title: Elevated serum cytokine levels in mesothelioma patients who have undergone pleurectomy or extrapleural pneumonectomy and adjuvant intraoperative photodynamic therapy.
abstract: Patients treated on a Phase-I clinical trial of photodynamic therapy (PDT) developed a systemic capillary leak syndrome that constituted the dose-limiting toxicity. We examined serum samples from patients treated at the maximally tolerated dose level for evidence of a systemic, cytokine-mediated inflammatory response. Patients underwent pleurectomy or extrapleural pneumonectomy (EPP) followed by intraoperative PDT of the thorax using Foscan at a dose of 0.1 mg/kg 6 days before surgery and 652 nm red light at a dose of 10 J/cm2. Levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12 were assayed before Foscan administration; after anesthetic induction, surgical resection and light delivery; in postoperative recovery and the day after the surgery. Of the analyzed patients, eight underwent a pleurectomy and one an EPP followed by PDT. IFN-gamma, TNF-alpha and IL-12 showed no elevation, but IL-1beta, IL-6, IL-8 and IL-10 levels were elevated after surgery and PDT. IL-1beta showed a statistically significant variation from baseline after surgery and IL-6, after PDT. The results suggest a systemically mediated inflammatory response resulting from thoracic surgery followed by PDT. Further investigation of specific mechanisms is warranted.
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Sue S
authors.initials: SS
authors.lastname: Yom
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Friedberg
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: Deborah
authors.initials: D
authors.lastname: Smith
authors.forename: Eli
authors.initials: E
authors.lastname: Glatstein
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use; D008654:Mesothelioma / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D008875:Middle Aged; D010778:Photochemotherapy; D035422:Pleural Cavity / Q000601:surgery; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D011013:Pneumonectomy
chemical_list: D016207:Cytokines; D008652:Mesoporphyrins; C072269:temoporfin