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The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer-Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination

Michaela Ramser, Rene Warschkow, Carsten T Viehl, Christoph Kettelhack, Andreas Zettl, Leonard A Lobbes, Markus Zuber & Benjamin Weixler

abstract

BACKGROUND
According to the common tenet, tumour progression is a chronological process starting with lymphatic invasion. In this respect, the meaning of bone marrow micrometastases (BMM) in patients with lymph node negative colon cancer (CC) is unclear. This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC.

METHODS
BM aspirates were taken from both pelvic crests and in vivo SLN mapping was done during open oncologic colon resection in patients with stage I and II CC. Stainings were performed with the pancytokeratin markers A45-B/B3 and AE1/AE3 as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their effects on survival was examined using Cox regression analysis.

RESULTS
In a total of 78 patients with stage I and II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+ /BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa = - 0.13 [95% confidence interval [CI] = - 0.4-0.14], p = 0.342) nor univariate (odds ratio [OR] = 0.39, 95%CI:0.07-1.50, p = 0.180) or multivariate (OR = 0.58, 95%CI: 0.09-2.95, p = 0.519) analyses. Combined detection of ITC+ /BMM+ demonstrated the poorest overall (HR = 61.60, 95%CI:17.69-214.52, p = 0.032) and recurrence free survival (HR = 61.60, 95%CI: 17.69-214.5, p = 0.032).

CONCLUSIONS
These results indicate that simultaneous and not interdependent presence of very early lymphatic and haematologic tumour spread may be considered as a relevant prognostic risk factor for patients with stage I and II CC, thereby suggesting the possible need to reconsider the common assumptions on tumour spread proposed by the prevalent theory of sequential tumour progression.
   
citation Ramser M, Warschkow R, Viehl C T, Kettelhack C, Zettl A, Lobbes L A, Zuber M, Weixler B. The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer-Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination. World J Surg 2021;.
   
type journal paper/review (English)
date of publishing 27-12-2021
journal title World J Surg
ISSN electronic 1432-2323
PubMed 34958413
DOI 10.1007/s00268-021-06399-4