Hyperthermic Intraperitoneal Chemotherapy

for Gastric Cancer

Wansik Yu, MD, FACSKyungpook National University

Taegu, Korea

Mechanism of Dissemination

Detachment of cancer cellsMovement through the peritoneal cavityAttachment to the peritoneumInvasion into the subperitoneal tissueProliferation

Management

SurgeryLeft upper abdominal eviscerationPeritonectomy

ChemotherapySystemic chemotherapyIntra-arterial chemotherapyIntraperitoneal chemotherapy

Heat

Diseases that medicines do not cureare cured by the knife.

Those that the knife does not cureare cured by fire.

Those that fire does not curemust be considered incurable.

Hippocrates

Principles of Hyperthermia

Direct cytocidal effect by hyperthermiadegeneration of proteinimpairment of nucleic acid synthesischromosomal damage

Vascular bedthrombosisocclusion

Augmentation of Cytotoxicity

HypoxiaLow pHHypoglycemiaRadiationEthanolSome anticancer drugsIncreased permeability

ChemoThermo-Sensitivity*

Normothermia Hyperthermia**

CDDP 5% 32%VP-16 0% 31%MMC 6% 38%ADM 0% 8%

* MTT assay with 21 gastric cancers** 43C for 1 hour

Methods of Hyperthermia

Systemic hyperthermiaRegional perfusion hyperthermia

Radiofrequency capacitive hyperthermia

Intracavitary hyperthermic perfusion

Hyperthermic IP Chemotherapy

Postoperative (closed method)Intraoperative (open method)

after reconstructionperitoneal cavity expander

before reconstructioncoliseum technique

manual stirring

Closed (Postoperative) Method

drugsthermistor

44~45Cpump

40~42C

48~50C

waterbath

Peritoneal Cavity Expander

filter

drugs

Peritoneal cavity expander

pump

Heat exchanger

43C

42C

Coliseum Technique

1

8

7

6

54

32

1 1. Chemotherapy reservoir2. In-flow pump3. Out-flow pump4. Heat exchanger5. Temperature probe6. Thermometer7. Temperature probes8. Smoke evacuator9. Thompson retractor

General Management

Control of intraperitoneal cavitytemperature monitoring

Replacement of serum proteinfresh frozen plasma / human albumin

Prevention of pulmonary edemahemodynamic monitoringdopamin / furosemide

Clinical Experience

A B CEffect 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

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

Peritonectomysystematic peritoneal stripping

Indicationlimited number of metastatic nodules

on the peritoneumwithout other distant metastasis

vessel

mesothelial cells

fibroblastcancer cells

drugsfibrosis

muscle

Peritonectomy

Heat

Peritoneal cavity

Drug

Complications

A B C DLeakage 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

34

36

38

40

42

44

46

48

0 15 30 45 60

Heat exchanger

Inflow

Tenckhoff

Douglas pouch

Esophageal

Mean TemperaturesC

Problems To Be Solved

Even distribution of heatEven distribution of drugMorbidity and mortalityDrug combinationSafety considerationsCost (equipments)

Treatment of AGC

Resection+ Systematic lymphadenectomy+ Perioperative IP Chemotherapy

(IO/with or without heat, EP) + Peritonectomy+ Systemic chemotherapy (?)

謝謝감사합니다 .

Thank you very much.