Screening for Lynch Syndrome
Molecular screening combined with immunohistochemical analysis can detect the Lynch syndrome, or hereditary nonpolyposis colorectal cancer, in patients with colorectal adenocarcinoma with greater accuracy than other criteria, reported Heather Hampel of Ohio State University, Columbus, and her colleagues.
In a group of 1,066 patients with colorectal adenocarcinoma, abnormalities of microsatellite instability were detected by immunohistochemical analysis in 123 of 132 tumors that had shown high-frequency microsatellite instability on genotyping. Only 10 of 70 tumors that had low-frequency microsatellite instability on genotyping showed abnormalities on immunohistochemical staining. Overall, 23 patients (2.2% of 1,066)—all with high-frequency microsatellite instability—had a deleterious mutation in a mismatch-repair gene (MLH1, MSH2, MSH6, or PMS2), which indicated that they had the Lynch syndrome (N. Engl. J. Med. 2005;352:1851–60).
Only 3 of those 23 patients fulfilled the Amsterdam criteria for the diagnosis of the syndrome. The Bethesda criteria for the syndrome would have diagnosed 15 of the patients. Five of the 23 patients did not fulfill either set of criteria. A mismatch-repair gene mutation was found in 52 of 117 relatives of the 23 patients; 14 of the 52 relatives had cancer related to the Lynch syndrome.
Sigmoidoscopy Yield Is Poor in Women
Flexible sigmoidoscopy is inadequate for predicting advanced neoplasia in the proximal colon in women, making colonoscopy the preferred method of screening for colorectal cancer in women, according to the results of a prospective study.
The study included 1,463 asymptomatic, average-risk women who underwent colonoscopy. Flexible sigmoidoscopy would have missed 94% (47 of 50) of advanced neoplasias in the proximal colon if the procedure extended to the junction of the sigmoid and descending colon and a finding of distal colorectal neoplasia had triggered a colonoscopy, reported Philip Schoenfeld, M.D., of the University of Michigan, Ann Arbor, and his associates. In a similar situation, 92% (36 of 39) of advanced neoplasias in the proximal colon would have been missed if sigmoidoscopy had been performed to the splenic flexure (N. Engl. J. Med. 2005;352:2061–8).
When the researchers matched men from the VA Cooperative Study 380 with women in the present study who had a negative fecal occult blood test and no family history of colorectal cancer, flexible sigmoidoscopy had a significantly higher yield for advanced neoplasia in men (66%, 126 of 190) than in women (35%, 19 of 54).
Hepatic Colorectal Metastases
Expression of the catalytic subunit of human telomerase reverse transcriptase independently predicts lower survival in patients who undergo curative resection for hepatic colorectal metastases, reported Julien Dômont, M.D., of the Institut Gustave Roussy, Villjuif, France, and colleagues.
In a retrospective multicenter study of 201 patients, positive staining for human telomerase reverse transcriptase (hTERT) in the nucleolus was associated with a twofold higher relative risk of dying after curative resection for hepatic colorectal metastases; the increase was statistically significant (J. Clin. Oncol. 2005;23:3086–93).
The median overall survival of patients with positive hTERT staining was significantly lower than survival of patients with negative staining after hepatic resection (23 months vs. 46 months). In a multivariate analysis, other independent risk factors for lower survival included more than two hepatic metastases and a disease-free interval of less than 12 months.
C. difficile Diarrhea Relapse
The prebiotic oligofructose prevents relapse of Clostridium difficile-associated diarrhea in significantly more inpatients than does placebo, reported Stephen Lewis, M.D., of Derriford Hospital, Plymouth, England, and his associates.
Of 72 patients who received oligofructose in a double-blind, randomized trial, 6 patients (8%) had a relapse of diarrhea, compared with 24 (34%) of 70 patients who received placebo.
However, the two groups did not differ in C. difficile culture positivity at 30 and 60 days after hospital discharge. At hospital discharge and at 60 days after discharge, oligofructose-treated patients carried significantly higher concentrations of fecal bifidobacteria and total anaerobes, but not aerobes, compared with placebo-group patients. “It is possible that the bifidobacterial metabolic products inhibited the metabolic activity of C. difficile,” the investigators suggested (Clin. Gastroenterol. Hepatol. 2005;3:442–8).
Most patients received metronidazole as first-line treatment for their initial or relapse episode of C. difficile-associated diarrhea. Oligofructose is a fructo-oligosaccharide found in plants such as chicory, asparagus, and artichoke.