Digital Public Defence: Olaf Sørensen

Cand.med. Olaf Sørensen at Institute of Clinical Medicine will be defending the thesis "Pharmacology of intraperitoneal mitomycin C in pseudomyxoma peritonei" for the degree of PhD (Philosophiae Doctor). 

The public defence will be held as a video conference over Zoom.

The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.

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Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.

Digital Trial Lecture - time and place

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Adjudication committee

  • First opponent: Professor Kurt Van der Speeten, Hasselt University, Belgium
  • Second opponent: Senior Consultant Wiebke Solass, Tübingen University Hospital, Germany
  • Third member and chair of the evaluation committee: Professor Øyvind Bruland,
    Institute of Clinical Medicine, University of Oslo

Chair of defence

Professor II Ragnhild A. Lothe, Institute of Clinical Medicine, University of Oslo

Principal Supervisor

Professor II Kjersti Flatmark, Institute of Clinical Medicine, University of Oslo

Summary

Pseudomyxoma peritonei (PMP) is a rare cancer usually originating in ruptured mucinous appendiceal tumor and with metastastasis to peritoneum. Treatment combines cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). The thesis consists of one clinical and three experimental studies.

The clinical study investigated outcome in 93 patients with PMP treated with CRS-PIC at the Norwegian Radium Hospital in 1994-2009. PIC was administered as early postoperative chemotherapy (EPIC) or hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC). Ten-years overall survival was 69%. Significant factors for improved survival were low-grade histological differentiation and female gender. The outcome was the same with EPIC and HIPEC.  

The first experimental study validated microdialysis (MD) technique to monitor MMC concentration. Then MD was used to investigate MMC pharmacokinetics in rats at intravenous (i.v.) and intraperitoneal (i.p.) administration. There was fast and even distribution of MMC between tissue, and area under time-concentration curves (AUC) were the same at i.v. and i.p. infusion.

Thereafter MD was used to investigate MMC pharmacokinetics in rats during intraperitoneal chemotherapy perfusion (IPEC) at 35°C and at 41°C, i.e. with use of hyperthermia (HT). The study demonstrated AUC-ratios i.p./i.v. of 69 and 79, and moderately increased concentration outside peritoneum. HT did not modify MMC pharmacokinetics. 

The last study investigated treatment efficacy of IPEC with MMC and HT after CRS in rats with high-grade PMP with signet ring cells. IPEC doubled survival and reduced tumor growth. Outcome was further slightly improved by HT.
Conclusion: The clinical study demonstrated outcome in line with international reference institutions. The experimental studies showed advantageous MMC distribution in IPEC, a substantial therapeutic effect of IPEC and modest additional effect of HT.

Additional information

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Published Aug. 18, 2021 9:35 PM - Last modified Aug. 31, 2021 10:53 AM