This month in Gastroenterology

This Month in

Gastroenterology By Karen E. Kim

Can Baseline Adenoma Characteristics Predict the Recurrence of Advanced Adenomas? he risk of developing colorectal cancer can be greatly reduced with proper colorectal cancer screening and surveillance. Recent studies suggest that distal adenomas may increase the risk for proximal lesions; however, there are controversial data on the link between the adenoma characteristics found during baseline colonoscopy and adenoma recurrence. Martinez et al. report the results of 1287 men and women who were randomized in the wheat bran fiber (WBF) study as a means to decrease the probability of adenoma recurrence over a 3-year period. Advanced adenomas were defined as those > 1 cm or with tubulovillousl villous histology. Recurrence of advanced adenomas was higher in patients with polyps> 1 cm or in those with proximal compared with distal adenomas. No association was observed with the histologic type or number of polyps identified. There was a location shift from distal baseline lesions (27.2%) to proximal recurrent adenomas (45.2%), including advanced lesions (42.8%), supporting the need for complete colonoscopy follow-up. . .. page 1077

T

Prognostic Value of Measuring Circulating Colorectal Cancer Cells espite medical and surgical ad-

D vances in the treatment of colo-

rectal cancer (CRC), the overall mortality remains <40%. Current staging methods are not accurate enough to predict disease recurrence or micrometastasis, and newer molecular techniques are being designed to improve both sensitivity and specificity. Detection of neoplastic cells in peripheral blood using reverse-transcription polymerase chain reaction

(RT-PCR) targeting tissue-specific gene transcripts has been an area of increasing interest. Bessa et a1. studied the prognostic value of preoperative carcinoembryonic antigen (CEA) messenger RNA (mRNA) expression using RT-PCR in 95 patients with histologically confirmed CRC, followed up for a mean of 42 months. While 72% of patients underwent presumed curative resection, 28% of these patients had postsurgical relapse. The probability of disease-free and overall survival was dependent on lymph node metastasis and degree of tumor differentiation, but not on the presence of preoperative peripheral CEA mRNA levels. The disease recurred in 27% of CEA mRNA-positive patients and in 28% of CEA mRNA-negative patients. The investigators conclude that preoperative detection of CEA mRNA does not have prognostic significance in patients with CRe. ... page 1084

Smoking Cessation and Crohn's Disease rohn's disease is a chronic, reinflammatory disease requiring lifelong therapy. Factors determining disease severity are unknown, but environmental factors such as cigarette smoking have been suggested to increase the risk of Crohn's disease and to adversely affect the clinical course of the disease. Smokers have an increased incidence of clinical relapse, develop more complications, and often require more immunosuppressive therapy than nonsmokers. Cosnes et al. performed a prospective interventional study on 474 smokers with Crohn's disease to determine predictors for smoking cessation, and to further determine the effect of smoking cessation on disease activity. Of the patients, 12% became quitters (stopped smoking for more than 1 year); predictors for smoking cessation

Clapsing

included socioeconomic status, women taking oral contraceptives, previous intestinal surgery, and physician support. Compared with both nonsmokers and continuing smokers, quitters had a decreased flare risk and need for steroids or increased immunosuppressive therapy similar to nonsmokers, the latter being increased in continuing smokers. The risk of surgery was similar among the 3 groups. This study suggests that smoking cessation for more than 1 year in patients with Crohn's disease can improve the course of the disease, similar to those who have never smoked. ... page 1093

Fat Digestion Modulates Gastrointestinal Symptoms

T

he sensation of postprandial bloating and fullness is mediated by a variety of physiologic changes stimulated by nutrient fat reaching the small intestine. These changes include gastric relaxation, modulation of motility, release of digestive hormones such as cholecystokinin, and pancreaticobiliary secretion. The induction of these gastrointestinal symptoms may be mediated by the breakdown of dietary fats into free fatty acids, which in tum provide feedback inhibition of gastric emptying, hormonal release, and secretion. Therefore, decreases in free fatty acid within the small intestinal lumen may improve postprandial symptoms. To test this hypothesis, Feinle et a1. studied the effects of intraduodenally infused medium-ehain triglycerides (MCTs), long-ehain triglycerides (lCTs), or nondigestible fats (sucrose polyester [SPED, with and without a lipase inhibitor, tetrahydrolipstatin, on 15 healthy subjects to assess the effects on gastrointestinal sensations. Both LCTs and MCTs increased gastric volume compared with SPE, whereas LCT coadministration eliminated this response. Hunger sensation decreased more during LCT

GASTROENTEROLOGY 2001;120:1071-1072

11:Jis Month 11/ <.astluentero~ cOtrtl1llled

than \\ ith MeT. ll1is study sllgge~t~ that bt digestion is n:qllired for the modulation of gastrointestinal sensations during gastric distention, and this effect depends on fatty acid chain length. . .. page f f 00 mfll~ion

Selectins in Experimental Colitis

R

ecruitment of leukocytes from the vascular compartment to the extravascular space is a critical component of inflammation and involves leukocyte-endothelial cell adhesive interactions. The selectin family of cell adhesion molecules (CAM) includes endothelial P- and E-selectins and leukocyte L-selectins and is essential for the initial phase of leukocyte recruitment. However, the role of selectins in experimental colitis is unknown. Sans et al. characterize rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. P- and E-selectin expression was markedly up-regulated in the colitic rats. The use of anti-P-selectin abrogated leu-

1072

kocyte rolling and decreased leukocyte adhesion, whereas anti-E-selectin or anti-L-selectin only attenuated leukocyte rolling and had no effect on adhesion. Colitic animals treated with dexamethasone, not anti-Pselectin, had a significantly lower macroscopic and histologic damage score. This study supports the role for P-selectin in leukocyte roIling and adhesions in TNBS-induced colitis. However, treatment directed against selectins does not appear to significantly improve colitis. ... page 1162

Pancreatic Cancer and Obesity pidemiologic studies have sugan association between pancreatic cancer and various factors, including smoking, diabetes, and obesity. Schneider et al. previously reported the effect of high-fat diets on the development of peripheral insulin resistance, with subsequent compensatory islet ceU proliferation, as a possible mechanism leading to pancreatic

Egested

carcinogenesis. They now examined whether blocking the islet ceU proliferation induced by a high-fat diet can inhibit pancreatic carcinogenesis. Two groups of hamsters fed a high-fat diet were studied. One group was given metformin (l, I-dimethyl-biguanide) in their drinking water, and the other group received normal water; both groups were then treated with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)an1ine. Metformin has been shown to be effective in improving insulin resistance and increasing glucose utilization. The metformin-treated group did not develop any malignant tumors and had fewer premalignant and hyperplastic lesions, but 50% of high-fat diet hamsters not given metformin developed malignant lesions. In both groups, most lesions were identified in the islet ceUs. This study further supports the role of islet ceUs in pancreatic carcinogenesis and may explain the association between pancreatic cancer, obesity, and peripheral insulin resistance. . .. page 1263