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Background Portal vein obstruction may be due to portal vein thrombosis ( PVT) or its sequale, the portal cavernoma. PVT is a common complication in liver cirrhosis, however, it may also occur as a primary vascular disorder, in absence of any liver disease. Aim To review the current knowledge on nomenclature, etiology, pathophysiology, clinical presentation, diagnostic workup and management of adult patients with obstruction in the portal vein, either as a primary vascular disease in adults, or as a complication of liver cirrhosis. Methods A structured search in PubMed was performed using defined keywords (portal vein obstruction, extra-hepatic portal vein obstruction, PVT and portal cavernoma), including full text articles and abstracts in English language. Results Several causes, operating both at local and systemic level, might play an important role in the pathogenesis of PVT. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernible. Diagnosis of portal vein obstruction depends on clinical presentation, imaging and laboratory investigations. Prompt treatment greatly affects the patient's outcome. Conclusions Portal vein obstruction occurring either due to thrombosis in the portal vein or due to the portal cavernoma, can contribute to significant morbidity and mortality in patients with or without cirrhosis. In recent years our understanding of etio-pathogenesis of portal vein obstruction has evolved tremendously, which has led to significant improvement in treatment outcomes. There are still areas where more studies are needed to better clarify the management issues of portal vein obstruction. [ABSTRACT FROM AUTHOR]

Background Serological markers such as anti-neutrophil cytoplasmic antibody ( ANCA) and anti- Saccharomyces cerevisiae antibody ( ASCA) may be associated with pouchitis after ileal pouch-anal anastomosis ( IPAA). Aim To perform a systematic review with meta-analysis of studies evaluating the association of ANCA and ASCA status with risk of acute and chronic pouchitis after IPAA. Methods We searched multiple databases (upto September 2012) for studies reporting ANCA and/or ASCA status along with risk of acute or chronic pouchitis after IPAA in adults with ulcerative colitis ( UC). We abstracted odds ratio ( OR) or raw data from the individual studies to calculate summary OR estimates with 95% CIs using random-effects model. Results Eight studies reporting 184 cases of acute pouchitis and six studies reporting 151 cases of chronic pouchitis were included. The odds of chronic pouchitis were 76% higher in ANCA-positive patients than ANCA-negative (six studies; OR: 1.76; 95% CI: 1.19-2.61; P < 0.01). ASCA-positivity was not associated with the risk of chronic pouchitis (three studies; OR: 0.89; 95% CI: 0.49-1.59; P = 0.68). Neither ANCA (eight studies; OR: 1.54; 95% CI: 0.79-3.02; P = 0.21) nor ASCA-positivity (two studies; OR: 1.28; 95% CI: 0.25-6.54; P = 0.77) were associated with the risk of acute pouchitis. Conclusions The risk of chronic pouchitis after IPAA is higher in ANCA-positive patients, but the risk of acute pouchitis is unaffected by ANCA status. ASCA status was not associated with the risk of acute or chronic pouchitis. This information may be used to counsel UC patients regarding their risk of pouchitis after IPAA. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2011; 34: 487-493 Summary Background Erosive oesophagitis appears to be more common in white vs. nonwhite patients with gastro-oesophageal reflux disease (GERD). Aim To evaluate the association between race and erosive oesophagitis healing in patients with GERD treated with once-daily proton pump inhibitors (PPIs). Methods Data from five double-blind trials of once-daily treatment with esomeprazole 40 mg vs. omeprazole 20 mg or lansoprazole 30 mg for erosive oesophagitis healing (evaluated at weeks 4 and 8 by endoscopy) were pooled and stratified by baseline race and Los Angeles (LA) severity grade. Multiple logistic regression models were fit with erosive oesophagitis healing (dependent variable) and race (independent variable), with adjustments for treatment, study, baseline LA grade, age, gender, BMI, Helicobacter pylori status, hiatal hernia and interactions of these factors with race. Results Of 11 027 patients, 91% were white. Nonwhite ( n = 978) and black ( n = 613) patients were less likely to have severe baseline erosive oesophagitis (LA grade C or D) than white patients [adjusted OR: 0.69 (95% CI, 0.61-0.79) and 0.67 (0.57-0.78), respectively; P < 0.0001]. At week 8, nonwhite and black patients had lower healing rates than white patients [OR: 0.75 (0.63-0.89) and 0.67 (0.54-0.83), respectively; P ≤ 0.001]. Greater odds of healing were associated with less severe baseline LA grade, increasing age, hiatal hernia, esomeprazole treatment (vs. lansoprazole or omeprazole) and lansoprazole treatment (vs. omeprazole) (all P ≤ 0.0009); no factor interacted significantly with race. Conclusions Nonwhite patients with GERD had less severe baseline erosive oesophagitis, but were less likely than white patients to have erosive oesophagitis healing after 8-week PPI therapy. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 105–112 Background Cirrhosis with arterial hypertension is not uncommon. Haemodynamic alterations in these patients and the effects of beta-blocker on hepatic venous pressure gradient (HVPG) and systemic haemodynamics have not been evaluated. Aims To compare the systemic haemodynamic alterations in hypertensive and normotensive cirrhotics, and to investigate the effects of propranolol on these parameters. Methods A retrospective analysis of consecutive hypertensive cirrhotic patients ( n = 33) who underwent haemodynamic assessment and paired HVPG measurement was done. Normotensive cirrhotics ( n = 50) served as controls. Results Hypertensive patients had a significantly higher heart rate, systemic (SVRI), and pulmonary vascular resistance. There was a significant reduction in mean arterial pressure (MAP) in the hypertensive cirrhotic group from 112 (107–130) mmHg to 95 (77–114) mmHg ( P < 0.01), but no change in the normotensives. SVRI remained the same in the hypertensive cirrhotic group, but it increased in the normotensives. There was no correlation between MAP reduction and HVPG reduction. Conclusions The frequency of HVPG response with propranolol treatment in hypertensive cirrhotics is similar to normotensive cirrhotics. Propranolol treatment reduces MAP significantly in hypertensive patients with cirrhosis. Treatment with a nonselective beta-blocker is a good strategy for hypertensive cirrhotic patients. [ABSTRACT FROM AUTHOR]

Background A beta-blocker is recommended for primary prophylaxis of variceal bleeding; however, only one-third have hepatic venous pressure gradient (HVPG) response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker and benefits of HVPG-guided ‘ a la carte’ approach remain unclear. Aim To determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of variceal bleeding using beta-blocker and ISMN. Patients and methods Consecutive patients of cirrhosis, with high-risk varices, with no previous variceal bleeding were included. After baseline HVPG, patients received incremental propranolol to achieve HR of 55/min. After one-month, HVPG was repeated to determine response (<12 mmHg or ≥20% reduction). ISMN was added in nonresponders and HVPG repeated. Patients were followed up for 24 months. Results Of 56 patients (age 47 ± 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta-blocker alone. Six additional patients responded to combination. Thus, overall 48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%) patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six (17%) with unknown response; P = N.S.]. The actuarial probability of variceal bleeding at median 24 months was 4% in responders and 22% in nonresponders ( P < 0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35 (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were grade IV varices and haemodynamic nonresponse. Conclusions For primary prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the response rate to about half of patients. The HVPG-guided ‘ a la carte’ approach may be considered for these patients. [ABSTRACT FROM AUTHOR]

Background Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole. Aim To assess the efficacy and safety of dexlansoprazole MR in healing erosive oesophagitis (EO). Methods Patients in two identical double-blind, randomized controlled trials ( n = 4092) received dexlansoprazole MR 60 or 90 mg or lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing procedure – first for non-inferiority, then superiority, vs. lansoprazole. Secondary endpoints included week 4 healing and week 8 healing in patients with moderate-to-severe disease (Los Angeles Classification grades C and D). Life-table and crude rate analyses were performed. Symptoms and tolerability were assessed. Results Dexlansoprazole MR achieved non-inferiority to lansoprazole, allowing testing for superiority. Using life-table analysis, dexlansoprazole MR healed 92–95% of patients in individual studies vs. 86–92% for lansoprazole; the differences were not statistically significant ( P > 0.025). Using crude rate analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies and 60 mg was superior in one study. Week 4 healing was >64% with all treatments in both studies. In an integrated analysis of 8-week healing in patients with moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All treatments effectively relieved symptoms and were well tolerated. Conclusion Dexlansoprazole MR is highly effective in healing EO and offers benefits over lansoprazole, particularly in moderate-to-severe disease. [ABSTRACT FROM AUTHOR]

The incidence of oesophageal adenocarcinoma continues to increase in the US and the Western world, with the 5-year survival rate for this cancer still being very dismal.The diagnosis of Barrett's metaplasia and dysplasia (i.e. screening and surveillance) currently requires endoscopy with biopsy of the abnormally appearing distal oesophagus. Surveillance endoscopy in patients with Barrett's oesophagus relies on the performance of random biopsies from the metaplastic segment, with the aim of identifying dysplasia and/or cancer. However, intestinal metaplasia and dysplasia are not uniformly distributed within the columnar-lined mucosa in the distal oesophagus, and the sensitivity of standard endoscopy with biopsy for the detection of these lesions is low.New techniques to improve the accuracy of endoscopic diagnosis, as well as to identify patients at high risk for neoplasia development, have recently been developed and most are currently being evaluated in clinical studies. The results with these techniques, although promising, are still preliminary. They hold promise for the improved detection of dysplasia and neoplasia at an early stage of development, with a greater chance for early treatment, and therefore a greater likelihood of either cure of adenocarcinoma or prevention of its development from dysplasia. [ABSTRACT FROM AUTHOR]

Barrett's oesophagus, a complication of chronic gastro-oesophageal reflux disease, is the premalignant lesion for oesophageal and gastro-oesophageal junction adenocarcinoma. Described in the 1950s by Norman Barrett, the diagnostic criterion for this lesion has evolved significantly over the last three decades. Endoscopic Barrett's oesophagus requires the recognition of columnar mucosa in the distal oesophagus; documentation of metaplastic tissue is confirmed by random biopsies. Given this changing definition of Barrett's metaplasia, the prevalence rates vary in the literature depending on the diagnostic criteria applied. However, it is generally accepted that approximately 10% of patients with chronic gastro-oesophageal reflux disease will be diagnosed with this condition. There are no population-based studies on the prevalence of Barrett's oesophagus, but emerging data indicate that it may be equally prevalent in asymptomatic individuals. These studies require confirmation. Although the incidence of oesophageal adenocarcinoma is increasing rapidly, it is unclear whether the true incidence of Barrett's oesophagus is increasing at the same time. On the other hand, metaplasia at the gastro-oesophageal junction appears to be distinct from Barrett's oesophagus, is probably not related to chronic gastro-oesophageal reflux disease and is a common finding if routine biopsies are obtained at the gastro-oesophageal junction. This article reviews our current understanding of the diagnosis, definition and prevalence of both of these lesions. [ABSTRACT FROM AUTHOR]

Despite implementation of screening and surveillance strategies, a significantly large number of patients with Barrett's oesophagus remain undiagnosed. In those who are identified, the management options include acid reduction therapies with proton pump inhibitors or anti-reflux surgery. Endoscopic ablative therapies have also been attempted. In addition to having inherent procedure-related risks with ablative therapies, these alternatives may be limited by high rates of failure, need for continued acid suppressive therapy, metaplasia persistence under otherwise normal appearing tissue, need for procedural expertise, and continued risk for adenocarcinoma development. Therefore, a widely applicable chemoprevention strategy that cost-effectively reduces the rate of progression from oesophagitis to adenocarcinoma in high-risk patients and perhaps those at lower rates of risk is highly desirable. The AspECT trial currently underway is seeking to determine the effects of high- and low-dose proton pump inhibitor therapy with and without low-dose aspirin as Barrett's oesophagus chemoprevention. [ABSTRACT FROM AUTHOR]

Summary A number of endoscopic techniques have been described for the treatment of reflux disease. These include endoscopic plicators, which place submucosal or transmural sutures around the lower oesophageal sphincter, the Stretta procedure, which places minute areas of thermal injury in the muscle of the lower oesophageal sphincter and cardia, and injection techniques, in which inert substances are injected into the mucosa or the muscle of the lower oesophagus. The mechanism of action of these procedures has been studied to varying degrees. The Stretta procedure is the only endoscopic technique that has been shown to be effective in a sham-controlled trial. Complication rates are generally low, but serious complications have been reported in some cases. The results with some of these techniques are promising, but all procedures described to date are limited by the absence of large, rigorously controlled trials against a form of treatment that has been proven to be both safe and effective (medical therapy). Future studies will need to use controls, validated outcome measures and pre-determined end-points and to provide comparative and long-term data. [ABSTRACT FROM AUTHOR]

Summary The falling prevalence of Helicobacter pylori infection and related diseases (peptic ulcer disease, gastric cancer) in developed countries has been paralleled by an increased recognition of gastro-oesophageal reflux and its complications. These epidemiological data do not support a role for H. pylori in the pathogenesis of reflux disease, but suggest a negative association with the increasing incidence of oesophageal diseases. This has led some investigators to propose a ‘protective’ role of H. pylori infection against the development of oesophageal diseases. In these patients, pre-existing lower oesophageal sphincter dysfunction, susceptibility to reflux, unmasking of latent reflux and the patterns and severity of gastritis are probably important factors contributing to the development of oesophageal diseases. The most likely mechanism by which H. pylori infection may protect against reflux is by decreasing the potency of the gastric refluxate in patients with corpus-predominant gastritis. The prevalence of H. pylori infection in patients with reflux disease is probably no greater than that in those without reflux, and there are conflicting data indicating that reflux symptoms or erosive oesophagitis develop after H. pylori eradication. It is also unclear whether H. pylori augments the antisecretory effects of proton pump inhibitors or accelerates the development of atrophic gastritis. [ABSTRACT FROM AUTHOR]

A response by P. Sharma and A. Kumar to a letter to the editor about their article "The propranolol therapy in cirrhotic patients" in the previous issue is presented.

A response from the authors of the article "portal vein obstruction - epidemiology, pathogenesis, natural history, prognosis and treatment" is presented.

A response by K. L. Goh and colleagues to their article "Erosive oesophagitis (EO) with particular reference to Asians," published in 2011 issue is presented.

Aliment Pharmacol Ther 31, 1268–1275 Background Treatment of refractory or recurrent benign oesophageal strictures is demanding and surgery may be the only available option. The role of self-expanding plastic stents (SEPS) in the treatment of these strictures is still controversial because of the conflicting results of various studies. Aim To analyse with regard to SEPS: technical and clinical success, factors associated with outcome, and safety . Methods Pooled-data analysis of a systematic review of the literature. Clinical success was defined as no need for further endoscopic or surgical treatment after SEPS removal. Results Data of 10 studies with 130 treated patients were included. SEPS insertion was technically successful in 128 of 130 patients (98%, 95% CI = 96–100%). Clinical success was achieved in 68 patients (52%, 95% CI = 44–61%) and this was found to be lower in those with a cervical localization of the stricture (33% vs . 54%; P < 0.05). Early (<4 weeks) migration of the stent was reported in 19 (24%, 95% CI = 14–32%) cases, while post-insertion endoscopic re-intervention was required in 25 (21%, 95% CI = 14–28%). Major clinical complications occurred in 12 patients (9%, 95% CI = 4–14%), resulting in death of one (0.8%) patient. Conclusions Our pooled-data analysis showed a favourable risk/benefit ratio when SEPS are applied in patients with recurrent or refractory benign oesophageal strictures. This supports the use of SEPS before referring patients to surgery, and they are a valuable alternative to repeat endoscopic dilation. [ABSTRACT FROM AUTHOR]

Background Mechanisms of symptom perception among patients with gastro-oesophageal reflux disease (GERD) remain to be fully elucidated. Aim To correlate quantitative reflux symptom scores with microscopic oesophageal histopathology. Methods Prior to endoscopy, patients with reflux symptoms completed a validated reflux disease questionnaire (score 0-36). Erosive oesophagitis (EO) was graded using the LA classification. Oesophageal biopsies were graded 0-2 for basal cell hyperplasia, papillary elongation, dilated intercellular spaces (DIS), necrosis or erosion, eosinophils and neutrophils by a blinded gastrointestinal pathologist as previously described. Additionally, lymphocyte density was also evaluated. Pearson's correlation coefficients were computed. Results Thirty-two EO and 21 non-erosive reflux disease (NERD) patients were prospectively enrolled. For EO vs. NERD, mean reflux symptom scores (10.7 vs. 8.8, P = 0.35) and histology scores were similar (4.29 vs. 4.25; P = 0.9). However, when symptom scores were compared with histology scores, a correlation was found in the EO group, but not in the NERD group (r = 0.34, P = 0.05 vs. r = 0.22, P = 0.36). On further analysis, DIS was associated with symptom scores in the EO group (P ≤ 0.001), but not in the NERD group (P = N.S.). Similarly, lymphocyte density was associated with symptom scores in the EO group (r = 0.56, P = 0.0009), but not in the NERD group (r = 0.002, P = 0.9). Conclusions Although mean symptom and histology scores were similar in the EO and NERD groups, a significant correlation of symptom scores with histology scores, DIS and lymphocytes was found in the former, but not in the latter. EO and NERD patients may have different symptom perception mechanisms and thus, dissimilar symptom resolution rates with acid suppression. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 1266–1274 Summary: Background  Factors associated with non‐erosive reflux disease (NERD) and erosive oesophagitis (EO) are incompletely understood and the overlap between the two entities is debated. Aim  To compare clinical, demographic, and endoscopic findings in a large cohort of NERD and EO patients. Methods  After they completed a validated GERD questionnaire, patients who presented for index endoscopy were enrolled and categorized as NERD or EO. Analysis was performed using Chi‐square, Mann–Whitney U‐test and multivariate logistic regression. Results  A total of 696 GERD patients [455 (65.4%) NERD; 241 (34.6%) EO]; mean age 57 years; 92% men and 82% Caucasian were prospectively enrolled. Using logistic regression, patients on PPI were more likely to be classified as NERD (OR: 3.2; P < 0.001). NERD patients were older (OR: 1.50; P = 0.05), less likely to have nocturnal symptoms (OR: 0.63; P = 0.04) and hiatal hernia (OR: 0.32; P < 0.001). Compared with PPI‐naïve NERD patients, those on PPI were more likely to have nocturnal symptoms (69% vs. 29%, P = 0.048) and less likely to have mild‐moderate symptoms (63% vs. 79%, P < 0.001) – similar to the EO group. Conclusions  Pre‐endoscopy PPI usage contributes significantly to the classification of GERD patients into the NERD‐phenotype. NERD patients on PPI therapy demonstrate some features that are significantly different from PPI‐naïve patients, but similar to EO patients. This observation supports the notion that some PPI NERD patients are actually healed EO patients, and that an overlap does exist between the GERD phenotypes. [ABSTRACT FROM AUTHOR]

Background : Barrett's oesophagus patients may continue to have abnormal oesophageal acid exposure on proton pump inhibitor therapy. The effect of factors such as Barrett's oesophagus length, hiatal hernia size and Helicobacter pylori infection on intra-oesophageal pH in Barrett's oesophagus patients has not been adequately studied. Aim : To evaluate oesophageal acid exposure in a large Barrett's oesophagus population on b.d. proton pump inhibitor therapy and determine clinical factors predicting normalization of intra-oesophageal pH on therapy. Methods : Barrett's oesophagus patients were studied using 24 h pH monitoring to evaluate intra-oesophageal acid suppression on b.d. dosing of rabeprazole. Results : Forty-six Barrett's oesophagus patients completed the study. Median total percentage time pH < 4 was 1.05% (range: 0–29.9%) in the entire group and respective values for upright and supine percentage time pH < 4 were 1.15% and 0%. However, 34 of the Barrett's oesophagus patients (73.9%) had a normal pH study (median total percentage time pH < 4: 0.2%) and 12 patients (26.1%) had an abnormal result (median total percentage time pH < 4: 9.3%). There were no significant differences between patients with a normal and abnormal 24 h pH result with respect to age, Barrett's oesophagus length, hiatal hernia size and presence of H. pylori infection. Conclusions : Approximately 25% of Barrett's oesophagus patients continue to have abnormal total intra-oesophageal pH profiles despite b.d. proton pump inhibitor therapy. Factors such as age, Barrett's oesophagus length and hiatal hernia size cannot be used to predict persistent abnormal intra-oesophageal pH on proton pump inhibitor. [ABSTRACT FROM AUTHOR]

The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may progress to the development of ulcers, strictures and GI bleeding. Pharmacological treatment with proton pump inhibitors is favoured over that with H2-receptor antagonists for the treatment of strictures. The treatment of strictures is accomplished with dilation and many favour the concomitant use of proton pump inhibitors. Most gastroenterologists are seeing far fewer oesophageal strictures these days since the introduction of proton pump inhibitors. In addition, research has shown that oesophageal complications have a greater impact on patients suffering from night-time GERD than on those suffering from daytime GERD. Barrett's oesophagus is a significant complication associated with persistent GERD and those at risk generally experience a longer duration of symptoms, especially those with a high degree of severity. In addition, there is a strong relationship between Barrett's oesophagus and oesophageal adenocarcinoma. This is in part due to the association of obesity and the development of hiatal hernias. Furthermore, endoscopic screening is being used to detect Barrett's oesophagus and oesophageal adenocarcinoma in persons suffering from chronic GERD, even though screening may not have an impact on outcomes (Sharma P, McQuaid K, Dent J,et al.A critical review of the diagnosis and management of Barrett's esophagus: The AGA Chicago Workshop. Gastroenterology 2004; 127: 310–30.). [ABSTRACT FROM AUTHOR]