bluuebunny/crossref_metadata_2025 huggingface dataset:
The best candidates for transarterial chemotherapy in patients with hepatocellular carcinoma awaiting liver transplantation: a cohort‐based characterization of dropout times
Authors: JANG J. W. , CHOI J. Y. , BAE S. H. , KIM C. W. , CHO S. H. , YOON S. K. , YANG J. M. , HAN J. Y. , LEE Y. S. , KIM D. G.
Published: July 2010

Background Although transarterial chemotherapy is used to retard tumour progression for hepatocellular carcinoma (HCC) patients awaiting orthotopic liver transplantation (OLT), information regarding the acceptable waiting time and appropriate patient selection for the therapy is lacking.

Aim To examine dropout times and determine the best candidates for pre‐transplant transarterial therapy in a cohort study.

Methods In total, 180 consecutive HCC candidates receiving pre‐transplant chemo‐lipiodolization were included in the study.

Results Overall, 70 (38.9%) patients dropped off the waiting list during the median follow‐up of 19 months. According to the Child–Pugh (C–P) classification, the estimated dropout rates at 1 and 2 years were 17.2% and 44.8% for the C–P A group and 33.4% and 81.3% for the C–P B/C group, respectively. C–P B/C patients experienced more frequent dropouts than C–P A patients (P < 0.001). Risk factor analysis identified C–P classification to be the strongest predictor of dropout (P < 0.001). On multivariate analysis, alpha‐fetoprotein (AFP) >100 ng/mL, tumour size >3 cm and multiple nodules remained independently predictive of dropout for C–P A group (all P < 0.05). Candidates with none of these factors were found to be at the lowest risk of dropout, with only a 22.5% dropout rate up to 41 months.

Conclusions This study suggests that Child–Pugh A patients with one nodule <3 cm and AFP < 100 ng/mL may be the best candidates for pre‐transplant chemo‐lipiodolization, with the lowest dropout rate. However, comparative studies with other therapeutic options are needed to assess the definitive role of transarterial therapy in this setting.
Efficacy of rabeprazole on heartburn symptom resolution in patients with non‐erosive and erosive gastro‐oesophageal reflux disease: a multicenter study from Japan
Authors: MIWA H. , SASAKI M. , FURUTA T. , KOIKE T. , HABU Y. , ITO M. , FUJIWARA Y. , WADA T. , NAGAHARA A. , HONGO M. , CHIBA T. , KINOSHITA Y. ,   THE ACID‐RELATED SYMPTOM (ARS) RESEARCH GROUP
Published: July 2010

Background  Few studies have compared the efficacy of proton pump inhibitors in resolving the symptoms of non‐erosive reflux disease (NERD) and of erosive gastro‐oesophageal reflux disease (GERD) in Japan.

Aim  To investigate and compare the efficacy of 4‐week course of rabeprazole 10 mg/day on symptom resolution in NERD and erosive GERD in Japan.

Methods  The modified Los Angeles classification was used to grade endoscopically GERD in patients with heartburn (Grades N and M: NERD, Grades A and B: mild reflux oesophagitis (RO), and Grades C and D: severe RO). Rabeprazole 10 mg/day was administered for 4 weeks to 180 patients who kept symptom diaries.

Results  Complete relief of the symptoms was achieved in 35.8% of the NERD group and 55.4% of the erosive GERD group (mild RO: 51.1% and severe RO: 77.8%). Rabeprazole was significantly more effective in erosive GERD than in NERD patients. Among the NERD subgroups (Grades N and M), no difference in symptom improvement was observed.

Conclusions  Four‐week, rabeprazole 10 mg/day acid suppression therapy was effective in resolving symptoms in Japanese GERD patients. This therapy was more effective in erosive GERD than in NERD patients, and in those with severe RO than in those with mild RO.
Enbucrilate for gastric varices: extended experience in 92 patients
Authors: CALDWELL S. H. , HESPENHEIDE E. E. , GREENWALD B. D. , NORTHUP P. G. , PATRIE J. T.
Published: July 2010

Aim We assessed N‐2‐butyl‐cyanoacrylate (enbucrilate) in 92 patients with gastric variceal bleeding under an FDA‐approved investigation. These results extend our prior report of the first 44 patients.

Method Injection was performed with enbucrilate and ethiodol (1:1). Eighty patients had portal hypertension and 12 had splenic vein thrombosis.

Results In the portal hypertensive group, re‐bleeding from gastric varices was seen in 4 of 80 (5%) from 0 to 72 h, 5 of 76 (6.5%) from > 72 h to 3 months and 9 of 51 (17%) from > 3 months to 1 year. Re‐bleeding and survival were significantly related to the Child‐Pugh class. In the splenic vein thrombosis group (n = 12), there was early rebleeding in 2 (17%) patients from 0 to 72 h, 1 (8%) from > 72 h to 3 months and none in the chronic phase (> 3 months to 1 year) although 1‐year survival in this group was only 6 (50%) due to the underlying malignancy in most. Serious embolization was suspected in 2 patients (2%).

Conclusion Enbucrilate offers an important intervention in gastric variceal bleeding which should be further studied in the US. A randomized trial is warranted to compare this intervention to radiological therapy.
Effect of a fermented milk containing Bifidobacterium animalis DN‐173 010 on the health‐related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double‐blind, controlled trial
Authors: GUYONNET D. , CHASSANY O. , DUCROTTE P. , PICARD C. , MOURET M. , MERCIER C.‐H. , MATUCHANSKY C.
Published: July 2010

Background  Health‐related quality of life (HRQoL) has been rarely evaluated as a primary endpoint in the assessment of the effect of probiotics on the irritable bowel syndrome (IBS).

Aim  To study the effects of fermented milk containing Bifidobacterium animalis DN‐173 010 and yoghurt strains on the IBS in a multicentre, double‐blind, controlled trial.

Methods  A total of 274 primary care adults with constipation‐predominant IBS (Rome II) were randomized to consume for 6 weeks either the test fermented milk or a heat‐treated yoghurt (control). HRQoL and digestive symptoms were assessed after 3 and 6 weeks on an intention‐to‐treat population of 267 subjects.

Results  The HRQoL discomfort score, the primary endpoint, improved (P < 0.001) in both groups at weeks 3 and 6. The responder rate for the HRQoL discomfort score was higher (65.2 vs. 47.7%, P < 0.005), as was the decrease in bloating score [0.56 ± (s.d.)1.01 vs. 0.31 ± 0.87, P = 0.03], at week 3 in the test vs. the control group. In those subjects with <3 stools/week, stool frequency increased (P < 0.001) over 6 weeks in the test vs. control group.

Conclusions  This study suggests a beneficial effect of a probiotic food on discomfort HRQoL score and bloating in constipation‐predominant IBS, and on stool frequency in subjects with <3 stools/week.
Cost‐effectiveness of suppressing hepatitis B virus DNA in immune tolerant patients to prevent hepatocellular carcinoma and cirrhosis
Authors: ENRIQUEZ A. D. , CAMPBELL M. S. , REDDY K. R.
Published: July 2010

Background  For patients with hepatitis B virus (HBV) infection in the immune tolerant phase, the current standard of care is to not offer treatment. However, the recent Risk Evaluation of the Viral Load Elevation and Associated Liver Disease/Cancer‐In study results show a striking relationship between high HBV DNA levels and risk for hepatocellular carcinoma and cirrhosis.

Aim  In a cost effectiveness analysis, to assess whether immune tolerant patients with high HBV DNA levels should undergo treatment.

Methods  We created a lifetime Markov model to evaluate the cost‐effectiveness of two strategies for immune tolerant hepatitis B: (i) HBV DNA suppression with lamivudine, (ii) no treatment. Patients cycled between the following health states: viral suppression, ongoing viremia, seroconversion, hepatocellular carcinoma, cirrhosis and death.

Results  Compared with the no treatment strategy, lamivudine therapy was more expensive but more cost‐effective with an additional cost of $5784 and $12 584 per quality adjusted life year gained in males and females, respectively. Treatment resulted in a gain in life expectancy and a decrease in lifetime risk of hepatocellular carcinoma and cirrhosis.

Conclusions  Suppressing HBV DNA to prevent hepatocellular carcinoma and cirrhosis in immune tolerant patients is very cost‐effective, and treatment of these patients may be considered. Future prospective clinical trials will need to be undertaken to confirm our findings.
Low serum HBV DNA levels and development of hepatocellular carcinoma in patients with chronic hepatitis B: a case–control study
Authors: FUNG J. , YUEN M.‐F. , YUEN J. C.‐H. , WONG D. K.‐H. , LAI C.‐L.
Published: July 2010

Aim

To investigate the level of hepatitis B virus (HBV) DNA in Chinese chronic hepatitis B (CHB) patients below which hepatocellular carcinoma (HCC) is unlikely to occur.

Methods  A total of 92 CHB patients diagnosed with HCC were recruited; 184 CHB patients without HCC, matched for age, sex and HBeAg status were included as controls. HBV DNA levels were performed at the time of HCC development and at the same age time points for control group.

Results  The median HBV DNA level in HCC patients was 1.7 × 106 copies/mL compared with 2.2 × 105 copies/mL in controls (P = 0.006). In HCC patients, 21 (22.8%) were HBeAg(+), with no significant difference in HBV DNA levels compared with controls. Seventy‐one (77%) HCC patients were HBeAg(−) with median HBV DNA level of 3.2 × 105 copies/mL, compared with 6.0 × 104 copies/mL in controls (P = 0.006). In HBeAg(−) patients, the control group had significantly greater proportion of patients having HBV DNA levels <105 and <104 copies/mL compared with HCC patients. Fifteen per cent of all HCC patients had HBV DNA levels <103 copies/mL.

Conclusions  In HBeAg(+) patients, HBV DNA levels were high in both HCC and control patients. In HBeAg(−) patients, HCC was more likely to develop in patients with HBV DNA level >104 copies/mL. However, 15% of the patients with HCC had HBV DNA levels <103 copies/mL.
Oesophageal hypersensitivity is associated with features of psychiatric disorders and the irritable bowel syndrome
Authors: RUBENSTEIN J. H. , NOJKOV B. , KORSNES S. , ADLIS S. A. , SHAW M. J. , WEINMAN B. , INADOMI J. M. , SAAD R. , CHEY W. D.
Published: July 2010

Background Twenty per cent of patients with heartburn do not respond to proton pump inhibitors (PPIs). Many have normal oesophageal acid exposure. We hypothesized that such PPI non‐responders have heightened oesophageal sensation, and that oesophageal hypersensitivity is associated with psychiatric features including somatization and anxiety.

Aim To compare oesophageal sensation in subjects with heartburn categorized by response to PPI, and to correlate oesophageal sensation with psychiatric features.

Methods Twenty‐one PPI responders, nine PPI non‐responders and 20 healthy volunteers completed questionnaires of psychiatric disorders and gastrointestinal symptoms. Subjects underwent oesophageal sensory testing with acid perfusion and balloon distension.

Results Healthy volunteers displayed higher thresholds for sensation and discomfort from balloon distension than heartburn subjects (sensation P = 0.04, discomfort P = 0.14). Psychiatric disorders were associated with increased intensity of sensation (P = 0.02) and discomfort from acid (P = 0.01). Somatization was associated with increased discomfort from balloon distension (P = 0.006). Features of irritable bowel syndrome were associated with increased sensation and discomfort.

Conclusions Heartburn subjects tend to have heightened oesophageal sensation, suggesting that oesophageal hypersensitivity may persist despite therapy with PPI. Oesophageal hypersensitivity is associated with features of psychiatric disease and with the irritable bowel syndrome, which might partly explain the aetiology of heartburn symptoms that are refractory to PPI.
The view of gastroenterologists on non‐cardiac chest pain in Asia
Authors: CHEUNG T. K. , LIM P. W. Y. , WONG B. C. Y.
Published: July 2010

Background  Non‐cardiac chest pain is an important disorder in Asia. The practice and views of gastroenterologists on non‐cardiac chest pain in this region are not known.

Aims  To determine the current understanding, diagnostic practice and treatment strategies among gastroenterologists on the management of non‐cardiac chest pain in Asia.

Methods  A 24‐item questionnaire was sent to gastroenterologists in Mainland China, Hong Kong, Malaysia, Indonesia, Philippines, Singapore, Taiwan and Thailand.

Results  186 gastroenterologists participated with a response rate of 74%. 98% of gastroenterologists managed patients with non‐cardiac chest pain over the last 6 months. 64% felt that the number of non‐cardiac chest pain patients was increasing and 85% believed that the most common cause of non‐cardiac chest pain was GERD. 94% of the gastroenterologists believed that they should manage non‐cardiac chest pain patients, but only 41% were comfortable in diagnosing non‐cardiac chest pain. The average number of investigations performed was four in non‐cardiac chest pain patients, and oesophago‐gastro‐duodenoscopy was the most commonly used initial test. A proton pump inhibitor was considered the first‐line treatment in non‐cardiac chest pain and was reported as the most effective treatment by the gastroenterologists.

Conclusion  Most gastroenterologists were practicing evidence‐based medicine, but frequent use of investigations and a lack of awareness of the role of visceral hypersensitivity in non‐cardiac chest pain patients were noted.
Review article: bowel preparation for colonoscopy – the importance of adequate hydration
Authors: LICHTENSTEIN G. R. , COHEN L. B. , URIBARRI J.
Published: July 2010

Background

Patient compliance with screening recommendations for colorectal cancer remains low, despite a 90% survival rate achieved with early detection. Bowel preparation is a major deterrent for patients undergoing screening colonoscopy. More than half of patients taking polyethylene glycol electrolyte lavage solution and sodium phosphate preparations experience adverse events, such as nausea and abdominal pain. Many adverse events may be associated with dehydration, including rare reports of renal toxicity in patients taking sodium phosphate products. Addressing dehydration‐related safety issues through patient screening and education may improve acceptance of bowel preparations, promote compliance and increase the likelihood of a successful procedure.

Aim

To evidence safety issues associated with bowel preparation are generally related to inadequate hydration.

Results

Dehydration‐related complications may be avoided through proper patient screening, for example, renal function and comorbid conditions should be considered when choosing an appropriate bowel preparation. In addition, patient education regarding the importance of maintaining adequate hydration before, during and after bowel preparation may promote compliance with fluid volume recommendations and reduce the risk of dehydration‐related adverse events.

Conclusions

Proper patient screening and rigorous attention by patients and healthcare providers to hydration during bowel preparation may provide a safer, more effective screening colonoscopy.
Randomized‐controlled trial of esomeprazole in functional dyspepsia patients with epigastric pain or burning: does a 1‐week trial of acid suppression predict symptom response?
Authors: TALLEY N. J , VAKIL N. , LAURITSEN K. , VAN ZANTEN S. V. , FLOOK N. , BOLLING‐STERNEVALD E. , PERSSON T. , BJÖRCK E. , LIND T. ,   ON BEHALF OF THE STARS I STUDY GROUP
Published: July 2010

Background

Early identification of true responders to acid suppression in functional dyspepsia patients with symptoms of epigastric pain or burning may enable clinicians to optimally tailor treatment.

Aim

To evaluate whether a 1‐w acid suppression trial is useful for identifying true responders in this population.

Methods

Patients (18–70 years) were randomized to either esomeprazole 40 mg q.d.s., b.d. or placebo for 1w, and then esomeprazole 40 mg q.d.s. or placebo for 7w. Epigastric pain and/or burning were recorded on a 4‐point scale (0 = none, 3 = severe). Trial‐week response was defined as symptom score sum ≤1 on last 3d of therapy; response at 8w was symptom score sum ≤1 over preceding 7d.

Results

1‐w response rates were 33% (199 of 597), 29% (188 of 629) and 23% (71 of 315) with esomeprazole q.d.s., esomeprazole b.d. and placebo, respectively (P = 0.002 for esomeprazole groups vs. placebo). At 8w, trial week sensitivity and specificity were 46% and 80%, respectively, for esomeprazole (40 or 80 mg), and 33% and 87%, respectively, for placebo. The positive and negative predictive values for esomeprazole were 60% and 69%.

Conclusion

Response to a 1‐w acid suppression trial is of limited use for predicting symptom response at 8w in patients with unexplained epigastric pain or burning.
Meta‐analysis: the utility and safety of heparin in the treatment of active ulcerative colitis
Authors: SHEN J. , RAN Z. H. , TONG J. L. , XIAO S. D.
Published: July 2010

Background

The use of heparin for the treatment of ulcerative colitis has been evaluated in several open and controlled trials, with varying outcomes.

Aim

To evaluate the efficacy and safety of heparin as supplemental therapy compared with conventional therapy in patients with ulcerative colitis.

Methods

All randomized trials comparing heparin supplementation to conventional therapy were included from electronic databases. Statistical analysis was performed with review manager 4.2.8 (The Cochrane Collaboration, Oxford, UK). Sub‐analysis and sensitivity analysis were also performed.

Results

Eight randomized‐controlled trials, investigating a total of 454 participants, met the inclusion criteria. The odds ratio (OR) for the efficacy of heparin supplementation vs. conventional therapy was 0.78 (95% CI = 0.50–1.21). Few serious adverse events were observed. The OR for the efficacy of unfractionated heparin and low‐molecular‐weight heparin vs. conventional therapy was 0.26 (95% CI = 0.07–0.93) and 0.92 (95% CI = 0.57–1.47), respectively. The OR for the efficacy of heparin vs. conventional therapy with placebo was 0.87 (95% CI = 0.53–1.44).

Conclusions

Our meta‐analysis suggests that administration of heparin in patients with ulcerative colitis is safe, but no additive benefit over conventional therapy is indicated.
Histological progression of non‐alcoholic fatty liver disease: a critical reassessment based on liver sampling variability
Authors: RATZIU V. , BUGIANESI E. , DIXON J. , FASSIO E. , EKSTEDT M. , CHARLOTTE F. , KECHAGIAS S. , POYNARD T. , OLSSON R.
Published: July 2010

Background

In non‐alcoholic fatty liver disease, histological lesions display a significant sampling variability that is ignored when interpreting histological progression during natural history or therapeutic interventions.

Aim

To provide a method taking into account sampling variability when interpreting crude histological data, and to investigate how this alters the conclusions of available studies.

Methods

Natural history studies detailing histological progression and therapeutic trials were compared with the results of a previously published sampling variability study.

Results

Natural history studies showed an improvement in steatosis, which was significantly higher than expected from sampling variability (47% vs. 8%, P < 0.0001). In contrast, no study showed a change in activity grade or ballooning higher than that of sampling variability. There was only a marginal effect on fibrosis with no convincing demonstration of a worsening of fibrosis, a conclusion contrary to what individual studies have claimed. Some insulin sensitizing drugs and anti‐obesity surgery significantly improved steatosis, while most did not significantly impact on fibrosis or activity.

Conclusions

Sampling variability of liver biopsy is an overlooked confounding factor that should be considered systematically when interpreting histological progression in patients with non‐alcoholic fatty liver disease.
Heterozygosity for IL23R p.Arg381Gln confers a protective effect not only against Crohn’s disease but also ulcerative colitis
Authors: BÜNING C. , SCHMIDT H. H.‐J. , MOLNAR T. , DE JONG D. J , FIEDLER T. , BÜHNER S. , STURM A. , BAUMGART D. C. , NAGY F. , LONOVICS J. , DRENTH J. P. H. , LANDT O. , NICKEL R. , BÜTTNER J. , LOCHS H. , WITT H.
Published: July 2010

Background  A recent study reported that a non‐synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease.

Aim  To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour.

Methods  We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn’s disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics.

Results  The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes.

Conclusions  The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.
Review article: increasing the dose of oral mesalazine therapy for active ulcerative colitis does not improve remission rates
Authors: SAFDI A. V. , COHEN R. D.
Published: July 2010

Background  Oral mesalazine (mesalamine, 5‐aminosalicylic acid) formulations are effective in the treatment of active ulcerative colitis. All formulations contain the same active drug but differ with regard to mechanisms to deliver the drug to the colon. Patients who fail to respond to initial therapy are often administered higher doses of the same formulation.

Aim  To review published trials of oral mesalazine formulations in treating active ulcerative colitis and to examine the effect of dose escalation on remission rates.

Results  Increasing the doses of oral mesalazine formulations does not result in higher remission rates, although increasing the doses of some formulations has been effective in increasing symptomatic improvement and/or response to treatment.

Conclusions  Because oral mesalazine formulations do not demonstrate a significant dose response with regard to induction of remission of active ulcerative colitis, simple dose escalation may not be the most effective course for patients who fail to respond to initial mesalazine treatment.
Review article: Helicobacter pylori eradication for the prevention of gastric cancer
Authors: DE VRIES A. C. , KUIPERS E. J.
Published: July 2010

Background  Gastric cancer is the fourth most common cancer and second leading cause of cancer‐related death worldwide. A clear association between Helicobacter pylori infection and gastric cancer was established years ago. H. pylori eradication may be an effective approach to decrease morbidity and mortality of gastric cancer.

Aim  To discuss current evidence of H. pylori eradication for prevention of gastric cancer.

Results  Recent studies have shown that the association between H. pylori and gastric cancer has probably been underestimated. This may have resulted from negative H. pylori status in subjects after loss of colonisation in the presence of atrophic gastritis and intestinal metaplasia, prior to development of gastric cancer. The recognition of the central role of H. pylori in carcinogenesis has increased expectations of gastric cancer prevention by H. pylori eradication. A primary preventive effect of eradication in subjects with H. pylori‐induced gastritis has been demonstrated. However, a secondary preventive effect in patients with pre‐malignant gastric lesions is still controversial, especially in patients with intestinal metaplasia and dysplasia.

Conclusions  At this moment, H. pylori eradication seems indicated at the earliest stage of gastric carcinogenesis. This treatment policy requires confirmation; results of ongoing randomised controlled trials are therefore eagerly awaited.
Review article: multimodality treatment of liver metastases increases suitability for surgical treatment
Authors: DE JONG K. P.
Published: July 2010

Background  Liver metastases of colorectal cancer occur frequently, but only 10–20% are eligible for liver surgery. Recent new developments changed the concepts of treating patients with colorectal liver metastases.

Aim  To describe the available modalities that can result in increasing resectability rate.

Methods  Potentials and drawbacks of portal vein embolization, radiofrequency ablation (RFA), trans‐ablated tumour hepatectomy, neoadjuvant chemotherapy and the approach to patients with extrahepatic metastases are described.

Results  Portal vein embolization is a well‐established technique to increase the volume of the future liver remnant. RFA should be applied if partial liver resection alone cannot make the liver tumour‐free. Neoadjuvant chemotherapy in patients with unresectable liver metastases can result in secondary resectability rates of 15–40%. Hepatotoxicity can lead to a higher complication rate after partial liver resection. A limited number of extrahepatic tumour localizations should be resected as well.

Conclusions  A more aggressive approach to patients with colorectal liver metastases improves resectability rate and survival. Unfortunately, these new options have not been thoroughly evaluated in randomized controlled trials. For some of these modalities, the currently available results are so promising that it might be difficult to start such trials in the future.
Review article: surgical management of chronic pancreatitis
Authors: VAN DER GAAG N. A. , GOUMA D. J. , VAN GULIK T. M. , BUSCH O. R. C. , BOERMEESTER M. A.
Published: July 2010

Background  The therapeutic approach to patients with chronic pancreatitis (CP) is complicated by the fact that patients are presented to the physician at different stages of disease and in the presence of varying clinical symptoms. Generally, an expectant approach is justified for patients with asymptomatic CP. At present, patients with symptoms related to gland destruction are initially treated by endoscopic means, while surgical treatment of CP is usually reserved for intractable abdominal pain, suspicion of cancer, and complications such as persistent pseudocysts.

Aim  To review the studies currently available evaluating surgical and/or endoscopic management of CP.

Results  Improvements in imaging techniques, as well as a better understanding of the pathophysiology of CP and mechanisms causing pain, have led to a more conscious selection of patients for surgery. Type of surgery depends on whether the pancreatic duct is dilated, presence of an inflammatory mass and occurrence of complications (pseudocysts, gastric outlet obstruction). Eventually, after initial endoscopic treatment, a substantial number of patients still need surgery for persistent complaints.

Conclusions  For patients with symptomatic CP, a multidisciplinary approach is indicated with low threshold to surgical intervention, since long‐term pain relief is accomplished more often after surgical treatment than after endoscopic treatment.
Review article: translumenal endoscopic debridement of organized pancreatic necrosis – the first step towards natural orifice translumenal endoscopic surgery
Authors: VOERMANS R. P. , BRUNO M. J. , VAN BERGE HENEGOUWEN M. I. , FOCKENS P.
Published: July 2010

Background  Over the last decades, gastrointestinal endoscopy has transformed from serving purely diagnostic purposes to therapeutic applications. One recent major progress is taking the endoscope beyond the gastrointestinal lumen into the peritoneal cavity for diagnostic and therapeutic procedures. The first step towards Natural Orifice Translumenal Endoscopic Surgery (NOTES) was translumenal endoscopic debridement of pancreatic necrosis.

Aim  To overview current status of endoscopic debridement of organized pancreatic necrosis. Finally, we take a short look into the potential future of translumenal endoscopic procedures.

Methods  Medical databases were searched for relevant publications, dealing with endoscopic debridement of pancreatic necrosis and NOTES.

Results  All current published studies concerning endoscopic debridement of organized pancreatic necrosis were retrospectivally performed and relatively small (largest n = 25). Succes rates varies from 80–93% and complication rates from 7–20%. There was no procedure related mortality reported. Published NOTES experiments showed feasibilty of a variety of transgastric, transcolonic and transvaginal procedures in the porcine model.

Conclusion  Endoscopic debridement seems to be an effective and relatively safe minimally invasive therapy in patients with symptomatic organized pancreatic necrosis and is the first step towards NOTES. Further comparative studies need to define its definitive role in the management of these patients.
Review article: management of diverticulitis
Authors: SZOJDA M. M. , CUESTA M. A. , MULDER C. M. , FELT‐BERSMA R. J. F.
Published: July 2010

Background and Aim  The incidence and therefore complications of (sigmoid) diverticular disease are increasing.

Methods  Review of current literature.

Results  From all patients, 15% will develop diverticulitis, 5% complications and 5% diverticular bleeding. Diagnosis is established with computerised tomography. Colonoscopy is needed to rule out malignancy. NSAIDs increase the risk of perforation; steroids, diabetes, collagen vascular disease and immune compromised are associated with complicated disease and death. In mild diverticulitis, antibiotics are recommended. In complicated disease with abscesses, <5 cm antibiotics are sufficient. Larger abscesses are drained under computerised tomography‐guidance. Peritonitis forms an indication for surgery. Diverticulitis recurrence rate is around 30%, most are uncomplicated. Recurrence after surgery is around 10%. Elective surgery is reserved for fistula closure and obstruction. The need for elective surgery to prevent recurrence has diminished because of new insights. Important is to identify risk groups. New issues are the possible relationship between diverticulitis and cancer, segmental colitis associated with diverticulitis, and treatment of diverticulitis with mesalazine and probiotics.

Conclusions  Uncomplicated diverticulitis is treated medically. Complicated diverticulitis with small abscesses is treated with antibiotics while larger abscesses are drained with computerised tomography‐guided puncture. Emergency surgery is reserved for peritonitis, elective surgery for fistula/stenosis. Surgery to prevent recurrence is indicated only in selected cases (e.g. immune compromised).
Alpha fetoprotein, ultrasound, computerized tomography and magnetic resonance imaging for detection of hepatocellular carcinoma in patients with advanced cirrhosis
Authors: SNOWBERGER N. , CHINNAKOTLA S. , LEPE R. M. , PEATTIE J. , GOLDSTEIN R. , KLINTMALM G. B. , DAVIS G. L.
Published: July 2010

Background  Serum alpha fetoprotein (AFP), ultrasound, computerized tomography scanning, and magnetic resonance imaging are commonly used to screen for hepatocellular carcinoma (HCC) in patients with cirrhosis.

Aim  To assess the accuracy of screening in advanced cirrhosis.

Methods  The study group consisted of 239 patients with proven HCC in the explanted liver at the time of liver transplant. AFP and imaging were done at referral and serially until transplant.

Results  Hepatocellular carcinoma was detected before liver transplant in 78% and discovered incidentally in 22%. The cause of cirrhosis was hepatitis C (HCV) (55%), hepatitis B (HBV) (17%), alcohol (9%), and other/unknown (19%). Although AFP was elevated 62%, the median level was 15 ng/mL. Only 26%, 15% and 13% were more than 100, 400 and 1000 ng/mL, respectively. By comparison, AFP was elevated in 20% without HCC, but exceeded 100 ng/mL in only 3%. The overall accuracy of AFP was poor regardless of the cutoff. Magnetic resonance imaging was more accurate than computerized tomography or ultrasound in detecting tumour, particularly when performed within 3 months of transplant.

Conclusions  Magnetic resonance imaging is most sensitive for imaging HCC and best reflects actual tumour size. AFP is insensitive and adds little to screening strategies, but has prognostic value when extremely elevated.
Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease
Authors: WEKSLER B. B.
Published: July 2010

Background  The pathophystology of thrombocytopenia in patients with chronic liver disease resulting from hepatitis C virus (HCV) infection is complex and involves several complementary mechanisms that likely act in concert.

Aim  To summarize the available data on the etiology of thrombocytopenia in patients with chronic liver disease.

Results  In patients with untreated hepatitis C, both prevalence and severity of thrombocytopenia increase in parallel with the extent of disease, usually becoming clinically relevant when patients develop extensive fibrosis and/or cirrhosis. Pathogenetic mechanisms include hypersptenism secondary to portal hypertension, bone marrow suppression resulting from either HCV itself or interferon treatment, aberrations of the immune system resulting in the formation of anti‐platelet antibodies and/or immune‐complexes that bind to platelets and facilitate their premature clearance, development of immunologically‐mediated extrahepatic manifestations including mixed cryoglobulinemia with or without associated joint, renal, or cutaneous involvement, and thrombopoietin (TPO) deficiency secondary to liver dysfunction. In chronic liver disease, the natural inverse relationship between TPO and platelet levels is not maintained; therefore, blood TPO levels fail to have clinical relevance or predictive value in assessing the thrombocytopenic status of a given patient.

Conclusions  The development of thrombocytopenisa in patients with chronic liver disease is complex and multifactorial.
Review article: the function and regulation of proteins involved in bile salt biosynthesis and transport
Authors: PELLICORO A. , FABER K. N.
Published: July 2010

Background  Bile salts are produced and secreted by the liver and are required for intestinal absorption of fatty food components and excretion of endobiotics and xenobiotics. They are reabsorbed in the terminal ileum and transported back to the liver via the portal tract. Dedicated bile salt transporters in hepatocytes and enterocytes are responsible for the unidirectional transport of bile salts in the enterohepatic cycle.

Aim  To give an overview of the function and regulations of proteins involved in bile salt synthesis and transport.

Methods  Data presented are obtained from PubMed‐accessible literature combined with our own recent research.

Result  Hepatocytes and enterocytes contain unique bile salt importers (sodium‐taurocholate cotransporting polypeptide and apical sodium‐dependent bile acid transporter, respectively) and exporters (bile salt export pump and organic solute transporter alpha‐beta, respectively). Enzymes involved in bile salt biosynthesis reside in different subcellular locations, including the endoplasmic reticulum, mitochondria, cytosol and peroxisomes. Defective expression or function of the transporters or enzymes may lead to cholastasis. The bile salt‐activated transcription factor Farnesoid X receptor controls expression of genes involved in bile salt biosynthesis and transport.

Conclusions  Detailed knowledge is available about the enzymes and transporters involved in bile salt homeostasis and how their defective function is associated with cholestasis. In contrast, the process of intracellular bile salt transport is largely unexplored.
Meta analysis: cancer risk in Barrett’s oesophagus
Authors: THOMAS T. , ABRAMS K. R. , DE CAESTECKER J. S. , ROBINSON R. J.
Published: July 2010

Background  Risk of cancer in Barrett’s oesophagus is reported to vary between studies and also between countries, where the studies were conducted as per several systematic reviews. Cancer incidence has implications on surveillance strategies.

Aim  To perform a meta‐analysis to determine the incidence of oesophageal cancer in Barrett’s oesophagus.

Methods  Articles retrieved by MEDLINE search (English language, 1966–2004). Studies had to necessarily include verified Barrett’s oesophagus surveillance patients, documented follow‐up and cancer identified as the outcome measure. A random effects model of meta‐analysis was chosen and results were expressed as mean (95% CI).

Results  Forty‐one articles selected for conventional Barrett’s oesophagus (length >3 cm); eight included short segment Barrett’s oesophagus (one additional article including only short segment Barrett’s oesophagus). Cancer incidence was 7/1000 (6–9) person‐years duration of follow‐up (pyd), with no detectable geographical variation [UK 7/1000 (4–12) pyd, USA 7/1000 (5–9) pyd and Europe 8/1000 (5–12) pyd]. Cancer incidence in the UK was 10/1000 (7–14), when two large studies were excluded. Cancer incidence in SSBO was 6/1000 (3–12) pyd. When short segment Barrett’s oesophagus compared to conventional Barrett’s oesophagus, there was a trend towards reduced cancer risk [OR 0.55, (95% CI: 0.19–1.6), P = 0.25].

Conclusion  We found no geographical variations in Barrett’s oesophagus cancer risk, but observed a trend towards reduced cancer risk in short segment Barrett’s oesophagus. There is a time trend of decreasing cancer incidence.
The effectiveness of rifabutin triple therapy for patients with difficult‐to‐eradicate Helicobacter pylori in clinical practice
Authors: VAN DER POORTEN D. , KATELARIS P. H.
Published: July 2010

Background  Failure of first line and subsequent Helicobacter pylori eradication therapy is a significant problem and alternative treatments are few.

Aims  To evaluate the efficacy of a rifabutin‐based triple therapy in clinical practice and determine the optimal strategy for its use.

Methods  Patients referred after first or subsequent treatment failure were prescribed rifabutin triple therapy consisting of standard dose proton pump inhibitor, amoxicillin 1 g and rifabutin 150 mg each b.d. for 10 days.

Results  In 67 patients, the main indications for treatment were dyspepsia (55%), peptic ulcer disease (24%) and increased gastric cancer risk (18%). The median number of previous treatments was 2 (range: 1–9). Eradication of Helicobacter pylori was achieved in 76% (48/63) per protocol and 72% (48/67) on an intention‐to‐treat basis. When used as second line therapy, 95% (18/19) achieved eradication compared with 68% (30/44) when two or more previous treatments had been used (P = 0.03). Outcome was independent of age, ethnicity, gender or indication for treatment. Adverse events were reported in 10%.

Conclusion  Rifabutin triple therapy is a well tolerated and effective second line therapy in the treatment of persistent Helicobacter pylori; however, its efficacy decreases with increasing number of failed previous therapies.
Systematic review: endoscopic dilatation in Crohn’s disease
Authors: HASSAN C. , ZULLO A. , DE FRANCESCO V. , IERARDI E. , GIUSTINI M. , PITIDIS A. , TAGGI F. , WINN S. , MORINI S.
Published: July 2010

Background  Endoscopic dilatation for Crohn’s disease has been evaluated only in some small and heterogeneous studies.

Aim  To evaluate any association between the main clinical variables and endoscopic variables and the efficacy and safety of endoscopic dilatation in Crohn’s disease.

Methods  A Medline search regarding pneumatic dilatation in Crohn’s disease was performed. Several technical and clinical variables were extracted from each study to build up a descriptive, pool‐data analysis. Data on individual patients were extracted from suitable studies to create a simulated population upon which a multivariate statistical analysis was performed.

Results  Thirteen studies enrolling 347 Crohn’s disease patients were reviewed. Endoscopic dilatation was mainly applied to postsurgical strictures, being technically successful in 86% of the cases. Long‐term clinical efficacy was achieved in 58% of the patients. Mean follow‐up was as long as 33 months, corresponding to 800 patient years of follow‐up. Major complication rate was 2%, being higher than 10% in two series. At multivariate analysis, a stricture length ≤4 cm was associated with a surgery‐free outcome (OR: 4.01; 95% CI: 1.16–13.8; P < 0.028).

Conclusions  Endoscopic dilatation is an effective and safe treatment for short strictures caused by Crohn’s disease, impacting substantially on the natural history of these patients.
Cumulative incidence of chronic constipation: a population‐based study 1988–2003
Authors: CHOUNG R. S. , LOCKE III G. R. , SCHLECK C. D. , ZINSMEISTER A. R. , TALLEY N. J.
Published: July 2010

Aim  To estimate the cumulative incidence of chronic constipation and evaluate potential risk factors.

Methods  In previous cross‐sectional studies in 1988, random samples of Olmsted County, MN residents were mailed valid gastrointestinal symptoms surveys. A similar survey was mailed in 2003 to all the remaining eligible subjects who had been mailed to previously. An incident case of chronic constipation was defined as no reported constipation or irritable bowel syndrome on their initial survey but reported constipation on the second survey.

Results  In all, 5507 (79%) subjects responded to the initial survey and 2298 (55%) subjects responded to the second survey in which chronic constipation could be defined. Over 12 years, the cumulative incidence of chronic constipation was 17.4% (14.5, 20.5). Among those less than age 50 years at baseline, the incidence of chronic constipation differed by gender (9.2% in men vs. 18.3% in women). In those over 70 years, the incidence of chronic constipation was more similar for men and women (20.6% vs. 25.0%). The other risk factor associated with new onset chronic constipation was the presence of abdominal pain at baseline [OR = 2.0 (1.3, 3.0)].

Conclusion  The cumulative incidence of chronic constipation over more than a decade was almost one in six, and more pronounced in women and the elderly.
Review article: lactose intolerance in clinical practice – myths and realities
Authors: LOMER M. C. E. , PARKES G. C. , SANDERSON J. D.
Published: July 2010

Background  Approximately 70% of the world population has hypolactasia, which often remains undiagnosed and has the potential to cause some morbidity. However, not everyone has lactose intolerance, as several nutritional and genetic factors influence tolerance.

Aims  To review current clinical practice and identify published literature on the management of lactose intolerance.

Methods  PubMed was searched using the terms lactose, lactase and diet to find original research and reviews. Relevant articles and clinical experience provided the basis for this review.

Results  Lactose is found only in mammalian milk and is hydrolysed by lactase in the small intestine. The lactase gene has recently been identified. ‘Wild‐type’ is characterized by lactase nonpersistence, often leading to lactose intolerance. Two genetic polymorphisms responsible for persistence have been identified, with their distribution concentrated in north Europeans. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhoea. Diagnosis is most commonly by the lactose hydrogen breath test. However, most people with hypolactasia, if given appropriate advice, can tolerate some lactose‐containing foods without symptoms.

Conclusion  In clinical practice, some people with lactose intolerance can consume milk and dairy foods without developing symptoms, whereas others will need lactose restriction.
Mutations in the interferon sensitivity‐determining region (nonstructural 5A amino acid 2209–2248) in patients with hepatitis C‐1b infection and correlating response to combined therapy of pegylated interferon and ribavirin
Authors: YEN Y.‐H. , HUNG C.‐H. , HU T.‐H. , CHEN C.‐H. , WU C.‐M. , WANG J.‐H. , LU S.‐N. , LEE C.‐M.
Published: July 2010

Background  Most reports suggest that mutations in the interferon sensitivity‐determining region (ISDR) correlate with response to conventional interferon‐based therapies in hepatitis C virus‐1b (HCV‐1b) patients. However, the correlation between ISDR region mutations and response to pegylated interferon plus ribavirin therapy in HCV‐1b patients remains unclear.

Aim  To assess whether ISDR mutations correlate with response to Peg interferon plus ribavirin therapy in HCV‐1b patients.

Patients and methods  Sixty HCV‐1b naive patients who had undergone 6 months of Peg interferon α‐2b plus ribavirin and a 6‐month follow‐up were enrolled. The amino acid sequences of the nonstructural 5A‐interferon‐induced RNA‐dependent protein kinase (NS5A–PKR)‐binding domain were determined by polymerase chain reaction and sequencing.

Results  Thirty (50%) patients achieved sustained virological response (SVR). Univariate analysis showed that the proportion of patients with ISDR mutations ≥4 and rapid virological response rate was higher in the sustained virological response group than in the non‐SVR group. Viral load was lower in the SVR group than in the non‐SVR group. Multivariate analysis revealed that ISDR mutations ≥4 and ribavirin ≥14 mg/kg/day were independent predictors of SVR.

Conclusion  Mutations of the ISDR correlate with SVR to Peg interferon α‐2b plus ribavirin therapy in HCV‐1b patients.
In vitro comparative study of three pancreatic enzyme preparations: dissolution profiles, active enzyme release and acid stability
Authors: ALOULOU A. , PUCCINELLI D. , SARLES J. , LAUGIER R. , LEBLOND Y. , CARRIÈRE F.
Published: July 2010

Background  Various pancreatic enzyme preparations are used for the treatment of pancreatic insufficiency but their bioequivalence is often unknown.

Aim  To determine in vitro the pH‐dependent release and acid resistance of enzymes from three commercially available pancreatin capsules, two containing enteric‐coated (Creon 25000; Eurobiol 25000) and one uncoated (Eurobiol 12500) microspheres.

Methods  Dissolution experiments were performed at pH values ranging from 4.0 to 5.8. Lipase, chymotrypsin and amylase activities were measured in the solution as a function of time.

Results  Eurobiol 25000 started to release its enzymes significantly at pH 5.0 (t1/2 = 71 min), whereas the enzymes from Creon 25000 were only released at higher pH value (5.4; t1/2 = 49.2 min). Unlike chymotrypsin, lipase and amylase were highly sensitive to acidic conditions at the lowest pH values tested. Both enzymes were also found to be sensitive to proteolytic inactivation at the highest pH values tested. Overall, Eurobiol 25000 released higher amounts of active amylase and lipase than Creon 25000 at the pH values usually found in duodenal contents. The uncoated Eurobiol 12500 preparation was, however, the only one that could immediately release rather high levels of active chymotrypsin and lipase at low pH (4.5).

Conclusion  These findings suggest that pH‐sensitive enteric‐coated pancreatin products containing similar amounts of enzymes might not be bioequivalent depending on the pH of duodenal contents.