What's new with tumor markers for colorectal cancer?

BACKGROUND/AIMS: Many tumor markers have been utilized in the follow-up care of colorectal cancer patients. No marker, however, has proven reliably accurate in detecting recurrent disease. METHODS: The strengths and weaknesses of currently available tumor markers are reviewed, with attention to related cost and efficacy. RESULTS: Tumor antigens, enzymes, and genetic markers have been used as tumor markers. CEA and CA 19.9 are the most widely utilized; however, genetic markers are the most promising for the future. CONCLUSIONS: Currently available markers have significant limitations. Development of genetic markers may greatly enhance our ability to predict prognosis and the need for adjuvant therapy. Marker-guided therapy may play an increasing role in this disease.

Limited utility of preoperative studies in preparation for colostomy closure.

Numerous diagnostic and therapeutic practices are used in an attempt to reduce the morbidity of colostomy closures. Our principal aim was to evaluate the role of preoperative studies, specifically barium enemas and endoscopic examinations, performed before colostomy closures. Additionally, we wished to identify other practices involved in the perioperative management of patients undergoing colostomy closure that influenced morbidity. The records of 100 consecutive patients who underwent elective colostomy closure at University of Louisville Hospital between January 1989 and July 1995 were reviewed. Wound infection was the most common complication (12%). Various bowel preparations were equivalent in efficacy and did not influence the complication rate. Intermittent wound irrigation with antibiotics for 3 days postoperatively, via subcutaneous drains, was associated with a low incidence of incision infection. Preoperative barium enema or sigmoidoscopy were often performed but rarely useful. Performing these examinations merely increased hospital cost without a corresponding decline in morbidity.

The natural resistance-associated macrophage protein gene is associated with Crohn's disease.

BACKGROUND: Identification of the genes causing inflammatory bowel disease (IBD) would enhance the understanding of and the treatment options for this disease. A hyperreactive immune response toward the intestinal flora has been implicated in the pathology of IBD. The natural resistance-associated macrophage protein (NRAMP) gene is believed to regulate macrophage function, especially the ability to fight intracellular pathogens. Genetic differences of NRAMP might, therefore, be associated with IBD. METHODS: Two DNA markers (D2S434 and D2S1323) near NRAMP were polymerase chain reaction (PCR) amplified and genotyped with DNA from 103 patients with Crohn's disease, 85 patients with ulcerative colitis, and 98 control subjects. Clinical data were obtained for all patients. Comparisons were made by chi-squared analysis. Disease association with significant haplotypes was expressed as odds ratio. RESULTS: Allele and genotype distributions were similar for both markers among all groups. Haplotype frequencies were different among Crohn's disease and control groups (p = 0.024). Two individual haplotypes of the patients with Crohn's disease were significant compared with control subjects: DA (p = 0.023; odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9) and EA (p = 0.001; odds ratio, 3.5; 95% confidence interval, 1.6 to 3.2). The haplotype distribution was different within three age-of-onset groups of patients with Crohn's disease (p = 0.05). CONCLUSIONS: This study is the first to report an association between the NRAMP gene and Crohn's disease.

Crohn's disease and ulcerative colitis are associated with the DNA repair gene MLH1.

OBJECTIVE: The purpose of this study was to determine whether there is an association between Crohn's disease and ulcerative colitis with MLH1. SUMMARY BACKGROUND DATA: Identification of genes involved in the etiology of inflammatory bowel disease may lead to the development of markers that objectively can define disease and permit therapy. The treatment of Crohn's disease of the colon and ulcerative colitis also is complicated by difficulties in differentiating the two conditions. METHODS: The DNA and clinical data were obtained on 126 unrelated individuals (45 Crohn's disease, 36 ulcerative colitis, and 45 control subjects without intestinal disease). Polymerase chain reaction products were analyzed by single-strand conformation polymorphisms (MLH1 exons 9, 11, 14, 15, and 16) and polyacrylamide gel electrophoresis (markers D3S1611 and D3S1768). All comparisons were analyzed by chi square test. The association between single haplotypes and disease was expressed as relative odds. RESULTS: MLH1 exons 9, 11, 14, and 16 were monomorphic. Two, four, and six alleles were detected in MLH1 exon 15, D3S1611, and D3S1768, respectively. Significant associations were observed for MLH1 exon 15/D3S1611 haplotypes AB (OR = 5.5; p = 0.007) and BA (p = 0.002) with Crohn's disease and for haplotypes AB (OR = 4.0; p = 0.042), BA (p = 0.035), and BC (OR = 6.1; p = 0.016) with ulcerative colitis. Family history of inflammatory bowel disease was associated with D3S1768/D3S1611 (p = 0.05) and MLH1 exon 15/D3S1611 haplotypes (p = 0.03). D3S1611/D3S1768 haplotype CD (OR = 11.3; p = 0.03) was associated with disease, whereas MLH1 exon 15/D3S1611 haplotype AA (OR = 0.25; p = 0.02) was protective. Comparisons of MLH1 exon 15/D3S1611 haplotypes of Crohn's colitis and patients with ulcerative colitis were significant (p = 0.037). CONCLUSIONS: This study identifies a novel genetic and clinical association between MLH1 and inflammatory bowel disease.

Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer.

PURPOSE: Preoperative radiation with combined chemotherapy is effective in shrinking advanced rectal cancer locally and facilitating subsequent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenous administration. This prompted us to evaluate suppository and intravenous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity. METHODS: Rectal, liver, lymph node, and lung tissue and systemic and portal blood were collected serially from male Sprague Dawley rats to determine drug concentrations following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment groups and received 5-fluorouracil suppositories, mitomycin C suppositories, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 days following this treatment, blood was collected, colonoscopy was performed, and rectal tissue was harvested for histologic examination. RESULTS: Mitomycin C suppository was significantly less toxic compared with intravenous delivery, and higher rectal tissue concentrations were observed from 10 to 30 minutes (P < 0.05). Compared with intravenous 5-fluorouracil administration and radiation, 5-fluorouracil suppository and radiation resulted in additive myelosuppression at day 6 (P < 0.05) with rapid recovery. CONCLUSIONS: 5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.