Data concerning the incidence of latent thyroid carcinoma (LTC) in populations with endemic goiter are scarce. Despite the introduction of iodine goiter prophylaxis in the early sixties, iodine supply is still insufficient in Austria and goiter remains endemic. This is the first detailed study dealing with epidemiological features of LTC at autopsy in Austria. A total of 118 thyroid glands were included in the study. The glands were serially sectioned at 2- to 3-mm intervals, embedded in paraffin and histologically examined for the presence of LTC. In addition, the incidence and severity of lymphocytic thyroiditis (LT) were evaluated. Ten thyroids were found to contain LTC (8.6%). All were of the papillary type. The mean tumor dimension was 4.9 mm +/- 3.2, the smallest lesion measuring 1 mm. Only the largest tumor slightly exceeded the extent of a microcarcinoma and measured 10.5 mm. Multifocal disease was present in three cases (30%). The prevalence of latent papillary thyroid carcinoma (LPTC) was 6.6% (n = 4) in females and 10.5% (n = 6) in males. The mean age of the subjects with LPTC was 67.7 +/- 14.4 yr, range 37 to 77 yr. Goitrous thyroids were seen in 33 cases (28%): One gland was diffusely enlarged and 32 (27.1%) enlarged glands were nodular goiters. The overall prevalence of LT was 30.5% (n = 36) and the only type of thyroiditis observed was focal lymphocytic thyroiditis (FLT). There was no correlation between the presence of LPTC and goiter, the presence of FLT and the subjects' age and sex. The incidence of LPTC in Austria is similar to that in nongoitrous regions. The adult population at large seems to be uniformly exposed to factors involved in the initiation and early growth of papillary thyroid carcinoma (PTC). This suggests that the levels of iodine intake only play a minor role in the early phase of the carcinogenesis of PTC, but may be of some importance in the progression of LPTC to clinically evident PTC.

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4122 Background: The VEGF pathway is the predominant mediator of angiogenesis in pancreatic cancer. Vatalanib (PTK787/ZK 222584) is a small molecule tyrosine kinase inhibitor of all known VEGF receptors. We initiated a phase I study of vatalanib and gemcitabine for advanced pancreatic cancer. Methods: Patients with newly diagnosed unresectable or metastatic pancreatic adenocarcinoma were enrolled. Previous adjuvant chemoradiotherapy with fluorouracil was allowed. Gemcitabine was given by fixed-dose rate infusion weekly x 3 in a 28-day cycle, and vatalanib was given orally daily. Dose-limiting toxicities (DLT) are defined as any grade 3/4 toxicity during the first cycle. The dose levels are as follows: Results: To date, 11 patients are evaluable for toxicity (5M/6F; median age 62 years, range 40–82 years; median KPS 90%). Thus far, 42 cycles have been given, with a median of four cycles per patient. Two patients have experienced DLT. The first patient (cohort 1) experienced grade 3 diarrhea and hypokalemia and grade 4 neutropenia occurring simultaneously and treated without sequelae. The second patient (cohort 3) developed grade 3 deep vein thrombosis. Beyond the first cycle, grade 3 toxicities included neutropenia (1), anemia (3), thrombocytopenia (1), hypertension (2), diarrhea (1), hypokalemia (1), thrombosis (1), and proteinuria (1). Three of eleven patients (27%) did not complete treatment to the first evaluation timepoint (2 cycles); two discontinued due to toxicity and one discontinued due to disease progression. Two of eleven patients (18%) had a partial response by RECIST. Six of eleven patients (55%) had stable disease as the best response ranging from 2–6 months. Conclusions: The combination of gemcitabine and vatalanib is generally well-tolerated with most grade 3/4 toxicities occurring late in the treatment course. Antitumor responses have been observed at initial dose levels and accrual to the final cohort with BID dosing of vatalanib continues. [Table: see text] No significant financial relationships to disclose.

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