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AIM: To study the therapeutic value of combination of cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer.METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study.Twelve patients had liver metastases.In all cases the tumors were considered unresectable after a comprehensive evaluation.Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously under guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT.A few patients received regional celiac artery chemotherapy.RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery.Some patients underwent repeat cryosurgery.125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases.Twenty patients, 10 of whom had hepatic metastases received regional chemotherapy.At 3 mo after therapy, CT was repeated to estimate tumor response to therapy.Most patients showed varying degrees of tumor necrosis.Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%.Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase.Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis.All adverse effects were controlled by medical management with no poor outcome.There was no therapy-related mortality.During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more.Overall, the 6-, 12-, 24-and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively.Eight patients had survival of 24 mo or more.The patient with the longest survival (40 mo) is still living without evidence of tumor recurrence.CONCLUSION: Cryosurgery, which is far less invasive than conventional pancreatic resection, and is associated with a low rate of adverse effects, should be the treatment of choice for patients with locally advanced pancreatic cancer.125Iodine seed implantation can destroy the residual surviving cancer cells after cryosurgery.Hence, a combination of both modalities has a complementary effect.