Is detection of intraperitoneal exfoliated tumor cells after surgical resection of rectal cancer a prognostic factor of survival?

Christian Arstad,Paulo Refinetti,Per Olaf Ekstrøm,Annette Torgunrud Kristensen,Karl-Erik Giercksky

doi:10.1186/s12885-017-3365-7

Christian Arstad, Paulo Refinetti + Show 3 more

Open Access

https://doi.org/10.1186/s12885-017-3365-7

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Abstract

BackgroundThe prognostic significance of free cancer cells detected in peritoneal fluid at the time of rectal surgery remains unclear. A substantial number of patients will develop metastatic disease even with successful local treatment. This prospective non-randomized study investigated the prognostic value of intraperitoneal free cancer cells harvested in peritoneal lavage after surgery for rectal cancer. Mutational hotspots in mitochondrial DNA were examined as potential molecular signatures to detect circulating intraperitoneal free cancer cells when present in primary tumor and in lavage.MethodsPoint mutations in mitochondrial DNA amplifications were determined in primary tumors and corresponding exfoliated intraperitoneal free cancer cells in lavage from 191 patients with locally advanced rectal cancer scheduled for radical treatment. Mitochondrial DNA target sequences were amplified by polymerase chain reaction and base substitutions were detected by denaturant, cycling temperature capillary electrophoresis. Detection of intraperitoneal free cancer cells was correlated to survival.ResultsOf 191patients analyzed, 138 (72%) were identified with somatic mitochondrial point mutations in rectal cancer tumors. From this fraction, 45 patients (33%) had positive lavage fluid with corresponding somatic mtDNA point mutations in lavage representing circulating intraperitoneal free cancer cells. There was no significant survival difference between patients identified with or without somatic mitochondrial DNA point mutations in the corresponding lavage.ConclusionSomatic mitochondrial DNA point mutations identified in primary rectal tumors enable detection of circulating intraperitoneal free cancer cells in lavage fluid.Intraperitoneal free cancer cells harvested from lavage immediately after surgery for rectal cancer does not represent an independent prognostic factor on survival.

Highlights

The prognostic significance of free cancer cells detected in peritoneal fluid at the time of rectal surgery remains unclear
Lavage analysis techniques (Cytology, Polymerase chain reaction (PCR), Immunocytochemistry) used to identify intraperitoneal free cancer cells (IPCC) vary with an average of 13%, as calculated from 11 studies involving more than 100 patients, reviewed by Passot et al [12]
Lavage fluids from these 138 patients were subsequently analyzed for corresponding mitochondrial DNA (mtDNA) mutations

Summary

Introduction

The prognostic significance of free cancer cells detected in peritoneal fluid at the time of rectal surgery remains unclear. A substantial number of patients will develop metastatic disease even with successful local treatment. This prospective non-randomized study investigated the prognostic value of intraperitoneal free cancer cells harvested in peritoneal lavage after surgery for rectal cancer. Mutational hotspots in mitochondrial DNA were examined as potential molecular signatures to detect circulating intraperitoneal free cancer cells when present in primary tumor and in lavage. Lavage analysis techniques (Cytology, PCR, Immunocytochemistry) used to identify IPCC vary with an average of 13%, as calculated from 11 studies involving more than 100 patients, reviewed by Passot et al [12]. The use of more sensitive methods to detect IPCC in studies with a large number of patients could determine if IPCC is of clinical relevance

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