A phase I pilot study evaluating the beneficial effects of black raspberries in patients with Barrett's esophagus.

Black raspberries inhibit a broad range of cancers in preclinical models which has led to clinical evaluations targeting premalignant lesions of the colon, oral cavity and esophagus. A phase I pilot study was conducted in twenty Barrett's esophagus (BE) patients to investigate the effect of lyophilized black raspberries (LBR) on urinary metabolites and markers of lipid peroxidation, DNA damage and tissue markers of cellular proliferation, detoxification, and inflammation. Surveys, biopsies, blood and urine samples were collected before and after 6 months of LBR treatment (32 or 45 g). LBR significantly reduced urinary excretion of 8-epi-prostaglandin F2α, a marker of lipid peroxidation linked to oxidative stress and free radical damage. Urinary levels of the ellagitannin metabolites, urolithin A-glucuronide, urolithin A-sulfate and dimethylellagic acid glucuronide were significantly increased following 12 and 26 weeks of LBR consumption and may prove useful as indicators of compliance in future clinical studies. Immunohistochemical staining of BE biopsies following LBR treatment showed significant increases in mean GST-pi levels, with 55.6% of subjects responding favorably. In summary, LBR significantly decreased urinary lipid peroxidation levels and significantly increased GST-pi, a marker of detoxification, in BE epithelium. Still, LBR may need to be formulated differently, administered at higher concentrations or multiple times a day to increase efficacy.

Transitioning from preclinical to clinical chemopreventive assessments of lyophilized black raspberries: interim results show berries modulate markers of oxidative stress in Barrett's esophagus patients.

Increased fruit and vegetable consumption is associated with decreased risk of a number of cancers of epithelial origin, including esophageal cancer. Dietary administration of lyophilized black raspberries (LBRs) has significantly inhibited chemically induced oral, esophageal, and colon carcinogenesis in animal models. Likewise, berry extracts added to cell cultures significantly inhibited cancer-associated processes. Positive results in preclinical studies have supported further investigation of berries and berry extracts in high-risk human cohorts, including patients with existing premalignancy or patients at risk for cancer recurrence. We are currently conducting a 6-mo chemopreventive pilot study administering 32 or 45 g (female and male, respectively) of LBRs to patients with Barrett's esophagus (BE), a premalignant esophageal condition in which the normal stratified squamous epithelium changes to a metaplastic columnar-lined epithelium. BE's importance lies in the fact that it confers a 30- to 40-fold increased risk for the development of esophageal adenocarcinoma, a rapidly increasing and extremely deadly malignancy. This is a report on interim findings from 10 patients. To date, the results support that daily consumption of LBRs promotes reductions in the urinary excretion of two markers of oxidative stress, 8-epi-prostaglandin F2alpha (8-Iso-PGF2) and, to a lesser more-variable extent, 8-hydroxy-2'-deoxyguanosine (8-OHdG), among patients with BE.

Using contrast-enhanced MR cholangiography with IV mangafodipir trisodium (Teslascan) to evaluate bile duct leaks after cholecystectomy: a prospective study of 11 patients.

OBJECTIVE: The purpose of our study was to determine whether contrast-enhanced MR cholangiography using IV mangafodipir trisodium can accurately detect the presence and location of bile duct leaks in patients who have undergone cholecystectomy. SUBJECTS AND METHODS: Our study group included 11 patients with suspected bile duct leaks after cholecystectomy. Axial single-shot fast spin-echo and gradient-echo images were acquired in all patients before and 1-2 hr after IV administration of mangafodipir trisodium. The contrast-enhanced MR cholangiograms were evaluated for image quality, degree of ductal or small bowel opacification, and the presence and location of bile duct leaks, strictures, and stones. MR cholangiograms were correlated with conventional contrast-enhanced cholangiograms obtained in all patients, including endoscopic retrograde cholangiography (n = 10) and percutaneous transhepatic cholangiography (n = 1). RESULTS: Excretion of mangafodipir trisodium was noted in the intrahepatic and extrahepatic bile ducts in all patients from 1 to 2 hr after IV administration. Bile ducts and fluid collections that contained excreted mangafodipir trisodium showed increased signal intensity on gradient-echo sequences and decreased signal intensity on single-shot fast spin-echo sequences. Conventional contrast-enhanced cholangiography showed the presence of bile duct leaks in six patients and the absence of bile duct leaks in five patients, with false-negative findings in one patient and false-positive findings in one patient for bile duct leak (sensitivity, 86%; specificity, 83%). CONCLUSION: Contrast-enhanced MR cholangiography with IV mangafodipir trisodium can successfully detect the presence and location of bile duct leaks in patients suspected of having such leaks after undergoing cholecystectomy. More research is necessary before acceptance of this examination as routine in the workup of these patients.