Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer

1. Hyperthermic Intraperitoneal Chemotherapyfor Gastric Cancer Wansik Yu, MD, FACS Kyungpook National University Taegu, Korea

2. Mechanism of Dissemination Detachment of cancer cells Movement through the peritoneal cavity Attachment to the peritoneum Invasion into the subperitoneal tissue Proliferation

5. Management Surgery Left upper abdominal evisceration Peritonectomy Chemotherapy Systemic chemotherapy Intra-arterial chemotherapy Intraperitoneal chemotherapy

6. Heat Diseases that medicines do not cure are cured by the knife. Those that the knife does not cure are cured by fire. Those that fire does not cure must be considered incurable. Hippocrates

7. Principles of Hyperthermia Direct cytocidal effect by hyperthermia degeneration of protein impairment of nucleic acid synthesis chromosomal damage Vascular bed thrombosis occlusion

8. Augmentation of Cytotoxicity Hypoxia Low pH Hypoglycemia Radiation Ethanol Some anticancer drugs Increased permeability

9. ChemoThermo-Sensitivity* Normothermia Hyperthermia** CDDP 5% 32% VP-16 0% 31% MMC 6% 38% ADM 0% 8% * MTT assay with 21 gastric cancers ** 43C for 1 hour

10. Methods of Hyperthermia Systemic hyperthermia Regional perfusion hyperthermia Radiofrequency capacitive hyperthermia Intracavitary hyperthermic perfusion

11. Hyperthermic IP Chemotherapy Postoperative (closed method) Intraoperative (open method) after reconstruction peritoneal cavity expander before reconstruction coliseum technique manual stirring

12. Closed (Postoperative) Method drugs thermistor pump 44~45C water bath 48~50C 40~42C

13. Peritoneal Cavity Expander drugs 43C pump Heat exchanger 42C filter Peritoneal cavity expander

14. Coliseum Technique 1 • Chemotherapy reservoir • In-flow pump • Out-flow pump • Heat exchanger • Temperature probe • Thermometer • Temperature probes • Smoke evacuator • Thompson retractor 2 3 4 5 6 7 1 8

16. General Management Control of intraperitoneal cavity temperature monitoring Replacement of serum protein fresh frozen plasma / human albumin Prevention of pulmonary edema hemodynamic monitoring dopamin / furosemide

17. Clinical Experience A B C Effect 32% 90%* Therapeutic# 16% no effect 47% Prophylactic† 52%:32%‡ 63%:43%‡ A; Kanazawa, B; Tottori, C; Lyon *Ascites control #2-year survival rate, †5-year survival rate ‡P<0.05

18. Survival Distribution (With macroscopical residual disease) % 100 HIC(-) (n=21) 50 HIC(+) (n=33) 0 0 2 4 6 years

19. Survival Distribution (After complete cytoreduction) % 100 50 HIC(+) (n=17) HIC(-) (n=13) 0 0 2 4 6 years

20. Peritonectomy Peritonectomy systematic peritoneal stripping Indication limited number of metastatic nodules on the peritoneum without other distant metastasis

21. Peritoneal cavity Heat Drug Peritonectomy muscle vessel fibroblast fibrosis mesothelial cells cancer cells drugs

22. Complications A B C D Leakage 3% 5% 4% 0% BM suppression 9% 0% 0% 6% Renal failure 6% 0% 0% 0% Perforation 2% 5% 0% 6% A; Kanazawa, B; Tottori, C; Lyon, D; Taegu

23. Mean Temperatures C

24. Problems To Be Solved Even distribution of heat Even distribution of drug Morbidity and mortality Drug combination Safety considerations Cost (equipments)

26. Treatment of AGC Resection + Systematic lymphadenectomy + Perioperative IP Chemotherapy (IO/with or without heat, EP) + Peritonectomy + Systemic chemotherapy (?)

28. 謝謝 감사합니다. Thank you very much.