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Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments.

OBJECTIVES: Recently, the development of technologies to culture intestinal epithelial cells in vitro as different forms of intestinal organoids causes drawing attention in this area. The isolation and culture of colorectal crypts were first demonstrated in the very recent decade with the identification of stem cell marker Lgr5. The growth of crypts into organoids provides an in vitro model for studying the mucosal physiology, colorectal cancer tumorigenesis, and regeneration. In the current study, cancer stem cell isolation, tissue decontamination, organoid freezing and thawing processes, and organoid culture media ingredients have been evaluated. The aim of this investigation is optimization and production of human colorectal cancer organoids. MATERIAL & METHODS: The colorectal cancerous tissues are collected from Dokuz Eylul University Hospital. Isolation method of cancer cell is performed by EDTA solution and agitation is provided by shaker. Matrigel is used to create optimal 3D structure to grow cancer stem cells up to colorectal tissue. L-WRN cell line has been used to produce secreted factors which are WNT-3A, Rspondin and Noggin in purpose of supporting the development of organoids. RESULTS: Different parameters have been evaluated to obtain more efficient organoids. The experiment is performed in our laboratory presented that, human colorectal cancer organoids have been generated and manipulated in our laboratory. CONCLUSIONS: The currency protocol explains how the generation of 3D organoid cultures from cancerous human colorectal tissue is manipulated. The in vitro 3D organoid model is a promising and novel approach which present us more real-like working material. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis (PC) or peritoneal metastases (PM) is an advanced stage of cancer and it is associated with a poor prognosis. It was considered untreatable and terminal stage of the disease; however, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) become a potential treatment strategy for those patients. Cytoreductive surgery aims the removal of the all visible tumor including peritonectomy procedures, organ resections was first initiated by Sugarbaker (1). The most important thing in CRS may be the residual, especially microscopically, disease after the resections. Sugarbaker describes the importance of the microscopical residual disease as "It's what the surgeon doesn't see that kills the patient" (2). Peritoneal metastases may present synchronously at the same time during the diagnosis of the primary tumor or may present as a metachronous disease. Most accepted hypothesis is the seed and soil hypothesis in which peritoneal metastases develops as a result of the growth of tumor that invades through the serosal lining of the organ including colon, stomach, intestines and tubes and ovaries allowing the exfoliation and shedding of malignant cells intraperitoneally. (3, 4). Also, it may develop iatrogenically after cancer surgery due to tumor manipulation during the surgical procedure including iatrogenic perforation of the tumor, transection of lymphatics or blood vessels, inappropriate surgical dissection. [5-9]. Figure 1a. shows PMs in small bowel mesentery and serosa originated from colon cancer. After successful removal of the all possible visible tumors (peritonectomy procedures and organ resections) to extend the macroscopical tumor removal to the microscopical clearance we introduce hyperthermic intraperitoneal chemotherapy (HIPEC) by special hyperthermia pumps for 30-90 minutes (Figure 1b). [ABSTRACT FROM AUTHOR]