L. Glória

Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.

BACKGROUND: Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. AIMS: The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. METHODS: Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136,556 (24,085) v 235,725 (38,636) v 400,998 (26,747 dpm/micrograms/DNA respectively; p = 0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p = 0.01) or with type III intestinal metaplasia (p = 0.15). CONCLUSIONS: Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents.

Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing oesophagogastric junctions: the same or two different entities?

Background—Endoscopic diagnosis of short segments of Barrett’s epithelium (SSBE) is difficult and its meaning in terms of the presence of specialised columnar epithelium (SCE) has not been prospectively evaluated. Aims—To evaluate the prevalence of SCE in patients with an endoscopic diagnosis of SSBE and in individuals with normal appearing oesophagogastric junctions, and to compare the clinical characteristics of these two groups. Patients—Thirty one patients with an endoscopic diagnosis of short Barrett’s oesophagus, less than 3 cm in length (group A), and 44 consecutive patients with normal appearing oesophagogastric junctions (group B). Methods—Multiple biopsies were performed in suspicious epithelium and at the oesophagogastric junction in groups A and B, respectively. Results—Age and sex distribution were similar in both groups. Reflux symptoms were more frequent in group A (p<0.001), as were endoscopic and histological signs of oesophagitis (p<0.0001 and p=0.001, respectively). SCE was found in 61.3% of group A patients compared with 25% in group B (p<0.002), with men predominating in group A while women were more frequent in group B (p=0.02). The differences in reflux symptoms and endoscopic/histological oesophagitis remained significant. Conclusions—These results show that endoscopic diagnosis of SSBE is associated with a high prevalence of SCE, significantly higher than that found in normal appearing oesophagogastric junctions. Differences between patients with SCE in the two groups suggest they may represent two different entities.

Folate status, DNA methylation and colon cancer risk in inflammatory bowel disease

*Servi¢os de Gastrenterologia e Laborat6rio de Biologia Molecular ~Servi¢o de Patologia Morfol6gica, Instituto Portugu#s de Oncologia Francisco Gentil, Lisboa Portugal, tServi¢o Universit~rio de Medicina Interna e de Gastrenterologia e do Hospital Pulido Valente, Portugal (Correspondence to MC, Servigo de Gastrenterologia, Instituto Portugu#s de Oncologia Francisco Gentil, Rua Prof. Lima Basto, 1093 Lisboa Codex, Portugal)

p53 Protein immunoexpression in esophageal squamous cell carcinoma and adjacent epithelium

Immunoreactivity for p53 tumor supressor gene product is commonly found in human malignancies and some premalignant lesions, but its role in cancer development and its value as a marker of tumor biologic behavior is still unclear.

DNA methylation and subclinical vitamin deficiency of folate, pyridoxal-phosphate and vitamin B12 in chronic alcoholics

Alcohol abuse is known to adversely affect folate, vitamin B12 and pyridoxal-phosphate metabolism, which are required for de novo synthesis of methionine. Methionine is the precursor of S-adenosylmethionine, the principal methylating agent in the organism, including DNA. The objective of this study was to measure DNA methylation in peripheral lymphocytes and the circulating concentrations of these three vitamins in chronic alcoholics. DNA methylation was assessed by measuring DNA methyl accepting capacity in the presence of Ssauthor methylase. Serum pyridoxal-phosphate and red blood cell folate concentrations were significantly depressed in alcoholics (P<0.0001 and P=0.02, respectively). DNA from patients who consumed 3.0 g/ethanol/kg/day or more, incorporated significantly more (3H) methyl groups, which reflects a lower state of intrinsic methylation (P=0.01). DNA hypomethylation was also more pronounced in malnourished alcoholics (P=0.03). We conclude that heavy ethanol consumption is associated with folate and vitamin B6 depletion, which may interfere with DNA methylation status by impairing de novo methionine synthesis.

Non-anesthesiologist administration of propofol sedation for colonoscopy is safe in low risk patients: results of a noninferiority randomized controlled trial

BACKGROUND AND STUDY AIMS Propofol provides the best sedation in colonoscopy. The safety of non-anesthesiologist administration of propofol (NAAP) is still a matter of debate. The aim of the current study was to evaluate sedation safety, colonoscopy quality, and patient satisfaction with NAAP. PATIENTS AND METHODS The study was a single-blinded, noninferiority, randomized controlled trial comparing NAAP (Group A) with anesthesiologist-administered sedation (Group B) performed at a single academic institution. Patients (18 - 80 years) who underwent colonoscopy and were at low anesthetic risk (American Society of Anesthesiologists class I - II) were included. The primary end point was the incidence of adverse events. Secondary end points were propofol dose, patient satisfaction and pain, colonoscopy quality indicators, and procedure and recovery times. RESULTS A total of 277 patients were included in the analysis. The incidence of adverse events was 39.3 % in Group A and 39.0 % in Group B (absolute difference - 0.3 %, 95 % confidence interval [CI] - 12.0 % to 11.4 %; P = 0.959). There were no sentinel adverse events. The following interventions (Group A vs. Group B) were necessary: atropine administration (0 % vs. 5.5 %; P = 0.004); airway repositioning (8.7 % vs. 4.7 %; P = 0.196); increased oxygen administration (6.7 % vs. 3.9 %; P = 0.317), and increased fluid rate (2.7 % vs. 0.8 %; P = 0.379). There were no differences in cecal intubation and adenoma detection rates. Recovery times were longer in Group B (58 ± 33 vs. 67 ± 29 minutes; P = 0.032). There were no differences in mean propofol dose, withdrawal time, painless colonoscopy, satisfaction, and amnesia. All but two patients (Group B) were willing to repeat the colonoscopy. CONCLUSIONS NAAP is equivalent to anesthesiologist-administered sedation in the rate of adverse events in a low risk population. TRIAL REGISTRATION ClinicalTrials.gov (NCT02067065).

Adenoma Detection Rate: I Will Show You Mine if You Show Me Yours

Background: Colorectal cancer (CRC) is the first cause of cancer-related mortality in Portugal. CRC screening reduces disease-specific mortality. Colonoscopy is currently the preferred method for screening as it may contribute to the reduction of CRC incidence. This beneficial effect is strongly associated with the adenoma detection rate (ADR). Aim: Our aim was to evaluate the quality of colonoscopy at our unit by measuring the currently accepted quality parameters and publish them as benchmarking indicators. Methods: From 5,860 colonoscopies, 654 screening procedures (with and without previous fecal occult blood testing) were analyzed. Results: The mean age of the patients was 66.4 ± 7.8 years, and the gender distribution was 1:1. The overall ADR was 36% (95% confidence interval [CI] 32-39), the mean number of adenomas per colonoscopy was 0.66 (95% CI 0.56-0.77), and the sessile serrate lesion detection rate was 1% (95% CI 0-2). The bowel preparation was rated as adequate in 496 (76%) patients. The adjusted cecal intubation rate (CIR) was 93.7% (95% CI 91.7-95.8). Most colonoscopies were performed under monitored anesthesia care (53%), and 35% were unsedated. The use of sedation (propofol or midazolam based) was associated with a higher CIR with an odds ratio of 3.60 (95% CI 2.02-6.40, p < 0.001). Conclusion: Our data show an above-standard ADR. The frequency of poor bowel preparation and the low sessile serrated lesion detection rate were acknowledged, and actions were implemented to improve both indicators. Quality auditing in colonoscopy should be compulsory, and while many units may do so internally, this is the first national report from a high-throughput endoscopy unit.

PP114-MON: Vitamin D in Patients with Crohn’s Disease

Rationale: Systemic sclerosis is a rare chronic autoimmune disease, characterized by fibrosis and inflammation and associated with a physical impairment and higher mortality. We assessed prevalence of sarcopenia and the impact of muscle strength and quality of life. Methods: Body composition was assessed with bioelectrical impedance analysis. Fat free mass was determined with algorithm suggested by Kyle et al and corrected for height. (FFMI, kg/m2). Values below 17.4 kg/m2 in men and <15 kg/m2 in women were considered indicative of sarcopenia. Maximal grip strength was measured with Jamar Dynamometer, and maximal knee extension strength with Digimax Dynamometer. Quality of Life was assessed with the validated SF 36. C-reactive protein was measured immunometric assay. Results: 107 patients were recruited (97 female, 59.3±14 years old, BMI 24.3±5 kg/m2). 41 (38.3%) patients were sarcopenic. Patients with sarcopenia did not differ from nonsarcopenic patients with regard to age, number of affected organs, comorbidities or treatment, but they exhibited significantly lower grip and knee strength, BMI (21.0±1.9 vs. 26.5±5.3, p < 0.0001) and CRP (7.7±12.9 vs. 2.8±3.6; p < 0.009). FFM correlated significantly with grip and knee extension strength (r = 0.64 and r = 0.37, p < 0.0001). There were no differences in quality of life.

Brief Case ReportsColonic cancer in a 34-yr-old woman: should it prompt microsatellite instability studies and mismatch repair gene testing?

It remains debatable whether young patients with colorectal tumors should undergo genetic testing with the aim of identifying new hereditary nonpolyposis colorectal cancer families. We describe a case of a young woman with colon cancer with no clinical criteria of hereditary nonpolyposis colorectal cancer, whose genetic analysis showed that the tumor displayed microsatellite instability, and in whom a truncated protein in hMSH2 gene was found, which was also present in two at-risk relatives.

Colonic cancer in a 34-yr-old woman: should it prompt microsatellite instability studies and mismatch repair gene testing?

It remains debatable whether young patients with colorectal tumors should undergo genetic testing with the aim of identifying new hereditary nonpolyposis colorectal cancer families. We describe a case of a young woman with colon cancer with no clinical criteria of hereditary nonpolyposis colorectal cancer, whose genetic analysis showed that the tumor displayed microsatellite instability, and in whom a truncated protein in hMSH2 gene was found, which was also present in two at-risk relatives.