Minimizing Systemic Leakage of Cisplatin during Percutaneous Isolated Pancreas Perfusion Chemotherapy: A Pilot Study.
OBJECTIVE
To evaluate the feasibility of percutaneous isolated pancreas perfusion (PIPP) by using a pig model.


METHODS
All experiments were approved by the institutional Animal Experiment Ethics Committee. Fifteen pigs were assigned to five groups, and PIPP was performed. Angiographic and dye injection studies were performed to confirm the patency of the PIPP system (group 1). Blood that contained cisplatin (1.5 mg per kilogram of body weight) in an extracorporeal circuit was circulated through the pancreas at three infusion rates (40, 60, and 80 mL/min) to determine the optimal infusion rate in terms of safety and pharmacologic effectiveness (groups 2, 3, and 4, respectively). Chronological laboratory data and histologic findings were assessed in group 5, which received the optimal infusion rate. Maximum platinum concentration (Cmax) and area under the platinum concentration-time curve were compared by using the Kruskal-Wallis and Mann-Whitney U tests.


RESULTS
Angiography and dye injection confirmed the patency of the PIPP system. Histopathologic examinations showed no abnormalities in the pancreas or other organs at a 40 mL/min infusion rate of cisplatin. However, edematous changes in the pancreas were observed at higher infusion rates. The pharmacologic effectiveness did not differ significantly among groups; therefore, the optimal infusion rate of 40 mL/min was selected. The median pancreatic-to-systemic exposure ratios were 71.8 for Cmax and 54.8 for the area under the curve. All laboratory data remained normal or returned to pretreatment levels within 1 week.


CONCLUSIONS
PIPP at a 40 mL/min infusion rate appears to be safe and feasible for perfusion of the pancreas.
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Satoru
S
Murata
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Shiro
S
Onozawa
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Takahiko
T
Mine
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Tatsuo
T
Ueda
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Fumie
F
Sugihara
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Daisuke
D
Yasui
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Shin-ichiro
S
Kumita
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Akira
A
Shimizu
From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).
Mitsuo
M
Satake
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000517:prevention & control*; D005240:Feasibility Studies; D005260:Female; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010865:Pilot Projects; D013552:Swine
D000970:Antineoplastic Agents; D002945:Cisplatin