Safety, feasibility, and application of intraperitoneal gas-based hyperthermia beyond 43°C in the treatment of peritoneal metastasis: An in-vivo pilot study

Abstract

Background43°Celsius (C) is currently the highest temperature used in the treatment of peritoneal metastasis (PM). Despite sufficient data on water- based hyperthermic solutions in PM treatment, there is currently no information on gas-based hyperthermia extending beyond 43°C. This study is the first to provide in-vivo data on different organ systems during and after intraperitoneal gas-based hyperthermia beyond 43°C. The aim of this study is to explore in-vivo feasibility, safety, and efficacy of this novel concept from a biological perspective.MethodsFor this study, three swine were subjected to laparoscopy and subsequent gas-based intraperitoneal hyperthermia at 48°, 49° and 50°C under a high-flow air stream. Intraoperative data from multiple temperature sensors were analysed. Additionally, intraoperative anaesthesiologic and gasometrical data was analysed. Postoperatively, swine were monitored for one week and laboratory work-up was performed on postoperative days 1, 3 and 7.ResultsDuring gas-based intraperitoneal hyperthermia, anesthesiologic parameters did not exhibit critical values. No intra- or postoperative complications were observed. Distinct temperature measurements on the skin, cystohepatic triangle and esophagus did not display any temperature increase. Postoperative laboratory workup did not show any changes in hemoglobin, white blood cell count, platelets, or kidney function.DiscussionBased on our data, there are no safety concerns for the application of gas-based hyperthermia between 48 - 50°C. In fact, no critical systemic temperature increase was observed. With respect to possible limitations, further in-vivo studies are required to evaluate whether gas-based intraperitoneal hyperthermia may be a therapeutic option for PM patients.

Triple-Therapy of Peritoneal Metastasis—Partial-Dehydration under Hyperthermic Condition Combined with Chemotherapy: The First Preliminary In-Vitro Results

“…The cytotoxic effects of chemotherapy on cancer cells are further enhanced by partially dehydrating the cells in a hyperthermic environment. The concept of feasibility of such an approach has already been demonstrated in vivo [ 35 , 36 , 37 ]. For the first time, we have now investigated the combination of all three therapeutic factors—hyperthermia, dehydration, and chemotherapy—as a possible procedure for PM treatment.…”

“…The application of hyperthermia through a gas-based system instead of a liquid-based carrier has a higher likelihood of improvement following laparoscopy. Previous in vivo swine model studies carried out by our research group showed that gas-based intraperitoneal hyperthermia is well tolerated and safe for these animals, and in vitro studies indicate cytotoxic effects on colorectal cancer cell lines, suggesting that this method could be used as a potential tool in PM treatment [ 35 , 36 ]. Based on this, the now presented data is a further indication that combining gas-based hyperthermia with chemotherapy is more cytotoxic on colorectal cancer cells and therefore could also potentially have an additive antitumoral effect in the management of PM than locoregional chemotherapy alone.…”

“…Therefore, there is an urgent need for novel and improved therapeutic concepts. A new concept based on a combination of intraperitoneal hyperthermia beyond 43 °C and peritoneal surface dehydration was recently proposed by Thelen et al [ 34 ] and then further introduced and tested in vivo for its safety and feasibility by Diakun et al [ 35 , 36 ]. It has been proposed that changing the peritoneal milieu through dehydration and extensive hyperthermia could interfere with PM growth and therefore be an effective tool to reduce PM progression [ 34 , 35 , 37 ].…”

“…It has been proposed that changing the peritoneal milieu through dehydration and extensive hyperthermia could interfere with PM growth and therefore be an effective tool to reduce PM progression [ 34 , 35 , 37 ]. Although it has been demonstrated that significant dehydration of the peritoneal cavity in a laparoscopic approach can be achieved, we do not have any data on how cancer cells react to the combined exposure of dehydration, hyperthermia, and chemotherapy in the same setting [ 36 ]. Currently, the described effects of peritoneal dehydration under hyperthermic conditions are peritoneal thinning or shrinking and a localized superficial vascular clotting process, which might be highly relevant for targeting neo-vascular structure [ 36 , 37 ].…”

“…Although it has been demonstrated that significant dehydration of the peritoneal cavity in a laparoscopic approach can be achieved, we do not have any data on how cancer cells react to the combined exposure of dehydration, hyperthermia, and chemotherapy in the same setting [ 36 ]. Currently, the described effects of peritoneal dehydration under hyperthermic conditions are peritoneal thinning or shrinking and a localized superficial vascular clotting process, which might be highly relevant for targeting neo-vascular structure [ 36 , 37 ]. The effect of this triple therapy (namely dehydration, hyperthermia, and chemotherapy) on cancer cells has never been evaluated.…”