Intraperitoneal Chemohyperthermia

HIPEC

(Hyperthermic Intraperitoneal Chemotherapy)

Intraperitoneal chemohyperthermia is a specific type of chemotherapy particularly effective because it combines heat effects and

the localization of the intervention. The high temperature has tumoricidal properties, favours the entering into cells of drugs and

potentiates their efficacy, whereas the localization of the intervention allows the exposure of the tumor to antitumoral drugs at

dosages hundred-thousand times higher than the ones utilized when given intravenously, minimizing the general undesired effects.

PERITONEAL CARCINOSIS

The Peritoneal Carcinosis represents the advanced evolutionary stage of several tumors that develop in abdominal organs, such as colon, ovary, appendix, stomach, pancreas and liver.
In smaller measure, it can occur as a terminal stage of extra-abdominal tumors.
It is a disease that seldom presents primitive cases (mesothelioma).

The peritoneal Carcinosis has become a relatively frequent disease because of the growth of cases of colon, ovary and stomach carcinomas. Moreover, the peritoneum is, after liver, the most frequent site of neoplastic diffusion after curative treatment of a colon carcinoma.

HOW IS IT CURED

For long time Peritoneal Carcinosis has been considered a not curable pathology, especially with a surgical operation. Actually, the peritoneum was not considered an organ. On the other hand, such as liver and lung, the peritoneum is subjected to metastasization by several tumors, and especially by those originated by the organs into the abdominal cavity. Furthermore, like any other organ, it can be the site of a primitive tumor, even though rare, defined peritoneal mesothelioma, and of other more rare tumors. The evolution of the surgical techniques and the availability of innovative therapeutical aids within surgical and anaesthesiological fields, have allowed the application of a surgical treatment even to peritoneum. The most innovative approach contemplates the combination between cytoreductive surgery and intraperitoneal chemohyperthermia. Thus, both the surgeon and and the medical oncologist play an essential role in the therapy: the surgical operation (peritonectomy) allows to remove the whole tumor or to leave a minimal residue of it. It is a long and difficult procedure that can last even up to sixteen hours, and consists in the removal of the whole parietal peritoneum and of several abdominal organs; it can be necessary the removal of stomach, spleen, part of colon, rectum, gall bladder and, in women, uterus and ovaries. What remains can be treated with Intraperitoneal Chemohypertermia, whose purpose is precisely the removal of eventual tumoral cells free into the abdomen.

INTRAPERITONEAL CHEMOHYPERTHERMIA: How does it work?

Intraperitoneal Chemohypertermia has proved to be particularly effective because it is able to bypass the so-called plasmatic-peritoneal barrier, represented by the submesothelial tissue or by the capillaries’ basal membrane, that limitate the reabsorption of some types of drugs. Actually, it seems that some molecules have the tendency to concentrate at peritoneum level only in a gradual way, for example hydrophilic drugs or those with high molecular weight, such as Mitomicine C, Cisplatinum and Doxorubicine. It has been demonstrated, for example, that Cisplatinum shows a better capacity to penetrate into the tumoral tissue if administrated in hyperthermic conditions. Furthermore, at 40-42 ° C the neoplastic cells become more chemo-sensitive, thanks to the increased intracellular concentration of drugs, the higher activation, especially for the alkylant agents, the decreased repair capacity of damages to DNA. These events are more intensive into the ovarian tumoral Cisplatinum resistant cells, than in those Cisplatinum-sensitive. The formation of DNA-Platin combinations after exposure to Cisplatinum is increased and its removal decreased in hyperthermic conditions, with a consequent relevant letal effect on cells. The same behaviour in hyperthermic conditions is typical of other drugs such as Mytomicine C and Doxorubicine (for Doxorubicine only from 42° C up).

Thus, chemohyperthermia combines the possibility to exploit on one side the heat effect (at approx. 42° - 43° C temperature) that, besides having properties able to kill tumors on its own, favours the entering into cells of some drugs and their antitumoral activities. On the other side, it permits to utilize antitumoral drugs at doses hundred times (in some cases even a thousand times) superior than those that can be obtained when the same substances are given intravenously. Everything with a minimal incidence of general undesired effects.

For what kind of cancer it is indicated

The indications of this procedure have regarded at first mesothelioma and pseudomixoma peritonei, but some studies have then demonstrated that it is effective even in the treatment of colon, stomach and ovary tumors.

How to execute it

It consists in a real “washing” of the abdominal side, that is executed through the insertion of four drains into the abdominal surface. These four cannulaes are linked to an external circuit that functions like a pump. Two of them are necessary for the liquid infusion, respectively into the right undercostal cavity and into the pelvis. The others, positioned respectively into the central abdominal cavity and superficially into the pelvis, are necessary for the liquid effusion. It consists in a mechanism similar to the one of the device for extracorporeal circulation but, instead of decreasing the temperature, it is increased until 42° - 43° C thanks to a heat exchanger. The liquid remains into the blood-stream for approx. one hour and a half, with a half liter and over flow / min. once the intraoperating perfusion is finished, the liquid into the abdomen is completely aspirated. Then, the operating equipe goes on with the surgical re-opening of the abdominal cavity for a further verification, in order to eliminate all blood clots and residual fragments.

The necessary device to execute this procedure shall provide a pump system, a thermostat or heat exchanger, an integrated system for the temperature monitoring, pressure and flow, a system for the data analysis with visualization in real time of parameters and their contextual registration and of an extracorporeal circuit (CEC). Several centers use the Performer LRT device.
(www.rand-biotech.com - www.performerlrt.com)