Early colorectal cancers

Kashida H, Kudo S (2006) Early colorectal cancer concept, diagnosis, and management. Inter J Clin Onco 1 11-8. 

One of the features that makes urinary DiAcSpm a particularly attractive candidate for use as a tumor marker is that the DiAcSpm level is more frequently elevated in patients in the early stages of colorectal and breast cancer compared to other tumor markers (Hiramatsu et al. 2005 Umemori et al. 2010 Nakayama et al. 2012). For instance, the level of DiAcSpm in the urine is higher than normal in 60 % of early colorectal cancers (i.e., those that are still restricted to the mucosal layers), whereas carcinoembryonic antigen (CEA) is elevated in only 10 % of these patients (Hiramatsu et al. 2005). A tumor marker that facilitates the detection of cancer at early clinical stages is valuable because it enables timely treatment. Importantly, more than 90 % of patients with stage 0 and I colorectal cancer may be cured of disease with proper treatment. 

However, already in an early clinical trial, rofecoxib was found to produce four times the number of myocardial infarctions than its comparator drug, naproxen. A subsequent trial of rofecoxib compared to placebo in colorectal cancer prevention demonstrated, after 18 months of study, that a greater number of myocardial infarctions occulted in the rofecoxib group. In 2004 the manufacturers of rofecoxib withdrew the diug from the market. A similar study of celecoxib compared to placebo in cancer prevention, showed that celecoxib also increased the risk of cardiovascular embolisms [3]. 

Signs and symptoms of colorectal cancer can be extremely varied, subtle, and nonspecific. Patients with early-stage colorectal cancer are often asymptomatic, and lesions are usually detected by screening procedures. 

Baseline laboratory tests should include complete blood cell count, prothrombin time, activated partial thromboplastin time, liver and renal function tests, and serum carcinoembryonic antigen (CEA). Serum CEA can serve as a marker for monitoring colorectal cancer response to treatment, but it is too insensitive and nonspecific to be used as a screening test for early-stage colorectal cancer. 

Carcinoembryonic cells CA 27.29 elevated in one-third of early-stage breast cancer and two-thirds of late-stage breast cancer Oncofetal glycoprotein expressed Colorectal cancer... 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

Irinotecan is a prodrug that is converted mainly in the liver by the carboxylesterase enzyme to the SN-38 metabolite, which is 1000-fold more potent as an inhibitor of topoisomerase I than the parent compound. In contrast to topotecan, irinotecan and SN-38 are mainly eliminated in bile and feces, and dose reduction is required in the setting of liver dysfunction. Irinotecan was originally approved as second-line monotherapy in patients with metastatic colorectal cancer who had failed fluorouracil-based therapy. It is now approved as first-line therapy when used in combination with 5-FU and leucovorin. Myelosuppression and diarrhea are the two most common adverse events. There are two forms of diarrhea an early form that occurs within 24 hours after administration and is thought to be a cholinergic event effectively treated with atropine, and a late form that usually occurs 2-10 days after treatment. The late diarrhea can be severe, leading to significant electrolyte imbalance and dehydration in some cases. 

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