Study of factors mediating effect of photodynamic therapy on bladder in canine bladder model

The canine bladder model was employed to study the factors mediating the effect of photodynamic therapy (PDT) on the bladder. The recovery (time taken for the bladder volume to return to pre-PDT value), gross and microscopic findings, implicate both bladder high filling pressure (60 cm H2O) and high light dose as factors mediating the effect of photodynamic therapy on bladder capacity. We recommend that photodynamic therapy to the bladder be performed under a filling pressure of 30 cm H2O, which is physiologic, and whole bladder illumination at a light dose not greater than 30 J/cm2.     

The morphological changes in rat bladder after photodynamic therapy with 5-aminolaevulinic acid-induced protoporphyrin IX

OBJECTIVE: To assess the optimum light energy needed to induce only superficial bladder wall damage during photodynamic therapy (PDT) as a treatment for bladder cancer. Materials and methods The urinary bladder (with normal epithelium) of 64 female rats was treated with PDT using a continuous-wave argon-ion laser as an energy source and aminolaevulinic acid (ALA)-induced protoporphyrin IX photosensitizer. Four hours after the intravenous administration of ALA (300 mg/kg) the bladders were intravesically exposed to light fluences of 20-80 J/cm2. The control rats received no ALA and were exposed to 20 J/cm2 light. After 1, 3, 7 and 21 days the animals were killed and the morphological changes in bladder wall analysed both macroscopically and using light and scanning electron microscopy. RESULTS: At the dose of ALA given, a fluence of 20-40 J/cm2 caused mainly superficial damage, whereas 80 J/cm2 produced full-thickness injuries to the bladder wall. The maximum effect of PDT occurred after 1 and 3 days of irradiation. After 3 weeks of PDT the histology showed few full-thickness injuries and only in those treated with 80 J/cm2 light. CONCLUSION: These results indicate that PDT can be used to safely induce a selective superficial removal of bladder mucosa with no fibrotic effects on detrusor musculature, when optimum photosensitizing drug and fluences are used. These findings support the use of PDT in the therapy of superficial bladder cancer.     

PHOTODYNAMIC THERAPY USING PORFIMER SODIUM AS AN ALTERNATIVE TO CYSTECTOMY IN PATIENTS WITH REFRACTORY TRANSITIONAL CELL CARCINOMA IN SITU OF THE BLADDER

Purpose

Photodynamic therapy combines a photosensitizer, such as porfimer sodium (Photofrin), with red laser light (630 nm.) to destroy cancer cells. Investigators have reported the effectiveness of photodynamic therapy in the treatment of patients with recurrent superficial bladder cancer. We assess the safety and efficacy of 1 or 2 photodynamic treatments using porfimer sodium and controlled uniform laser light (630 nm.) as an alternative to cystectomy in patients with refractory vesical carcinoma in situ of the bladder.

Materials and Methods

A total of 36 patients with carcinoma in situ were treated with whole bladder photodynamic therapy as an alternative to cystectomy. In all patients at least 1 course of bacillus Calmette-Guerin (BCG) had failed. Each patient received a single whole bladder photodynamic therapy treatment, consisting of 2 mg./kg. porfimer sodium intravenously followed 40 to 50 hours later by intravesical red light (630 nm.) at 15 J./cm.². Post-photodynamic therapy evaluations included weekly telephone contact to assess acute adverse reactions, and assessment of efficacy and bladder toxicity at 3 months and quarterly thereafter.

Results

At initial clinical evaluation at 3 months 58% of the patients had a complete response as indicated by negative cystoscopy, bladder biopsy and urine cytology but in 42% treatment failed. At a mean followup of 12 months (range 9 to 48) 10 of the 21 complete responders had recurrence for an overall durable response rate of 31%. Fourteen patients subsequently underwent cystectomy for persistent carcinoma in situ (12) and carcinoma in situ recurrence (2). Of the 36 patients 7 experienced bladder contracture.

Conclusions

The initial results are encouraging for a single whole bladder photodynamic treatment of patients in whom prior intravesical therapy for carcinoma in situ has failed. While followup is short, porfimer sodium photodynamic therapy appears potentially promising as an alternative to cystectomy in patients with refractory carcinoma in situ.     

Photodynamic therapy for esophageal cancer using a 180° windowed esophageal balloon

Although delivery of uniform circumferential light is desirable during photodynamic therapy of advanced esophageal cancer in humans, early esophageal cancer may need only targeted treatment. Studies were performed in the canine esophagus of eight animals to investigate whether use of a “windowed” (shaded) centering balloon would improve targeted illumination of esophageal mucosa for photodynamic therapy. Shaded balloons were developed with a 2-cm-long, 360° or 180° clear “window.” Photofrin 4 mg/Kg was used as the photosensitizer. Light at 630 nm was delivered at 300 J/cm or 600 J/cm. Isotropic probes placed on the balloon wall allowed real-time measurement and verification of relatively uniform light doses delivered to esophageal mucosa during balloon photodynamic therapy. With the windowed balloon, targeted delivery of photodynamic therapy was possible. Using the 180° balloon, mucosa exposed to illumination was destroyed, whereas mucosa protected from light by the balloon shading was undamaged. Healing was complete and strictures did not occur. The shading of the balloon protected normal mucosa and prevents the formation of esophageal strictures. The “windowed” centering balloon provides a technology and technique that allows targeted delivery of uniform light during esophageal PDT. © 1994 Wiley-Liss, Inc.     

Whole bladder photodynamic therapy for transitional cell carcinoma of bladder

Our preliminary studies indicate that the bulb-tip technique for whole bladder photodynamic therapy (PDT) illuminates the entire bladder mucosa and is applicable to the management of superficial transitional cell carcinoma of the bladder. This treatment modality may be an option to patients who are failures to other standard treatments. A randomized clinical study is needed to decide on PDT as a primary treatment of choice for transitional cell carcinoma of the bladder.     

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma

OBJECTIVE: To assess the effect of whole-bladder photodynamic therapy (PDT) on a rat model with orthotopic superficial bladder cancer, as PDT is an alternative intravesical therapy for treating superficial bladder cancer, based on an interaction between a photosensitizer and light energy to induce oxygen radicals that destroy tissue by lipid peroxidation. MATERIALS AND METHODS: In all, 76 female Fischer F344 rats were inoculated intravesically with AY-27 tumour cells. After establishing superficial tumour, 24 rats were treated with PDT using aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer, and a continuous-wave argon pumped-dye laser (638 nm). At 4 h after intravenous (300 mg/kg) or intravesical (100 mg/mL) administration of ALA the bladders were intravesically exposed to a 40 J/cm(2) light dose; 12 rats received no ALA but were exposed to the same light dose. Before administering ALA, urine cytology samples were taken for analysis. At 3 or 21 days the treated rats were killed and morphological changes in the bladder walls analysed by light microscopy. Forty rats served as controls to examine the presence of tumour. RESULTS: The tumour established in 33 of 40 rats (83%) in the controls, but after PDT with intravesical ALA there was carcinoma in only in one of 12 (P < 0.001, Pearson's chi(2) test). After PDT with intravenous ALA there was carcinoma in five of 11 rats (P = 0.063, Pearson's chi2 test). In the control group of 12 rats receiving only light energy there was carcinoma in three (P = 0.001, Pearson's chi(2) test). Histologically, at 3 days after PDT there was only mild superficial damage in all six rats treated intravesically. Bladder wall destruction reached the muscular layer, with an abscess in one of six rats treated intravenously. After 3 weeks of PDT there was muscular necrosis with perforation and abscess from catheterization two of six rats treated intravesically and in three the bladder wall totally recovered. In the intravenous group the bladder walls were normal or had only mild superficial damage. Cytology of the urine sediment failed to detect half the tumours in the treatment groups. CONCLUSION: These results support the use of PDT with intravesical ALA-induced protoporphyrin X for treating superficial bladder carcinoma. Intravesical was better than intravenous ALA in eradicating bladder carcinoma with PDT.     

Whole bladder wall photodynamic therapy with in situ light dosimetry for carcinoma in situ of the bladder.

We report on the preliminary results of 12 patients with multifocal carcinoma in situ of the bladder treated with whole bladder wall photodynamic therapy. The total light dose (scattered plus nonscattered light) measured in situ was 100 joules per cm.2 in the first 6 patients (group 1) and 75 joules per cm.2 in the remaining 6 (group 2). These light doses correspond on the average to 27 joules per cm.2 and 15.5 joules per cm.2 nonscattered light as reported by other investigators. Followup ranged from 6 to 22 months (average 11.5). In group 1, 2 tumors recurred after 6 and 9 months, respectively, and 2 other patients had a permanently shrunken bladder without evidence of disease. In group 2, 1 tumor recurred 5 months after photodynamic therapy. In this group the bladder capacity increased on the average to 135% of the pretreatment value 3 months after photodynamic therapy. All recurrences were in patients with a history of invasive bladder cancer (stages T1 and T2). These preliminary results demonstrate the importance of in situ scattered light dosimetry for minimizing local side effects of whole bladder photodynamic therapy.     

Integral laser photodynamic treatment of refractory multifocal bladder tumors

Integral photodynamic therapy with hematoporphyrin derivative was performed on 35 patients who had resistant transitional cell carcinoma of the bladder, mainly carcinoma in situ. The light source was an argon ion pumped dye laser (wavelength 630 nm.) using rhodamine B. Two types of laser light scattering diffuser developed at our department were used: a motor driven laser light scattering diffuser with computer regulation, and an endoscope modified light scattering diffuser tipped with a small quartz bulb containing a lipid nutritious solution as the scattering medium. The total energy density used was 10 to 30 J./cm.2. Of the 35 patients 24 (68.6%) achieved a complete response and 5 (14.3%) a partial response at 3 months. In 10 of the 24 patients there was no recurrence with an average tumor-free interval of 20.9 +/- 16.7 months, ranging from 5 to 60 months. Bladder capacity was decreased to approximately 150 ml. for 3 months after the integral photodynamic therapy without any evidence of hydronephrosis on excretory urograms, except for 2 patients who had a contracted bladder before photodynamic therapy. Integral photodynamic therapy may prove to be useful for the treatment of carcinoma in situ of the bladder.     

The use of photodynamic therapy (PDT) for the treatment of superficial tumours on the bladder wall

The use of photodynamic therapy (PDT) for the treatment of superficial tumours on the bladder wall is described. Details are given on the laser, methods of delivering light into the bladder, suitable commercial dosimetry systems and instrumentation suitable for making light measurements on the bladder wall during therapy. New alternative photosensitizers are discussed in some detail. Some early clinical results are presented and the current problems with this type of therapy are highlighted.     

Photodynamic therapy of superficial bladder tumors

Photodynamic therapy (PDT), using hematoporphyrin derivative (HPD) and the red light (wavelength 630 nm) of an argon-dye laser as the source of excitation energy was performed on 46 patients with superficial bladder tumors. Two methods of laser irradiation, (1) focal PDT using a 400 micron quartz fiber through a cystourethroscope in 22 patients with superficial bladder tumors and (2) whole bladder wall total PDT using a motor-driven laser light scattering device in 24 patients with multifocal carcinoma in situ and/or dysplasia of bladder mucosa associated with multicentric concurrent superficial tumors, were used. The patients in (2) had been referred for total cystectomy, and 19 of these 24 patients had a history of several transurethral resections, hyperthermia and/or instillation therapy. HPD 2-4 mg/kg was i.v. injected 48 to 72 hours before PDT. Judging from the results of 60 protrusions treated by focal PDT, the light power should be 200 mW/cm2 for 5-10 minutes or more and the total light energy should be 100 J/cm2 or more in tumors up to 2 cm in size. With focal PDT, 4 of the 22 patients had no recurrence with the mean tumor free time of 20.8 months. In 6 of the 24 patients treated with total PDT using 10, 20 or 30 J/cm2 of light energy, there was no recurrence with a mean tumor-free time of 7.5 months and there was no significant relationship between the recurrence rate and total light energy used.     

5‐Aminolevulinic acid‐mediated photodynamic therapy for bladder cancer

Photodynamic therapy using 5‐aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5‐aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low‐invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5‐aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low‐energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low‐invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5‐aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment‐resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5‐aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer.     

Photodynamic therapy.

The preliminary data suggest that red-light whole-bladder photodynamic therapy is safe and effective in the treatment of Tis and may be useful in the prophylactic management of superficial bladder cancer. Theoretically, whole-bladder photodynamic therapy has the advantage of higher efficacy after a single treatment than most conventional modalities for superficial bladder cancer. In patients with Tis, the complete response rate is 88%, and 25% have recurrences during a mean follow-up of 20 months (range 12-60). In patients undergoing prophylaxis, the recurrence rate is 31% and the median time to recurrence is 18 months. Importantly, none of the high-risk patients treated with whole-bladder photodynamic therapy has developed disease progression in stage or grade at the time of recurrences. Whole-bladder therapy also has the potential advantage of repeat treatment without increased tumor resistance or increased morbidity. Data from the present phase II-III clinical trials involving a large number of patients will define the role of photodynamic therapy in the management of superficial bladder cancer.     

The morphological and functional changes in rat bladder following photodynamic therapy with phthalocyanine photosensitization

We have studied photodynamic therapy (PDT) in the rat bladder with a new photosensitizer, aluminium sulfonated phthalocyanine (AlSPc) given intravenously and intravesically. The microscopic distribution of photosensitizer fluorescence in the bladder wall was studied by laser fluorescence microscopy. Prior to PDT the bladder capacity and compliance were assessed by filling cystometry. Intravesical red light (675 nm.) from a copper vapour pumped dye laser was used to activate the photosensitizer using light doses of 20 to 200 J/cm2. Urodynamic and histologic changes were studied at intervals for up to three months. The fluorescence studies showed that AlSPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 hours there was four times as much fluorescence from the mucosa and lamina propria compared to the deeper muscle. Control bladders illuminated with laser light alone showed no effects at these light doses. Animals treated 24 hours after sensitization showed a reduction in bladder capacity of up to 78% (20 J/cm2. light and 1.5 mg./kg.AlSPc). An initial reduction in compliance recovered in two weeks after low doses (0.5 mg./kg.) of AlSPc but was still abnormal at three months after higher doses (1.5 mg./kg.); though there was no long term histologic abnormality seen. Aluminium sulfonated phthalocyanine is a promising photosensitizer for bladder photodynamic therapy and using low doses of the drug it is possible to produce a superficial necrosis without muscle damage across a range of light doses. This heals by epithelial regeneration with no long term functional impairment. Direct absorption of this photosensitizer following intravesical administration seems unreliable.     

Complications of whole bladder dihematoporphyrin ether photodynamic therapy

Photodynamic therapy with dihematoporphyrin ether was used to treat superficial bladder tumors in 7 patients with a followup of at least 1 year. Each patient received treatment to the whole bladder and those with papillary lesions received additional focal treatment. At 3 months 4 of the 5 patients with papillary tumors (stages Ta and T1) and 1 of the 2 with diffuse carcinoma in situ (Tis) were free of disease. However, at 1 year only 3 patients remained free of disease. Of 5 patients with an increase in irritative bladder symptoms 4 had a contracted bladder, hydroureteronephrosis and vesicoureteral reflux. Deep bladder biopsies showed replacement of smooth muscle by fibrous tissue. Six patients had mild to moderate skin phototoxicity. We conclude that although photodynamic therapy is an attractive and exciting method to treat cancer, its use with dihematoporphyrin ether in cases of bladder carcinoma can be associated with significant complications. The correct treatment parameters for safe, effective therapy are not known to date.     

Photodynamic therapy for esophageal lesions: selectivity depends on wavelength, power, and light dose

BACKGROUND: Photodynamic therapy with 5-aminolevulinic acid-induced photosensitization could selectively eliminate esophageal epithelial lesions. This study aimed at optimizing laser parameters for 5-aminolevulinic acid photodynamic therapy of the normal rat esophagus. METHODS: Sixty rats received 200 mg/kg 5-aminolevulinic acid orally and were illuminated 3 hours later with either 633 or 532 nm light (n = 30 for each group) through an endoesophageal balloon catheter. Rats received either 8.3 or 25 J/cm diffuser, applied with a 33, 100, or 300 mW/cm diffuser. During illumination, tissue fluorescence measurements and light dosimetry were done. Rats were sacrificed at 48 hours after photodynamic therapy. RESULTS: During illumination, protoporphyrin IX fluorescence declined faster when a higher power output was used. Fluence rate at the esophageal surface was highest for 633-nm light. At 532 nm, light caused less damage to the epithelium and muscle than 633-nm light. Illumination with 33 mW resulted in selective epithelial ablation, whereas illumination with 300 mW caused muscle damage with minor epithelial damage. CONCLUSIONS: The assumed selective epithelial damage of 5-aminolevulinic acid photodynamic therapy in the esophagus largely depends on the combination of wavelength, power, and light dose applied. Most selective epithelial damage was found when low-power 633-nm light was used.     

δ-Aminolevulinic Acid and Blue Light Photodynamic Therapy for Treatment of Multiple Basal Cell Carcinomas in Two Patients with Nevoid Basal Cell Carcinoma Syndrome

BACKGROUND: Patients with nevoid basal cell carcinoma syndrome suffer from multiple basal cell carcinomas, requiring numerous surgical procedures that over time leave them with multiple disfiguring scars. Photodynamic therapy with delta-aminolevulinic acid using red light (approximately 630 nm) sources has been reported as effective in treatment of superficial and small nodular basal cell carcinomas. To our knowledge, the blue light source (417 nm peak irradiance) approved by the FDA for treatment of actinic keratoses has not been used for photodynamic therapy with delta-aminolevulinic acid of basal cell carcinoma. OBJECTIVE: We report treatment of two nevoid basal cell carcinoma syndrome patients, women aged 21 and 47, with 20%delta-aminolevulinic acid solution and 417-nm blue light source (irradiance 10 mW/cm(2)). METHODS: delta-Aminolevulinic acid was applied topically on lesions 1 to 5 hr before light treatment. Lesions were illuminated with 417+/-5-nm blue light for 1000 sec (10 J/cm(2)). Two consecutive treatments 1 week apart were administered as a therapeutic course. Each patient underwent two courses of photodynamic therapy with delta-aminolevulinic acid 2 to 4 months apart. The reported assessment was made 8 months after initial treatment. In most sessions the entire face, rather than visible basal cell carcinomas only, was treated. The treated basal cell carcinomas were clinically subdivided to superficial or nodular type guided by their morphologic features. A total of 9 superficial and 16 nodular basal cell carcinomas on the face and 27 superficial basal cell carcinomas on the lower extremities were treated. RESULTS: Complete clinical response was observed in 8 of 9 (89%) superficial basal cell carcinomas and 5 of 16 (31%) nodular basal cell carcinomas on the face and in 18 of 27 (67%) of superficial basal cell carcinomas on the lower extremities. The remaining 21 lesions showed partial clinical resolution. No new basal cell carcinomas were observed during the 8-month follow-up period in areas treated with a broad application technique. Resolution of the lesions was accompanied by an excellent cosmetic outcome and decreased prominence of old surgical scars in the more severely affected patient. Treatments were well tolerated, but associated with moderate to severe stinging during illumination. CONCLUSION: To our knowledge this is the first use of photodynamic therapy with delta-aminolevulinic acid with 417-nm blue light for treatment of multiple basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome. Our clinical results demonstrate that the blue light reduces cutaneous tumor burden in such patients. Further studies are needed to confirm that broad-area photodynamic therapy with delta-aminolevulinic acid may eradicate subclinical tumors in nevoid basal cell carcinoma syndrome sufferers, as suggested by a strikingly decreased incidence of new basal cell carcinomas in our patients.     

Whole bladder photodynamic therapy for orthotopic superficial bladder cancer in rats: a study of intravenous and intravesical administration of photosensitizers

PURPOSE: Photodynamic therapy after intravenous injection of Photofrin (QLT Phototherapeutics, Vancouver, British Columbia, Canada) results in a contracted bladder and skin photosensitivity, which limits its clinical application. In an attempt to overcome these limitations photodynamic therapy after intravesical instillation of Photofrin or 5-aminolevulinic acid (ALA) in an orthotopic rat bladder tumor model was explored and compared with intravenous Photofrin for photodynamic therapy efficacy and phototoxicity. MATERIALS AND METHODS: At 2 weeks after bladder implantation of 1.5 x 10(6) AY-27 tumor cells animals were randomly grouped. Photofrin was administered (5 mg./kg. intravenously and 2 mg./ml. intravesically). The ALA concentration for intravesical instillation was 300 mM. Whole bladder photodynamic therapy with graded doses of light (lambda = 630 nm.) was performed 4 hours after drug administration. Tumor control and complications were evaluated. RESULTS: Photodynamic therapy with intravenous Photofrin plus 100 J./cm.(2) light resulted in severe bladder damage. Of 10 rats 6 died and 2 of the 10 that received 50 J./cm.(2) died. There were no photodynamic therapy related deaths in groups receiving intravesical instillation of Photofrin or ALA that also received 50 to 100 J./cm.(2) Median survival in rats treated with ALA intravesically plus 75 J./cm.(2) (77 days), Photofrin intravesically plus 50 (67) or 100 J./cm.(2) (76) and Photofrin intravenously plus 50 J./cm.(2) (60) were significantly different from that in controls (44). CONCLUSIONS: Intravesical instillation of Photofrin or ALA can achieve the same photodynamic therapy efficacy as intravenous Photofrin in this orthotopic rat bladder tumor model with less phototoxicity to normal tissues.     

Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumours

OBJECTIVES: To assess (i) the optical properties and depth of penetration of varying wavelengths of light in ex-vivo human bladder tissue, using specimens of normal bladder wall, transitional cell carcinoma (TCC) and bladder tissue after exposure to ionizing radiation; and (ii) to estimate the depth of bladder wall containing cancer that could potentially be treated with intravesical photodynamic therapy (PDT), assuming satisfactory tissue levels of photosensitizer. Materials and methods The study included 11 cystectomy specimens containing invasive TCC (five from patients who had previously received external-beam bladder radiotherapy, but with recurrent TCC) and three 'normal' bladders removed from patients treated by exenteration surgery for extravesical pelvic cancer. Full-thickness bladder wall and tumour samples were taken from these specimens and using an 'intravesical' and a previously validated interstitial model, the optical penetration depths (i.e. the tissue depth at which the light fluence is 37% of incident) were calculated at wavelengths of 633, 673 and 693 nm. RESULTS: There were no significant differences in light penetration between normal and tumour-affected bladder tissue at each wavelength. There were significant differences in light penetration among wavelengths; light at 693 nm penetrated approximately 40% further than light at 633 nm (P < 0.002). The light currently used in bladder PDT (633 nm) has a mean (SEM) optical penetration depth of 4.0 (0.1) mm within TCC. In addition, at this wavelength, there was 29% greater light penetration in previously irradiated than in unirradiated bladder wall (P = 0.001). This did not occur in the tumour-affected bladder. CONCLUSIONS: Bladder tissue is relatively more translucent than other human tissues and there is therefore great potential for PDT in the treatment of bladder cancer. As there is no difference in light penetration between TCC and normal bladder tissue, a tumour-specific response with diffuse illumination of the bladder will depend on drug localization within the tumour. The currently used wavelength of 633 nm can be expected to exert a PDT effect within bladder tumour up to a depth of 20 mm. Increasing the wavelength will allow deeper pathology to be treated.     

Urinary cytokines following photodynamic therapy for bladder cancer. A preliminary report

This preliminary study was undertaken to test for the presence of urinary cytokines whose detection would provide evidence in support of the theory that photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2, and tumor necrosis factor-alpha were assayed for in the urine of 4 patients treated with photodynamic therapy for bladder cancer, in 7 control patients undergoing transurethral surgical procedures, and in 5 healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy nor in any of the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer.     

Treatment system for whole bladder wall photodynamic therapy with in vivo monitoring and control of light dose rate and dose

A system is described for in vivo monitoring and control of light dose rate and dose during whole bladder photodynamic therapy (PDT). A modified cystoscope admits an isotropic light source (fiber with diffusing tip, connected to a dye laser) and three translucent nylon catheters that are unfolded in three directions along the bladder wall. An isotropic light detector (0.8 mm. diameter probe on 200 microns. fiber) is inserted into each catheter and connected to an amplifier displaying light dose rate (in mW/cm.2) and integrated light dose (in J/cm.2) for each probe. Before treatment a low light level is used to optimize the position of the light source, requiring equal readings by each of the three dosimetry probes. Uniformity of irradiation is checked by moving the probes through their respective catheters along the bladder wall. With red light (wavelength 630 nm.) a dose rate uniformity of +/- 20% could be achieved in vivo in dog bladder. With green light (514.5 nm.) uniform irradiation was difficult, most likely due to a much smaller contribution of scattered light. Measurements during clinical PDT show that optimizing the light source position by suprapubic transvesical ultrasound may not secure uniform irradiation. Half-way into the treatment a difference of 100% between the readings of two probes was noted. Adjusting the position of the light source resulted in integrated light dose variations of less than 20% among the three probes at the end of treatment.