Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives

Abstract

(1) Background: Tumors of the peritoneal serosa are called peritoneal carcinosis. Their origin may be primary by primitive involvement of the peritoneum (peritoneal pseudomyxoma, peritoneal mesothelioma, etc.). This damage to the peritoneum can also be a consequence of the dissipation of cancers—in particular, digestive (stomach, pancreas, colorectal, appendix) and gynecological (ovaries) ones in the form of metastases. The aim of the treatment is a maximal reduction of the macroscopic disease called “cytoreduction” in combination with hyperthermic intra-abdominal chemotherapy to treat residual microscopic lesions. (2) Methods: In this narrative review, we fundamentally synthetize the evolution of this process over time and its impact on clinical applications. (3) Results: Over the last past decade, different evolutions concerning both delivery modes and conditions concerning hyperthermic intra-abdominal chemotherapy have been realized. (4) Conclusion: The final objective of these evolutions is the improvement of the global and recurrence-free survival of primary and secondary malignant peritoneal pathologies. However, more large randomized controlled trials are needed to demonstrate the efficacy of such treatments with the help of molecular biology and genetics.

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

“…In clinical i.p. chemotherapy, a handful of chemotherapeutics are used to treat PM from the different gastro-intestinal origins [ 24 , 62 – 64 ]. However, that does not mean that one drug alone is effective in treating every type of PM.…”

Current Trends in Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Disease from Appendiceal and Colorectal Malignancies

“…This principle has been theorized to overcome the chemoresistance observed with some HIPEC agents [ 163 ]. Further studies have established favorable pharmacokinetic and safety profiles, efficacy for isolated refractory PC, and ease of repeated administration [ 161 , 162 , 164 , 165 , 166 , 167 , 168 ]. However, few studies have directly compared HIPEC to PIPAC.…”

“…Combined with systemic neoadjuvant therapies, neoadjuvant intraperitoneal chemotherapy aims to reduce the overall peritoneal tumor burden to make CRS feasible and improve rates of complete cytoreduction [ 167 ]. For ovarian, gastric, and CRCs, NIPS has shown low morbidity and mortality and indeed shown higher rates of complete cytoreduction [ 167 , 171 , 172 ]. Yonemura and colleges described the survival benefit of using NIPS for gastric cancer [ 173 , 174 ].…”

“…Additional studies evaluating NIPS with non-traditional systemic chemotherapies are underway [ 177 ]. Survival outcomes following NIPS remain mixed for cancers other than gastric, however, and require further prospective studies [ 167 , 178 ]. One upcoming trial aims to evaluate the effect of neoadjuvant systemic chemotherapy and PIPAC prior to CRS/HIPEC for CRC (NCT04475159).…”

Treatment for Peritoneal Metastasis of Patients With Colorectal Cancer

“…Surface intrusion and migration, invasion into the submesothelial tissue, and spontaneous or traumatic (associated with previous surgeries) perforation by tumor cells that www.coloproctol.org Treatment for Peritoneal Metastasis of Patients With Colorectal Cancer Young Jin Kim and Chang Hyun Kim are potentially adapted or enabled by mutations. Different cell signaling pathways linked to each step of peritoneal dissemination imply several molecules: (i) tumor shedding and detachment (Ecadherin and epithelial-to-mesenchymal transition); (ii) transport within the peritoneum (actin microfilament system); (iii) dissemination (intercellular adhesion molecule 1), vascular adhesion molecule 1, tumor cell receptors (cluster of differentiation 44), cytokines (tumor necrosis factor alpha, interleukin-1 beta, and interleukin-1 gamma); (iv) invasion (metalloproteinases and integrins); and (v) proliferation and angiogenesis (epidermal growth factor receptor, epidermal growth factor, tumor growth factor α, insulinlike growth factor-1, hypoxia-inducible factor, vascular endothelial growth factor [VEGF], and VEGF receptor) [10].…”