Patient-specific 3D-tissue slices from peritoneal metastases - An in vitro model for individual susceptibility analysis.

Abstract

Objectives: The prognosis of patients with peritoneal metastases (PM) is poor, and these patients have a brief overall survival. Most patients with advanced PM receive palliative therapy to maintain their quality of life. In our current study, we investigated whether patient-specific 3D-tissue slices from patients with PM subjected to pressurized intraperitoneal aerosol chemotherapy could be cultured in vitro.

Methods: Biopsies from gastric cancer patients with PM were characterized for cytokeratin-positive tumor cells and the proliferation marker Ki-67. Biopsies from seven patients were cut to 350 µM thick slices in a standardized manner, cultured with 10 µM 5-fluorouracil, doxorubicin, cisplatin, oxaliplatin, or irinotecan for 96 h, and then examined histopathologically and via immunohistochemistry for persistent cytokeratin and Ki-67 expression.

Results: In vitro cultured slices revealed a similar morphology to un-cultured specimens, and Ki-67-positive tumor cell areas were present after 96 h. The total amount of tumor cells per slice was determined by pan-cytokeratin staining. In the doxorubicin-treated slices, the cytokeratin-positive tumor cell fraction and proliferative (Ki-67pos) cells were decreased. Patient-specific 3D-tissue-slice cultures from peritoneal biopsies were cultured in vitro for up to 4 days.

Conclusions: Potentially, these cultures are a reliable model to evaluate the chemosensitivity of patients with PM. Further investigation is needed to match the chemosensitivity with the clinical course of these patients.