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BACKGROUND AND OBJECTIVE The role of endothelial progenitor cells in patients with cirrhosis has seldom been investigated. This study was conducted to assess the clinical significance of circulating endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma. METHODS A blood sample was collected once from patients with cirrhosis alone (n = 34) or cirrhosis and hepatocellular carcinoma (n = 46) and healthy controls (n = 27) for assessing levels of endothelial progenitor cells and vascular endothelial growth factor. Blood cells staining positive for CD34/CD133/KDR using flow cytometry were characterized as endothelial progenitor cells. Plasma vascular endothelial growth factor was quantified by ELISA. RESULTS The levels of CD34/KDR-positive endothelial progenitor cells, CD133/KDR-positive endothelial progenitor cells, and vascular endothelial growth factor were higher in patients with cirrhosis ± hepatocellular carcinoma than in healthy controls (P = 0.017, P < 0.001 and P < 0.001, respectively). The levels of endothelial progenitor cells and vascular endothelial growth factor did not show statistical difference according to Child-Turcotte-Pugh class. There was a moderately significant correlation between vascular endothelial growth factor levels and hepatocellular carcinoma stage (ρ = 0.464, P = 0.001). Smoking, ascites, and portal vein thrombosis were independently related to lower levels of circulating CD34/KDR-positive endothelial progenitor cells, higher levels of CD133/KDR-positive endothelial progenitor cells, and higher levels of vascular endothelial growth factor, respectively (P = 0.041, P = 0.023, and P < 0.001, respectively). CONCLUSION Circulating endothelial progenitor cells and plasma vascular endothelial growth factor levels were higher in patients with liver cirrhosis ± hepatocellular carcinoma compared to healthy controls. The increase in endothelial progenitor cells and vascular endothelial growth factor may have a possible role in the development of complications, especially ascites and portal vein thrombosis, or in progression of hepatocellular carcinoma.

Background and aim Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, characterized by cognitive deficits that negatively impact patients' quality of life. The mild, minimal hepatic encephalopathy (mHE) can only be detected by psychometric tests and early mHE detection can prevent more severe complications or even survival times. Here, we aimed to investigate the feasibility and validity of the novel-developed electronic number connection test (eNCT), which is designed as a fast and easy-to-perform mHE patient self-test. Methods The eNCT design was inspired by the paper-pencil number connection test version A, showing 25 numbers on the screen (1-25), in a random order. The time required to tap on all digits in the correct order was measured. A total of 238 individuals (112 patients with liver cirrhosis) were enrolled in this study and eNCT times were compared with well-established paper-pencil tests. The Psychometric Hepatic Encephalopathy Score test battery was used to detect mHE and cut-off values for mHE detection by the eNCT were defined. Results Overall, cirrhotic patients showed significantly slower test completion times compared with control participants. The eNCT performance was inversely correlated with Psychometric Hepatic Encephalopathy Score test performance in cirrhotic patients, independent of the HE status. Thirty cirrhotic patients fulfilled the mHE criteria and receiver operating characteristic curve analysis showed high sensitivity (>82%) and specificity (>85%) for mHE detection. Finally, the eNCT showed excellent test-retest reliability (intraclass correlation coefficient=0.94). Conclusion The novel eNCT is a reliable HE self-test to monitor cognitive function and detect cognitive impairment in cirrhotic patients.

We read with concern the paper of McNicholl et al. 1 on the accuracy of GastroPanel (GP) in the diagnosis of atrophic gastritis (AG). The major conclusions of the paper are in sharp contrast with the earlier literature 2–6 and the most recent international consensus statements. The skewed GP results reported in the study 1 could be due to any or all of three main reasons: (a) poor laboratory techniques; (b) misclassification bias of the study endpoint (AG); and (c) inadequate statistical power (n=85, 10 with AG). First of all, it should be noted that the ‘Biohit-Deltaclon GastroPanel’s Lab’ in Spain, where the authors reported their analyses had been carried out 1, has no contract in force with Biohit Oyj (Helsinki, Finland), and accordingly no rights to use either the name Biohit or GastroPanel in this context. It is emphasized that the GP test (Biohit Oyj) is an enzyme-linked immunosorbent assay test and has not been optimized (or even tested) by the manufacturer for use as a chemiluminescent enzyme immunoassay 1. This type of technical modification inevitably entails that the manufacturer-recommended cutoff values are not valid in the new application. Chemiluminescent assay should have been validated against the reference GP test to confirm the appropriateness of the cutoff values that the authors have used (Figure 1) 1. Even minor deviations from the appropriately validated cutoff values in a study with a limited number of cases (only 10 with AG) would lead to markedly distorted results. Plasma pepsinogen I (PGI) levels and severity of AG show a practically linear relationship 2–5. PGI levels less than 25 µg/l and PGI/PGII ratio less than 3.0 are consistent with moderate or severe AG of the corpus 3. Therefore, it is surprising that the mean serum level of PGI for patients with AG of the corpus reported in this study is 101 µg/l (Table 1) 1. On the basis of extensive clinical series, such PGI values are impossible in patients with biopsy-confirmed moderate or severe AG of the corpus 2–6. The GP test is optimized to be used in context with the Updated Sydney System (USS) for classification of gastritis 2,6. The five diagnostic categories – (a) normal mucosa, (b) superficial gastritis, (c) atrophic antrum gastritis, (d) atrophic corpus gastritis, and (e) atrophic pangastritis – are common to both the GP test and the USS, which enables direct assessment of their concordance using, for example, weighted κ (intraclass correlation coefficient) testing. When this is done in an adequately powered study based on validated USS classification, an interassay (GP-to-USS) agreement is usually in the range of 0.7 to greater than 0.8 (substantial to almost perfect) 2,6. This information on the overall test agreement was missing in the present report 1. The lack of this key information invalidates the correct interpretation of the GP results and also precludes any meaningful calculations on GP performance as an indicator of the AG (study endpoint). Mild AG of the corpus should never be used as the study endpoint in calculating the performance indicators of the PGI, PGI/PGII, as repeatedly emphasized 2–6. This fact has been neglected in the present study, in which the GP cutoff values presented in Figure 1 algorithm are indicated for AG in general and not stratified according to the grade of AG 1. The only appropriate way of calculating the predictive indicators of PGI and PGI/PGII ratio for AG of the corpus is to use the combined moderate/severe AG as the study endpoint. This approach in an adequately powered study with validated USS classification gives receiver operating characteristic (area under the curve) values above 0.970 for PGI and greater than 0.950 for the PGI/PGII ratio 2–6. Another unique feature of the GP test is the interpretation of the results by specific software (GastroSoft Biohit Oyj, Helsinki, Finland), which is almost mandatory in their correct interpretation. The authors did not report using GastroSoft in their study 1. The role of the G-17 biomarker is more complex. Low levels of G-17 are not exclusively inherent to antral AG, but may also reflect high gastric acid output, whereas high volumes may result from the use of proton pump inhibitors 2,7,8. In fact, the use of G-17 is not recommended by the GP manufacturer for the diagnosis of antral AG. Finally, in a study including only 10 patients with (unclassified) AG in a clinical setting, one cannot draw any conclusions whatsoever on the use of the GP test in a screening setting. Such a setting would necessitate an adequately powered cohort of population-derived (asymptomatic) individuals, all being tested by GP, with all test positives (and random 5% of test negatives) to be confirmed by gastroscopy and validated biopsy classification, and, importantly, all performance indicators being corrected for verification bias by special statistical treatment.

Cyclic vomiting syndrome (CVS) is a rare abnormality of the neuroendocrine system that affects 2% of children. It is a frequently missed diagnosis in the emergency department and may require a number of emergency department visits before the diagnosis is made. The objectives of this review are to identify the clinical features that suggest a diagnosis of CVS and to review the literature on its management. The MEDLINE and EMBASE databases were searched from January 1948 to October 2011 using the keywords 'Cyclic' or 'Vomiting'. Papers were excluded if they did not follow the consensus guidelines or if they were case reports. This review analysed 1093 cases of cyclic vomiting in 25 papers that fulfilled the inclusion criteria. All except one paper were retrospective studies. The size of these cohort studies ranged from three to 181 patients, with a mean patient size of 29. This review found that over 40% of patients have headaches/migraines, with associated anxiety and depression in ≈ 30% of cases. There is a family history of headaches/migraines in 38.9%, and this association was much stronger in the adult CVS cohort compared with the paediatric cohort. Compared with paediatric CVS, adults have a longer duration of attacks and they occur more frequently (5.9 vs. 3.4 days, 14.4 vs. 9.6 episodes/year). Limited data are available on the treatment of the acute phase of CVS, but in adults, sumatriptan has been shown to be effective. For prophylactic treatment, tricyclics are effective in both adult and paediatric CVS, with a clinical response in 75.5 and 67.6% of patients, respectively, in nonplacebo-controlled cohort studies. Furthermore, propranolol has been shown to be useful in children. CVS is an intractable illness with a major impact on the patient's quality of life. There is a long duration between the onset of symptoms and the diagnosis of the condition. There is a high association with headaches/migraines and anxiety/depression. The symptoms are more severe in adult-onset CVS. Tricyclic antidepressants have good efficacy in reducing the frequency/duration or the intensity of attacks. There is limited evidence on the acute management of CVS.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin exert irritant and toxic effects upon the organs of the gastrointestinal tract. NSAID toxicity in the gastrointestinal tract is related, at least in part, to the inhibition of the cyclo-oxygenase (COX) enzyme, leading to a reduction of 'cytoprotective' prostaglandin synthesis. In this paper, examples in which NSAIDs exert beneficial effects in the gastrointestinal tract are discussed. NSAIDs, particularly aspirin, are showing promise in the chemoprevention of colorectal, and, to a lesser degree, oesophageal cancers. The clinical value of NSAIDs in the treatment of established gastrointestinal tract cancers is also worthy of further study. There is good clinical evidence showing the value of diclofenac for the treatment of biliary colic and aspirin or ibuprofen for the prevention of gallstones. NSAIDs also have therapeutic potential against other inflammatory gastrointestinal diseases in the oesophagus and possibly pancreas and liver. To a lesser degree, there is some evidence that NSAIDs may have a therapeutic potential in certain gastrointestinal motility disorders, such as aspirin in the post-irradiation syndrome. It therefore follows that in these cancerous, inflammatory and motility pathologies, prostaglandins exert deleterious effects. The paradox of prostaglandins being 'cytoprotective' and potentially damaging can be explained by considering the enzymic origin of prostaglandins. COX-1 is expressed physiologically while inducible COX-2 is expressed in pathological situations. The beneficial clinical effects of selective COX-2-inhibiting NSAIDs in the gastrointestinal tract deserve further study. This paper challenges the concept of 'cytoprotection'.

The discovery of Helicobacter pylori (H. pylori) opened the doors to new insight and therapy for peptic ulcer disease. Earlier eradication treatment modalities based on bismuth compounds, with or without additional antimicrobials, were not well accepted mainly because of the, at least hypothetical, risks for neurological and/or renal side effects. The first proton pump inhibitor, omeprazole, had been proven as a very effective short-term anti-ulcer therapy, but after withdrawal of the drug, the recurrence rate was high. theoretically, acid suppression was believed to increase the H. pylori infestation as the environment became more neutral. On the other hand, acid suppression could increase the effect of acid labile antimicrobials. This was not investigated before the studies presented in this thesis were performed.A small pilot study (Paper I) in 24 patients showed that 7 out of 8 patients treated for fourteen days with omeprazole 40 mg o.m. + amoxicillin 750 mg b.i.d. were cleared of H. pylori, while it remained in 7/8 patients on omeprazole as monotherapy and in 2/7 patients on amoxicillin as monotherapy. However, the eradication rates 4 weeks after treatment were 5/8, 0/8 and 1/7 in the three groups, respectively. These results were confirmed in a large study (Paper II) comprising 248 consecutive patients with active duodenal ulcer disease. All had an initial treatment period for two weeks with omeprazole 40 mg o.m., followed by continued omeprazole in combination with amoxicillin 750 mg b.i.d. or amoxicillin placebo for a further two weeks. In the dual therapy group, 54% of patients were H. pylori eradicated compared to 4% in the omeprazole mono therapy group. Furthermore, the duodenal ulcer relapse rate was significantly lower in the combination group compared to the monotherapy group (p

In recent years, panintestinal capsule endoscopy (PCE) with double-headed capsules has been used to perform complete, single-sitting exploration of both small bowel and colon in different clinical conditions. Double-headed capsules for colonic examination (CCE) have been exploited first in this setting, followed by newer generations of capsules (i.e. PillCam Crohn, PCC) specifically engineered for this purpose. The aim of this study was to evaluate the feasibility of PCE in the form of a systematic review. We performed a comprehensive literature search to identify papers in which CE was specifically used for a PCE of the gastrointestinal tract. Data on CE, bowel preparation regimen, rate of cleanliness and completeness, and data on transit times were analyzed. The primary outcome was to assess the feasibility of a whole-gut exploration with CE. Sixteen (n = 16) studies including 915 CE procedures with CCE1 (n = 134), CCE2 (n = 357) and PCC (n = 424) were included. 13/16 studies were performed in the setting of Crohn's disease. Cleanliness and completeness rates were acceptable in all studies, ranging from 63.9% and 68.6% to 100%, respectively. In conclusion, PCE is a feasible technique, although further structured studies are needed to explore its full potential.

Objectives Anti-TNFα agents have been a staple of Crohn's disease treatment for 20 years, but they have weaknesses. New treatments have more recently become available. The aim of this paper is to examine the Crohn's disease patient population for whom anti-TNF treatments are not preferred and where new mechanisms of action should be considered. Methods A representative sample of 100 Italian physicians with documented expertise with biological treatment of moderate-to-severe Crohn's disease were interviewed. A literature review on Crohn's disease treatment was also conducted to identify patient populations for whom anti-TNFs are unsuitable. Results On the basis of the interviewed physicians, about 9% of moderate-to-severe Crohn's disease patients were noneligible to anti-TNFα due to contraindication or possible risk of intolerance, while 11% had discontinued anti-TNFα treatment due to complications or intolerance/hypersensitivity. Patients with severe heart disease and at high risk of infections were more frequently considered unsuitable. The proportion of patients considered unsuitable among elderly patients and in those with recurrent infections, cancer, and other comorbidities ranged between 40 and 60%. Conclusions We provided additional quantitative and qualitative information to help identify patients who are less suitable to anti-TNF agents, who could benefit from newer biologic agents with different mechanisms of action.

Hepatic encephalopathy (HE) is associated with a poor prognosis. There is no study on the prevention of recurrence of encephalopathy with L-ornithine L-aspartate (LOLA).We conducted a double-blind randomized controlled trial at a tertiary center. Consecutive patients with cirrhosis who had recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer-based randomization for 6 months. Patients were assessed by psychometric HE scores using five paper-pencil tests, critical flicker frequency test, arterial ammonia, and sickness impact profile scores at inclusion. Primary end point was development of overt HE.Of 306 patients, 150 patients were enrolled. HE recurred in nine (12.3%) of 73 and in 20 (27.7%) of 72 patients receiving LOLA and placebo, respectively (P=0.02), with hazard ratio of 0.389 (95% confidence interval=0.174-0.870). Mortality was similar in both groups (6.8 vs. 13.8%, P=0.18). At 6 months follow-up, there was a significant change in the psychometric hepatic encephalopathy score (2.53±2.18 vs. -0.01±1.92, P0.001), ammonia level (-23.58±14.8 vs. 1.41±13.34 μmol/l, P0.001), CFF (5.85±4.82 vs. 0.58±4.53, P0.001), and SIP scores (-7.89±5.52 vs. -0.95±4.25, P0.001) in patients treated with LOLA compared with placebo. On multivariate analysis, only MELD score predicted the recurrence of overt HE, with odds ratio of 2.21 (95% confidence interval: 1.526-3.204, P0.001).LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in psychometric hepatic encephalopathy score, ammonia level, critical flicker frequency scores, and health-related quality of life.

BACKGROUND Adenoma detection rate (ADR) is defined as the number of colonoscopies with at least one adenoma, expressed as the ratio of the total number of colonoscopies performed. Recently, an application of a conversion factor to estimate the ADR from the polyp detection rate (PDR) was described. AIM In this meta-analysis, we examined the correlation between ADR and PDR in the published studies and assessed the relative ratio of these ratios for a better and more accurate estimation. METHODS English Medical literature searches were performed for 'PDR' AND 'ADR'. A meta-analysis was carried out for papers that fulfilled the inclusion criteria using comprehensive meta-analysis software. RESULTS Twenty-five studies and 42 sets of data, including 31 623 patients, from nine countries published till 31 August 2017, were found. Funnel plot did not indicate a significant publication bias. relative ratio for ADR calculated from PDR was 0.688, 95% confidence intervals: 0.680-0.695, P value of less than 0.0001 in the meta-analysis fixed model. Heterogeneity (the proportion of inconsistency in individual studies) between studies was significant, with Q=492.753, d.f. (Q) 41, P

Aim/Objective/Background Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. Methods A systematic search of case reports on the MEDLINE database encompassing the years 2008–2016 was carried out.Additional references were obtained following a manual search of the retrieved papers. We report two new cases of adverse events occurred in patients treated with rivaroxaban (20 mg/die) to prevent systemic embolism, who presented with hepatocellular liver injury with onset at 8 weeks after initiation of the drug intake. Results Twenty-six cases were retrieved from MEDLINE (57.7% female, 42.3% male). Using the Roussel Uclaf Causality Assessment Method (RUCAM) scale, liver injury was classified as hepatocellular (42.3%), cholestatic (26.9%), or mixed (15.4%). Older age (≥65 years) was present as a risk factor in 57.7%. The time lapse between initiation of treatment and onset of hepatic injury ranged from 2 to 180 days (median: 15 days). Our two new patients were diagnosed with drug-induced liver injury (hepatocellular pattern) using the ‘consensus criteria’, for drug-induced liver injury. Their RUCAM scores were calculated and assessed as highly probable and probable, respectively. A clinical recovery after rivaroxaban withdrawal was observed. Conclusion Direct-acting oral anticoagulants have been commonly prescribed, even if safety issues regarding the use of these drugs are still an ongoing concern, especially in patients experiencing chronic liver disease. Dedicated postauthorization safety studies should be undertaken to better define rivaroxaban-induced drug-induced liver injury.

Patients with cirrhosis have a high incidence of portal vein thrombosis (PVT), and optimal management of PVT in cirrhotic patients remains unclear. Currently, there is no paper on optimal doses of enoxaparin for the management of PVT with cirrhosis.To evaluate the efficacy and safety of anticoagulation therapy with different doses of enoxaparin for PVT in cirrhotic patients with hepatitis B.Sixty-five patients with hepatitis B-related cirrhosis and acute PVT were treated by different doses of enoxaparin. All the patients were assigned randomly to two groups: one group received enoxaparin 1 mg/kg subcutaneously every 12 h and the other group received enoxaparin 1.5 mg/kg subcutaneously every 24 h. Clinical, biochemical evaluation, Doppler ultrasound, and contrast-enhanced computed tomography were performed during the anticoagulation treatment.Of the 65 patients, 51 patients (78.5%) achieved complete/partial recanalization of PVT after 6 months of anticoagulation therapy. Child-Pugh scores were lower in the 51 patients who achieved complete/partial recanalization than those of the 14 nonresponders (P0.01). No patients showed variceal bleeding during anticoagulation therapy in the two groups. The rates of nonvariceal bleeding with the use of 1.5 mg/kg every 24 h (23.5%) were higher than those with the use of 1 mg/kg every 12 h (6.4%).Anticoagulation therapy with different doses of enoxaparin for PVT in hepatitis B patients with cirrhosis is efficient and safe, and 1 mg/kg enoxaparin subcutaneously every 12 h is a better anticoagulation regimen in the treatment of PVT in cirrhotic patients.

Background and study aims The wide use of PET-CT for the staging of neoplasms has extended to enlarged lymph nodes of unknown origin. Nevertheless, upper abdominal and mediastinal nodes are accessible to endoscopic ultrasonography-fine needle aspiration (EUS-FNA), providing a cytological diagnosis, with a high diagnostic yield in previous reports. In this paper, we have compared the accuracy of both procedures in this particular setting. Patients and methods After the finding of a lymphadenopathy in a conventional CT, both PET-CT and EUS-FNA were performed. The endoscopist had no information about PET-CT results. FNA was performed after a systematic EUS exam, with a 25 G needle and no suction. We considered the pathologic results as the gold standard or, if not available, the patients' outcome as a surrogate marker. Results A total of 54 patients were included. Common locations of nodes included subcarinal space (33.3%), porta hepatis (31.5%), upper mediastinum (15%), peripancreatic (7.4%), and other locations (12.8%). Adequate specimens were obtained in 48/54 patients (89%). The most common diagnoses based on cytology were benign/reactive (42%), epidermoid carcinoma (8.4%), lymphoma (8.4%), and ductal adenocarcinoma of pancreatic origin (6.3%). PET was positive in 67% of patients. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of EUS-FNA were 91.3, 100, 100, 92.5, and 95.8%, respectively. The same values for PET-CT were 75, 25, 50, 50, and 50%, respectively. Conclusion In our series, EUS-FNA has proven to be the best diagnostic procedure to accurately establish the etiology of isolated adenopathies, showing a much better diagnostic yield than PET-CT, the role of which should be re-evaluated in this setting.

In recent years, laparoscopic cholecystectomy (LC) has become the standard surgical practice for the treatment of cholecystolithiasis. As a recognized technical difficulty, it may be associated with the mechanical injury of the gallbladder and/or spilling some of the gallstones into the abdominal cavity. The actual incidence of the latter complication is ~10%. The removal of lost stones from the abdominal cavity is rather elaborate if not infeasible. There is little information about the behaviour of retained gallstones in the free abdominal cavity. Publications report on subsequent intraperitoneal abscesses and fistulas or on the extreme localization of the impacted gallstones. This paper presents two cases with late complications of the abandoned gallstones or gallbladder. Case 1: A 56-year-old female patient underwent an LC 7 years ago. She was recently admitted with a chronic septic condition and suspected autoimmune disease. Preoperative examinations indicated hepatic abscess. Surgery showed gallstones impacted in the gallbladder bed. Case 2: A 59-year-old male patient underwent an LC a year before his admission. His operation was followed by the development of a septic condition and a subphrenic abscess was identified. During his reoperation, a remnant gallbladder containing bile stones was found and removed. Special attention should be paid to careful revision of residual stones during LC.

Refractory ascites and recurrent variceal bleeding are among the serious complications of portal hypertension and cirrhosis for which a transjugular intrahepatic portosystemic shunt (TIPS) can be used. Cirrhotic patients have varying degrees of haemodynamic derangement, mainly characterized by peripheral arterial vasodilatation, central underfilling and activation of several vasoactive systems. These changes affect the heart, the lungs and the kidneys in particular. The cardiac effects of TIPS are immediate and are related to the redirection of blood from the splanchnic circulation into the systemic circulation, resulting in worsening of the hyperdynamic circulation with increasing cardiac output and decreasing systemic vascular resistance; further, TIPS may unmask a latent diastolic dysfunction of the heart. However, the renal effects of TIPS seem to be beneficial as renal function tends to improve in patients with the hepatorenal syndrome. The clinical and haemodynamic effects of TIPS have been studied intensively and will be reviewed in the present paper. Considerable knowledge on the effects of TIPS on the pathophysiology of cirrhosis has been gained, but studies on the central haemodynamic effects are warranted to refine the already applied treatments and develop new treatment modalities.

To analyze the subgingival microflora composition of inflammatory bowel disease (IBD) patients with untreated chronic periodontitis and compare them with systemically healthy controls also having untreated chronic periodontitis.Thirty IBD patients [15 with Crohn's disease (CD) and 15 with ulcerative colitis (UC)] and 15 control individuals participated in the study. All patients had been diagnosed with untreated chronic periodontitis. From every patient, subgingival plaque was collected from four gingivitis and four periodontitis sites with paper points. Samples from the same category (gingivitis or periodontitis) in each patient were pooled together and stored at -70 °C until analysis using a checkerboard DNA-DNA hybridization technique for 74 bacterial species.Multiple-comparison analysis showed that the groups differed in bacterial counts for Bacteroides ureolyticus, Campylobacter gracilis, Parvimonas micra, Prevotella melaninogenica, Peptostreptococcus anaerobius, Staphylococcus aureus, Streptococcus anginosus, Streptococcus intermedius, Streptococcus mitis, Streptococcus mutans, and Treponema denticola (P0.001). CD patients had significantly higher levels of these bacteria than UC patients either in gingivitis or in periodontitis sites (P0.05). CD patients harbored higher levels of P. melaninogenica, S. aureus, S. anginosus, and S. mutans compared with controls both at gingivitis and at periodontitis sites (P0.05). UC patients harbored higher levels of S. aureus (P=0.01) and P. anaerobius (P=0.05) than controls only in gingivitis sites.Our study showed that even with similar clinical periodontal parameters, IBD patients harbor higher levels of bacteria that are related to opportunistic infections in inflamed subgingival sites that might be harmful for the crucial microbe-host interaction.

BACKGROUND AND STUDY AIMS Propofol is increasingly being used in sedated colonoscopy. This paper assesses the safety and efficacy of nonanesthesiologist-administered propofol in a large series of colonoscopies. PATIENTS AND METHODS A prospective registry of consecutive American Society of Anesthetics (ASA) class I and II outpatients undergoing colonoscopy was carried out. Propofol, administered by a nurse under an endoscopist's supervision, was the sole sedative agent used. RESULTS Of the 1000 patients (563 women/437 men, mean age 57, range 8-89 years) included in the study, 57.4% showed ASA I and 42.6% ASA II characteristics. The cecal intubation rate was 96.9%. 48.2% of the procedures were for therapeutic purposes. The mean propofol dose was 177 mg (range 50-590 mg). Doses correlated inversely with patient age (r=-0.38; P

Before the discovery of Helicobacter pylori infection some 12 years ago, three major disturbances in gastric physiology had been identified in patients with duodenal ulcer disease. These abnormalities were: impaired acid inhibition of gastrin release from the antral mucosa, increased basal and stimulated acid secretion by the body of the stomach and increased acid load in the duodenum. Some of these abnormalities in gastric function can now be explained by the effects of H. pylori infection. The increased release of gastrin by the antral mucosa in duodenal ulcer patients, for example, can be entirely explained by the effects of this organism. Other abnormalities, however, appear to have a genetic basis or may be due to environmental factors. Much work has been conducted on the relationship between H. pylori and the development of duodenal ulcer disease and this paper aims to review recent studies in the field and to give an overview of the latest understanding of the pathophysiology of this disease.

The annual incidence of peptic ulcer disease in developed countries is around one to three per thousand inhabitants. Since the introduction of acid-secretion inhibitors, the indirect costs of this disease, which has a high rate of relapse, have steadily decreased, although direct costs have been increasing. The possibility of healing the patient through Helicobacter pylori eradication has the potential for a huge economic impact considering the long-term cost: benefit ratio. A recent study has shown that H. pylori eradication therapy can save between US$750,000 and US$1,000,000 per year per million inhabitants in western Europe compared to maintenance or episodic therapy. This paper reviews the cost implications of various management strategies for peptic ulcer disease, comparing the cost: benefit ratios of five different treatment regimens.

Clopidogrel is a thienopyridine derivative with a relatively low occurrence of adverse side effects. Increasing evidence, however, suggests that clopidogrel may cause severe liver injury. Until now, five cases of clopidogrel-induced acute hepatitis have been reported. We describe the case of an 80-year-old man who developed symptomatic liver disease 6 weeks after 1 x 75 mg/day clopidogrel intake as adjunctive antiplatelet therapy for a renal artery stent implantation. Histological examination revealed severe acute hepatitis with extensive hepatocanalicular cholestasis and focal cell necrosis with a preferential zone-3 distribution of hepatic damage. In the present paper, we describe the clinico-histopathological characteristics of a case of clopidogrel-induced acute hepatitis and discuss the current literature.

The UK Department of Health states that there is suggestive, although not conclusive, evidence for the efficacy of cognitive behavioural therapy (CBT) in irritable bowel syndrome (IBS) and that CBT should be considered as a treatment option for the syndrome. This paper provides a general introduction to CBT, the principles which underlie it and how they can be applied to IBS. The components of CBT for IBS are described in some detail. Guidelines for gastroenterologists are provided on how these principles can be used to inform their practice and the existing outcome data are reviewed.

This review in depth considers the thiopurines azathioprine, 6-mercaptopurine and 6-thioguanine, methotrexate, ciclosporin, infliximab and less well-established immunomodulators (including thalidomide, mycophenolate, tacrolimus and natalizumab among others) in their role of modifying the course of ulcerative colitis and Crohn's disease. The five papers are preceded by an overview on the therapeutic order of precedence, the indications and duration of therapy, as well as future concepts.

We report the case of a 21-year-old woman with a giant (20 cm) benign mesothelial splenic cyst and a high CA 19-9 serum level (1240 U/ml). The patient underwent resection of the cyst and splenectomy. True non-parasitic splenic cysts are very rare. Only 10 cases of benign true splenic cysts, with a high CA 19-9 serum level, have ever been published in the medical literature written in English. These are reviewed in this paper. We believe that the inner cellular lining of the cyst wall produces CA 19-9, which causes the high CA 19-9 serum level. This is supported by the facts that (1) the inner cellular lining is strongly positive for immunohistochemistry with CA 19-9, and (2) the CA 19-9 serum level returned to normal after resection of the cyst.

Background Many patients with gastro-oesophageal reflux disease (GORD) report that coffee aggravates their symptoms and doctors tend to discourage its use in GORD. Objective To assess the effect of coffee ingestion on gastro-oesophageaI acid reflux. Design A randomized, controlled, crossover study. Participants Seven GORD patients and eight healthy subjects. Methods After 1 day of coffee abstinence, participants underwent 24-h oesophageal pH and manometric monitoring. At well-defined times, they ingested either 280 ml of regular paper-filtered coffee or 280 ml of warm water. Coffee or water was drunk 1 h after breakfast, during lunch, 1 h after dinner and after an overnight fast. Reflux and oesophageal motility parameters were assessed for the first hour after each coffee or water intake. Results Coffee had no effect on postprandial acid reflux time or number of reflux episodes, either in GORD patients or in healthy subjects. Coffee increased the percentage acid reflux time only when ingested in the fasting period in the GORD patients (median 2,6, range 0-19.3 versus median 0, range 0-8.3; P = 0.028), but not in the healthy subjects. No effect of coffee on postprandial lower oesophageal sphincter pressure (LOSP), patterns of LOSP associated with reflux episodes or oesophageal contractions was found. Conclusion Coffee has no important effect on gastrooesophageal acid reflux in GORD patients, and no effect at all in healthy subjects, Eur J Gastroenterol Hepatol 11:1271-1276 (C) 1999 Lippincott Williams & Wilkins.

Background Development of de novo autoimmune liver disease has not been well documented in patients with malignant diseases. Methods/results In this paper we report on a series of six patients with neoplastic disorders who acquired liver disease with autoimmune features. Five patients had suffered from haematological neoplasms and one from colonic cancer. In two patients, liver disease was detected at the time of presentation with malignancy. In the remaining four, all of whom were successfully treated for malignancies, features of liver disease presented at intervals 24-72 months after the cancer diagnosis. Twelve liver specimens (11 biopsies and one hepatectomy specimen) were obtained at time intervals of 1 - 76 months after initial presentation of neoplastic disease. Biopsies from three patients showed features of hepatitis (one acute, one sub-acute, one chronic). Two patients had histological features suggestive of an overlap syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient had features of autoimmune cholangiopathy. All but one responded well to steroid therapy with complete clinical and biochemical remission obtained 4 weeks to 8 months after steroid introduction. We discuss briefly possible aetiologies of autoimmune liver disease in these patients. Conclusions Autoimmune liver disease may be precipitated by therapy for neoplastic disease or malignant disease itself. The unusually heterogeneous clinicopathological findings in this group as well as the response to treatment support the concept of a wide spectrum of manifestations of autoimmune liver disease. The results may also suggest that autoimmune liver disease may be possibly added to the list of paraneoplastic syndromes. Further prospective studies are required to confirm a causal association and to determine whether the mechanisms involved are disease- or treatment-related.

This paper contains a brief review of the metabolism and physiological actions of eicosanoids, with a discussion of the potential clinical implications of disturbances in eicosanoid metabolism, particularly in NSAID-induced upper gastrointestinal damage and inflammatory bowel disease. There follows a summary of current evidence for the role of eicosanoids in the pathogenesis of colorectal neoplasia.

Objective : There is currently no reliable tool for providing a global measurement of the severity of dyspepsia in patients with a variety of upper gastrointestinal disorders. We have designed a questionnaire which records frequency of symptoms, effect on routine activities, time off work, frequency of medical consultations, clinical investigations and use of over-the-counter and prescribed medications. The objective of the paper was to assess this questionnaire with respect to reproducibility, validity, responsiveness and performance time. Methods and results : For intra-observer variation, one author interviewed 50 subjects (25 males) including 20 healthy volunteers and 30 with a variety of upper gastrointestinal pathologies. The interview was repeated one week later by the same author who was blinded to the dyspepsia score for the first interview. The second author, who was blinded to the diagnoses and subject identity, scored all the questionnaires. The mean dyspepsia score was 6.78 on Day 1 and was similar at 6.80 on Day 2. The coefficient of variation between Days 1 and 2 was 2%. For inter-observer variation, 30 patients with non-ulcer dyspepsia (NUD) were interviewed by one author and the interview was repeated on a separate occasion within 24 h by a second author who was blinded to the score from the first interview. The mean dyspepsia score for the first author was 10.7 and for the second author 10.9 with a coefficient of variation between the two authors of 8%. Validity was assessed by comparing the dyspepsia scores in healthy volunteers and patients with upper gastrointestinal diseases. The mean score in 80 healthy volunteers was 1.16 (range : 0-7) and was significantly higher in 70 duodenal ulcer (DU) patients (mean score 11.1, range : 6-16) and 80 NUD patients (mean score 10.5, range : 6-17) (P

The particular perianal manifestations of Crohn's disease can pose major challenges to both physician and surgeon. The spectrum of pathology and symptomatology is diverse and management must embrace all aspects of the problems encountered. Historically, local surgery has been viewed with pessimism, but there is increasing evidence that aggressive surgery can be beneficial in selected cases, thereby delaying or preventing protectomy. The papers reviewed in this article describe the various ways in which the different pathologies encountered have been managed

Fulminant hepatic failure is commonly complicated by hepatic encephalopathy and cerebral oedema which is frequently fatal. The toxic factor(s) causing these complications is unknown. This paper summarizes the evidence pointing to the role of the polyamine putrescine in mediating blood-brain barrier breakdown and cerebral oedema. It also summarizes the recent evidence of polyamine control of the N-methyl-D-aspartate receptor which is the major receptor involved in glutamatergic neuroexcitatory transmission. Overstimulation of this receptor in the presence of excess polyamines could result in excess calcium ion inflow and cytotoxicity; a method by which this happens is considered and related to hepatic encephalopathy

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic and recurrent abdominal symptoms with no associated organic abnormalities. Although IBS has traditionally been considered to be more common in western cultures, a review of the literature reveals that IBS is truly a worldwide illness, affecting people in many different cultural and geographic areas. According to this review, a reasonable range for the worldwide prevalence of IBS is between 5 and 15%. Several theories for varying prevalence rates around the world are presented in this paper and methodological difficulties are discussed. Finally, this short review provides an analysis of cultural, biological, and socioeconomic differences in IBS presentation and treatment around the world.

Over the 14 years since Helicobacter pylori came to the attention of the medical community, we have reached the position that the organism is generally believed to be a serious pathogen. It causes a chronic infection with complications that include gastric and duodenal ulcer, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. It is therefore an important cause of morbidity and mortality. We still do not have a perfect treatment for the infection, but enormous strides have been made since its discovery and acceptable treatments are now available. The best of these are the acid pump inhibitor- and ranitidine bismuth citrate-based triple therapies that provide 85-95% eradication in most studies. Better treatments and vaccination programmes may become available now that the Helicobacter genome has been decoded, raising the possibility of 'designer' antibiotics and vaccines. In the meantime, the current key questions are: How can our current therapies be improved? Who should be treated? What, if any, are the potential risks of widespread H. pylori eradication? And how is the organism transmitted ? Without doubt, many of these questions will be addressed in the succeeding years. The papers presented in these proceedings represent an up-to-date analysis (much of it based on new data) by recognized experts. The views expressed are often provocative, but are backed by scientific data.

Much of what is currently accepted regarding Helicobacter pylori-associated gastritis and its relationship with gastric adenocarcinoma rests on the assumption that atrophic gastritis can be correctly identified and reproducibly recognized. Several studies have indicated that pathologists have a low level of agreement on this topic, and the terms 'gastric atrophy' and 'atrophic gastritis' remain imprecisely defined and poorly understood. Furthermore, the genesis and progression of the atrophic changes that take place in the gastric mucosa of some individuals infected with H. pylori are incompletely characterized. The lack of a strict definition of atrophic gastritis is at least partially responsible for recent concerns regarding the effects of prolonged pharmacological gastric acid inhibition in patients with H. pylori infection. One recent paper concluded that patients with reflux oesophagitis and H. pylori infection who are treated with longterm acid inhibition have an increased risk of atrophic gastritis. As this term evokes associations with an increased risk of gastric cancer, the possibility was subsequently raised that anti-secretory maintenance therapy might increase the risk of cancer in H. pylori-positive patients. A second report, however, concluded that long-term acid-inhibitory therapy for an average of three years is no different from fundoplication in the development of gastric atrophy. Also, because no intestinal metaplasia developed in any of the patients, and only atrophic gastritis associated with intestinal metaplasia is considered a precursor of gastric cancer, there is no evidence to support the hypothesis that long-term acid inhibition in individuals with H. pylori infection increases the risk of gastric cancer.