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Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer Wansik Yu, MD, FACS Kyungpook National University Taegu, Korea
Mechanism of Dissemination Detachment of cancer cells Movement through the peritoneal cavity Attachment to the peritoneum Invasion into the subperitoneal tissue Proliferation
Management Surgery Left upper abdominal evisceration Peritonectomy Chemotherapy Systemic chemotherapy Intra-arterial chemotherapy Intraperitoneal chemotherapy
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
Principles of Hyperthermia Direct cytocidal effect by hyperthermia degeneration of protein impairment of nucleic acid synthesis chromosomal damage Vascular bed thrombosis occlusion
Augmentation of Cytotoxicity Hypoxia Low pH Hypoglycemia Radiation Ethanol Some anticancer drugs Increased permeability
ChemoThermo-Sensitivity* Normothermia Hyperthermia** CDDP5%32% VP-160%31% MMC6%38% ADM0% 8% * MTT assay with 21 gastric cancers ** 43 C for 1 hour
Methods of Hyperthermia Systemic hyperthermia Regional perfusion hyperthermia Radiofrequency capacitive hyperthermia Intracavitary hyperthermic perfusion
Hyperthermic IP Chemotherapy Postoperative (closed method) Intraoperative (open method) after reconstruction peritoneal cavity expander before reconstruction coliseum technique manual stirring
Closed (Postoperative) Method drugs thermistor 44~45 C pump 40~42 C 48~50 C water bath
Peritoneal Cavity Expander filter drugs Peritoneal cavity expander pump Heat exchanger 43 C 42 C
Coliseum Technique 1 8 7 6 5 4 32 1 1. Chemotherapy reservoir 2. In-flow pump 3. Out-flow pump 4. Heat exchanger 5. Temperature probe 6. Thermometer 7. Temperature probes 8. Smoke evacuator 9. Thompson retractor
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
Clinical Experience ABC Effect32%90%* Therapeutic # 16%no effect47% Prophylactic † 52%:32% ‡ 63%:43% ‡ A; Kanazawa, B; Tottori, C; Lyon *Ascites control # 2-year survival rate, † 5-year survival rate ‡ P<0.05
Survival Distribution 0 2 4 6 years % 100 50 0 HIC(-) (n=21) HIC(+) (n=33) (With macroscopical residual disease)
HIC(+) (n=17) HIC(-) (n=13) % 50 0 100 0 2 4 6 years Survival Distribution (After complete cytoreduction)
Peritonectomy systematic peritoneal stripping Indication limited number of metastatic nodules on the peritoneum without other distant metastasis
vessel mesothelial cells fibroblast cancer cells drugs fibrosis muscle Peritonectomy Heat Peritoneal cavity Drug
Complications A B C D Leakage3% 5% 4% 0% BM suppression9% 0% 0% 6% Renal failure6% 0% 0% 0% Perforation2% 5% 0% 6% A; Kanazawa, B; Tottori, C; Lyon, D; Taegu
Mean Temperatures CC
Problems To Be Solved Even distribution of heat Even distribution of drug Morbidity and mortality Drug combination Safety considerations Cost (equipments)
Treatment of AGC Resection + Systematic lymphadenectomy + Perioperative IP Chemotherapy (IO/with or without heat, EP) + Peritonectomy + Systemic chemotherapy (?)
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