Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma.

BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. METHODS: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. RESULTS: Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.

Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer.

PURPOSE: CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic colorectal cancer. We report the results from a Phase II trial of preoperative radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal cancer. METHODS AND MATERIALS: Between April 1999 and August 2001, 32 patients (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study. All patients underwent endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT-11 (50 mg/m(2), Days 1, 8, 15, and 22) and 5-FU (200 mg/m(2) daily, 7 d/wk, Days 1-33). Surgical resection was performed 6-10 weeks after completing chemoradiotherapy. RESULTS: Acute toxicity was frequently observed, and 18 patients (56%) required either a chemotherapy dose reduction or RT interruption of >3 days. One patient withdrew because of diarrhea and abdominal cramping (Grade III) after 10 days of treatment. Although no Grade IV toxicity was observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the disease of 23 (71%) was downstaged. The average length of hospitalization was between 5 and 12 days, with 1 patient staying 33 days. All patients were followed for disease-free survival. CONCLUSION: Although associated with frequent acute toxicity, the regimen is associated with significant tumor "downstaging." Additional patients and longer follow-up are necessary to define the role of this regimen fully.

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis.

BACKGROUND: Published data on the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis are conflicting. A meta-analysis was performed to synthesize available publications and to compare the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis. METHODS: By using MEDLINE and manual search methods, studies were identified that compared the risk of colorectal neoplasia (dysplasia and carcinoma) in patients with ulcerative colitis with and without primary sclerosing cholangitis. In addition, citations were reviewed in relevant articles and proceedings from gastroenterology meetings, and investigators were contacted when data were incomplete. The summary odds ratio (OR) was then calculated for the risk for patients with ulcerative colitis and primary sclerosing cholangitis of having colorectal neoplasia develop compared with that of patients with ulcerative colitis without primary sclerosing cholangitis. RESULTS: Eleven studies met all eligibility criteria for the meta-analysis. Patients with ulcerative colitis and primary sclerosing cholangitis are at increased risk of colorectal dysplasia and carcinoma compared with patients with ulcerative colitis alone; OR 4.79: 95% CI [3.58, 6.41] with the Mantel-Haenszel method, and OR 5.11: 95% CI [3.15, 8.29] with the Der Simonian and Laird method. This increased risk is present even when the risk of colorectal carcinoma alone is considered; OR 4.09: 95% CI [2.89, 5.76] and OR 4.26: 95% CI [2.80, 6.48] by using, respectively, the Mantel-Haenszel and the Der Simonian and Laird methods. CONCLUSIONS: Patients with ulcerative colitis and primary sclerosing cholangitis have a significantly higher risk for the development of colorectal neoplasia than patients with ulcerative colitis but not primary sclerosing cholangitis. More intensive colonoscopic surveillance should be considered for patients with ulcerative colitis and primary sclerosing cholangitis.

Management of esophageal strictures in children with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is a rare, genetically transmitted skin disorder characterized by blister formation and scarring in response to minor trauma. One of the most debilitating features of the disease is the development of esophageal strictures, which produces profound dysphagia, exacerbating an already highly compromised nutritional status common to these patients. Due to the extreme fragility of epithelial surfaces, the optimal therapeutic approach to esophageal strictures in this setting has not been established. METHODS: We have developed an approach to treatment of esophageal strictures in children with epidermolysis bullosa combining upper endoscopy using small caliber endoscopes, endotracheal intubation, and fluoroscopically assisted balloon dilatation. We report our experience using this technique in 22 children who have undergone a total of 109 dilatations. RESULTS: Upper endoscopy, endotracheal intubation, and balloon dilatation were well tolerated by even very young children with epidermolysis bullosa. Dysphagia was markedly reduced post-procedure, permitting resumption of normal diet for age, including solids, within six hours of the procedure. Post-procedure recovery has been rapid and does not require admission to the hospital. Complications have been infrequent, minor, and limited to the first year of our experience. The mean interval between dilatations for all children is 11 months. All children have gained weight, and have not required steroids or phenytoin. CONCLUSIONS: Balloon dilatation is a safe and effective therapy for esophageal strictures in children with recessive dystrophic epidermolysis bullosa. Limited upper endoscopy and endotracheal intubation are well tolerated by these children. This approach should be considered as primary therapy in this clinical setting.