Long-term safety of anti-TNF treatment in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection.

OBJECTIVES: The aim of this prospective study was to examine the safety of anti-tumour necrosis factor (TNF) therapy in patients with rheumatic disease and hepatitis B virus (HBV) infection. METHODS: 14 patients with chronic HBV infection, 19 HBV-vaccinated patients and 19 patients with resolved HBV infection were included in the study. All HBV-infected patients received combination therapy with oral antivirals and anti-TNF agents. During treatment the levels of hepatitis B surface antibodies (anti-HBs) in HBV-vaccinated patients and of serum HBV DNA in patients with chronic or resolved HBV infection were monitored. RESULTS: No viral reactivation was observed in patients with resolved HBV infection while anti-HBs titres decreased during anti-TNF treatment in vaccinated patients, similarly to patients treated with methotrexate alone. None of the HBV-infected patients developed liver decompensation or a significant increase in alanine aminotransferase levels. One patient (7%) treated with lamivudine and etanercept showed viral reactivation due to the emergence of a lamivudine-resistant mutant strain. CONCLUSIONS: Anti-TNF agents represent a safe option for patients with chronic HBV infection when combined with antiviral therapy, as well as in patients previously exposed to HBV receiving no HBV prophylaxis. Resistant HBV strains may arise in patients with chronic hepatitis B, necessitating the initial use of anti-HBV agents with a low risk of resistance.

Serum hepcidin levels are related to the severity of liver histological lesions in chronic hepatitis C.

Hepcidin is synthesized in the liver and has a crucial role in iron homoeostasis. Its synthesis is up-regulated in chronic inflammation and iron excess. We examined the determinants of serum hepcidin and liver hepcidin mRNA levels and their association with histological lesions in patients with chronic hepatitis C (CHC) and healthy controls. We studied 96 patients with CHC and 30 controls. Serum hepcidin levels were measured by an in-house competitive ELISA. Hepcidin mRNA levels were determined by a one-step qRT-PCR in total RNA extracted from liver biopsy specimens of 27 patients with CHC and six disease controls. Histological lesions were evaluated according to Ishak's classification. Serum hepcidin was significantly lower in patients with CHC than healthy controls (14.6 ± 7.3 vs 34.6 ± 17.3 ng/mL, P < 0.001). In patients with CHC, serum hepcidin correlated positively with aspartate aminotransferase (r = 0.334, P = 0.001) and insulin resistance (r = 0.27, P = 0.016) and had a trend for correlation with alanine aminotransferase (r = 0.197, P = 0.057) and serum haemoglobin (r = 0.188, P = 0.067) but not with ferritin. A significant positive correlation was also found between serum hepcidin levels and both necroinflammation (r = 0.259, P = 0.011) and fibrosis (r = 0.214, P = 0.036). Serum hepcidin was among others an independent predictor of cirrhosis (odds ratio: 1.145, P = 0.039). Liver hepcidin mRNA levels did not differ between patients and controls and were relatively lower in patients with than without cirrhosis (19.3 ± 21.7 vs 38.3 ± 26.0, P = 0.067). Patients with CHC have reduced serum hepcidin levels, which correlate with worse necroinflammation and fibrosis. The previously mentioned observations suggest a viral effect on hepatic hepcidin production, but might also support its involvement in the inflammatory process.

Survivin expression in colorectal carcinomas: correlations with clinicopathological parameters and survival.

BACKGROUND: Survivin is a new member of the Inhibitor of apoptosis protein family that has a dual function as a mitotic regulator and apoptosis inhibitor. Survivin is prominently expressed in transformed cell lines and in many human cancers, including colorectal carcinoma. The aim of this study is to investigate the expression of survivin in colorectal carcinomas and its possible associations with clinicopathological parameters and patient survival. MATERIALS AND METHODS: Sections of formalin-fixed paraffin-embedded tissues from 77 colorectal carcinomas were immunohistochemistry stained for survivin. RESULTS: Survivin was mainly detected in the bottom of the glands of normal mucosa with mainly cytoplasmic localization. No survivin expression was found in infiltrating lymphocytes, fibroblasts, smooth muscle cells or neural tissue. Survivin staining was detected in 68/77 (88.3%) colorectal carcinomas. Survivin expression was found to be significantly associated with tumor differentiation (P = 0.02) but not with gender, age or Dukes stage. Survival did not differ according to survivin expression. CONCLUSION: Survivin was found in the majority of colorectal carcinomas, suggesting that its expression is an early event in colorectal carcinogenesis. Its expression is statistically significantly associated with tumor differentiation but not with patient survival.

Prevalence of glucose intolerance in patients with chronic hepatitis B or C: a prospective case-control study.

Despite several studies, the association of glucose intolerance with chronic hepatitis B (CHB) or C (CHC) virus infection remains controversial. We evaluated the prevalence of glucose intolerance by oral glucose tolerance test (OGTT) in patients with CHB or CHC in comparison with matched controls. In total, 189 consecutive outpatients with CHB or CHC and 189 subjects individually matched for age, sex and body mass index (BMI) were included. OGTT was performed in all cases, except in known diabetics, and glucose intolerance was defined as impaired glucose tolerance (IGT), OGTT-diabetes or known diabetes. Most patients with abnormal OGTT had normal fasting glucose (IGT: 69.8%, OGTT-diabetes: 54.5%). Compared with their own controls, CHB patients had a higher prevalence of IGT (13.6% vs 2.5%, P = 0.018) and family history of diabetes (34.6% vs 16.0%, P = 0.011), while CHC patents had higher prevalence of glucose intolerance (37.0% vs 15.7%, Rho = 0.001), mostly because of more frequent IGT (21.3% vs 6.5%, Rho = 0.003). After age and BMI adjustment, patients with CHC compared with those with CHB had significantly higher prevalence of glucose intolerance (37.0% vs 29.6%, P = 0.037). In conclusion, increased prevalence of glucose intolerance is documented by OGTT both in CHC and CHB patients compared with age, sex and BMI matched controls. Glucose intolerance is more frequent in CHC than CHB patients, regardless of known risk factors. An OGTT might be necessary at the baseline work-up of CHB or CHC patients, as a normal fasting glucose value does not exclude IGT or OGTT-diabetes.

Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection.

BACKGROUND AND AIMS: In chronic hepatitis C and non-alcoholic fatty liver disease, apoptotic caspases are activated in liver, and serum caspase activity has been suggested as a sensitive marker of early liver injury. An investigation was carried out into whether the serum levels of caspase-generated fragments of cytokeratin-18 (CK-18) are associated with the severity of liver lesions in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Patients/ METHODS: CK-18 fragment serum levels were determined in 115 treatment-naive, consecutive HBV patients and 30 healthy controls. Hepatic-expression of CK-18 fragments was evaluated by immunocytochemistry in chronic hepatitis B patients. RESULTS: CK-18 fragment levels (U/l) were significantly lower in healthy controls (mean (SD), 154 (31)) than in 53 inactive carriers (172 (24), p = 0.003) and in 62 chronic hepatitis B patients (474 (488), p<0.001). The receiver operating characteristic curve showed excellent diagnostic accuracy (c-statistic: 0.87) for differentiating inactive carriers from chronic hepatitis B patients. A CK-18 fragment cut-off level of 240 U/l gave a sensitivity of 60%, and a specificity and positive predictive value of 100% for chronic hepatitis B diagnosis. CK-18 fragment levels were also lower in inactive carriers than in 16 chronic hepatitis B patients with transiently normal alanine aminotransferase (ALT; 327 (256), p = 0.001), offering good accuracy for such a differentiation (c-statistic: 0.78). In chronic hepatitis B patients, serum CK-18 fragments correlated positively with ALT/aspartate aminotransferase (AST), viraemia, grading score and their immunohistochemical hepatic expression, and negatively with platelet counts, but not with fibrosis or steatosis severity. CONCLUSIONS: Serum apoptotic caspase activity is strongly associated with the presence of liver injury in patients with HBeAg-negative chronic HBV infection. CK-18 fragment levels seem to be a very useful marker for differentiation between the inactive HBV carrier state and HBeAg-negative chronic hepatitis B, but not for estimation of the severity of liver histological lesions among HBeAg-negative chronic hepatitis B patients.

Correlation of NK T-like CD3+CD56+ cells and CD4+CD25+(hi) regulatory T cells with VEGF and TNFalpha in ascites from advanced ovarian cancer: Association with platinum resistance and prognosis in patients receiving first-line, platinum-based chemotherapy.

BACKGROUND: Several cytokines have been associated with immune regulation and prognosis in ovarian cancer. CD4+CD25+ Tregs and CD3+CD56+ NK-like T cells are involved in the immune response against the tumor. We have investigated the association of cytokines in the ascites from patients with ovarian cancer with these populations, the platinum resistance and the prognosis of these patients. PATIENTS AND METHODS: Ascites from 64 patients with ovarian cancer was analysed. Forty-two patients were studied at diagnosis (FIGO stage III in 40 cases) and were treated with cytoreductive surgery and platinum-based chemotherapy. Ascites from 9 patients with cirrhosis was used as control. Vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), interleukin-10 (IL10) and interleukin-12 (IL12) in ascites and serum were measured by enzyme-linked immunosorbent assay (ELISA), while lymphocytic populations were studied with three-colour flow cytometry. RESULTS: VEGF ascites levels were inversely correlated with CD3+CD56+ cells (rho=-0.316, p=0.012), while a similar correlation was observed between TNFalpha ascites levels and CD4+CD25+(hi) cells (rho=-0.332, p=0.041). Among patients receiving first-line chemotherapy, VEGF levels <1900 pg/ml and TNFalpha levels >35 pg/ml were associated with platinum sensitivity (p=0.021 and p=0.028, respectively) and improved progression-free survival (PFS) (p=0.007 and p=0.045, respectively). Low VEGF levels were also associated with improved overall survival (p=0.026). CONCLUSION: VEGF and TNFalpha ascites levels are associated with prognosis in advanced ovarian cancer. Their prognostic significance may be due to their association with immunologically important populations, namely the NK T-like CD3+CD56+ cells and the Tregs CD4+CD25+(hi) cells.

Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment.

Patients with cirrhosis and impaired coagulation often pose major therapeutic problems during bleeding episodes or invasive procedures. Recombinant activated factor VII (rFVIIa), which has been licensed for the treatment of haemophilia patients with factor VIII or IX inhibitors, has been occasionally used in cirrhotic patients. We present five patients with cirrhosis and coagulopathy who received 1-4 recombinant activated factor VII infusions either prophylactically in order to safely undergo an invasive procedure or therapeutically in order to control a severe bleeding episode which did not respond to standard supportive care. In particular, recombinant activated factor VII infusions were given in two patients before a percutaneous liver biopsy, in one patient before teeth extraction and in two patients with haemoperitoneum after an invasive procedure. Infusions of recombinant activated factor VII achieved rapid correction of prothrombin time in all cases allowing the safe performance of invasive procedures or resulting in efficient control of the bleeding episode. In conclusion, recombinant activated factor VII seems to be a rather promising agent for the prevention or treatment of complications of haemostasis impairment in cirrhotic patients. However, its exact role in this setting needs to be evaluated within well-designed, controlled clinical trials.

Hepatic steatosis in chronic hepatitis B develops due to host metabolic factors: a comparative approach with genotype 1 chronic hepatitis C.

BACKGROUND/AIMS: Hepatic steatosis has not been adequately studied in chronic hepatitis B, while it is considered to be a cardinal feature in chronic hepatitis C and to be mainly metabolically induced in patients infected with genotype 1. We investigated the prevalence of and the parameters associated with steatosis in HBeAg-negative chronic hepatitis B. METHODS: We studied 213 patients with HBeAg-negative chronic hepatitis B and compared them with 163 patients with genotype-1 chronic hepatitis C. Steatosis was semi-quantitatively graded. RESULTS: Steatosis was significantly less frequent in chronic hepatitis B than chronic hepatitis C (60% versus 72%, P=0.016), but there was no difference in the prevalence of moderate/severe steatosis. In chronic hepatitis B, steatosis was associated only with higher body mass index (P=0.002), while moderate/severe steatosis was associated only with higher body mass index (P=0.043) and diabetes (P=0.031). Steatosis was relatively less frequent in chronic hepatitis B than chronic hepatitis C non-diabetic, normal-weight patients (45.6% versus 62.5%, P=0.063), but it did not differ in diabetic and/or overweight/obese patients with chronic hepatitis B or chronic hepatitis C. CONCLUSIONS: Hepatic steatosis in HBeAg-negative chronic hepatitis B (a) is less frequent than in genotype-1 chronic hepatitis C, (b) is mainly associated with presence of host metabolic factors, such as high body mass index and diabetes and (c) does not seem to be associated with the severity of liver histological lesions.

Liver transplantation in Greek patients: epidemiological data, morbidity, and mortality of 71 patients from a single center with 6 years of mean follow-up.

Liver transplantation remains an underdeveloped technique in Greece; currently there is no information on outcomes in Greek patients. In this study, data were provided on the outcomes of liver transplantation in 71 patients with a mean follow-up of 6 (0.1 to 16) years in our center. Mean age at transplantation was 46 +/- 13 years, while the main cause for transplantation was hepatitis B (16 patients, 23%) or C (six patients, 8%) virus. In the first posttransplantation year, three patients died, while 18 (25%) required at least one hospitalization with a median stay of 30 days. At the end of follow-up, 56 patients (79%) are alive. The leading cause of death was de novo malignancies (40%), appearing at a mean of 5.2 +/- 3.3 years. Late adverse effects of immunosuppressive therapy included hypertension (42%), hyperlipidemia (24%), chronic renal failure (21%), and diabetes mellitus (24%). With the exception of diabetes, all the above abnormalities were significantly associated with cyclosporine-based but not with tacrolimus-based immunosuppressive regimens. Relapse of primary disease in liver transplants occurred in 21 (29.6%) patients at a mean time of 1.5 +/- 1.4 years, of whom 67% were related to viral hepatitis. The quality of life (Karnofsky scale 1 to 6) was excellent in 64% of surviving patients, affordable in 21%, and poor in 15%. In conclusion, after 6 mean years, the majority of Greek liver transplant recipients conduct a normal life, although metabolic abnormalities are often observed. A national registry is needed to provide more solid evidence of outcomes.

Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes.

OBJECTIVE: To determine: (a) whether the components of metabolic syndrome (MetS) cluster more frequently than predicted by chance alone and (b) whether increased risk for MetS is associated also with values of each component below, but close to the cutoff points defining MetS. RESEARCH DESIGN AND METHODS: Anthropometrical and biochemical measurements were performed and a dietary questionnaire was filled-in in 1833 randomly selected non-diabetic subjects, 916 men and 917 women, 20-74 years old, in nine centres in five Mediterranean countries. The prevalence of MetS and of possible combinations of its individual components was measured. The expected frequencies of the above combinations were calculated according to the mathematical formula of probabilities. RESULTS: The overall prevalence of MetS was 27.2%, but varied greatly among countries, from 5.8% in Algeria to 37.3% in Greece. The observed prevalence of each combination diagnostic of MetS was higher than the expected by chance. Thus, the observed overall prevalence of MetS was also higher than the expected, 27.2 vs 24.0%, P=0.03. Furthermore, for each individual component (except high-density lipoprotein), as values in the normal range, approached the cutoff point, the risk of having MetS (i.e. clustering of the other components) increased significantly (odds ratio 2.2-4.6, P<0.001). CONCLUSIONS: The MetS is not related to the Mediterranean type of diet and its prevalence varies greatly among five Mediterranean countries. The clustering of the components defining the MetS is not due to chance and moreover even 'high normal' levels of each component confer increased risk for the syndrome.

Short-course therapy with amoxycillin-clarithromycin triple therapy for 10 days (ACT-10) eradicates Helicobacter pylori and heals duodenal ulcer. ACT-10 Study Group.

BACKGROUND: Whilst the role of Helicobacter pylori eradication in managing duodenal ulcers has been established, consensus regarding the ideal regimen has not been achieved. METHODS: Patients with H. pylori-positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT-10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C-urea breath testing (13C-UBT) were performed pre-treatment to assess H. pylori infection. H. pylori eradication was established at 4-6 weeks follow-up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C-UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4-6 weeks. RESULTS: Two hundred and sixty-seven (267) patients were randomized to ACT-10 (n = 137) or Dual therapy (n = 130). By per-protocol and intention-to-treat analyses, H. pylori eradication at 4-6 weeks follow-up was 91% (115/127) and 88% (120/136), respectively, for ACT-10 patients and 59% (68/115) and 55% (72/130), respectively, for Dual therapy patients (P < 0.001 for both analyses). Ulcer healing was high in both treatment groups: ACT-10, 93% (118/127) and 90% (122/136), respectively; and Dual therapy, 91% (104/114) and 85% (111/130), respectively. Pre-treatment resistance to clarithromycin was low (4%, 8/214) as compared to metronidazole resistance which was over 40%. Emergence of resistance to clarithromycin was observed in 2% of patients receiving ACT-10 and in 25% of those receiving Dual therapy. ACT-10 and Dual therapy patients experienced similar rates of drug-related adverse events (33% vs. 32%, respectively) and discontinuation from therapy due to an adverse event (1.5% vs. 5%, respectively). More than 90% of patients were compliant with each prescribed medication. CONCLUSION: In patients with active duodenal ulcer, a 10-day course of amoxycillin-clarithromycin-based triple therapy without additional acid suppression is highly effective in eradicating H. pylori and healing duodenal ulcer.

Six-month maintenance treatment of duodenal ulcer with sucralfate: influence on antral gastritis and Helicobacter pylori antral colonization--a prospective uncontrolled study.

Fifty-four patients (41 men, 13 women), aged 17 to 78 years (mean +/- SD, 48.13 +/- 13.5 years), with endoscopically confirmed healing of their duodenal ulcer after treatment with sucralfate (2 gm BID for 4 to 8 weeks) were recruited for this study. They were started on a 6-month maintenance treatment with sucralfate 1 gm BID. Endoscopy was done at the end of the 6-month period or whenever there was any evidence of ulcer relapse. Helicobacter pylori antral colonization (CLO test) and antral gastritis were estimated from biopsy samples taken before, and at the end of, the healing treatment, as well as at the end of the maintenance treatment. Cumulative relapse rate after 6 months was 15% (8 of 54). No patient discontinued treatment because of side effects. No influence of sucralfate on H pylori antral colonization or antral gastritis was observed after the healing or maintenance treatment. It is concluded that sucralfate 1 gm BID for 6 months is an effective maintenance treatment for duodenal ulcer, but has no beneficial effect on either H pylori antral colonization or antral gastritis.

Cisapride, metoclopramide, and ranitidine in the treatment of severe nonulcer dyspepsia.

Cisapride, a prokinetic drug with a novel mechanism of action, was compared with another prokinetic drug, metoclopramide, and an H2-blocker, ranitidine, in the treatment of nonulcer dyspepsia. In a double-blind study, 60 patients with severe dyspeptic symptoms received cisapride 5 mg TID, metoclopramide 10 mg TID, or ranitidine 150 mg BID for 8 weeks. Symptoms were evaluated during treatment and 4 weeks after the end of therapy. All three drugs effectively controlled the symptoms of chronic functional upper gastrointestinal tract disorders. The prokinetic drugs, particularly cisapride, were significantly better than ranitidine in controlling symptoms, especially reflux symptoms. All three drugs were generally well tolerated; cisapride in particular was associated with fewer adverse effects.

High eradication rate of Helicobacter pylori using a four-drug regimen in patients previously treated unsuccessfully.

The objective of this study was to assess the efficacy of a new regimen in eradicating Helicobacter pylori (Hp) in patients with duodenal ulcer (DU) who were previously treated unsuccessfully with standard triple therapy (tripotassium dicitratobismuthate [TDB] 120 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or proton-pump inhibitor (PPI) dual therapy (omeprazole 20 mg BID and amoxicillin 500 mg QID). The study included 133 consecutive patients aged 17 to 83 years with endoscopically diagnosed DU (diameter > or = 5 mm) in whom standard triple therapy or PPI dual therapy had failed to eradicate Hp. A rapid urease (CLO) test was performed on four biopsy specimens at study entry and at least 1 month after the end of treatment to confirm Hp colonization and eradication, respectively. Patients were considered to be Hp positive if any CLO test was positive within 2 hours, and Hp was considered to be eradicated if all CLO tests were still negative after 24 hours. In 31 randomly selected patients, Hp eradication was confirmed histologically as well. Patients were given omeprazole 60 mg/d (20 mg in the morning and 40 mg in the evening) plus amoxicillin 500 mg QID for 10 days and subsequently were given metronidazole 500 mg TID for 10 days plus TDB 120 mg QID for 6 weeks. One hundred and twenty-four patients were followed up; five (4%) withdrew because of side effects (protracted diarrhea, stomatitis, skin rashes). Per-protocol analysis showed Hp eradication in 113 of 119 patients (95%) and ulcer healing in 118 of 119 (99%). Intent-to-treat analysis showed an Hp eradication rate of 85% (113 of 133 patients) and an ulcer healing rate of 89% (118 of 133 patients). In per-therapy analysis, the Hp eradication rate was 91% (113 of 124 patients), and the ulcer healing rate was 95% (118 of 124 patients). Side effects were observed in 39 of 119 patients (33%) and were generally mild. The four-drug regimen used in this study, when given to patients previously treated unsuccessfully with standard triple therapy or PPI dual therapy, was highly effective in eradicating Hp and healing DUs and had no major side effects.

Biochemical modulation of fluorouracil: comparison of methotrexate, folinic acid, and fluorouracil versus folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial.

Recent advances in biochemical pharmacology have revealed the basis for the biological modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and folinic acid (FA). Sequential use of MTX given 24 h prior to 5-FU has resulted in enhanced cell kill in vitro and in vivo. In addition, administration of FA prior to 5-FU has led to potentiation of 5-FU action by stabilization of the ternary complex of thymidine synthase. In the present randomized study, two groups of patients with advanced colorectal cancer were treated as follows: 43 patients (pts) in group A received 5-FU + FA, whereas 45 pts in group B received 5-FU + FA + MTX. The dosage was as follows: group A received FA i.v. at 300 mg/m2 per day, prior to i.v. 5-FU at 500 mg/m2 per day on days 1-4; group B was given MTX i.v. at 130 mg/m2 per day on day 0, followed 24 h later by FA at 15 mg q6h x 6, and 5-FU + FA was started on day 1 and given at the same doses and schedule described for group A. Objective responses were achieved by 8/43 pts in group A (1 complete response and 7 partial responses) and by 18/45 pts in group B (3 complete and 15 partial responses), all occurring in the liver. There was no significant difference in the median time to progression (group A 6.1 months, group B 6.8 months) or the median survival (group A 9.2 months, group B 10.3 months). Toxicity was significantly greater in group B [grade 2-3 mucositis 20% versus only 2% in group A (P < 0.0001); grade 3 diarrhea in group B 15% versus 3% in group A (P < 0.001)]. According to our results, double biological modulation of 5-FU with MTX + FA led to an enhanced response rate with increased toxicity as compared with the 5-FU + FA regimen given at less than its maximally tolerated dose.

The status of antimicrobial resistance of Helicobacter pylori in eastern Europe.

OBJECTIVE: To evaluate the primary, secondary and combined resistance to five antimicrobial agents of 2340 Helicobacter pylori isolates from 19 centers in 10 countries in eastern Europe. METHODS: Data were available for centers in Bulgaria, Croatia, the Czech Republic, Estonia, Greece, Lithuania, Poland, Russia, Slovenia and Turkey. Susceptibility was tested by agar dilution (seven countries), E test (five countries) and disk diffusion (three countries) methods. Resistance breakpoints (mg/L) were: metronidazole 8, clarithromycin 1, amoxicillin 0.5, tetracycline 4, and ciprofloxacin 1 or 4 in most centers. Primary and post-treatment resistance was assessed in 2003 and 337 isolates respectively. Results for 282 children and 201 adults were compared. RESULTS: Primary resistance rates since 1998 were: metronidazole 37.9%, clarithromycin 9.5%, amoxicillin 0.9%, tetracycline 1.9%, ciprofloxacin 3.9%, and both metronidazole and clarithromycin 6.1%. Isolates from centers in Slovenia and Lithuania exhibited low resistance rates. Since 1998, amoxicillin resistance has been detected in the southeastern region. From 1996, metronidazole resistance increased significantly from 30.5% to 36.4%, while clarithromycin resistance increased slightly from 8.9% to 10.6%. In centers in Greece, Poland, and Bulgaria, the mean metronidazole resistance was slightly higher in adults than in children (39% versus 31.2%, P > 0.05); this trend was not found for clarithromycin or amoxicillin (P > 0.20). Post-treatment resistance rates exhibited wide variations. CONCLUSIONS: In eastern Europe, primary H. pylori resistance to metronidazole is considerable, and that to clarithromycin is similar to or slightly higher than that in western Europe. Resistance to amoxicillin, ciprofloxacin and tetracycline was detected in several centers. Primary and post-treatment resistance rates vary greatly between centers.

Ranitidine versus ranitidine plus octreotide in the treatment of acute non-variceal upper gastrointestinal bleeding: a prospective randomised study.

AIM: To compare the efficacy of ranitidine with that of ranitidine plus octreotide in the treatment of non-variceal upper gastrointestinal (UGI) bleeding. DESIGN: Prospective, randomised, open study. PATIENTS AND METHODS: Upper GI endoscopy was carried out during the first 24 hours in all patients with UGI bleeding who had been admitted within a period of 18 months. Patients with variceal bleeding, and those who had undergone any type of gastric operation, were excluded. Eighty-four patients (58 men and 26 women) aged 21-92 years (mean age: 61.2 +/- 15.0 SD) were included. Patients were randomised to receive ranitidine 50 mg tid intravenously alone (Group A: 44 patients, 29 men), or in combination with octreotide 100 micrograms tid subcutaneously, the second drug given for three days only (Group B: 40 patients, 29 men). The study end-points were discharge without operation, emergency surgical intervention or death. The number of blood units given and the days of hospitalization were also recorded. RESULTS: Aspirin and non-aspirin NSAID use before bleeding was reported by 16/44 (36%) patients in Group A and by 19/40 (47.5%) patients in Group B (p = 0.38, OR = 0.63, 95% CI = 0.26-1.51). The endoscopically detected pathology and bleeding stigmata did not differ between the groups (p = 0.86, p = 0.64, OR = 0.78, 95% CI = 0.3-1.99, respectively). Mean use of blood units (p = 0.16) and days of hospitalization (p = 0.25) did not differ. Three patients in Group A (6.8%) and three in Group B (7.5%) required surgical intervention (p = 1.0, OR = 1.1, 95% CI = 0.21-5.84). CONCLUSION: Ranitidine plus subcutaneous octreotide is not superior to ranitidine alone in the management of patients with acute non-variceal UGI bleeding.

Jejunogastric intussusception presented with hematemesis: a case presentation and review of the literature.

BACKGROUND: Jejunogastric intussusception (JGI) is a rare but potentially very serious complication of gastrectomy or gastrojejunostomy. To avoid mortality early diagnosis and prompt surgical intervention is mandatory. CASE PRESENTATION: A young man presented with epigastric pain and bilous vomiting followed by hematemesis,10 years after vagotomy and gastrojejunostomy for a bleeding duodenal ulcer. Emergency endoscopy showed JGI and the CT scan of the abdomen was compatible with this diagnosis. At laparotomy a retrograde type II, JGI was confirmed and managed by reduction of JGI without intestinal resection. Postoperative recovery was uneventful. CONCLUSIONS: JGI is a rare condition and less than 200 cases have been published since its first description in 1914. The clinical picture is almost diagnostic. Endoscopy performed by someone familiar with this rare entity is certainly diagnostic and CT-Scan of the abdomen could also help. There is no medical treatment for acute JGI and the correct treatment is surgical intervention as soon as possible.

Preliminary evaluation of the potential prognostic value of serum levels of immunoglobulins (IgA, IgM, IgG, IgE) in patients with gastric cancer.

Sixty patients with advanced gastric carcinoma who refused to receive cytotoxic chemotherapy were examined for serum immunoglobulin levels (IgG, IgM, IgA, IgE). Three samples were obtained every two months thereafter. The group of patients who had above-normal values of one or more of the examined immunoglobulins had a longer survival than the other (p < 0.024). Immunoglobulin values were independent of the Helicobacter pylori antibody titer and of acute phase reactants. It is concluded that survival potentially correlates with serum immunoglobulin levels. Further studies including larger numbers of patients and correlating serum immunoglobulin levels with specific clinical parameters are needed to establish the prognostic role of serum immunoglobulins in patients with gastric carcinoma.

The CLO test is unreliable in diagnosing H. pylori infection in post-surgical stomach; is there any role of H. pylori in peptic ulcer recurrence?

AIM: To evaluate the validity of the CLO test in detecting Helicobacter pylori in patients with gastric operation and to investigate the relationship of H. pylori with peptic ulcer recurrence in these patients. METHODS: In this prospective study, 110 consecutive patients, the majority of whom had undergone gastric operation for benign disease (n = 102), were included. Eighty patients (62 males), aged 38-87 years, had had a gastrectomy (10 Billroth I, 70 Billroth II), and 30 patients (27 males), aged 36-73 years, had had a vagotomy (13 vagotomy plus gastroenterostomy, 17 vagotomy plus pyloroplasty). H. pylori was sought on multiple biopsy specimens, using CLO test and histology (modified Giemsa stain). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the CLO test were estimated using histology as 'gold standard'. RESULTS: Overall, 21 gastrectomy patients (26%) were H. pylori-positive by CLO and 25 (31 %) were H. pylori-positive by histology. The estimated sensitivity, specificity, PPV and NPV of the CLO test, using histology as 'gold standard', were 68%, 91%, 77% and 86%, respectively. The CLO test was positive in 67% of vagotomy patients (20 of 30), while 50% (15 of 30) were H. pylori-positive by histology. The estimated sensitivity, specificity, PPV and NPV of the CLO test were 87%, 53%, 65% and 80%, respectively. H. pylori prevalence by histology was 50% in patients with vagotomy and 31% in those with gastrectomy (P = 0.0787). Recurrent ulcers were observed in 8/30 patients (27%) after vagotomy and in 10/72 patients (14%) after gastrectomy. Recurrent ulcer was documented in 6/15 H. pylori-positive patients with vagotomy (40%), and in one of 25 H. pylori-positive patients with gastrectomy (4%). This difference was significant (Fisher's exact test, P = 0.007, relative risk 5.091, 95% CI 0.819-31.64). CONCLUSION: The CLO test seems to be unreliable in diagnosing H. pylori in post-surgical stomach. The H. pylori prevalence is higher, although not significantly, in vagotomized patients compared with gastrectomized patients, and in this group is closely related to the presence of recurrent ulcer. So, at least in this group of patients, it is strongly recommended to look for and eradicate H. pylori.