C Schröder

Technique and results of hyperthermic (41°C) isolated lung perfusion with high-doses of cisplatin for the treatment of surgically relapsing or unresectable lung sarcoma metastasis

OBJECTIVE A technique of hyperthermic isolated lung perfusion (ILP) chemotherapy was developed. METHODS Since April 1999, four patients with unilateral (n=2) or bilateral (n=2) sarcoma metastasis confined to a lobe (n=2) or entire lung (n=2) entered into a pilot study of hyperthermic (41 degrees C) ILP with high doses of cisplatin (70 mg/m(2)). Eligibility included drug resistant metastasis and at least four previous surgical metastectomies. The ILP of the lung segments was carried out following metastectomy, for 20-40 min at a rate of 0.3-0.5 l/min, a mean perfusion pressure lower than the own mean pulmonary artery pressure, and an inflow temperature of 41 degrees C or higher. Before and following ILP, the isolated lung segments were flushed with normothermic saline (1 l). Flow was continuously maintained by a centrifugal pump. RESULTS All patients successfully completed 31.7+/-9 min perfusion time at 41.4+/-0.3 degrees C, and this time-point corresponded to the maximal platinum lung-uptake (93.8 ng/mg tissue). The total vascular isolation was confirmed by continuously low systemic cisplatin plasma levels. There was no systemic drug-related toxicity but all patients experienced transient pulmonary toxicity as non-cardiogenic edema of the treated lung segments. With a median follow-up of 12 months, three patients are alive and disease-free and one died from cerebral metastasis without autopsy evidence of local recurrence 13 months following ILP. CONCLUSION Hyperthermic perfusion chemotherapy can be done safely and effectively. It represents a new treatment modality and deserves further investigations for patients with advanced, drug resistant or surgically refractory, lung sarcoma metastasis. However, further studies are needed to limit the ILP-induced pulmonary toxicity.

Absence of PERV specific humoral immune response in baboons after transplantation of porcine cells or organs

Abstract Xenotransplantation of pig organs seems a promising way of overcoming the prevailing limitation on allotransplantation due to donor numbers. However, as porcine endogenous retroviruses (PERVs) can infect human cells in vitro, there is substantial concern regarding the risk of a PERV infection in xenogeneic transplant recipients. Cultured porcine endothelial cells, stimulated peripheral blood mononuclear cells, and pancreatic islet cells can release PERV infectious for human cells in vitro, but it is currently unknown whether PERV is released in vivo, whether these viral particles can infect the transplant recipient, and whether they are pathogenic. In a retrospective study 15 immunosuppressed baboons were tested for a specific immune response against PERV after transplantation of porcine endothelial cells, mononuclear blood cells, and lungs. Anti‐PERV antibody expression was analyzed with peptide‐based, enzyme‐linked immunosorbent assays and highly sensitive Western Blot assays. This xenotransplantation study using nonhuman primates found no evidence of PERV specific humoral immune response. Our data suggest that no productive PERV infection and no continuous PERV release takes place in the nonhuman primates analyzed in this study.