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Purpose To assess the feasibility and efficacy of intraoperative ultrasound-guided implantation of 125I seeds for the treatment of unresectable pancreatic carcinoma, and analyze the associated prognostic factors.Methods and Materials Twenty-eight patients with pancreatic carcinoma who underwent laparotomy and were considered to have unresectable tumors were included in this study.Nine patients were pathologically diagnosed with Stage Ⅱ disease, and nineteen patients with Stage Ⅲ disease.Twenty-eight patients received intraoperative ultrasound-guided 125I seed implantation and received a D90 (at least 90% of the tumor volume received the reference dose) ranging from 60 to 163 Gy, with a median of 120 Gy.Seven patients received an additional 35-50 Gy by external beam radiotherapy after seed implantation, and ten patients received two to ten cycles of chemotherapy.Overall survival of the patients was calculated and prognostic factors were evaluated.Results Of the patients, 94.1% (16/17) achieved partial to complete pain relief.The tumor response rate was 78.6% (22/28), and local control was achieved in 85.7% (24/28) of patients.The 1-, 2-and 3-year survival rates were 30%, 11% and 4%, and the median survival was 10.1months (95% CI: 9.0-10.9).Analysis using the Cox proportional hazards model suggested that patients younger than 60 years and patients who received a D90 higher than 110 Gy may survive for a longer period.Conclusions 125I seed implantation provides a safe and effective method to relieve pain, control local tumor growth and, to some extent, prolongs the survival of patients with stage Ⅱ and Ⅲ pancreatic disease,without additional complications.Age and accumulated dose may be factors predictive of a favorable outcome for patients with unresectable pancreatic carcinoma treated with 125I seeds.These findings need to be validated by conducting further studies with larger cohorts.