A. Merighi

Myeloperoxidase-Positive Cell Infiltration in Colorectal Carcinogenesis as Indicator of Colorectal Cancer Risk

Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in ×100 optical fields under a light microscope. Patients with colorectal tumors had a higher mean number of MPO-positive cells in normal mucosa than controls (mean ± SD, 2.7 ± 2.0 versus 1.4 ± 1.4; P = 0.017). MPO-positive cell number was tightly linked to dysplasia in aberrant crypt foci and adenomas, and it was higher in carcinomas microsatellite unstable than those microsatellite stable (21.6 ± 15.5 versus 11.9 ± 8.0; P < 0.01). MPO immunohistochemistry is a simple and reliable technique for the quantification of inflammation in colorectal mucosa., and it may be a potential marker of colorectal cancer risk. Microsatellite instability seems to influence host immune responses to colorectal carcinoma. These observations strongly support a key role of inflammation in colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2291–7)

Capsule enteroscopy in small bowel transplantation.

BACKGROUND Enteroscopy plays a key role in the post-operative monitoring of patients with small bowel transplantation for the early detection of post-transplant complications and for the assessment of the grafts integrity. Routine surveillance enteroscopies (trans-stomal terminal ileoscopy or jejunoscopy) are invasive, may be unsafe in frail patients, and only allow incomplete exploration of the transplanted graft, which may be unsatisfactory. since the distribution of the lesions is often patchy or segmental. AIMS. To evaluate the potential of capsule enteroscopy, a new, minimally invasive technique which allows complete exploration of the small bowel. in small bowel transplant recipients. METHODS Five small bowel transplanted patients underwent capsule enteroscopy with the GIVEN endoscopy system. The results of capsule enteroscopy were compared with those of trans-stomal ileoscopy. RESULTS Capsule enteroscopy was better tolerated than ileoscopy and good quality images of the small bowel were obtained in four patients. The terminal ileum was normal both on ileoscopy and capsule enteroscopy. Mucosal changes in segments not reached by ileoscopy were detected by capsule enteroscopy in three of four patients. CONCLUSIONS Capsule enteroscopy is better tolerated than ileoscopy, allows complete exploration of the transplanted graft and can detect mucosal changes in segments not reached by ileoscopy.

Proposal of a new clinical index predictive of endoscopic severity in ulcerative colitis.

Assessment of disease activity by clinical parameters in ulcerative colitis is still controversial. Different clinical indexes have been proposed. Colonoscopy provides detailed information on mucosal damage. The aim of this study was to identify, among 21 clinical and laboratory parameters, which were predictive of endoscopic activity. We included 137 consecutive patients with ulcerative colitis who underwent colonoscopy, clinical examination, and blood tests within 4 weeks. Endoscopic severity was recorded using a simple score (range, 0–30). The multiple stepwise regression coefficient of each significant variable predictive of mucosal damage was used to develop a new activity index predictive of endoscopic appearance (Endoscopic–Clinical Correlation Index; ECCI). We tested the ability of our score to discriminate patients with severe endoscopic disease, calculating the area under the receiver operator characteristic curve, and we compared it to activity indexes proposed by other authors. Endoscopic severity was significantly influenced by four parameters: bloody stool, nocturnal bowel movements, body temperature >37.5°C, and serum albumin. The new scoring system was calculated as ECCI = {[serum albumin × (−26)] + (bloody stool × 17) + (nocturnal bowel movements × 16) + [fever (0 or 1) × 39]} + 107. The ECCI accurately identified patients with severe endoscopic disease in our sample (sensitivity = 81%, specificity = 95%). In conclusion, the ECCI should be useful in clinical practice because it is simple and strongly related to endoscopic activity.

A complication of SASP therapy: Hair loss

mg/kg. A discrepancy of 100-fold strongly suggests that the histamine control rats were injected with an inappropriate dose of histamine. If this were the case, the parallelism of the histamine control and spermine-treated data could be accounted for on the basis of a simple factor of dosage rather than an effect of the putative antagonist, inasmuch as a monotonic dose-response relationship does exist between 1 and 20 mg/kg of histamine base (9). This is precisely the kind of phenomenon that independent confirmation is supposed to prevent. We do not dispute the acid and volume dose-response relationships depicted in their Figure 1 (6). The reason that we did not attempt to replicate the Shay rat experiments with a histamine dosage which we know to be effective is that no one really agrees on the mechanisms which enhance volume and acid secretion under these conditions (11). Under these circumstances we feel that the authors were not justified in suggesting that spermine would be an antisecretory agent in any other preparation than the pylorus-ligated rat. (Extrapolation of their dosage to dogs would produce an emetic response instead.) An extrapolation to man on the basis of the use of this rat model alone (even if our criticisms are without foundation) is without support. RYUKICHI HADA, MD JOHN S. MARTIN, PHD MARTIN F. TANSY, PHD Temple University Department of Physiology and Biophysics Philadelphia, Pennsylvania

Low molecular weight heparin does not increase bleeding and mortality post-endoscopic variceal band ligation in cirrhotic patients

Anticoagulants are commonly indicated in cirrhotic patients due to high rate of (pro)thrombotic conditions. Low molecular weight heparin (LMWH) is safe in patients with esophageal varices. However, the safety of LMWH is unknown in patients undergoing prophylactic endoscopic variceal ligation (EVL). To define the 4‐week risk of bleeding and death after prophylactic EVL in cirrhotic patients continuously treated with LMWH.

A hyaluronic acid- and chondroitin sulfate-based medical device improves gastritis pain, discomfort, and endoscopic features

Gastritis is an inflammation of the gastric mucosa. In this study, we investigated the efficacy of a medical device, Esoxx®, based on hyaluronic acid and chondroitin sulfate on gastritis-related upper abdominal pain/discomfort and endoscopic features. Fifty patients, affected by gastritis, were randomised to receive the medical device or placebo. The primary endpoint was the medical device efficacy on upper abdominal pain/discomfort associated with gastritis and measured by Visual Analogue Scale (VAS). The secondary endpoints were the efficacy of the medical device on gastritis-related mucosal erosions, blood oozing, and hyperemia (redness)/edema, as assessed by endoscopy, and the patients’ rating of their compliance with the treatments. A significant reduction in VAS pain was observed in the treatment group after a 5-week treatment, if compared with placebo (p < 0.001). In summary, administration of a medical device, based on hyaluronic acid and chondroitin sulfate, improves gastritis-related upper abdominal pain/discomfort and decreases mucosal erosions, blood oozing, and hyperemia (redness)/edema at 5-week follow-up in patients affected by gastritis.

Myeloperoxidase-positive cell infiltration of normal colorectal mucosa is related to body fatness and is predictive of adenoma occurrence

Body fatness is a risk factor for colorectal cancer, and promotes an inflammatory environment. Indeed, inflammation in normal colorectal mucosa may be a factor linking body fatness to colorectal carcinogenesis. In this study, we evaluated myeloperoxidase (MPO)-positive cells infiltration of normal colorectal mucosa as a marker of cancer-promoting inflammation in overweight and obese subjects. One hundred and three subjects with normal colonoscopy entered the study. Waist circumference (WC) and body mass index (BMI) were measured, and MPO-positive cells on histological sections of biopsies of normal colorectal mucosa were counted under a light microscope. The occurrence of adenomas was then evaluated on follow-up colonoscopies. Mean MPO-positive cell count (±s.e.m.) was higher in subject with a WC equal or above the obesity cutoff values according to gender (2.63±0.20 vs 2.06±0.18, P=0.03), and in subjects with BMI equal or above 25 kg m−2 (2.54±0.18 vs 1.97±0.20, P=0.03). A Cox proportional hazard model showed that mean MPO-positive cell count in normal colorectal mucosa was the only factor independently related to occurrence of adenomas in follow-up colonoscopies. Though preliminary, these results show that MPO-positive cell infiltration in normal colorectal mucosa is related with body fatness, as evaluated by WC and BMI, and it may be considered a useful and simple marker to estimate adenoma occurrence risk.

3342 Gi endoscope reprocessing: microbiologic surveillance.

Patient infection from contaminated GI endoscopes can generally be attributed to failure to follow appropriate reprocessing guidelines, but the application of cleaning-disinfection procedures requires adequate staff training and a specific work organization. In 1996 we adopted a quality assurance program to assess the effectiveness of our procedures, and suggested to perform a yearly microbiologic surveillance of disinfection ( Gastrointest Endosc,1966;43:457 ). In the last two years the number of procedures performed at our endoscopy unit increased significantly, with important changes in work organization. We therefore defined a quality assurance program to re-assess the effectiveness of cleaning and disinfection. Every 3 months bacteria contamination was tested by sampling: -the distal end of the endoscope by contact-plate and of biopsy channel by washing with 10 mL saline; -water in the automatic washing machine reservoir. During the first 6 months of monitoring, a significant contamination (bacterial load >20 CFU/mL) was found on the surface and/or in channels of both colonoscopes (in 5 out of 6 random tests) and duodenoscopes (in 1/6 tests),whereas on gastroscopes a light contamination ( Pseudomonas spp (mainly P aeruginosa ), but in one occasion also Escherichia coli and Klebsiella oxitoca were isolated.In the same period, no significant contamination was found in the water reservoir of the washing machine. Two corrective interventions of the disinfection procedures were then applied: 1)prolonged exposure to 2% glutaraldehyde (from 20 to 30 min) for both colonoscopes and duodenoscopes; 2)use of dedicated washing machines for gastroscopes, colonoscopes and duodenoscopes. After these interventions, Pseudomonas spp was virtually eliminated (isolated only in 1 out of 37 random tests performed in a 15-month period, and only a light contamination of the endoscopes was found (in 3 out of 37 tests) by Staphilococcus spp . This prompted us to pay more attention to post-processing endoscope manipulation and storage. In conclusion, our observations suggested that: -a microbiologic surveillance program should be intensified when the workload and work organization in the endoscopy suite change significantly; -increasing time of exposure of colonoscopes and duodenoscopes to glutaraldehyde, and the adoption of a regimen of washing machines dedicated to specific endoscopes would result in a significant reduction in the level of contamination.

4706 The rockall score is a useful prognostic tool in gastroduodenal ulcer haemorrhage.

Background and aim. Gastroduodenal ulcer bleeding is the major cause of endoscopic examination on emergency. Patients with acute upper gastrointestinal haemorrhage (UGIH) are routinely hospitalized regardless of the clinical status or the stigmata of bleeding. The Rockalls score (1) was recently tested for its prognostic value after UGIH. The aim of the present study was to validate Rockalls score in a set of patients with gastroduodenal ulcer bleeding in an Italian teaching hospital and to prove his usefulness in improving quality of care. Material and methods. From May/96 to May/97 100 consecutive patients, admitted as emergencies for UGIH, underwent endoscopy within 6 hours of admission and were found affected by gastroduodenal ulcer (peptic or malignant). All the patients with active bleeding (42) and most of the ones with stigmata of recent haemorrhage were treated endoscopically by injection of 10-20 ml 1:10,000 adrenaline. Initial Rockalls score (iR - based on age and presence of shock and comorbidity) and total Rockalls score (tR - sum of iR and a score related to endoscopic findings) were calculated for each patient. Results. Initial haemostasis was achieved in all cases, but 19 patients recurred; 12 died, 9 after at least one rebleeding. Median iR and median tR were 2 (range 0-6) and 4 (1-9) for non-rebleeders vs. 3 (0-7) and 6 (3-10) for rebleeders ( p 8 rebled and died. The average length of hospital stay was 10.3 days for all patients and 4.4 for the group with tR