Serum adiponectin levels in different types of non alcoholic liver disease. Correlation with steatosis, necroinflammation and fibrosis.

BACKGROUND AND STUDY AIMS: In recent studies adiponectin has been implicated in the pathogenesis of non alcoholic liver disease (NAFLD), a common chronic liver disease with a broad spectrum of histopathologic findings. The aim of this study was to investigate the correlation between serum adiponectin levels and steatosis, necroinflammation and fibrosis in different types of NAFLD patients. PATIENTS AND METHODS: Forty three patients with elevated liver enzymes and biopsy proven non alcoholic fatty liver disease and 38 patients with clinically diagnosed NAFLD and permanently normal liver enzymes were prospectively enrolled in the study. Patients with biopsy proven NAFLD were divided into two groups: non alcoholic steatohepatitis (NASH): 25 patients and simple steatosis: 18 patients. Serum adiponectin levels were measured with an ELISA immunoassay, and BMI, fasting serum glucose, total and HDL cholesterol, fasting triglyceride levels and insulin resistance were determined. RESULTS: Groups did not differ in age, sex, BMI, waist circumference and HOMA - IR. Only patients with confirmed NASH had lower serum adiponectin levels in comparison to NAFLD patients with both abnormal (6.6 +/- 4.7 microg/mL vs 10.8 +/- 5.6 microg/mL, p = 0.01) as well as normal liver enzymes (6.6 +/- 4.7 microg/mL vs 9.2 +/- 4.8 microg/mL, p = 0.01). For the whole NAFLD group with elevated liver enzymes no correlation was found between serum adiponectin levels and the degree of liver steatosis or fibrosis stage. Also no correlation was found between adiponectin levels and BMI, ALT, AST, gamma GT or HOMA-IR. CONCLUSIONS: Patients with established NASH have lower serum adiponectin levels than NAFLD patients with normal or abnormal liver enzymes. Adiponectin was not associated with the severity of hepatic fibrosis.

Endoscopic retrogade cholangiopancreatography is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians.

BACKGROUND AND AIM: Diagnosis and treatment of pancreatic and biliary diseases represents a special problem in old patients who often suffer from one or more concomitant diseases. The aim of this study was to evaluate the safety and efficacy of ERCP in very old patients (octogenarians). PATIENTS AND METHODS: Patients 80 years or older who underwent ERCP from October 2001 to December 2005 were studied retrospectively. RESULTS: A total of 209 patients (121 women, 88 men), with a mean age 86 +/- 4.4 years old (80-102) underwent 251 ERCPs. All but three patients tolerated the procedure well. Three procedures were not completed due to patients' discomfort (1.4%). Two of these patients underwent percutaneous transhepatic cholangiography and the other one was treated conservatively. A cholangiogram was obtained in 193 cases (92.3%), although in 7 patients an additional attempt was required. The main endoscopic findings were common bile duct stones in 51.8% (100/193) and cancer in 28% (54/193) of patients. Based on the diagnostic findings, a therapeutic intervention was indicated in 189 patients (90.4%) and was achieved in 181 of them (95.8%). Complications were observed in 9.6% of ERCPs (24/251). Post - ERCP mild pancreatitis was the more frequent complication in 11 procedures (4.4%). No severe pancreatitis was observed. Six procedures were complicated by cholangitis (2.4%) and two by cholecystitis (0.8%). Early surgical intervention was required in 2 cases because of oesophageal perforation and retroperitoneal perforation respectively. Two patients died (0.8%); one patient with pancreatic cancer died due to septic shock after inadequate biliary drainage and the other one died after operation for retroperitoneal perforation. CONCLUSIONS: In conclusion, ERCP is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians despite the high comorbidity in this group of patients.

Capecitabine in pretreated metastatic cholangiocarcinoma. A case report and review of the literature.

Cholangiocarcinoma is one of the most aggressive malignancies. Patients with advanced or metastatic disease have a particularly dismal prognosis. The role of chemotherapy remains a matter of debate. A number of recent trials have shown that capecitabine in combination with other agents seems to be active as first-line treatment in advanced biliary cancer. Clinical data regarding the activity of capecitabine in pretreated patients are limited. In this report we describe a patient with previously treated, metastatic cholangiocarcinoma who developed stabilization of the disease for 7 months following chemotherapy with capecitabine. The patient had previously received 2 lines of chemotherapy. Capecitabine was tolerated fairly well without serious adverse events. We consider this observation to be important given the absence of active, non-surgical treatments in unresectable tumors.

Evidence for intestinal oxidative stress in patients with obstructive jaundice.

BACKGROUND: Obstructive jaundice results in failure of the intestinal barrier with consequent systemic endotoxemia associated with septic complications. We have recently shown that gut barrier failure in experimental obstructive jaundice is associated with high intestinal oxidative stress. This study was undertaken to investigate whether oxidative alterations occur in the intestinal mucosa of patients with obstructive jaundice. PATIENTS AND METHODS: Fifteen patients with malignant biliary obstruction and no signs of cholangitis and 15 control patients were subjected to duodenal biopsy to assess intestinal oxidative stress, estimated by lipid peroxidation (malondialdehyde - MDA) and glutathione redox state [reduced glutathione (GSH), glutathione disulphide (GSSG) and GSH/GSSG ratio]. In addition, mucosal biopsies were examined histologically and intestinal mucosal protein content was determined biochemically as an index of intestinal trophic state. RESULTS: Patients with obstructive jaundice presented high levels of intestinal oxidative stress, with significantly increased lipid peroxidation (P < 0.001). Glutathione redox state was also suggestive of high intestinal oxidative stress in jaundiced patients, indicated by significantly decreased GSH (P = 0.001) and GSH/GSSG ratio (P = 0.006) and increased GSSG (P = 0.026). Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in obstructive jaundice, whereas duodenal architecture remained intact and epithelial continuity was retained. Duodenal mucosa was atrophic in jaundiced patients as indicated by a significant reduction of mucosal protein content compared with controls (P = 0.001). Among oxidative stress parameters, intestinal GSH exhibited a significant positive correlation with mucosal protein content (r = 0.588, P = 0.021). CONCLUSIONS: Obstructive jaundice in humans induces intestinal oxidative stress, which may be a key factor contributing to intestinal barrier failure and the development of septic complications in this patient population.

Gastric ulcers and risk for cancer. Is follow-up necessary for all gastric ulcers?

The aim of this study was to determine the accuracy of initial endoscopy combined with histology and to define whether there is a point in following-up all gastric ulcers until complete healing. We have studied all patients with gastric ulcers documented at endoscopy during a 6-year period. Ulcers were macroscopically characterised as benign or suspicious for malignancy, and biopsies were taken. A follow-up endoscopy and histology was performed 4-6 weeks and 3 months after an anti-ulcer treatment. Resistant ulcers were treated surgically. All patients were followed-up clinically and endoscopically for a year after complete ulcer healing. 802 patients with gastric ulcers were enrolled. At initial endoscopy, 732 ulcers (91.3%) were macroscopically characterised as benign and 70 ulcers (8.7%) as suspicious for malignancy. In the group of endoscopically benign ulcers, only one (0.1%) had malignancy detected by biopsy in the first examination. None of these ulcers turned out to be malignant on subsequent examinations. From the suspicious for malignancy ulcers, 20 (28.6%) were proven to be malignant. Endoscopy may recognise with great accuracy benign ulcers, but it overestimates the malignant ones. The cost-benefit of serial follow-up endoscopies should be re-evaluated in ulcers that appear benign, and biopsies are negative at the initial examination.

Predictors of hemostatic failure after adrenaline injection in patients with peptic ulcers with non-bleeding visible vessel.

BACKGROUND: Non-bleeding visible vessel (NBVV) in patients with bleeding peptic ulcer is associated with a high risk of rebleeding. The aim of this study was to define factors associated with failure of endoscopic hemostasis and rebleeding in patients with NBVV. METHODS: Clinical and endoscopic parameters related to failure of endoscopic hemostasis with adrenaline in 191 bleeding peptic ulcer patients with NBVV were evaluated. RESULTS: Endoscopic hemostasis was permanently successful in 154 patients (80.6%). Emergency surgical hemostasis for rebleeding was required in 37 patients (19.4%). Univariate analysis showed that therapeutic failure was significantly related to the presence of shock on admission (P=0.003), posterior duodenal ulcers (P=0.001), peptic ulcer history (P=0.001), previous peptic ulcer bleeding (P=0.002), or lack of history of non-steroidal anti-inflammatory drugs consumption, when compared to use of such drugs (P=0.04). Patients where therapy failed had lower hemoglobin levels at admission (7.8+/-1.9 g/dL versus 10+/-2.4 g/dL, P=0.005). In a multivariate analysis low hemoglobin (P<0.001) as well as history of previous peptic ulcer bleeding (P=0.002) and posterior duodenal ulcers (P=0.001) were negative predictors. Using the mean value of hemoglobin as the cut-off point, it is noteworthy that only 2 out of 81 patients (2.5%) who had none of these predictive factors required emergency surgical hemostasis, whereas 34 out of 110 patients (30.9%) with at least one predictive factor required emergency surgery. CONCLUSION: It is possible, by employing specific characteristics, to define a subgroup of high-risk patients for rebleeding in patients with NBVV despite therapeutic endoscopy and thus candidates for a complementary endoscopic method of hemostasis or emergency surgical intervention.

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.

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.

Prevalence of intrapulmonary vascular dilatations in normoxaemic patients with early liver cirrhosis.

BACKGROUND: The aim of this study was to determine the prevalence of intrapulmonary vascular dilatations (IPVD) in normoxaemic patients with early liver cirrhosis and to compare their occurrence in progressive alcoholic versus postviral hepatic insufficiency. METHODS: Pulmonary function tests and arterial blood gas measurements were performed in 75 consecutive patients with cirrhosis of alcoholic and postviral aetiology. Contrast-enhanced echocardiography was used to identify IPVD. RESULTS: All patients were grade A or B in accordance with the Child-Pugh modified classification. Arterial blood gas analyses showed normoxaemia in all patients. Eight of 75 patients (10.7%) had a positive contrast echocardiogram, all with a decreased diffusion capacity (D1CO < 75% of the expected value). The abnormality was more prominent with advancing stage of liver failure (4.5% in grade A versus 19.4% in grade B; P < 0.05) and more common in patients with alcoholic cirrhosis (17.5% in alcoholic versus 2.9% in postviral cirrhosis; P < 0.05). CONCLUSION: In normoxaemic patients with early liver cirrhosis subclinical pulmonary vasodilatation, as assessed with contrast echocardiography, can occur. The finding is more prominent in alcoholic cirrhosis and possibly reflects an advancing degree of liver insufficiency.

Evaluation of contrast echocardiography and lung perfusion scan in detecting intrapulmonary vascular dilatation in normoxemic patients with early liver cirrhosis.

BACKGROUND/AIMS: Intrapulmonary vascular dilatations (IPVD) are extrahepatic complications occurring in liver transplant candidates, that can result in severe hypoxemia. The aim of this study was to compare the use of two diagnostic modalities, contrast echocardiography and lung perfusion scan, in detecting IPVD in normoxemic patients with early liver cirrhosis. METHODOLOGY: Fifty-six consecutive outpatients with biopsy-proven cirrhosis had contrast-echocardiography, a lung perfusion scan, pulmonary function tests, and arterial blood gas estimations. All patients were grade A or B according to the Child-Pugh classification. Patients with chronic intrinsic lung disease, heart failure or malignancy were excluded from the study. RESULTS: All patients had normal arterial blood-gas analyses. Eight out of 56 patients (14.3%) had a positive contrast echocardiogram, all with a decreased diffusion capacity (DLCO < 75% of the predicted value). An isolated DLCO impairment was observed in 40% of the patients with normal spirometry. None of the patients with echocardiography-proven IPVD had a positive lung perfusion scan (p<0.005). CONCLUSIONS: In normoxemic cirrhotic patients, subclinical pulmonary vasodilatation and gas-exchange abnormalities can occur. Contrast-enhanced echocardiography is the most valuable screening test in detecting IPVD in the early stages of hepatic insufficiency.

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.

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.