Hyperthermic intraperitoneal chemotherapy: Rationale and technique

Abstract

The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms, either primary or secondary to digestive or gynecologic malignancy. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivered in the operating room once the cytoreductive surgical procedure is finalized, constitutes the most common form of administration of perioperative intraperitoneal chemotherapy. This may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIC). HIPEC combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs, which results in regional dose intensification, with the direct cytotoxic effect of hyperthermia. Hyperthermia exhibits a selective cell-killing effect in malignant cells by itself, potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered drug. The chemotherapeutic agents employed in HIPEC need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic effect. Delivery of HIPEC requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the procedure. An open abdomen (Coliseum) or closed abdomen technique may be used, with no significant differences in efficacy proven to date. Specific technical training and a solid knowledge of regional chemotherapy management are required. Concerns about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are used. Different HIPEC drug regimens and dosages are currently in use. A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy, so-called "HIPEC plus") has been observed in recent years, with the aim to further enhance the cytotoxic potential of HIPEC. Future trials to ascertain the ideal HIPEC regimen in different diseases and to evaluate the efficacy of new drugs or drug combinations in this context are warranted.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy

“…Following intraperitoneal delivery of the cytotoxic drug, high regional concentrations can be achieved even whilst keeping systemic concentrations low. The concentration differential is in part due to the slow movement of the drug from the peritoneal cavity into the plasma [36]. The peritoneal plasma barrier maintains continuous high concentration gradient of chemotherapeutic drug between the peritoneal cavity and the plasma compartment [32].…”

Safety considerations for Health care Workers involved in Cytoreductive Surgery and Perioperative chemotherapy

“…This exposes the healthcare workers involved in the process to antineoplastic agents. The commonly used antineoplastic drugs HIPEC and EPIC are mitomycin C, cisplatin, oxaliplatin, doxorubicin, paclitaxel, 5 -FU, melphelan, irinotecan and carboplatin [45].…”

“…Instrument should be dealt with similarly. Standard protective clothing should be word during the cleaning [45,76]. & Dealing with exposure and personnel contamination Contamination of protective equipment or clothing, or direct skin or eye contact should be treated by:…”

The Role of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer

“…This regional dose intensification ie-a high intraperitoneal concentration of the drug with a low plasma concentration is maintained by the plasma-peritoneal barrier [30]. Hyperthermia synergistically enhances the effects of intraperitoneal chemotherapy by both direct cytotoxic action (impaired DNA repair, denaturation of proteins and increase in the lysosomal activity within the tumor cells) and indirect cytotoxic effects (increased penetration of the drug into the tumor nodule and increased drug uptake in the tumor cells) [30,31]. Intraperitoneal chemotherapy is best delivered either at the time of surgery or immediately following it since the cytotoxic activity of perioperative intraperitoneal chemotherapy destroys the cancer cells within the fibrin produced as part of the wound healing process.…”