BACKGROUND/OBJECTIVES:Correlation of photodynamic activity (PDT) and fluorescence signaling for free and pegylated meta-tetrahydroxyphenylchlorin (mTHPC) in nude mice with mesothelioma xenografts.STUDY DESIGN/MATERIALS AND METHODS:Twelve animals received light delivery (20 J/cm(2), 150 mW/cm(2), spot size 1.2 cm) on the tumor and the hind leg 3 days after sensitization with 0.15 mg/kg free mTHPC (n = 6) or equimolar-dosed pegylated mTHPC (n = 6). Groups of three animals each were sensitized with 0.15 and 0.5 mg/kg free mTHPC or equimolar dosed pegylated mTHPC followed after 3 days by fluorescence microscopy measurements.RESULTS:Pegylated mTHPC resulted in a similar extent of PDT-related tumor necrosis but in lower skin phototoxicity than free mTHPC. Both mTHPC formulations were heterogeneously distributed in the tumor and were mainly localized in perivascular areas. Pegylated mTHPC revealed a higher tumor to skin fluorescence intensity ratio than free mTHPC (P<0.001).CONCLUSIONS:Fluorescence signaling measurement has the potential to predict the photodynamic activity for both mTHPC formulations in mesothelioma xenografts.

Background. Antegrade and retrograde doxorubicin-based isolated lung perfusions were compared in rodents bearing a sarcomatous tumor in the perfused lung. Inasmuch as these tumors derive their vascularization from the bronchial artery system, we hypothesized that retrograde isolated lung perfusion through the pulmonary vein might result in an improved tumor drug uptake.Methods. Single-pass antegrade (n = 9) and retrograde (n = 9) isolated left lung perfusions were performed with 100 mu g of doxorubicin in Fischer rats 10 days after subpleural tumor cell injection. The perfusion, washout, and recirculation times were 20, 10, and 60 minutes, respectively, followed by harvesting of the lung. The doxorubicin concentration and compartmental distribution in the tumor and in normal parenchyma of each perfused lung were measured by high-pressure liquid chromatography (6 animals of each group) and fluorescence microscopy (3 animals of each group).Results. Doxorubicin concentration and pattern of doxorubicin-based fluorescence signaling were comparable for both perfusion techniques in normal lung tissue. Antegrade and retrograde isolated lung perfusion resulted in similar tumor drug uptake, which was lower than in normal lung parenchyma, and in weak and sporadic fluorescence signaling emerging from the tumor periphery and from blood vessels situated within the tumor tissue.Conclusions. Retrograde isolated lung perfusion did not confer a better doxorubicin uptake in the tumor as compared with antegrade lung perfusion despite the fact that the tumor vascularization in this model is based on the bronchial artery circulation.

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/cm2 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/cm2 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.

Isolated cytostatic lung perfusion (ILP) is an attractive technique allowing delivery of a high-dose of cytostatic agents to the lungs while limiting systemic toxicity. In developing a rat model of ILP, we have analysed the effect of the route of tumour cell injection on the source of tumour vessels. Pulmonary sarcomas were established by injecting a sarcoma cell suspension either by the intravenous (i.v.) route or directly into the lung parenchyma. Ink perfusion through either pulmonary artery (PA) or bronchial arteries (BA) was performed and the characteristics of the tumour deposits defined. i.v. and direct injection methods induced pulmonary sarcoma nodules, with similar histological features. The intraparenchymal injection of tumour cells resulted in more reliable and reproducible tumour growth and was associated with a longer survival of the animals. i.v. injected tumours developed a PA-derived vascular tree whereas directly injected tumours developed a BA-derived vasculature.

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.

We report 2 cases of congenital aneurysm, 1 of the left atrium and 1 of the left atrial appendage. The patients were 14 and 27 years of age, respectively. Their common symptoms were paroxysmal palpitations and dyspnea. Diagnoses were suggested by chest radiographic films that revealed prominent convexity at the upper left border of the heart and were confirmed by echocardiography, which demonstrated a large cystic mass attached to the left atrium in each case. Aneurysmectomy was performed through a median sternotomy or a left thoracotomy, with cardiopulmonary bypass in 1 patient and without it in the other. Both patients were discharged, free of symptoms, in sinus rhythm. We conclude that echocardiography can provide a clear diagnosis and that aneurysmectomy is the treatment of choice.