Current 5-year survival after complete resection of pulmonary metastases is ≈ 30%, and many patients develop pulmonary recurrences. Obviously new treatment options are needed for this indication. Isolated lung perfusion (ILuP) is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. Recently, a phase I trial of ILuP combining 45 mg melphalan followed by pulmonary metastasectomy for resectable lung metastases proved to be feasible and safe.

The current 3-center phase II study (including University Hospital Antwerp/P. van Schil and Anthonius Hospital Nieuwegein/F. Schramel) allows patients with resectable lung metastases from colorectal cancer, soft tissue- and osteosarcoma to be treated with ILuP prior to metastasecomy.

At Leiden University Medical Center we treated 8 patients: 4 with colorectal cancer (age 54–59 y), 2 osteosarcoma (19–20 y), 1 sarcoma NOS of bone (38 y) and 1 sarcoma NOS (56 y) of soft tissue. The number of metastases was 1–2 and one patient had resection of 9 metastases. The procedure was uncomplicated in 7 cases and 1 patient had reversible pulmonary edema. Hospital admission duration was 6–8 days in the uncomplicated group and 14 days in the one patient with a complication. No long term toxicity was observed with extensive follow-up including lung function tests. With a median follow-up of 7 months (range 2–16), only the patient with 9 metastases had a recurrence and died of disease.

Our single center prelimininary data show that ILuP is feasible and does not lead to irreversible or severe toxicity. Compared to retrospective data with metastasectomy alone, perfusion did not add toxicity. Follow-up is too short to draw any conclusions on efficacy.

Purpose: Adolescent idiopathic scoliosis (AIS) is know to occur in families and research has shown that in populations or predominantly Northern European origin, 97% of AIS patients are related to families with AIS. It affects 1–2% of the population and results in deformities treated by bracing and surgery. Brace prescription is empirical and surgery is reserved for late cases and brace failures. Identifying the genetic markers for AIS would allow creation of a diagnostic gene-based test that may also have prognostic value for differentiating progressive and non-progressive curves.

Methods: A 21 million name data base of the original European pioneers in Utah was assembled including 3 million descendents and 18 million ancestors. 500 DNA samples from affected and first degree unaffected relatives were collected and genotypes determined with capillary electrophoresis using 763 autosomal markers and gene chip scanning for 116 000 SNPs. Disease haplotypes were also scanned with a 500K SNP chip to further narrow the position of each loci.

Results: Two markers were identified with LOD scores of 7.0 and 7.3. p-values from SNP scanning were highly significant. More detailed descriptions of these genotypes will be presented.

Conclusion: Two genetic markers were identified, one of which was present in 95% of patients with AIS greater than 40°. In our population, no one with AIS less than 40° had these markers. A genotype test for AIS may be possible that would offer both diagnostic and prognostic value. Further characterization of the genes and their mutations could give information concerning the molecular pathway that lead to disease expression.