from the single fiber irradiation study were then used to plan for multi-fiber interstitial PDT treatments with a goal of achieving a larger treatment volume for practical purpose. The data indicate that the lesion size from the multiple fiber treatment could be predicted based on the single fiber treatment with the light pattern summed from all sources.