Abstract
Pseudomyxoma peritonei (PMP) is a rare cancer commonly originating from appendiceal neoplasms that presents with mucinous tumor spread in the peritoneal cavity. Patients with PMP are treated with curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The value of adding HIPEC to CRS has not been proven in randomized trials, and the objective of this study was to investigate the efficacy of intraperitoneal mitomycin C (MMC) and regional hyperthermia as components of this complex treatment. Xenograft tissue established from a patient with histologically high-grade PMP with signet ring cell differentiation was implanted intraperitoneally in 65 athymic nude male rats and the animals were stratified into three treatment groups; the cytoreductive surgery group (CRSG, CRS only), the normothermic group (NG, CRS and intraperitoneal chemotherapy perfusion (IPEC) with MMC at 35 ºC), and the hyperthermic group (HG, CRS and IPEC at 41 ºC). The main endpoints were survival and tumor weight at autopsy. Adequate imitation of the clinical setting and treatment approach was achieved. The median survival was 31 days in the CRSG, 60 days in NG and 67 days in HG. The median tumor weights at autopsy were 34 g in CRSG, 23 g NG and 20 g in HG. In conclusion, the addition of IPEC with MMC after CRS doubled the survival time and reduced tumor growth compared to CRS alone. Adding regional hyperthermia resulted in a modest improvement of treatment outcome.
Highlights
Pseudomyxoma peritonei (PMP) is rare cancer that most commonly originates from a ruptured mucinous neoplasm in the appendix [1]
The mitomycin C (MMC) concentration in the peritoneal perfusion fluid (PPF) was in both groups acceptably stable during the course of intraperitoneal chemotherapy perfusion (IPEC) and decreased from 28.6 to 23.0 μM in the normothermic group (NG) g and from 27.6 to 21.0 μM in the hyperthermic group (HG) (Fig. 1)
Given the large number of questions that need to be answered relating to issues such as hyperthermic intraperitoneal chemotherapy (HIPEC) technique, carrier solution, choice of drug, drug dose, temperature and exposure time, there is a need for preclinical models to investigate some of these important details in patient management
Summary
Pseudomyxoma peritonei (PMP) is rare cancer that most commonly originates from a ruptured mucinous neoplasm in the appendix [1]. It is characterized by accumulation of mucinous tumor in the peritoneal cavity which leads to abdominal distension, pain and bowel obstruction. Cytoreductive surgery (CRS) aiming at complete removal of all visible cancer tissue and hyperthermic intraperitoneal chemotherapy (HIPEC) have emerged as standard-of-care for treatment of patients with PMP. During HIPEC, the peritoneal cavity is continuously perfused with a heated chemotherapy solution, aiming to provide high intraperitoneal drug concentration combined with limited systemic absorption and toxicity [8]. In vitro experiments suggest enhanced efficacy of MMC in combination with hyperthermia [10, 11], but the benefit of adding hyperthermia to intraperitoneal chemotherapy with MMC is poorly documented and should be further examined
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