title: The prognostic value of micrometastases and isolated tumour cells in histologically negative lymph nodes of patients with colorectal cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Detection of occult tumour cells in lymph nodes of patients with stage I/II colorectal cancer is associated with decreased survival. However, according to recent guidelines, occult tumour cells should be categorised in micrometastases (MMs) and isolated tumour cells (ITCs). This meta-analysis evaluates the prognostic value of MMs and of ITCs, separately.
  
  
  METHODS
  PubMed, Embase, Biosis and the World Health Organization International Trials Registry Platform were searched for papers published until April 2013. Studies on the prognostic value of MMs and ITCs in lymph nodes of stage I/II colorectal cancer patients were included. Odds ratios (ORs) for the development of disease recurrence were calculated to analyse the predictive value of MMs and ITCs.
  
  
  RESULTS
  From five papers, ORs for disease recurrence could be calculated for MMs and ITCs separately. In patients with colorectal cancer, disease recurrence was significantly increased in the presence of MMs in comparison with absent occult tumour cells (OR 5.63; 95%CI 2.4-13.13). This was even more pronounced in patients with colon cancer (OR 7.25 95% CI 1.82-28.97). In contrast, disease recurrence was not increased in the presence of ITCs (OR 1.00 95% CI 0.53-1.88).
  
  
  CONCLUSIONS
  Patients with stage I/II colorectal cancer and MMs have a worse prognosis than patients without occult tumour cells. However, ITCs do not have a predictive value. The distinction between ITCs and MMs should be made if the detection of occult tumour cells is incorporated in the clinical decision for adjuvant treatment.
authors.affiliation: Department of Surgery, Gelre Hospital, Albert Schweitzerlaan 31, 7334 DZ Apeldoorn, The Netherlands; Department of Surgery, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: D A M
authors.initials: DA
authors.lastname: Sloothaak
authors.affiliation: Department of Surgery, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sahami
authors.affiliation: Department of Epidemiology, Gelre Hospital, Albert Schweitzerlaan 31, 7334 DZ Apeldoorn, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: van der Zaag-Loonen
authors.affiliation: Department of Surgery, Gelre Hospital, Albert Schweitzerlaan 31, 7334 DZ Apeldoorn, The Netherlands.
authors.forename: E S
authors.initials: ES
authors.lastname: van der Zaag
authors.affiliation: Department of Surgery, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Tanis
authors.affiliation: Department of Surgery, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Bemelman
authors.affiliation: Department of Surgery, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: c.j.buskens@amc.uva.nl.
authors.forename: C J
authors.initials: CJ
authors.lastname: Buskens
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D000368:Aged; D001707:Biopsy, Needle; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016001:Confidence Intervals; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D061206:Neoplasm Micrometastasis / Q000175:diagnosis / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D016017:Odds Ratio; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis
keywords: Colorectal neoplasm; Lymph nodes; Occult tumour cells; Staging