Photodynamic therapy of C3H tumours in mice: Effect of drug/light dose fractionation and misonidazole

C3H mammary carcinomas transplanted to the feet of mice were treated with haematoporphyrin derivative (HPD) or Photofrin II(PII) and laser light at 630 nm. While fluence rates lower than 100 mW cm⁻² gave minimal hyperthermic effects, a slight but significant growth delay was observed in unsensitized tumours exposed to a fluence rate of 150 mW cm⁻² which induced tumour temperatures in the range 40–50°C. Different modes of fractionation of the light fluence and of the HPD dose were tested but were found to give poorer rather than better results than the application of a single light exposure 24 h after intraperitoneal injection of HPD. Different PII doses were applied together with different light fluences, keeping the product of the drug dose and light fluence constant. In the dose range 6.25–50 mg/kg body weight the resulting effect on tumours was constant, allowing for a slight effect of hyperthermia at the highest light fluences, and possibly a photodegradation of PII. Misonidazole given before photodynamic treatment (PDT) slightly reduced the effect of PDT on the tumour growth. When given after PDT, however, misonidazole improved the therapeutic results significantly.     

Photodynamic laser cyclodestruction with chloroaluminum sulfonated Phthalocyanine (CASPc) or photofrin®(PII) Vs. Nd:YAG laser cyclodestruction in a pigmented rabbit model

Background and Objective: To investigate Photofrin® (PII) and CASPc for photodynamic therapy (PDT) of the ciliary body in rabbits. Study Design/Materials and Methods: PII (10 mg/kg) or CASPc (1 mg/kg) was given by ear vein. Pharmacokinetics were studied in frozen sections by fluorescence microscopy (CCD camera based low light detection system with digital image processing) at 1 and 24 h (8 rabbits;16 eyes). Laser light was delivered (argon pumped dye laser;630 and 675 nm;8 rabbits;16 eyes) by contact fiberoptic. To compensate for iris attenuation, irradiance was 125 mW/cm² (20, 40, 80, or 160 J/cm²). Controls (4 rabbits;8 eyes) received laser light without photochemicals (OD) and for comparison, continuous wave Nd:YAG laser by fiberoptic (0.8–1.2J;OS). Results: Localization studies showed intravascular distribution with some selective ciliary body distribution at 24 h (PII > CASPc). Rabbits treated with PII or CASPc exhibited variable amounts of gross ciliary body edema, infarction, and necrosis by 24–48 h. This response was not seen in PDT control tissues;damage was seen in the iris and ciliary body, with partial vacuolization of the pigment epithelium. Conclusion: PDT may offer a more selective approach to ciliary body destruction. A small but significant thermal effect was seen during PDT from melanin photon uptake with damage to iris and ciliary body. Thermal damage and potential interaction with ocular visual pigments may limit use of these photochemicals and wavelengths for PDT of the ciliary body © 1995 Wiley-Liss, Inc.     

Intraoperative photodynamic therapy of the chest cavity in malignant pleural mesothelioma bearing rats

BACKGROUND AND OBJECTIVE: Experimental assessment of anticancer effect, normal tissue damage, and toxicity of intrathoracic mTHPC-mediated photodynamic therapy (PDT) combined to surgery in malignant pleural mesothelioma (MPM) bearing rats. STUDY DESIGN/MATERIALS AND METHODS: Six days after implantation of syngenic malignant mesothelioma cells in the left chest cavity of Fischer rats (n = 21) and 4 days after sensitization (0.1 mg/kg mTHPC), a left-sided pneumonectomy was performed, followed by intraoperative light delivery (652 nm, fluence 20 J/cm(2)), either by spherical illumination of the chest cavity (fluence rate 15 mW/cm(2)) or by focal illumination of a tumor area (fluence rate 150 mW/cm(2)). Controls comprised tumor-bearing untreated animals, tumor-bearing animals undergoing pneumonectomy, and tumor-bearing animals undergoing pneumonectomy and light delivery without sensitization or sensitization without light delivery. No thoracocentesis was performed during follow-up. RESULTS: An invasively growing sarcomatous type of mesothelioma was found in all animals at day 10, without tumor necrosis in control animals. PDT resulted in 0.5-1 mm deep inhomogeneous tumor necrosis after spherical, and in a 1-2 mm deep tumor necrosis after focal illumination. No injury to mediastinal organs was observed, neither after PDT with spherical nor with focal light delivery except focal interstitial lung fibrosis at the mediastinal area of the opposite lung. All animals with pneumonectomy followed by spherical PDT of the entire tumor-bearing chest cavity died within 72 hours whereas all other animals survived. All animals that died presented massive pleural effusion. CONCLUSIONS: PDT following pneumonectomy in mesothelioma bearing rats was technically feasible and allowed to study its effect on tumor and normal tissues. PDT-related tumor necrosis was observed after spherical and focal light delivery, however, pneumonectomy followed by PDT with spherical light delivery to the tumor-bearing chest cavity resulted in fatal complications.     

Intrapleural photodynamic therapy: Results of a phase I trial

Background: The management of pleural neoplasms, specifically mesothelioma, remains difficult. We performed a phase I trial in 54 patients with isolated hemithorax pleural malignancy to determine (a) the feasibility of intraoperative, intrapleural photodynamic therapy after debulking surgery; (b) the influence of light dose/sensitizer interval on postoperative morbidity in order to define the photodynamic therapy (PDT) maximal tolerated dose (MTD); and (c) whether first order dosimetry could be applied to this complex geometry. Methods: Cohorts of three patients were given escalating intraoperative light doses of 15–35 J/cm² 48 h after i.v. delivery of 2.0 mg/kg Photofrin II (Quadra Logic Technologies, Vancouver, British Columbia, Canada), and then escalating light doses of 30–32.5 J/cm² after a 24-h sensitizer/operation interval. Twelve patients could not be debulked to the prerequisite 5 mm residual tumor thickness. The remaining 42 patients underwent 19 modified pleuropneumonectomies, five lobectomy-pleurectomies, and 18 pleurectomies. Intrapleural PDT was delivered using 630 nm light from two argon pump-dye lasers, and real-time and cumulative light doses were monitored using seven uniquely designed, computer-interfaced photodiodes. Results: There was one 30-day mortality from intraoperative hemorrhage. In the 48-h sensitizer/operation group (n=33), possible PDT-related complications included an empyema with late hemorrhage in one of three patients at 17.5 J/cm² and a bronchopleural fistula at 35 J/cm². At each of these light doses, three additional patients were treated without complication. Two patients subjected to 24-h sensitizer dosing and 32.5 J/cm² developed esophageal perforations after pleuropneumonectomy at identical sites. The MTD was declared as 30 J/cm² light with a 24-h dosing interval when none of the six patients (three original, three repeat) at that level developed toxicity. Conclusions: These data demonstrate that resection and intrapleural PDT can be performed safely with currently available sensitizers and lasers. Phase II and III trials are now warranted at this MTD in a homogeneous population of patients with pleural malignancies.The results of this study were presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.Work of the US government. Not subject to copyright in the United States.     

Polyhematoporphyrin-mediated photodynamic therapy and decortication in palliation of malignant pleural mesothelioma: a clinical pilot study

The aim of this study was to evaluate the additional effect of intraoperative photodynamic therapy (PDT) under hyperbaric oxygenation (HBO) when compared with decortication alone. From 1/1993 to 8/2002, palliation with decortication was done in 25 patients suffering from advanced malignant pleural mesothelioma. Fourteen patients received additional intraoperative PDT under HBO. The surgery and PDT/HBO was done 48 h after photosensitization with a polyhematoporphyrin, 2 mg/kg/BW using a diode laser delivering red light at 630 nm through a microlens. The light dose was calculated for 300 J with a distance of 1 cm from the tumor surface. At 6-month follow up local tumor control and survival showed a significant difference in both groups. Although the study only includes a small number of patients not allowing definite conclusions, it indicates that the additional PDT/HBO represents a safe and technically feasible approach in the palliative setting of advanced malignant mesothelioma of the pleura.     

Photodynamic therapy for colorectal cancer: a quantitative pilot study

Ten patients with colorectal cancers unsuitable for operation were treated with endoscopic photodynamic therapy (PDT). The patients were assessed before treatment, and at 1 week and 1 month after treatment by colonoscopy with biopsy and endoluminal ultrasound examination. The depth of tumour was measured and the effect of PDT was quantified by measuring the reduction in tumour depth. All patients were sensitized with 2.5 mg kg-1 of haematoporphyrin derivative, 48 h before phototherapy. A standard treatment protocol of light exposure was used. Up to four parts of the tumour were treated with 50J of red light (630 nm) from a tuneable dye laser, through a flexible optical fibre passed through the colonoscope and inserted into the tumour. Two patients with small lesions are tumour-free 20 and 28 months after PDT. One treatment of an advanced tumour was complicated by a haemodynamically significant secondary haemorrhage. PDT may be most suitable for the treatment of small tumours or for small areas of persistent tumour where the bulk has been removed by alternative techniques.     

Response of normal canine ureter to photodynamic therapy using a cylindrical fiber

Photodynamic therapy (PDT) was performed utilizing a cylindrical optical fiber to determine feasibility of distal ureteral treatment on 10 study and two control NIH foxhounds. The study animals were administered three mg./kg. dihematoporphyrin ether (Photofrin II) intravenously followed 48 hours later by open cystotomy. One ureter was irradiated with 42 joules of 630 nm. light delivered by a 660 micron diameter optical fiber modified for cylindrical light distribution. Intravenous urography was performed both at three days and six weeks post PDT. Hydroureteronephrosis was revealed in one treated ureter and one untreated ureter. Mild dilatation of the ureter was noted by urography in another treated ureter and in one ureter that did not undergo light irradiation; no distal obstruction was revealed in either case by proximal infusion of saline or by histopathology. Nine of the 10 treated ureters were found to have either no abnormal pathology or only minimal lymphocytic infiltration. In this study, the normal ureter was shown to tolerate photodynamic therapy at energy densities equivalent to those used to effect tumor regression and the feasibility of using a cylindrical optical fiber for treatment of ureteral malignancies was confirmed.     

Laser Therapy in Pulmonary Medicine

In this review, the different laser applications for diseases in the thoracic cavity are presented. The different laser types, Nd-YAG, CO₂, diode lasers and photodynamic therapy (PDT) and their indications are presented. The indications for endobronchial laser vary from benign disorders like granuloma to the more frequent ablation of endobronchial tumours. The promising use of treatment with PDT in early stage lung cancer and its adjuvant role in surgical resection of pleural malignancies is discussed. Emphasis is given to the data obtained so far for the different laser applications. Paper received 4 March 1997; accepted in final form 10 November 1997.     

Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model

OBJECT: Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of resection, indicating that a more aggressive local therapy could be beneficial. Photodynamic therapy (PDT) is a local treatment involving the administration of a tumor-localizing photosensitizing drug, in this case aminolevulinic acid (ALA). The effect depends on the total light energy delivered to the target tissue, but may also be influenced by the rate of light delivery. METHODS: In vitro experiments showed that the sensitivity to ALA PDT of BT4C multicellular tumor spheroids depended on the rate of light delivery (fluence rate). The BT4C tumors were established intracranially in BD-IX rats. Microfluorometry of frozen tissue sections showed that photosensitization is produced with better than 200:1 tumor/normal tissue selectivity after ALA injection. Four hours after intraperitoneal ALA injection (125 mg/kg), 26 J of 632 nm light was delivered interstitially over 15 (high fluence rate) or 90 (low fluence rate) minutes. Histological examination of animals treated 14 days after tumor induction demonstrated extensive tumor necrosis after low-fluence-rate PDT, but hardly any necrosis after high-fluence-rate treatment. Neutrophil infiltration in tumor tissue was increased by PDT, but was similar for both treatment regimens. Low-fluence-rate PDT administered 9 days after tumor induction resulted in statistically significant prolongation of survival for treated rats compared with nontreated control animals. CONCLUSIONS: Treatment with ALA PDT induced pronounced necrosis in tumors only if the light was delivered at a low rate. The treatment prolonged the survival for tumor-bearing animals.     

Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC

BACKGROUND AND OBJECTIVES: Experimental assessment of photodynamic therapy (PDT) for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC). STUDY DESIGN/MATERIALS AND METHODS: (a) PDT was tested on H-meso-1 xenografts (652 nm laser light; fluence 10 J/cm(2); 0.93, 9.3, or 27.8 mg/kg of PEG-mTHPC; drug-light intervals 3-8 days). (b) Intraoperative PDT with similar treatment conditions was performed in the chest cavity of minipigs (n = 18) following extrapleural pneumonectomy (EPP) using an optical integrating balloon device combined with in situ light dosimetry. RESULTS: (a) PDT using PEG-mTHPC resulted in larger extent of tumor necrosis than in untreated tumors (P < or = 0.01) without causing damage to normal tissue. (b) Intraoperative PDT following EPP was well tolerated in 17 of 18 animals. Mean fluence and fluence rates measured at four sites of the chest cavity ranged from 10.2 +/- 0.2 to 13.2 +/- 2.3 J/cm(2) and 5.5 +/- 1.2 to 7.9 +/- 1.7 mW/cm(2) (mean +/- SD). Histology 3 months after light delivery revealed no PDT related tissue injury in all but one animal. CONCLUSIONS: PEG-mTHPC mediated PDT showed selective destruction of mesothelioma xenografts without causing damage to intrathoracic organs in pigs at similar treatment conditions. The light delivery system afforded regular light distribution to different parts of the chest cavity.     

Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma

Background: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon α-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence or survival. Methods: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT. The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n=25) and no PDT (n=23) were similar with respect to age, sex, tumor volume, and histology. Results: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT). There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT, 21; no PDT, 17; stage IV, PDT, 0; 0; no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar. Conclusions: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM. Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

A controlled trial of Nd-YAG laser vs photodynamic therapy for advanced malignant bronchial obstruction

A prospective randomized study was set up to evaluate the efficacy of photodynamic therapy (PDT) compared with Neodymium Yttrium Aluminium Garnet (Nd-YAG) laser used endoscopically in patients with stage III inoperable lung cancer and substantial (>50%) endobronchial luminal obstruction: of the 26 patients in the study 11 were allocated to Nd-YAG laser treatment (Group I) and 15 to PDT (Group II). Patients were assessed clinically, radiologically, functinally and endoscopically before and at 1 monthly intervals after treatment for 3 months, then 3 monthly when applicable. Age, sex, pulmonary function and mean percentage of bronchial luminal opening before treatment were comparable in the two groups, and not statistically different. At 1 month after treatment all patients had subjective amelioration of their symptoms and objectively responded to treatment by a substantial increase in bronchial luminal opening. There was however a significantly greater improvement in the PDT (Group II) than the Nd-YAG laser treatment Group I (p<0.0006). The bronchial disobliteration was attended by improvement in pulmonary function which again was significantly greater in Group II (PDT) than in Group I (Nd-YAG). It was concluded that endoscopic PDT in patients with extensive lung cancer and major airway obstruction is more effective than Nd-YAG laser treatment.     

Photodynamic therapy for the treatment of induced mammary tumor in rats

The objective of this work was to evaluate photodynamic therapy (PDT) by using a hematoporphyrin derivative as a photosensitizer and light-emitting diodes (LEDs) as light source in induced mammary tumors of Sprague–Dawley (SD) rats. Twenty SD rats with mammary tumors induced by DMBA were used. Animals were divided into four groups: control (G1), PDT only (G2), surgical removal of tumor (G3), and submitted to PDT immediately after surgical removal of tumor (G4). Tumors were measured over 6 weeks. Lesions and surgical were LEDs lighted up (200 J/cm² dose). The light distribution in vivo study used two additional animals without mammary tumors. In the control group, the average growth of tumor diameter was approximately 0.40 cm/week. While for PDT group, a growth of less than 0.15 cm/week was observed, suggesting significant delay in tumor growth. Therefore, only partial irradiation of the tumors occurred with a reduction in development, but without elimination. Animals in G4 had no tumor recurrence during the 12 weeks, after chemical induction, when compared with G3 animals that showed 60 % recurrence rate after 12 weeks of chemical induction. PDT used in the experimental model of mammary tumor as a single therapy was effective in reducing tumor development, so the surgery associated with PDT is a safe and efficient destruction of residual tumor, preventing recurrence of the tumor.     

A phase I study of Foscan-mediated photodynamic therapy and surgery in patients with mesothelioma

BACKGROUND: Photodynamic therapy (PDT) is a light-based cancer treatment that, in the correct setting, can be delivered intraoperatively as an adjuvant therapy. A phase I clinical trial combining surgical debulking with Foscan-mediated PDT was performed in patients with malignant pleural mesothelioma. The purpose of the study was to define the toxicities and to determine the maximally tolerated dose (MTD) of Foscan-mediated PDT. METHODS: A total of 26 patients completed treatment. Tumor debulking was accomplished with either an extrapleural pneumonectomy (7 patients) or a lung-sparing pleurectomy-decortication (19 patients). Patients were injected with Foscan before surgery, and 652 nm light was delivered intraoperatively after completion of surgical debulking. Four light sensors were placed in the chest, allowing delivery of light to a uniform measured dose throughout the hemithorax. RESULTS: Four dose levels were explored. The MTD was 0.1 mg/kg of Foscan injected 6 days before surgery in combination with 10 J x cm(-2) 652 nm light. Dose limiting toxicity at the next higher dose was a systemic capillary leak syndrome leading to death in 2 of 3 patients treated at that dose. Other PDT-related toxicities included wound burns and skin photosensitivity. In all, 14 patients were treated at the MTD without significant complications. CONCLUSIONS: Foscan-mediated PDT can be safely combined with surgery at the established MTD. Unlike most other surgery-based multimodal treatments for mesothelioma, Foscan-mediated PDT affords the option, in selected patients, of accomplishing tumor debulking with a lung-sparing procedure rather than an extrapleural pneumonectomy. A phase II study is warranted.     

Tolerance of small bowel anastomoses in rabbits to photodynamic therapy with dihematoporphyrin ethers and 630 nm red light

Photodynamic therapy (PDT) is being evaluated in experimental clinical trials in patients with peritoneal malignancies. Some patients require partial small bowel resection with re-anastomosis prior to PDT because of bulky tumor or focal involvement of the small bowel by tumor. To assess the safety of PDT in this setting, the tolerance of small bowel anastomoses in New Zealand white rabbits to PDT with dihematoporphyrin ethers (DHE) and 630 nm light was studied. With conventional DHE doses of 1.5–2.5 mg/kg given 24 hours prior to surgery and light doses of 0–20 J/cm² of 630 nm light, no adverse effects were seen on the healing of small bowel anastomoses. Higher photosensitizer doses of 10 mg/kg and 20 mg/kg in conjunction with 20 J/cm², however, induced failure and breakdown of fresh anastomoses in 2/3 and 4/4 animals, respectively. © 1993 Wiley-Liss, Inc.     

Photodynamic therapy for esophageal tumors

Between 1982 and 1987, 40 patients with esophageal tumors (19 adenocarcinomas, 19 squamous carcinomas, and two melanomas) in whom conventional treatments were unsuccessful were treated with photodynamic therapy (PDT) after injection with either hematoporphyrin derivative or dihematoporphyrin ether. Patients underwent endoscopy again two to three days and one month after PDT and as needed when symptoms recurred. At one month, the average minimal diameter opening of 28 assessable tumors increased from 6 to 9 mm. Of the 35 patients who could be evaluated one month after PDT, the average improvement in food intake was from a liquid to a soft diet. Average survival time (from time of first treatment) was 7.7 months (n = 17) for adenocarcinoma, 5.8 months (n = 12) for squamous cell carcinoma, and 25 months (n = 2) for melanoma. Two patients with stage I adenocarcinoma were alive with no evidence of disease at 11 and 23 months. One patient with stage I squamous cell cancer died 18 months after PDT, with recurrence of tumor above the treated area noted eight months after treatment. One patient with stage I melanoma died of a synchronous colon cancer 31 months after PDT, with no evidence of residual melanoma.     

Preclinical comparison of mTHPC and verteporfin for intracavitary photodynamic therapy of malignant pleural mesothelioma

Efficacy and tumour selectivity of photodynamic therapy with two clinically approved sensitizers (mTHPC, verteporfin) were assessed for focal intracavitary photodynamic therapy (PDT) in rodents with malignant pleural mesothelioma (MPM) at recommended drug-light conditions and at escalating sensitizer dosages. MPM tumours were generated in 15 Fischer rats by subpleural mediastinal tumour cell injection followed after 5 days by intracavitary PDT with light delivery monitored by in situ dosimetry. Animals were intravenously sensitized either with mTHPC (0.1 mg/kg, n = 3; 0.2 mg/kg, n = 3) followed after 4 days by illumination with 20 J/cm(2) at 652 nm, or with verteporfin (0.6 mg/kg, n = 3; 1.2 mg/kg, n = 3) followed after 20 min by illumination with 100 J/cm(2) at 689 nm. Three untreated tumour-bearing animals served as controls. Histological evaluation of the treated tumour and of adjacent normal organs was performed 10 days after tumour implantation. The extent of PDT-induced tumour necrosis was compared to the non-necrosed area and expressed in percentage. A locally invasive growing MPM tumour (3.1 +/- 1 mm diameter) without spontaneous necrosis diameter was found in all animals. For both sensitizers, focal intracavitary PDT was well tolerated at drug-light conditions recommended for clinical applications. Mediastinal organs were spared for both sensitizers but verteporfin resulted in a higher extent of tumour necrosis (80%) than mTHPC (50%). Drug dose escalation revealed a higher extent of PDT-related tumour necrosis for both sensitizers (mTHPC 55%, verteporfin 88%), however, verteporfin-PDT was associated with a higher toxicity than mTHPC-PDT.     

Successful treatment of empyema thoracis with polymethylmethacrylate antibiotic-impregnated beads in the guinea pig

Two hundred nine Duncan-Harley guinea pigs had intrathoracic inoculation with 10(8) Staphylococcus aureus, accompanied by blood and umbilical tape. One hundred fifty-two animals were excluded because of clinical recovery, early death, or complications related to intrathoracic polymethylmethacrylate (PMMA) bead placement. The remaining 57 animals had clinical signs of empyema thoracis and were the subjects of this study. Group I animals (N = 24) served as the controls and had no therapy. Group II animals (N = 14) were treated by intrathoracic placement of placebo PMMA beads. Group III animals (N = 19) were treated by intrathoracic placement of tobramycin sulfate-impregnated PMMA beads. There were no differences between the groups in pleural reaction or pneumonia scores. These findings demonstrate a similar host response to the established infection. Group III, however, had a higher sterilization rate than Groups I and II (p less than 0.05), a finding underlining the therapeutic effect of tobramycin-treated PMMA beads. We conclude that intrathoracic local antimicrobial therapy with slow-release tobramycin-impregnated PMMA beads may enhance empyema treatment by increasing the rate of local sterilization. More experiments are necessary to assess the efficacy of this potentially important therapeutic arm for the treatment of thoracic empyema.     

Morphological effects of photodynamic therapy on rabbit bladder using Photofrin II and Photosan intravesically and intravenously.

Photodynamic therapy (PDT) has proved effective against superficial papillary bladder tumours and focal and diffuse carcinoma in situ. Effective topical administration of the sensitiser would be a welcome improvement. The morphological effects of PDT on the normal bladder were examined in 13 rabbits when 2 photosensitisers (Photofrin II and Photosan III) were applied intravesically (5 mg/kg for 1 h) and compared with intravenous administration (3 or 5 mg/kg). Four animals served as controls without a sensitiser. Intravesical red light (630 nm) from an argon dye laser was used to activate the photosensitiser, using light doses of 12 or 24 J/cm2. The animals were sacrificed either 1 or 5 to 7 days after the laser treatment. Intravenous dosage induced bladder wall oedema/haemorrhage and total necrosis of the epithelium. There was no difference between the effects of the 2 sensitisers. Intravesical application induced superficial epithelial necrosis. The control animals treated with laser light alone showed slight superficial injury to the cell layer.     

Photodynamic Therapy of Malignant Ovarian Tumours Cultivated on CAM

The disappointing results with either surgery alone and/or chemotherapy in the treatment of malignant ovarian tumours have led to an increased interest in additional treatment schedules. Photodynamic therapy (PDT), a modality involving the use of a photosensitising drug and activating light, is being used increasingly as a local treatment for neoplastic lesions. The synthesis and evaluation of new photosensitisers for the treatment of gynaecological lesions and malignancies continues to be an active area of investigation for proper application of the photodynamic process in the gynaecological field. The effect of PDT using methylene blue (free and combined with liposomes) as a photosensitiser for treating human ovarian malignant tumours cultivated on the chorioallantoic membrane was evaluated. Two days after PDT, the treated implanted tumours were markedly decreased in size. Areas of necrosis with black coloration, dryness and eschar formation were observed. Five days after PDT, tumour remission was clearly observed in all the treated tumours. Photodynamic therapy using methylene blue (aqueous and coupled with liposomes) is effective for treating the ovarian malignancies and it will be capable of achieving complete eradication of visible tumours in patients with superficial lesions. Paper received 3 January 1998; accepted after revision 2 July 1998.