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Detection of free intraperitoneal tumour cells in peritoneal lavage fluid from patients with peritoneal metastasis before and after treatment with pressurised intraperitoneal aerosol chemotherapy (PIPAC)
  1. Martin Graversen1,2,3,
  2. Claus Fristrup1,3,
  3. Thomas Kielsgaard Kristensen4,
  4. Trine Rennebod Larsen5,
  5. Per Pfeiffer3,6,
  6. Michael Bau Mortensen1,3,
  7. Sönke Detlefsen3,4
  1. 1 Department of Surgery, Odense University Hospital, Odense, Denmark
  2. 2 Odense Patient data Exploratory Network - OPEN, Odense University Hospital, Odense, Denmark
  3. 3 Odense PIPAC Center, Odense University Hospital, Odense, Denmark
  4. 4 Department of Pathology, Odense University Hospital, Odense, Denmark
  5. 5 Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark
  6. 6 Department of Oncology, Odense University Hospital, Odense, Denmark
  1. Correspondence to Dr Martin Graversen, Department of Surgery, Odense University Hospital, Odense 5000, Denmark; martin.graversen{at}rsyd.dk

Abstract

Aims In this study, we investigated whether free intraperitoneal tumour cells (FITC) were detectable in ascites or peritoneal lavage fluid (PLF) from patients with peritoneal metastasis (PM) before and after treatment with pressurised intraperitoneal aerosol chemotherapy (PIPAC).

Methods Ascites or PLF retrieved at the first and third PIPAC procedures was analysed by conventional cytology, carcinoembryonic antigen (CEA) and total protein concentration, and quantitative reverse transcriptase PCR (qRT-PCR) for mRNA expression of CEA, epithelial cell adhesion molecule (EpCAM) and cancer antigen 125 (CA-125). Conventional cytology and qRT-PCR were also performed in a negative control group (benign PLF specimens and inflammatory ascites). The treatment response was compared with the histological response based on repeated peritoneal biopsies evaluated by the Peritoneal Regression Grading Score (PRGS).

Results Thirty-five patients with PM of various origins were included from 2015 to 2016. At the first PIPAC procedure, FITC were detected by conventional cytology (sensitivity 0.58, specificity 1.00), CEA protein (cut-off 0.4 µg/L, sensitivity 0.71), CEA mRNA (sensitivity 0.75, specificity 1.00), EpCAM mRNA (sensitivity 0.71, specificity 1.00) and CA-125 mRNA (sensitivity 0.43, specificity 1.00). The combination of CEA/EpCAM mRNA had a sensitivity of 0.88 and a specificity of 1.00. The evaluation of ascites or PLF retrieved at the third PIPAC procedure failed to detect treatment response, when compared with the histological PRGS.

Conclusions The evaluation of CEA and EpCAM mRNA detects FITC with a high sensitivity and an excellent specificity, but is not useful for response evaluation in patients treated with PIPAC.

Trial registration number NCT02320448.

  • peritoneal metastasis
  • PIPAC
  • free intraperitoneal tumor cells
  • CEA
  • EpCAM
  • CA-125
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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors The study was designed by the entire group of authors. Data collection was done by MG, PP, MBM and SD. Data were analysed and interpreted by MG, CF, TKK, TRL and SD. The article was drafted by MG and critically revised by all coauthors. The final version was approved by all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The study was conducted according to the Helsinki Declaration and approved by The Regional Committees on Health Research Ethics for Southern Denmark (Project-ID:S-20140211) and the Danish Data Protection Agency (Project-ID: 14/52603). All participants gave oral and written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Participant data will be retained at the study facility for 5 years after completion of the trial according to Danish law. After this time period, it will be de-identified and made available for other researchers upon reasonable request to the corresponding author.

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