Summary Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The (Faber, 1988). Improved local control does require additional measures, but the disease responds poorly to radio-and chemotherapy (Lerner et al., 1983). As photodynamic therapy (PDT) has been reported to be effective in human mesothelioma xenografts (Feins et al., 1990), it might allow for an appropriate 'clean-up' of the thoracic cavity after surgery. For clinical purposes, the currently used sensitisers for PDT are haematoporphyrin derivatives (HpD) and dihaematoporphyrin ether (DHE) . However, PDT with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC) was superior to DHE-PDT with respect to antitumour activity and tissue selectivity in rodents without causing significant toxicity (Berenbaum, 1989). mTHPC might therefore be better fitted to large surface PDT as required for diffuse malignant mesothelioma treatment. A pilot study was done to evaluate mTHPC-PDT for diffuse malignant mesothelioma with respect to its antitumour activity and the feasibility of a combined modality approach under clinical conditions. Patients and methodsFour patients underwent mTHPC-PDT for diffuse malignant mesothelioma. Each patient was informed in detail about the experimental nature of the procedure and consent was obtained from each patient and from the local Human Investigations Committee of our institution.The four men were aged 46 (patient 1), 48 (patient 2), 65 (patient 3) and 50 years (patient 4), all having had possible occupation related exposure to asbestos. The main symptoms at admission were dyspnoea due to pleural effusion, chest pain and loss of weight. There was no evidence of disease in the peritoneal and contralateral chest cavity on CT-scans at admission. The right side was involved in patients 1, 2 and 4 and the left in patient 3. Previous biopsies revealed an epithelial (Figure la), a biphasic (Figure 2a), a sarcomatous and a mixed type of mesothelioma in the four patients and was confirmed in every case by immunohistologic examinations.Preliminary PDT To establish the efficacy of mTHPC-PDT and to optimise its tumouricidal effect, preliminary PDT was performed in patients 1 and 2 prior to its definitive application. Modulations of mTHPC dose, light dose and of the time interval between mTHPC application and activation were tested. mTHPC (Scotia Pharmaceuticals Ltd, Guildford, UK) was dissolved in 20% ethanol, 30% polyethylene glycol 400 and 50% H20 and administered over 15 min i.v. through a bacterial filter under sterile conditions within 60 min of preparation. Argon-pumped dye laser light of 650 nm (Coherent Innova 200 and Dye CR 599, GMP SA, Lausanne, Switzerland) was delivered through a sterilised optical fibre on tumour areas of 3 cm diameter. The power at the end of the optical fibre was measured wi...

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The influence of the time interval (TI) between drug administration and laser activation on selectivity of meta-tetrahydroxyphenylchlorin(mTHPC)-mediated photodynamic therapy (PDT) for tumour tissue was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Following i.p. administration of 0.3 mg/kg mTHPC, a light dose of 10 J/cm2 and 0.1 W/cm2 was delivered at 650 nm on the tumour and an equal-sized area of the hind leg after 4, 12, 24 and 36 hr and 2, 3, 4, 5 and 6 days to groups of 6 animals (surface irradiance). Then, 72 hr after light delivery, the depth of necrosis was measured in the tumour and in the skin and underlying muscle of the hind leg. Photosensitized necrosis occurred in normal tissue at TI from 4 hr to 3 days and in the tumour at TI from 12 hr to 4 days. The therapeutic ratio of mTHPC-PDT varied significantly with the time interval between drug administration and laser activation and was greatest at an interval of 3 days. mTHPC concentration was measured in 3 control unirradiated animals at all time points in normal tissues and in tumour tissue, and found to be the same in both tissues. Thus the tissue concentration of mTHPC was of limited use as regards the prediction of photosensitizing effects in the tumour model.

A total of 482 percutaneous transluminal angioplasties (PTAs)

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Complete recovery following rapid rewarming is described in three tourists who were admitted in a state of profound hypothermia with total cardiorespiratory arrest (rectal temperature ranging from 19 to 24 C). In all three patients, respiration and circulation had ceased during the rescue operation. Rapid core rewarming was achieved by thoracotomy and continuous irrigation of the pericardial cavity with warm fluids in one patient, whereas in the other two patients rewarming was accomplished with extracorporeal circulation using femoro-femoral bypass. In the first patient, the heart could not be defibrillated earlier than 90 minutes following thoracotomy; in the other patients rewarming was attained very rapidly, and within half an hour after institution of bypass, resuscitation of the heart was successful. The patients fully recovered their intellectual and physical abilities, despite the prolonged periods of circulatory arrest lasting from 2 1/2 to 4 hours. We conclude that rapid core rewarming is the adequate therapy for profound accidental hypothermia with circulatory arrest or low cardiac output. If feasible extracorporeal circulation represents the method of choice because it combines the advantage of immediate central rewarming with the benefit of efficient circulatory support, the heart is rewarmed before the shell, thus preventing the "rewarming shock" due to peripheral vasodilatation. Resuscitative efforts should be promptly initiated and vigorously pursued, even in the state of clinical death; in profound hypothermia neurologic examination is inconclusive regarding prognosis.

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Background and Objective Since there is no satisfactory treatment modality for diffuse malignant mesothelioma of the chest, we assessed surgical tumor resection followed by intraoperative photodynamic therapy with mTHPC in a phase I study. Study Design/Materials and Methods Since 1990, eight patients have undergone intraoperative photodynamic therapy with m‐tetrahydroxyphenylchlorin (mTHPC‐PDT) following thoracotomy and surgical tumor resection. Results mTHPC‐PDT‐mediated tumor necrosis was characterized by tumor infarction due to tumor vessel necrosis and thrombosis, and its extent depended on drug‐light conditions; 650 nm light delivered at 0.1 W/cm2 for 10 J/cm2 48 h after iv administration of 0.3 mg mTHPC/kg resulted in a 10‐mm‐deep complete tumor necrosis. Skin photosensitivity was related to the drug dose applied and occurred up to 17 days after iv administration of 0.3 mg mTHPC/kg, mTHPC‐PDT of brachial plexus infiltrated by mesothelioma resulted in pain relief without deterioration of nerve function. Conclusion Tumor resection and intraoperative mTHPC‐PDT of the chest cavity is feasible under clinical conditions and offers local tumor control of sites involved. However, distant tumor spread was not prevented by this combined treatment modality and optimization of mTHPC‐PDT is warranted for further intraoperative application. © 1996 Wiley‐Liss, Inc.