Evangelos Katsakoulis

Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis

BACKGROUND/AIMS The usual clinical practice is to screen all patients with established cirrhosis at the time of diagnosis by upper endoscopy for the presence of varices. Patients with large varices should be treated with non-selective beta blockers to reduce the incidence of first variceal bleeding. However, fewer than 50% of cirrhotic patients have varices at screening endoscopy and most have small sized varices, with a low risk of bleeding. The aim of the present study was to determine whether clinical or laboratory non-endoscopic parameters could predict the presence of large oesophageal varices. PATIENTS/METHODS Seventeen variables considered relevant to the prevalence of oesophageal varices were tested in 184 patients with cirrhosis, who underwent screening endoscopy. Small varices were regarded as those which flatten with insufflation or slightly protrude into the lumen, while large varices are those which protrude into the lumen or touch each other. None of the patients was on beta blockers or other vasoactive drugs or had a history of variceal bleeding. RESULTS Oesophageal varices were present in 92 patients (50%), and large varices in 33 patients (17.9%). Variables associated with the presence of large oesophageal varices on univariate analysis were the presence of ascites and splenomegaly either by clinical examination or by ultrasound (p < 0.01), the presence of spiders (p = 0.02), platelet count (p < 0.0001), and bilirubin (p = 0.01). Factors independently associated with the presence of large oesophageal varices on multivariate analysis were platelet count, size of spleen and presence of ascites by ultrasound. Using mean values as cut-off points, it is noteworthy that only five out of 39 patients (12.8%) with platelets > or = 18(x 10(9)/l), spleen length < or = 135 mm and no ascites had varices. Moreover, all these patients had small sized varices. On the other hand, 15 out of 18 patients (83.3%) with a platelet count < 118 x 10(9)/l, spleen length > 135 mm and ascites had varices. Moreover, five out of those 18 patients had large varices (28.3%). CONCLUSION Thrombocytopenia, splenomegaly and ascites are independent predictors of large oesophageal varices in cirrhotic patients. We suggest that endoscopy could be avoided safely in cirrhotic patients with none of these predictive factors, as large varices are absent in this group of patients.

Changes in aetiology and clinical outcome of acute upper gastrointestinal bleeding during the last 15 years.

Objectives The diagnostic and therapeutic approaches to patients with acute upper gastrointestinal bleeding have been improved during the last decades. The aim of this study was to compare the aetiology and clinical outcome of acute upper gastrointestinal bleeding (AUGIB) between two distinct periods during the last 15 years. Methods The causes of AUGIB and clinical outcome of 668 patients hospitalised with the problem in 1986–1987 were compared to 636 patients with AUGIB in 2000–2001. Patients were admitted to our hospital or they bled while they were inpatients for other reasons. No patient was excluded because of age or concurrent diseases. Endoscopic haemostasis with adrenaline injection for bleeding peptic ulcers was performed in the second period while no endoscopic method of haemostasis was performed in the first period. Results We observed an increase in the age of patients (56.5 ± 16.9 vs 62.9 ± 17.5 years, P < 0.0001) and the percentage of patients who received non-steroidal anti-inflammatory drugs (NSAIDs) before bleeding (from 44% to 63.5%, P < 0.0001). An increase in the diagnosis rate of gastric ulcer (12% vs 19.2%, P = 0.005) and varices (13.2% vs 3.3%, P < 0.001) with a simultaneous decrease in that of erosive gastroduodenitis (18.4% vs 7.2%, P < 0.0001) and duodenal ulcer (48.7% vs 33.3%, P < 0.0001) as a cause of bleeding was also observed. In peptic ulcer bleeding, emergency surgical haemostasis was reduced from 14% to 5.3%, P < 0.001. Overall mortality was also reduced from 5.2% to 3.1% and in peptic ulcer bleeding patients from 3.3% to 2.4%, respectively, but the differences are not statistically significant. Conclusion The aetiology of AUGIB has changed during the last 15 years probably due to the better therapeutic approach to chronic duodenal ulcers and increasing use of NSAIDs in the elderly. Emergency surgical haemostasis has been reduced but the reduction of mortality was not significant.

Factors associated with failure of endoscopic injection haemostasis in bleeding peptic ulcers.

BACKGROUND The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. METHODS In the period 1992 to 1998, we prospectively studied all patients suffering from peptic ulcer bleeding and identified endoscopically as being either bleeding actively or carrying a visible vessel. A total of 427 patients (343 men and 84 women; mean age 58.6 +/- 16.6 years) were all subjected to endoscopic injection with adrenaline solution on an emergency basis. Patients who eventually required surgical intervention for permanent haemostasis were considered as endoscopic haemostasis failures, whereas those who did not were considered as endoscopic treatment successes. We evaluated all clinical and endoscopic parameters that might have been related to failure of endoscopic injection therapy. RESULTS Endoscopic injection haemostasis was successful in 341 patients (79.9%) and a failure in 86 (20.1%) who finally underwent emergency surgical haemostasis. On analysing the examined parameters, failure was significantly related to shock on admission (OR 2.31, 95% CI 1.33, 6.97), spurt bleeding at endoscopy (OR 2.45, 95% CI 1.51, 3.98), posteriorly located duodenal ulcer (OR 2.48, 95% CI 1.37, 7.01) and anastomotic ulcer (OR 3.39, 95% CI 1.37, 7.29). Endoscopic injection haemostasis therapy was less effective in patients with chronic ulcers compared to those who had acute NSAID-related ulcers. A history of peptic ulcer (OR 1.57, 95% CI 1.14, 3.05), previous peptic ulcer bleeding (OR 2.45, 95% CI 1.51, 3.98) or non-use of NSAIDs (OR 2.81, 95% CI 1.33, 4.62) were negative predictors for the outcome of endoscopic haemostasis. CONCLUSION With the use of specific clinical and endoscopic characteristics it is possible to define a subgroup of high-risk patients for continued bleeding or rebleeding despite endoscopic injection therapy. These patients may be candidates for intensive monitoring, early surgical intervention or possibly complementary endoscopic haemostatic methods.Background: The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. Methods:

Seasonality in the prevalence of acute upper gastrointestinal bleeding

The seasonal fluctuations of acute upper gastrointestinal bleeding treated from 1991 to 1996 in Patras, Greece, were analyzed retrospectively. During that period, 1992 patients with acute upper gastrointestinal bleeding were admitted to our hospital. After patients who were not residents of the region served by our hospital were excluded, the remaining 1879 cases were reviewed. We observed seasonal fluctuation with low prevalence in winter and an increase in spring and autumn with two peaks in April and October (p < 0.00001). The seasonal prevalence parallels that of duodenal ulcer bleeding, which follows a similar fluctuation (p < 0.00001). Bleeding due to gastric ulcers or other causes presented no periodicity. Seasonal fluctuation, both in total numbers of upper gastrointestinal bleeding and in duodenal ulcer bleeding, was statistically significant only in patients not receiving nonsteroidal anti-inflammatory drugs (p < 0.00001). We conclude that upper gastrointestinal bleeding shows a seasonal fluctuation parallel to duodenal ulcer bleeding and is not related to nonsteroidal anti-inflammatory drugs. The seasonal pattern supports the traditional view of duodenal ulcer exacerbations.

The effect of octreotide as an adjunct treatment in active nonvariceal upper gastrointestinal bleeding

Goals The aim of this study was to determine the effect of octreotide on active or recent gastrointestinal bleeding from benign peptic ulcers. Study This is a prospective, randomized study including 110 patients with gastric or duodenal peptic ulcers presenting with active spurting or oozing bleeding or nonbleeding visible vessel. All patients were subjected to endoscopic hemostasis by injection of noradrenaline, and they were then randomized to either receive octreotide (55 patients) or placebo (55 patients). The groups did not differ with respect to age, sex, use of nonsteroidal antiinflammatory drugs, previous history of ulcer or bleeding, Helicobacter pylori infection, site, and severity of bleeding. Results The rebleeding rate was 36% in placebo and 32% in octreotide group, which does not present a statistically significant difference. Surgical intervention was required for 18 patients (32.7%) in the placebo group and for 16 patients (29%) in the octreotide group. The mortality rate was 2 patients (3.6%) in the placebo and 4 patients (7.2%) in the octreotide group. All the above presented no statistical difference. In addition, there was no statistically significant difference between the 2 groups with respect to the number of blood units transfused and hospital stay. Conclusions The use of octreotide as an adjunct treatment in patients with acutely bleeding benign peptic ulcer or/and visible vessel did not seem to offer significant benefits regarding their outcome.

The Effect of Endoscopic Injection Therapy on the Clinical Outcome of Patients with Benign Peptic Ulcer Bleeding

BACKGROUND Our aim was to investigate the effect of endoscopic injection therapy on the clinical outcome of patients with benign peptic ulcer bleeding. METHODS In this study 1203 patients admitted with peptic ulcer bleeding over a 5-year period (January 1987 to April 1991) before endoscopic therapy and 1028 patients admitted with peptic ulcer bleeding after introduction of endoscopic therapy (May 1991 to March 1996) were assessed. Endoscopic therapy was performed in all patients with active bleeding or non-bleeding visible vessels during emergency endoscopy with injection of adrenaline, 1:10,000 in 0.9% saline. RESULTS The introduction of injection therapy was associated with a reduction in transfusion requirements (from 5.1 +/- 2.6 to 3.4 +/- 1.8 units), hospitalization days (from 10.8 +/- 6.5 to 7.8 +/- 5.1 days), surgical interventions (from 50.6% to 23.6%), and mortality (from 12.9% to 4.6%) in patients with active bleeding or non-bleeding visible vessels (P < 0.05) but remained unchanged in the rest. Patients with gastric ulcer had a more pronounced reduction in emergency surgical haemostasis and mortality than patients with duodenal ulcer. There were no deaths or procedure-related complications. CONCLUSION Endoscopic injection therapy with adrenaline/saline is a simple, low-cost, and safe method that improves the clinical outcome and reduces the mortality in patients with peptic ulcer bleeding.

Changes in indications for upper gastrointestinal tract endoscopy and endoscopic findings during the last fifteen years in south-western Greece.

Background:During the past years, major advances in the management of upper gastrointestinal diseases have been achieved. The aim of this study was to determine if changes in indications for upper gastrointestinal endoscopy and endoscopic findings have occurred during the last 15 years in our area. Methods:Indications for upper gastrointestinal tract endoscopy and endoscopy findings of patients who underwent upper endoscopy in years 1990, 1995, 2000, and 2005 in our department were compared. Results:Over the 15-year period, the number of diagnostic endoscopies performed in our department in years 1990, 1995, 2000, and 2005 increased (953, 1245, 2350, and 2528, respectively). Acute upper gastrointestinal bleeding had become less frequent (40%, 42.8%, 19.7%, 14.3%, P < 0.001), but dyspepsia (24.4%, 33.6%, 54.3%, 51.3%, P = 0.002) and reflux (1.8%, 1.3%, 5.1%, 10.8%, P = 0.005) more frequent indications for upper endoscopy. The endoscopic findings of duodenal ulcer (39.1%, 22.5%, 20.5%, 9.3%, P < 0.001), gastric ulcer (15.9%, 8.3%, 5.7%, 4.6%, P = 0.036) as well as erosive gastroduodenitis (35.6%, 22.2%, 15.3%, 4.7%, P < 0.001) decreased, whereas that of reflux esophagitis (3.1%, 10.1%, 12%, 16%, P = 0.034) increased. Moreover, the percentage of patients with negative endoscopy or minimal endoscopic findings (eg, nonerosive gastritis) increased (12.8%, 33.7%, 54.1%, 64.4%, P < 0.001). Conclusions:In south-western Greece, dyspepsia and reflux as an indication for upper endoscopy have been increasing, whereas acute upper gastrointestinal bleeding has been decreasing. The finding of peptic ulcers at the upper gastrointestinal tract endoscopy has become significantly less frequent, while the percentage of patients with negative results of endoscopy seems to have been increasing rapidly.

Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their value for detection of adenomas and adenocarcinomas

Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas. Expression levels of Uc160, Uc283 and Uc346 were lower in neoplastic tissues from 64 CRC patients (statistically significant for Uc160, p<0.001), compared to non-malignant tissues, while methylation levels displayed the inverse pattern (p<0.001, p=0.001 and p=0.004 respectively). In colon cancer cell lines, overexpression of Uc160 and Uc346 led to increased proliferation and migration rates. Methylation levels of Uc160 in plasma of 50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis predicted the presence of CRC with 35% sensitivity and 89% specificity (p=0.016), while methylation levels of the combination of all three T-UCRs resulted in 45% sensitivity and 74.3% specificity (p=0.013). In conclusion, studied T-UCRs’ expression and methylation status are deregulated in CRC while Uc160 and Uc346 appear to have a complicated role in CRC progression. Moreover their methylation status appears a promising non-invasive screening test for CRC, provided that the sensitivity of the assay is improved.

Increased number of circulating gamma/delta TCR+ T cells in active ulcerative colitis

Objective: To determine the percentage and absolute numbers of gamma/delta T-cell receptor (TCR) positive T cells in patients with active and quiescent ulcerative colitis. Patients: The study included 55 patients with ulcerative colitis and 17 healthy controls. Methods: Lymphocyte subsets were determined using immunofluorescence microscopy following incubation with monoclonal antibodies to T total (CD5) and T gamma/delta cells (TCR-gamma/delta-1) Results: Increased levels of circulating gamma/delta TCR+ T cells were found in patients with active ulcerative colitis compared with patients in remission or normal controls; this increase was more profound in patients with pancolitis compared with those with rectosigmoiditis. Increased values returned to control levels on remission. Conclusion: These results suggest that there is a correlation between circulating gamma/delta TCR cell levels in ulcerative colitis patients and the activity and extent of the disease.