Ménétrier's disease diagnosed by enteroclysis CT: a case report and review of the literature.

This study reports a case of Ménétrier's disease (MD) in an adult who presented with epigastric pain and peripheric edema. We focused in particular on the imaging and diagnostic aspects of the presenting case as well as clinical, histologic, and therapeutic aspects. Computed tomography (CT) enteroclysis is a new imaging technique which combines enteroclysis and spiral multislice CT. To the best of our knowledge this is the first report on a MD in an adult patient diagnosed by CT Enteroclysis.

Long-term prevention of post-operative recurrence in Crohn's disease cannot be affected by mesalazine.

BACKGROUND: Prevention of post-operative recurrence has a central role in the management of Crohn's Disease (CD). Many drugs have been evaluated in prospective randomised controlled trials (RCTs) but the results are disappointing. Mesalazine, the drug more extensively investigated, has been shown to be effective for preventing recurrence in the short-term; however, the overall benefit is small and no data are available on the long-term effectiveness. AIM: To compare the long-term occurrence of post-operative recurrence in patients who received regular prophylactic treatment with mesalazine with patients who did not receive prophylaxis after the first radical resection for ileo-caecal CD. PATIENTS AND METHODS: The records of 216 patients with ileo-caecal CD at their first resection were reviewed: 146 patients (67.6%) received post-operative prophylaxis with mesalazine while 70 patients (32.4%) received no prophylaxis. Allocation of patients in the two groups was determined by patients' preferences and by different policies in the post-operative prophylactic approach. The mean follow-up after surgery was 153.7 months (range 12-544). The co-primary endpoints were post-operative clinical and surgical recurrence. STATISTICAL ANALYSIS: Kaplan-Meier survival method, Chi-square, Student t-test. RESULTS: The two groups were comparable with regard to gender, age at surgery, smoking habits, pattern of CD (perforating/not perforating), and disease duration before surgery. One year after surgery, a small, not statistically significant, risk reduction in clinical recurrence was observed in mesalazine treated group (-7.6%; 95% CI -18.0% to 2.8%). Within 10 years after surgery, the cumulative probability of clinical recurrence and surgical recurrence were similar in the two groups (Log Rank test p=0.9 and p=0.1 respectively). CONCLUSION: Mesalazine prophylaxis is not effective for preventing the long-term post-operative recurrence in ileo-caecal Crohn's disease.

Chemoprevention in gastrointestinal adenocarcinoma: for few but not for all?

Despite the general progress of the last two decades in oncogenesis mechanism comprehension, in screening and surveillance programs, in technological support to diagnosis and in treatment protocols, the long-term survival of gastrointestinal (GI) cancer patients is not substantially changed. Therefore chemoprevention strategies still appear as a possible alternative to screening and surveillance programs in reducing the incidence and the mortality for GI cancer, at an acceptable cost/effectiveness ratio. The present review is focused on three GI cancers: esophageal adenocarcinoma, gastric cancer and colorectal cancer and their respective precarcinogenic lesions. The authors examine, for each neoplasia, the available chemopreventive agents, their mechanism of action in preventing cancer, the potential targets in the cell growth process, the cost/effectiveness ratio and, whenever present in literature, a comparison with other cancer prevention strategies. The authors conclude that, at present, with the available agents, chemoprevention is not indicated for all patients at low or moderate risk for GI cancer, and should not be considered as a substitute for endoscopic surveillance. In high-risk patients only, both chemoprevention and surveillance could be used. In future more specific agents and combined therapies should be tested in specific group of patients identified by their genomic susceptibility to develop cancer and responsiveness to therapy.

Colectomy rate in acute severe ulcerative colitis in the infliximab era.

BACKGROUND: Severe ulcerative colitis is a potentially life-threatening condition. Due to advances in medical therapy, the mortality rate has dropped to <2% over the past 30 years, but the colectomy rate reaches 30%. Recently, infliximab has been shown to be effective as rescue therapy but little is known about long-term benefits. AIM: To evaluate short-and long-term colectomy rates for severe ulcerative colitis in the era of biological treatment and to identify predictive factors of long-term colectomy. PATIENTS AND METHODS: From 2001 to 2006 all in-patients with severe ulcerative colitis, according to Truelove and Witts criteria, were retrospectively reviewed. All patients had received intravenous steroid treatment; infliximab (5 mg/kg at 0, 2 and 6 weeks) was used as rescue therapy in steroid-refractory patients; colectomy was performed in patients who deteriorated whilst on steroid treatment or failed to respond to infliximab. RESULTS: Of the 314 ulcerative colitis patients hospitalized during the study period, 52 (16.5%) met the criteria of severe ulcerative colitis. After median 7 days (range 4-15) on intravenous steroids, 37/52 (71%) patients showed a clinical response, while 15/52 (29%) were steroid-refractory. Of these, four underwent urgent colectomy and 11 received infliximab. A clinical response was observed in all infliximab-treated patients. In the long-term, another six patients underwent elective colectomy. The overall colectomy rate, following the acute attack, was 19%; the cumulative probability of a course without colectomy was 90%, 86%, 84%, 81%, after 6, 12, 18 and 24 months, respectively. No deaths occurred. The long-term colectomy risk was comparable in patients treated with infliximab and in steroid-responsive patients (18% vs. 11% respectively; OR 1.9; 95% CI 0.26-14.5). No predictive factors of colectomy, in the long-term, were identified. CONCLUSIONS: Surgery continues to play an important role in acute severe ulcerative colitis. Infliximab can avoid urgent colectomy in steroid-refractory patients but the risk of elective colectomy, in the long-term, is not modified.

Is early endoscopic retrograde cholangiopancreatography useful in the management of acute biliary pancreatitis? A meta-analysis of randomized controlled trials.

AIMS: To compare early endoscopic retrograde cholangiopancreatography with conservative management for the treatment of acute biliary pancreatitis: a meta-analysis of prospective randomized trials. METHOD: Pertinent studies were selected from the Medline, Embase, and the Cochrane Library Databases, references from published articles and reviews. Conventional meta-analysis according to DerSimonian and Laird method was used for the pooling of the results. The rate difference (95% CI) and the number needed to treat were used as a measure of the therapeutic effect. RESULTS: Five prospective randomized trials including 702 patients were selected. Overall complications and mortality rates were 31% and 6%, respectively. In predicted severe pancreatitis the pooled rate difference for complications in early endoscopic retrograde cholangiopancreatography was 38.5% (95% CI -53% to -23.9%); p < 0.0001; number needed to treat = 3. In predicted mild pancreatitis the pooled rate difference for complications in early endoscopic retrograde cholangiopancreatography was 1.8% (95% CI -5.6% to 9.3%); p = 0.6. No mortality was observed in predicted mild pancreatitis. In predicted severe pancreatitis the pooled rate difference for mortality in the early endoscopic retrograde cholangiopancreatography group was 4.3% (95% CI -16% to 7.5%); p < 0.24. CONCLUSIONS: Early endoscopic retrograde cholangiopancreatography reduces pancreatits-related complications in patients with predicted severe pancreatitis although mortality rate is not affected. In predicted mild pancreatitis early endoscopic retrograde cholangiopancreatography has no advantage compared to conservative management.

Early versus late surgery for ileo-caecal Crohn's disease.

BACKGROUND: Surgical resection is almost inevitable in Crohn's disease. Surgery is usually performed for refractory or complicated disease: no studies appear to have been carried out, so far, to evaluate the potential benefits of performing surgery early in the course of the disease. AIM: To compare the long-term course of Crohn's disease following ileo-caecal resection performed at the time of diagnosis (early surgery) or during the course of the disease (late surgery). Patients and methods Overall 207 patients with ileo-caecal Crohn's disease at their first resection were reviewed: 83 patients underwent surgery at the time of diagnosis (early surgery), while 124 underwent surgery 54.2 months (range 1-438) after diagnosis (late surgery). The mean follow-up after surgery was 147 months (range 12-534). The primary endpoint was clinical recurrence, defined as need for corticosteroids for symptomatic disease in the presence of endoscopic and/or radiologic recurrence. Secondary endpoints were need for immunosuppressants and surgical recurrence. STATISTICAL ANALYSIS: Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS: Within 10 years after surgery, the cumulative probability of clinical recurrence was significantly lower in the early surgery group (Log Rank test P = 0.01). A trend was observed regarding the need for immunosuppressants (P = 0.05). No difference was observed regarding surgical recurrence. At multivariate analysis, early surgery was the only independent variable associated with a reduced risk of clinical recurrence (Hazard ratio, HR = 0.57; 95% CI 0.35 to 0.92, P = 0.02), but not with need for immunosuppressants and surgical recurrence (HR = 0.51; 95% CI 0.20 to 1.30, P = 0.15; HR = 0.66; 95% CI 0.33 to 1.35, P = 0.25, respectively). CONCLUSION: Early surgery prolongs clinical remission compared to surgery performed during the course of the disease, but the natural history of disease is not modified.

Meta-analysis: the use of non-steroidal anti-inflammatory drugs and pancreatic cancer risk for different exposure categories.

BACKGROUND: A better understanding of predictors of risk for pancreatic ductal adenocarcinoma (PDAC) could inform preventive efforts against this lethal cancer. While aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDS) might protect against several gastrointestinal cancers, their role in the development of PDAC remains unclear. AIM: To conduct a systematic review and meta-analysis on the relation between ASA/NSAIDs exposure and the risk of PDAC. Methods We searched Pubmed, Embase, Scopus, Cochrane database of systematic reviews and reference lists of identified papers and included observational (cohort or case-control) studies and randomized controlled trials examining exposure to ASA and/or NSAIDs and the incidence or mortality of PDAC. We defined three categories (low, intermediate, high), based on exposure duration and dose. RESULTS: Eight studies fulfilled our inclusion criteria (four cohort, three case controls, and one randomized controlled trial studies) enrolling 6301 patients between 1971-2004; all but one study took place in the US. The pooled OR were 0.99 (0.83-1.19), 1.11 (0.84-1.47) and 1.09 (0.67-1.75) in the low, intermediate and high exposure groups respectively, with considerable heterogeneity (I(2) ranging 60-86%). Sensitivity analysis by ASA use only, study design or sex did not reveal additional important information. CONCLUSIONS: This study did not show an association between ASA/NSAIDs and PDAC. The large baseline exposure in controls in North-America may have obscured an association. There is need for additional studies, especially in Europe, to clarify this issue.

Mucosal features and granulocyte-monocyte-apheresis in steroid-dependent/refractory ulcerative colitis.

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.

Probiotics: from research to consumer.

Intestinal microflora has metabolic, trophic and protective functions, and can be modified in pathological conditions and by the exogenous administration of probiotics. Probiotics are defined as living microorganisms which resist gastric, bile, and pancreatic secretions, attach to epithelial cells and colonize the human intestine. In the last twenty years research has been focused on the identification of the role of planktonic flora and adhesive bacteria in health and disease, and on the requisite of bacterial strains to become probiotic product which can be marketed. Probiotics can be commercialized either as nutritional supplements, pharmaceuticals or foods, but the marketing as a pharmaceutical product requires significant time, complex and costly research, and the demonstration of a well-defined therapeutic target. This review examines the sequential steps of research which, from the identification of a possible probiotic strain, lead to its production and marketing, summarizing the whole process existing behind its development, through its growth in laboratory, the studies performed to test its resistance to human secretions and stability, microencapsulation technologies, and safety tests.

Evolution of clinical behaviour in Crohn's disease: predictive factors of penetrating complications.

BACKGROUND AND AIMS: Crohn's disease is a heterogeneous entity. The Vienna Classification defines three different clinical patterns: 'non-stricturing, non-penetrating', 'stricturing' and 'penetrating'. Aim of this study was to assess the change in clinical behaviour over time and to evaluate whether an evolution towards penetrating complications can be predicted. METHODS: A total of 139 patients with non-penetrating behaviour at the time of diagnosis were included. The mean follow-up was 4.84 years (range 1-23.2 years). The clinical behaviour, according to the Vienna Criteria, was assessed at the diagnosis and at the end of follow up. Statistical analysis was performed by means of the Kaplan-Meier method and standard logistic regression analysis. RESULTS: The cumulative probability of a change in clinical behaviour was 22, 38 and 63% at 3, 6 and 12 years, respectively, and the cumulative probability of developing penetrating complications was 22, 33 and 55% at 3, 6 and 12 years, respectively. Young age at diagnosis (<40 years) and a stricturing behaviour are independent risk factors of developing major penetrating complications (internal fistula, mass or abscess): OR=6.0, 95% CI 1.1-30.5; OR=4.0, 95% CI 1.5-10.9, respectively, but not perianal disease. CONCLUSIONS: The behavioural classification of Crohn's disease is a dynamic model in which each status should be considered as not fixed but evolutive. Perianal disease should be considered a distinct pattern of penetrating behaviour.

Long-term liver histology improvement in patients with chronic hepatitis C and sustained response to interferon.

A retrospective multicentre survey was conducted to evaluate, in patients with chronic hepatitis C, the long-term liver histological changes induced by interferon (IFN). A total of 112 patients (mean age 46.4 years) were studied. All patients had received a 6-12-month IFN-alpha course (6-18 MU/week) and had successively undergone clinical, biochemical and virological follow-up for at least 36 months (range: 36-76). In each patient, two liver biopsies had been performed: 1-6 months before treatment and, 12-76 months after its completion. In 87 patients with biochemical and virological sustained response persisting for 12 months after therapy, post-treatment liver necroinflammation and fibrosis mean(+/-SD) scores (Knodell index) were significantly lower than pretreatment scores (2.9 +/- 2.2 vs 6.8 +/- 2.9 and 0.8 +/- 1.0 vs 1.2 +/- 1.1, respectively; P < 0.01). In 25 patients who relapsed within 1 year, necroinflammation and fibrosis post-treatment mean scores were similar to pretreatment scores (7.4 +/- 3.2 vs 6.9 +/- 3.1 and 1.8 +/- 1.3 vs 1.6 +/- 1.2, respectively; P > 0.05). On an individual basis, necroinflammation decreased in 87% of sustained responders but only in 36% of relapsers (P < 0.001), whereas fibrosis decreased in 44% of sustained responders but only in 14% of relapsers (P < 0.001). In sustained responders with biopsies performed 12-23 months (n=34), 24-35 months (n=26) or more than 36 months (n=27) after treatment, a progressive decrease of mean necroinflammatory score was observed (-2.6 +/- 2.1, -4.1 +/- 3.4 and -5.2 +/- 3.7 points, respectively; P < 0.01). A similar pattern was observed in fibrosis score (-0.3 +/- 0.6, -0.3 +/- 0.7 and -0.7 +/- 0.9 points, respectively; P < 0.05). Hence, among chronic hepatitis C patients treated with IFN, those with a 12-month sustained response, unlike those who relapse, have a long-term progressive reduction and, in some cases, a complete regression of liver histological damage.

Effects of guar gum, ispaghula and microcrystalline cellulose on abdominal symptoms, gastric emptying, orocaecal transit time and gas production in healthy volunteers.

BACKGROUND: Dietary fibres are carbohydrates that resist hydrolysis by human intestinal enzymes but are fermented by colonic microflora. Soluble dietary fibres are fermented by anaerobic bacteria with production of gases, short chain fatty acids and other metabolic products believed to cause symptoms such as bloating, abdominal distension, flatulence. Insoluble fibres are only partially fermented, serving almost exclusively as bulking agents that result in shorter transit time and increased faecal mass. AIMS: To evaluate effect of a supplementation of a single 5 g dose of dietary fibre to a solid meal on gastric emptying, orocaecal transit time, gas production and symptom genesis, in healthy volunteers. Three different dietary fibres were tested, two soluble (guar gum and ispaghula] and one insoluble (microcrystalline cellulose). PATIENTS AND METHODS: After a 24-hour low fibre diet, 10 healthy subjects had a standard meal consisting of white bread and one 70 g egg the yolk of which was mixed with 100 mg of 13C octanoic acid and fried. Breath samples were collected for 13CO2 measurements with a mass spectrophotometer and excretion curve (Tlag, T1/2) evaluation. Further breath samples were collected and analysed with a gas chromatograph for the evaluation of H2 and CH4 production and orocaecal transit time. Each evaluation was repeated adding to standard meal, diluted in 300 ml tap water, respectively: a single 5 g dose of microcrystalline cellulose, guar gum or ispaghula. Subjects were asked to report all symptoms experienced from time of meal ingestion over 24 hours, evaluating the intensity. RESULTS: Dietary fibres did not significantly change gastric emptying (Tlag, T1/2) and orocaecal transit time of standard meal. Subjects experienced more symptoms when meals were supplemented with guar gum (p=0.009 vs standard meal) and ispaghula (p=0.048 vs standard meal). There was a poor, but significant, correlation between gas production and symptoms (r=0. 38, p=0. 01). CONCLUSIONS: Addition of different dietary fibres to a solid meal did not influence gastric emptying and orocaecal transit time. Microcrystalline cellulose caused fewer symptoms than guar gum and ispaghula probably due to the insoluble nature and the dimensions of the particles of this micronised cellulose.

Budesonide in the treatment of Crohn's disease: a meta-analysis.

AIM: To perform a meta-analysis to assess the effectiveness and safety of oral budesonide for inducing remission in active Crohn's disease and for preventing relapse in Crohn's disease with medically- or surgically-induced remission. METHODS: All randomized, double-blind controlled trials involving oral budesonide therapy in Crohn's disease were retrieved from a Medline search, reviews articles or their bibliographies. Of 83 articles retrieved, 12 met the inclusion criteria. Data extraction was performed by three independent observers and scoring disagreements were resolved by consensus. RESULTS: Six trials tested budesonide in active disease and six in quiescent disease. Budesonide was less effective than conventional corticosteroids for inducing remission of active Crohn's disease (pooled rate difference, RD -8.5%; 95% CI: -16.4 to -0.7%; P=0.02), but corticosteroid-related adverse events were reduced (RD -22.4%; 95% CI: -32 to -12.8%; P < 0.001). In quiescent Crohn's disease, budesonide was as effective as placebo for preventing relapse in medically induced remission (RD -0.8%; 95% CI: -9.9 to 8.3%; P=0.42) and endoscopic recurrence in surgically induced remission (RD -3.5%; 95% CI: -16.9 to 9.8%; P=0.30). In the long term treatment, budesonide had an occurrence rate of corticosteroid-related adverse effects similar to placebo (RD 5.3%; 95% CI: -3.9 to 14.5%; P=0.30). CONCLUSIONS: Budesonide is significantly less effective than conventional corticosteroids for inducing remission in active Crohn's disease, but the risk of corticosteroid-related adverse effects is significantly reduced. Budesonide is not effective in preventing relapse of Crohn's disease after medically- or surgically-induced remission.

Prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury: risk factors for serious complications.

BACKGROUND: 1-2% of all patients under non-steroidal anti-inflammatory drug therapy are exposed to serious upper gastrointestinal complications. The policy of prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury by using misoprostol or suppressing acid secretion is still a matter of debate. AIMS: To discuss the effectiveness of prophylaxis of a gastrointestinal complication during non-steroidal anti-inflammatory drug treatment, according to the number and relevance of risk factors. PATIENTS: A total of 8.843 patients with rheumatoid arthritis, admitted to the widest prospective multicentre mega-trial, on 6-month complication prevention of non-steroidal anti-inflammatory drug-induced ulcers. METHODS: The results are presented in terms of the number of patients to be treated (number needed to treat) in order to prevent one serious upper gastrointestinal complication, and corrected for the number of patients, that receiving the prophylaxis therapy, would lead to one additional withdrawal (number needed to harm). RESULTS: The base-line risk for a complication strongly depended on the number and relevance of risk factors: history of peptic ulcer disease, of gastrointestinal bleeding, of cardiovascular disease, and age. In the general study population, the relative risk reduction of gastrointestinal complications with misoprostol was 40%: thus the number needed to treat to prevent 1 event was 250 in the experimental period (6 months) or 125 when normalized at one-year treatment (1 year number needed to treat]. When considering the prophylaxis gain in intermediate (risk 1-2%) or high risk subjects (patients with a probability of an event over 2%, for the presence of 1 important risk factor or multiple factors), the 1-year number needed to treat rapidly drops from about 100 to about 17. The number needed to harm for one withdrawal was 18. The number needed to treat corrected for withdrawals in order to avoid major complications rises from 125 to 132 in the general population of non-steroidal anti-inflammatory drug users; from 102 to 105 in subjects at intermediate risk, such as patients with history of cardiovascular disease; in the groups at high risk, from 26 to 27 (patients with history of peptic ulcer disease), and from 16 to 17 (patients with history of peptic ulcer disease, cardiovascular disease and aged over 65 years). CONCLUSIONS: Patients at intermediate and high risk for complications from non-steroidal anti-inflammatory drug-induced ulcers should be considered for prophylaxis. In this group of patients, misoprostol prevention of severe complications is effective, and its clinical relevance similar to that of other preventive measures in medical practice.

[Lansoprazole: an analysis of the clinical trials in the 3 years of 1997-1999]. / Lansoprazolo: analisi delle esperienze cliniche nel triennio 1997-1999.

Aim of this overview was to evaluate the main clinical trials with lansoprazole published from 1997 to 1999 in English-language journals, regarding gastroesophageal reflux disease, peptic ulcer, NSAID-induced ulcer, and ZES. Results of clinical trials for therapy and prevention of lesions/symptoms have been evaluated separately. In direct comparisons, lansoprazole alone (not combined with antibiotics) proves to be equieffective to other PPI and more effective than H2-RA in both therapy and prevention of GERD, peptic ulcer (a part from anti-Hp regimens) and NSAID-induced ulcer. Among Hp-eradicating regimens in patients with peptic ulcer or functional dyspepsia, lansoprazole-based triple therapy is equal in efficacy to other PPI-based or RBC-based triple therapies and, in any case, significantly better than dual therapies. The in vitro anti-Hp activity of lansoprazole, more marked than with other PPI, does not seem to effort clinical advantages. Safety of lansoprazole is largely satisfactory and no different from other PPI and H2-RA.

Acute ischaemic colitis following intravenous cocaine use.

Intestinal ischaemia is an uncommon complication of recreational cocaine abuse. We report the case of a 36-year-old male who underwent emergency surgery for acute abdomen. At laparotomy, the transverse colon appeared markedly oedematous, dilated and with subserosal haemorrhage. Segmental resection was performed and microscopic examination of the resected specimen showed focal necrosis of the mucosa with a patchy polymorphonuclear and mononuclear infiltrate. The submucosa was markedly thickened due to oedema; focal haemorrhage was observed and blood vessels were dilated but showed no structural abnormalities or thrombosis. These findings were consistent with ischaemic colitis. No risk factors for intestinal ischaemia were present but the patient stated that he had injected cocaine i.v. the day before the onset of symptoms. He was not a cocaine abuser but occasionally sniffed, smoked or injected cocaine. Cocaine use should be considered in the aetiological diagnosis of intestinal ischaemia in young patients.

Omeprazole 20 or 40 mg daily for healing gastroduodenal ulcers in patients receiving non-steroidal anti-inflammatory drugs.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulcers, and the management of patients with NSAID-associated ulcers represents a common clinical dilemma. AIM: To assess NSAID-associated ulcer healing during treatment with either standard (20 mg) or high dosage (40 mg) omeprazole. METHODS: One hundred and sixty-nine patients chronically ingesting diclofenac, ketoprofen, indomethacin or naproxen for osteoarthritis or rheumatoid arthritis, who had abdominal pain and an endoscopically proven gastroduodenal ulcer, were evaluated in a randomized, double-blind, dose regimen trial with omeprazole 20 mg o.m. (n = 81) or omeprazole 40 mg o.m. (n = 88). Ulcer healing was assessed endoscopically at 4 and 8 weeks in the case of unhealed ulcers. Patients continued their usual daily dose of anti-inflammatory medication throughout the study period. RESULTS: One hundred and fifty-six patients completed the study (77 patients taking 20 mg omeprazole and 79 patients taking 40 mg omeprazole); 12 patients were lost during follow-up and one patient reported an adverse event. Cumulative ulcer intention-to-treat healing rates at 8 weeks were 88% (95% confidence interval (CI) = 79-95%) for the 20 mg omeprazole group and 96.2% (95% CI = 89-99%) for the 40 mg group, and 97.1% (95% CI = 90-100%) for the 20 mg omeprazole group and 98.6% (95% CI = 93-100%) for the 40 mg group by per protocol analysis. There were no statistically significant differences between the two groups. Symptom relief did not differ significantly between the two treatment groups. CONCLUSION: Both standard and high doses of omeprazole are equally safe and effective regimens for the treatment of NSAID-induced gastroduodenal ulcers when anti-inflammatory treatment is not discontinued.

DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: thirteen-year follow-up study on a cohort of patients.

Intestinal metaplasia identifies Barrett's esophagus (BE) and is associated with an increased risk for esophageal adenocarcinoma. Dysplasia occurs as an intermediate step. However, progression from metaplasia to neoplasia without the demonstration of dysplasia has been described. The role of dual-parameter flow cytometry (FC) as a predictor of neoplastic risk in dysplasia-free cases was evaluated. DNA/protein FC and histology were performed on 362 samples from 30 dysplasia-free BE patients, followed up since 1985 once every 1-2 years. Nine cases were aneuploid, five of which (group IV) were frankly aneuploid; in the other four cases (group III), aneuploidy was detectable by dual-parameter analysis only. Twenty-one patients were diploid. Twelve (group II) also had an abnormally high G1-phase protein content compared to group I (nine patients), which were diploid with a low-moderate protein content. In three patients of group IV an adenocarcinoma in situ was diagnosed, after 5, 6, and 10 years, respectively. In two patients of group III, a low- and a high-grade dysplasia were observed at 3 and 6 years follow-up, respectively. One patient of group I first acquired a high protein content, then an aneuploid DNA content, and then progressed to adenocarcinoma (12 years). None of the still diploid patients (17 cases) have progressed to dysplasia or cancer compared with 6 of 13 presently aneuploid patients (P < 0.01). In conclusion, DNA/protein FC is a marker of increased malignant potential and thus may be used to detect patients at higher risk in dysplasia-free BE and assist in understanding the various stages of malignant transformation in long-term follow-up studies.