Determinants of recurrence after intended curative resection for colorectal cancer.

Despite intended curative resection, colorectal cancer will recur in ∼45% of the patients. Results of meta-analyses conclude that frequent follow-up does not lead to early detection of recurrence, but improves overall survival. The present literature shows that several factors play important roles in development of recurrence. It is well established that emergency surgery is a major determinant of recurrence. Moreover, anastomotic leakages, postoperative bacterial infections, and blood transfusions increase the recurrence rates although the exact mechanisms still remain obscure. From pathology studies it has been shown that tumors behave differently depending on their location and recur more often when micrometastases are present in lymph nodes and around vessels and nerves. K-ras mutations, microsatellite instability, and mismatch repair genes have also been shown to be important in relation with recurrences, and tumors appear to have different mutations depending on their location. Patients with stage II or III disease are often treated with adjuvant chemotherapy despite the fact that the treatments are far from efficient among all patients, who are at risk of recurrence. Studies are now being presented identifying subgroups, in which the therapy is inefficient. Unfortunately, only few of these facts are implemented in the present follow-up programs. Therefore, further research is urgently needed to verify which of the well-known parameters as well as new parameters that must be added to the current follow-up programs to identify patients at risk of recurrence.

Blood-based Biomarkers at Large Bowel Endoscopy and Prediction of Future Malignancies.

Soluble cancer-related protein biomarker levels may be increased in subjects without findings at large bowel endoscopy performed due to symptoms associated with colorectal cancer. The present study focused on a possible association between increased biomarker levels in such subjects and subsequent development of malignant diseases. In a major study of 4,990 subjects undergoing large bowel endoscopy, 691 were without pathology and comorbidity. Plasma levels of TIMP-1, CEA, CA19-9, and YKL-40 were determined in samples collected just before endoscopy and compared with subsequent development of a malignant disease within a period of 7-8 years. The upper 90% limits of the reference levels of every single protein were used to differentiate between normal and increased levels. The levels were separated into three groups: 0, none of the biomarkers increased; 1, one biomarker increased; 2, two or more biomarkers increased. A total of 43 subjects developed a primary malignant disease in the observation period. Univariatly, increase of all four biomarkers was significantly associated with subsequent development of a malignant disease. A multivariate analysis showed that increased biomarker levels were associated with subsequent development of a malignant disease (P = 0.002). The cumulative risk of developing malignant disease within the first 5 years after endoscopy was group 0, 3.3%; group 1, 5.8%; group 2, 7.8%. It is concluded that increased levels of plasma TIMP-1, CEA, CA19-9, and serum YKL-40 at large bowel endoscopy without findings may be associated with an increased risk of developing a subsequent malignant disease.