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Introduction: Stage IV colorectal cancer (CRC) is a heterogeneous disease with many treatment options. The optimum management algorithm is yet to be established. The aim of this study was to evaluate the prognostic factors of survival and to determine the operative benefit of resection of the primary tumour followed by chemotherapy. Methods: Seven hundred twenty-eight consecutive patients who presented with stage IV CRC from 1999 to 2007 were identified. The demographics and clinicopathological characteristics of these patients were reviewed. Survival curves were constructed using the Kaplan-Meier method. Multivariate analysis assessed independent prognostic factors. Results: In the surgical management of the primary, 79% ( n = 572) were performed electively, 18% ( n = 134) as an emergency procedure and 3% ( n = 22) did not have any surgery. Twelve percent ( n = 78) had a permanent stoma. Major morbidity was 4.3% ( n = 31), and 30-day mortality was low at 6% ( n = 46). Ten percent ( n = 71) had a subsequent metasectomy. Patients who underwent curative resections tended to be female ( p = 0.05), of a younger age group (age, ≤50; p = 0.005), as well as had better haemoglobin ( p = 0.0001) and albumin levels ( p = 0.0001). For the study cohort, the cancer-specific survival (CSS) at 1 year was 47.9% [95% confidence interval (CI), 44.2-51.6%], 3-year CSS was 10.8% (95% CI, 3.3-13.3%) and 5-year CSS was 7.0% (95% CI, 4.8-9.2%). CSS was significantly higher in patients that underwent colonic resection. In cases where resection of the primary was possible, multivariate analysis revealed that CEA value >40 ng/ml, low albumin levels ≤34 g/l, poorly differentiated tumours, advanced tumour stage (T3/T4), nodal disease (N1/N2) and presence of diffuse metastasis were all significant factors associated with poorer cancer-specific survival. Conclusion: This study has shown a good survival benefit in stage IV CRC when an aggressive policy of primary resection is adopted. Resection of metastases with curative intent should be performed whenever possible. [ABSTRACT FROM AUTHOR]

The role of stem cells in the development of solid tumors remains controversial. In colorectal cancers (CRC), this is complicated by the conflicting "top-down" or "bottom-up" hypotheses of cancer initiation. We profiled the expressions of genes from the top (T) and bottom (B) crypt fractions of normal-appearing human colonic mucosa (M) at least 20 cm away from the tumor as a baseline and compared this to the genes of matched mucosa adjacent to tumors (MT) in twenty-three sporadic CRC patients. In thirteen patients, the genetic distance (M-MT) between the B fractions is smaller than the distance between the T fractions, indicating that the expressions diverge further in the top fractions (B < T). In the remaining patients, the reverse effect is observed (B > T). Assuming that a greater genetic divergence in the top or bottom fractions indicates that position as the initiation site, it is thus equally likely that human CRC initiates from 'top-down' via de-differentiated colonocytes or 'bottom-up' via dysregulated intestinal stem cells. Dysregulated genes that persist until tumor stage are not limited to tumor suppressors or oncogenes but include metabolic and transporter genes such as CA7, PHLPP2, and AQP8. [ABSTRACT FROM AUTHOR]