Marianne Ortner

Association between intraepithelial Escherichia coli and colorectal cancer

BACKGROUND & AIMS Although multiple studies have focused on Helicobacter pylori, little is known about the mucosa-associated flora of the colon. The aim of this study was to detect bacteria directly in colonic mucosa from patients screened for colorectal cancer. METHODS Bacteria were quantified with the polymerase chain reaction and identified by comparative sequence analysis in colonoscopic biopsy specimens from 31 asymptomatic and 34 symptomatic controls with normal colonoscopic findings, 29 patients with colonic adenoma, and 31 patients with colorectal carcinoma. In 41 patients, intra- and extracellular location of bacteria was confirmed with the gentamicin protection assay. RESULTS No bacteria were detected in biopsy specimens from 97% of asymptomatic and 69% of symptomatic controls. In contrast, bacterial concentrations of 10(3)-10(5) colony-forming units per microliter were detected in biopsy specimens from both malignant and macroscopically normal tissue in 90% and 93% of patients with adenoma and carcinoma, respectively. E. coli and coli-like bacteria were shown to colonize the colonic mucosa in 82% of these patients. The gentamicin protection assay indicated that E. coli was partially intracellular in 87% of patients with adenoma and carcinoma and in none of the controls. CONCLUSIONS The colonic mucosa of patients with colorectal carcinoma but not normal colonic mucosa is colonized by intracellular E. coli.

Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.

BACKGROUND: In Crohns disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohns disease. METHODS: Sixteen Crohns disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohns disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohns disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohns disease.

Cancer Prevention in Ulcerative Colitis: Long-term Outcome Following Fluorescence-guided Colonoscopy

Background: Patients with long‐standing ulcerative colitis require repeated endoscopies for early detection of neoplasias, which, however, are frequently missed by standard colonoscopy. Fluorescence‐guided colonoscopy is known to improve the detection rate but the long‐term effects of fluorescence‐guided colonoscopy are unknown. Methods: Colitis patients with negative findings at index fluorescence‐guided colonoscopy entered a prospective long‐term study with conventional colonoscopies at 2‐year intervals. Risk and time to progression were evaluated. The positive predictive value was assessed in patients with neoplasias at index fluorescence‐guided colonoscopy who underwent immediate total colectomy. Results: Thirty‐one patients with negative fluorescence‐guided colonoscopy were surveyed for a mean of 7.8 ± 0.9 years. Neoplasia was observed in only two of them (6%) after 7 and 8 years of follow‐up, respectively. Neoplasia at index fluorescence‐guided colonoscopy was observed in 10 patients. In all of them, multiple flat low‐grade intraepithelial neoplasia was diagnosed. At immediate colectomy performed in eight of them, the diagnosis of flat low‐grade intraepithelial neoplasia was confirmed, corresponding to a positive predictive value of 100%. However, synchronous more advanced neoplasia was detected in three of the eight patients (38%). All patients, those with and those without neoplasia, were alive at the end of the study. Conclusions: Fluorescence‐guided colonoscopy misses, in contrast to standard colonoscopy, few, if any, patients with neoplasia. Most neoplasia‐negative patients remain negative during prolonged follow‐up. However, when low‐grade dysplasia is diagnosed by fluorescence‐guided colonoscopy, colectomy is recommended because more than a third of the patients harbor synchronous, more advanced neoplasia. (Inflamm Bowel Dis 2012;)

Endoscopic detection of early malignancies in the upper gastrointestinal tract using laser-induced fluorescence imaging

Fluorescence images were recorded simultaneously with white light images to detect dyspasia or early malignancies during regular endoscopy of the upper gastrointestinal tract, after topical administration of 5-aminolaevulinic acid. Biopsies were taken at locations where fluorescence intensity were high compared with the mean fluorescence intensity of the image. Prompt and delayed fluorescence spectra of biopsies were subsequently recorded ex vivo, and normalized fluorescence intensities of Protoporphyrin IX derived from these spectra were compared with routine histology. In contrast to routine endoscopy, one early carcinoma and one signet-ring carcinoma were found in the stomach, and malignancies in a duodenal polyp. In addition, intestinal metaplasia could be visualized in the stomach of two patients, which had not been detected in biopsies taken prior to fluorescence endoscopy.

Fluorescence imaging in the upper gastrointestinal tract for the detection of dysplasic changes

During endoscopy of the esophagus fluorescence images were recorded at a delay of 20 ns after pulsed laser excitation simultaneously with conventional reflected white light images. To label malignant cells (dysplasia, tumor) 5-aminolaevulinic acid was applied prior to fluorescence guided bi-opsy. In this way pre-malignant and malignant lesions were detected not seen previously during routine endoscopy.

Endoscopic injection of mitomycin adsorbed on activated carbon particles versus brachytherapy for advanced esophageal cancer

Background: In a pilot study we could show that local injections of mitomycin adsorbed on activated carbon particles (MMCCH) therapy is an effective, well tolerated treatment for non-resectable esophageal tumors. The Aim of this study is to compare brachytherapy (RTL) and endoluminal MMCCH in nonresectable esophageal carcinomas. Methods: Twelve patients with non-resectable esophageal carcinoma (7stage IV, 5 stage III; 5 suprabifurcal, 7 infrabifurcal) were randomized to RTL and recieved four weekly 5 Gy with a bougie applicator using a t92 iridium source, resulting in 20 Gy. Fifteen patients (12 stage IV, 3 stage III; 8 suprabifurcal, 7 infrabifurcal) were randomized to four weekly injections of 15 mg MM CH via a 5 mm sclerotherapy needle into the endoscopically visualized tumor, resulting in a total dose of 60 mg. In both groups (6 RTL group, 10 MMC-CH group) metal stents were implanted additionally before therapy if the lumen was obstructed and there was enough distance to the upper sphincter (lcm). Primary outcome parameter was time to local tumor progress, secondary parameters were dysphagia, Quality of Life (Karnofsky index) and survival time. Tumor staging (CT chest, endosonography, gastroscopy, esophagogramm), symptom scores, life quality index (Spitzer index), were performed before and every other month after therapy. Results: Median time (weeks) to local tumor progress was 19.62 +_ 19.13 in the RTL group and 11.63 +7.99 in the MMC CH group (n.s.). Dysphagia score and Karnofsky-index improved in both groups, life quality index only in the MMC-CH group (Fig.). Esophagitis occured in 9/11 patients (81.8%) in the RTL group (mean 1.27 ± 0.9 grade) and fever and cyanosis during injection in 1/15 patients (6.6%) in the MMC-CH group.