The Onset of In-Vivo Dehydration in Gas -Based Intraperitoneal Hyperthermia and Its Cytotoxic Effects on Colon Cancer Cells

Abstract

BackgroundPeritoneal metastasis (PM) is an ongoing challenge in surgical oncology. Current therapeutic options, including intravenous and intraperitoneal (i.p.) chemotherapies display limited clinical efficacy, resulting in an overall poor prognosis in affected patients. Combined hyperthermia and dehydration induced by a high-flow, gas-based i.p. hyperthermic procedure could be a novel approach in PM treatment. Our study is the first to evaluate the therapeutic potential of i.p. dehydration, hyperthermia, as well as the combination of both mechanisms in an in-vivo setting.MethodsFor this study, three swine were subjected to diagnostic laparoscopy under a high-flow air stream at 48°, 49° and 50°Celsius (C). Hygrometry of the in- and outflow airstream was measured to calculate surface evaporation and i.p. dehydration. To analyze the effects of this concept, in vitro colon cancer cells (HT-29) were treated with hyperthermia and dehydration. Cytotoxicity and cell viability were measured at different time intervals. Additionally, structural changes of dehydrated cells were analyzed using scanning electron microscopy.ResultsAccording to our results, both dehydration and hyperthermia were cytotoxic to HT-29 cells. However, while dehydration reduced cell viability, hyperthermia did not. However, dehydration effects on cell viability were significantly increased when combined with hyperthermia (p<0.01).ConclusionsChanges to the physiological milieu of the peritoneal cavity could significantly reduce PM. Therefore, limited dehydration of the abdominal cavity might be a feasible, additional tool in PM treatment. Further studies are required to investigate dehydration effects and their applicability in PM management.

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 ].…”

“…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 ]. 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 ].…”

Thermosensitive methyl-cellulose-based injectable hydrogel carrying oxaliplatin for the treatment of peritoneal metastasis in colorectal cancer

“…However, systematic chemotherapy not only brings side effects attributed to its non-targeted killing but also the restricted effective drug concentration. 10 Recently, some studies have reported the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of patients with CRC having PM. 11 However, CRS has the problem of incomplete tumor resection.…”