A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire.

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

Double-headed small-bowel capsule endoscopy: Real-world experience from a multi-centre British study.

INTRODUCTION: Capsule endoscopy (CE) is well established the investigation of small-bowel (SB) pathology. We compared the use of double-headed (DH) capsules, to conventional single-headed (SH), in a real-world patient cohort in the first multicentre British study. METHODS: Over 9 months, patients referred for routine SBCE at 4 tertiary referral centres in the UK underwent DH CE instead of conventional SH using MiroCamⓇ MC2000 as per local protocols. One head (L/R) was chosen at random and reported by an expert reviewer. The DH recordings, anonymised and randomised, reported by another expert or re-read after a 4-week interval. For each CE, numbers and types of findings and overall conclusion/diagnosis were compared between SH and DH examinations. RESULTS: 211 CEs were performed. 7 failed to reach the SB; 204 analysed. Indications were: SB bleeding (n = 94); ?SB inflammation or reassessment of known inflammatory bowel disease (IBD) (n = 84); ?SB neoplasia including suspicious radiological imaging (n = 15); and, others e.g. ?celiac disease (n = 11). For SB bleeding: 27/94 (28.7%) examinations reported differences between SH and DH readings. In 17 (18.1%) the findings were clinically significant. SH CE missed angiectasias (5 pts), SB inflammation (7 pts), oesophagitis (2 pts) and SB masses (2 pts). In 1 patient, the extent of angiectasias seen was greater on the DH reading. For IBD: findings differed in 30/84 (35.7%) of CEs; 11 (13.1%) were clinically significant. In 5, signs of active inflammation were missed by the SH reading. In 6, assessment of extent/severity differed. For?SB neoplasia findings differed in 2/15 (13.3%) of examinations. Both were clinically significant. For others: 1/11 (9.1%) examinations differed; however, not deemed clinically significant. Overall, use of DH CE impacted the diagnosis in 30/204 (14.7%). CONCLUSIONS: The use of DH CE provides more information with the potential to change clinical diagnosis and therefore management. Therefore, the routine adoption of DH CE in SB assessment should be considered.

Repeat capsule endoscopy in suspected gastrointestinal bleeding.

Objectives: This study aims to review the utility of repeat capsule endoscopy (CE) with on-going concern of small bowel (SB) bleeding following initial SB investigation with CE. Materials and methods: A specifically designed database of CE examinations performed over 13 years, with hospital records, was retrospectively interrogated for patients undergoing multiple CEs to investigate iron deficiency anaemia (IDA) or suspected SB bleeding. Results: 1335/2276 (58.7%) of CEs were performed to investigate IDA or SB bleeding; 92 were repeat CEs carried out for ongoing clinical concern. The median time interval between initial and repeat CE procedures was 466.5 (range 1-3066) days. Twenty-four patients had initially normal CE; on repeat examination, abnormalities were detected in 11/24 (45.8%). 3/21 (14.2%) of patients with angioectasia on first CE had alternative causes for IDA or GI bleeding detected on repeat CE. Six patients with active bleeding, without an identifiable source on initial CE, undergoing repeat CE had a cause isolated in 5/6 (83.3%). Changing CE device did not affect diagnostic yield (DY) compared to repeat CE using the same device (27.5% to 26.8%). Conclusions: It is known that CE can miss clinically relevant and serious lesions. Our results suggest that patients with an initially negative or inconclusive CE frequently have a cause of SB bleeding detected on repeat CE. The DY of repeat CE is highest in those with bleeding on their initial CE (83.3%) and lower in those with initially normal examinations (45.8%) or when an alternative cause, such as angioectasia is seen (14.2%).

Index serum hyaluronic acid independently and accurately predicts mortality in patients with liver disease.

BACKGROUND: Hyaluronic acid is a recognised noninvasive marker of liver fibrosis. However, its prognostic ability has not been extensively studied. AIMS: To investigate the ability of an index serum hyaluronic acid measurement to independently predict transplant-free survival in patients with liver disease of varying aetiology and severity. METHODS: This was a retrospective single-centre cohort study. Serum hyaluronic acid was measured at the discretion of the attending clinicians, in patients attending the liver clinic, to assess disease severity. Patients with a hyaluronic acid measurement between 1995 and 2010 were identified. Patient characteristics at the point of hyaluronic acid measurement were recorded from medical records. Follow-up was from date of index hyaluronic acid measurement to date of death, date of transplant or censor date (July 01, 2015). Primary outcomes were all-cause and liver-related mortality. Kaplan-Meier analysis was used to compare survival in 3 patient groups with hyaluronic acid levels of <100 µg/L, 100-300 µg/L and >300 µg/L. Survival models were constructed using Cox proportional hazard and prediction accuracy was assessed by Harrell's C-statistic. RESULTS: Five hundred and eighty nine patients fulfilled inclusion criteria. Median follow-up was 5.6 years (range 0.1-19.7). Transplant-free survival was significantly different between patients with hyaluronic acid <100 µg/L, 100-300 µg/L and >300 µg/L for liver-related as well as all-cause mortality (P < 0.001). Hyaluronic acid level was an independent predictor of survival (liver-related: HR 1.39, 95% CI 1.20-1.60, P < 0.001; all-cause: HR 1.04, 95% CI 1.02-1.06, P = 0.001). The liver-related prediction accuracy of hyaluronic acid was 0.74 (Standard error 0.03). CONCLUSION: Index hyaluronic acid measurement can accurately and independently predict liver-related and all-cause mortality in patients with liver disease.

Randomised clinical study: comparison of acceptability, patient tolerance, cardiac stress and endoscopic views in transnasal and transoral endoscopy under local anaesthetic.

BACKGROUND: Transnasal endoscopy (TNE) with ultrathin endoscopes has been advocated as an attractive alternative, for diagnostic upper endoscopy. AIM: To assess tolerability, acceptability and quality of TNE, in comparison with standard upper endoscopy (SOGD, standard oesophago-gastro-duodenoscopy) under local anaesthetic. METHODS: We prospectively recruited 157 patients (83 females/74 males) mean age 57 years. The Fujinon EG530N (5.9 mm) and EG530WR (9.4 mm) endoscopes were used. The endoscopist and all patients completed detailed questionnaires regarding tolerability, acceptance and quality of endoscopy using standard visual analogue scales (VAS). Oxygen saturation (SaO2 ), heart rate (HR) and systolic blood pressure (SBP) were recorded. Quality of biopsies was evaluated. RESULTS: Analysis included 161 procedures (TNE:79, SOGD:82) with duodenal intubation achieved in all patients. VAS scores for patient comfort were significantly better in the TNE group (7.3 vs. 5.3 respectively, P < 0.001). Twenty patients with previous experience of standard endoscopy were randomised to TNE and 19 of them (95.5%) preferred the TNE. Gagging was significantly less in the TNE group (0.12 vs. 3.41 respectively, P < 0.001). Cardiovascular stress was significantly less in the TNE group irrespective of the degree of gagging or comfort. TNE biopsies were smaller, but adequate for definitive diagnosis, similarly to standard endoscopy. CONCLUSIONS: Transnasal endoscopy is superior to SOGD in terms of comfort and patient acceptance with significantly less cardiovascular stress. TNE can routinely be used as alternative to SOGD under local anaesthetic, for diagnosis and should be preferentially offered in cardiorespiratory compromised patients.

Scoring system to identify patients at high risk of oesophageal cancer.

BACKGROUND: Identification of a patient cohort at high risk of developing oesophageal cancer might enable a greater proportion of patients with curable disease stages to be identified and permit better use of investigative resources. The aim of this study was to develop a scoring system that identifies patients with dysphagia at greatest risk of having oesophageal cancer. METHODS: Data on 435 patients with dysphagia were recorded. Univariable and multivariable analyses were performed to identify parameters predictive of cancer. These were used to create the Edinburgh Dysphagia Score (EDS), which was then validated in a second cohort of patients. RESULTS: The EDS contained six parameters: age, sex, weight loss, duration of symptoms, localization of dysphagia and acid reflux. It stratified the development cohort into a group at higher risk, containing 39 of 40 patients with cancer, and a group at lower risk, comprising 36·0 per cent of referrals (sensitivity 97·5 per cent, negative predictive value 99·3 per cent). On validation, the EDS divided the referrals into a higher-risk group identifying all 26 cancers and a lower-risk group comprising 30·0 per cent of referrals. CONCLUSION: From 574 referrals, the EDS correctly classified as higher risk all but one patient with cancer. Some 34·0 per cent of patients identified as lower risk could have been investigated less urgently. This simple scoring system permits sensitive prioritization of patients referred with dysphagia, and enables more efficient use of investigative resources.

Review article: omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease affects 10-35% of the adult population worldwide; there is no consensus on its treatment. Omega-3 fatty acids have proven benefits for hyperlipidaemia and cardiovascular disease, and have recently been suggested as a treatment for non-alcoholic fatty liver disease. AIMS: To review the evidence base for omega-3 fatty acids in non-alcoholic fatty liver disease and critically appraise the literature relating to human trials. METHODS: A Medline and PubMed search was performed to identify relevant literature using search terms 'omega-3', 'N-3 PUFA', 'eicosapentaenoic acid', 'docosahexaenoic acid', 'non-alcoholic fatty liver disease' and 'NAFLD'. RESULTS: Omega-3 fatty acids are important regulators of hepatic gene transcription. Animal studies demonstrate that they reduce hepatic steatosis, improve insulin sensitivity and reduce markers of inflammation. Clinical trials in human subjects generally confirm these findings, but have significant design inadequacies. CONCLUSIONS: Omega-3 fatty acids are a promising treatment for non-alcoholic fatty liver disease which require to be tested in randomized placebo-controlled trials.

Treating bleeding oesophageal varices with vasoactive agents: good value for money?

This article provides an editorial commentary to accompany the publication of an article on the economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with cirrhosis by Wechowski et al. From a clinical standpoint, the successful management of bleeding oesophageal varices should be based on definitive treatments such as therapeutic endoscopy or transjugular intrahepatic portosystemic stent shunt (TIPSS). Vasoactive agents such as terlipressin can be useful and potentially cost-effective additional therapy, however, particularly in patients where endoscopic treatment is likely to be delayed or is contraindicated.

The multidisciplinary team meeting improves staging accuracy and treatment selection for gastro-esophageal cancer.

The object of this article is to assess current staging accuracies for individual modalities and to investigate the influence of the multidisciplinary team (MDT) on clinical staging accuracies and treatment selection for patients with gastro-esophageal cancer. Patients newly diagnosed with gastric or esophageal cancer and who were deemed suitable for surgical resection by the MDT were studied. Patients were staged with a combination of computerized tomography (CT), endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS). Additionally, the MDT determined an overall clinical stage for each patient after discussion at the MDT meeting. Treatments were selected according to this final clinical stage. Final histopathological staging (pTNM) was available for all patients and was used as the gold standard for determining staging accuracy. Suitability of treatment selection was assessed once final pTNM was available. One hundred and eighteen patients were studied. Endoscopic ultrasound was the most accurate individual staging modality for the loco-regional assessment of esophageal tumors (T stage accuracy 78%, N stage accuracy 70%). Laparoscopic ultrasound was the most accurate modality in T staging of gastric cancers (91%). The MDT stage was more accurate than each individual staging modality for T and N staging for both gastric and esophageal cancers (accuracy range: 88-89%) and was better for the assessment of nodal disease than each individual modality (CT P < 0.001, EUS P < 0.01, LUS P < 0.01). Overall staging accuracy as determined at the MDT meeting was increased and resulted in only 2/118 (2%) patients being under-treated. The MDT significantly improves staging accuracy for gastro-esophageal cancer and ensures that correct management decisions are made for the highest number of individual patients.

Review article: recent advances in the management of bleeding gastric varices.

Gastric variceal bleeding can be challenging to the clinician. Tissue adhesives can control acute bleeding in over 80%, with rebleeding rates of 20-30%, and should be first-line therapy where available. Endoscopic ultrasound can assist in better eradication of varices. The potential risks of damage to equipment and embolic phenomena can be minimized with careful attention to technique. Variceal band ligation is an alternative to tissue adhesives for the management of acute bleeding, but not for secondary prevention due to a higher rate of rebleeding. Endoscopic therapy with human thrombin appears promising, with initial haemostasis rates typically over 90%. The lack of controlled studies for thrombin prevents universal recommendation outside of clinical trials. Balloon occluded retrograde transvenous obliteration is a recent technique for patients with gastrorenal shunts, although its use is limited to clinical trials. Transjugular intrahepatic portosystemic stent shunt is an option for refractory bleeding and secondary prophylaxis, with uncontrolled studies demonstrating initial haemostasis obtained in over 90%, and rebleeding rates of 15-30%. Non-cardioselective beta-blockers are an alternative to transjugular intrahepatic portosystemic stent shunt for secondary prophylaxis, although the evidence is limited. Shunt surgery should be considered in well-compensated patients. Splenectomy or embolization is an option in patients with segmental portal hypertension.

Alcoholic hepatitis: from pathogenesis to treatment.

UNLABELLED: Alcoholic hepatitis is a serious complication of alcohol abuse due to its high mortality rates particularly at short term. It may complicate pre-existing alcoholic fatty liver or cirrhosis and is mainly diagnosed on clinical and laboratory grounds although liver biopsy is occasionally needed to exclude other pathology and confirm the diagnosis. Accumulating evidence suggests that cytokines and immunity are actively involved in its pathogenesis. Management includes abstinence and supportive care. Treatment with corticosteroids has been studied in several clinical trials with conflicting results. However, recent evidence supporting the beneficial effect of TNF-alpha inhibition provides an encouraging alternative. Here we summarise the current state in diagnosis and management of alcoholic hepatitis and briefly review the latest advances in pathophysiology that may lead to new therapeutic strategies for this difficult clinical condition. DATA SOURCES: Medline 1966-2005, EMBASE/Excerpta Medica 1980-2005, The Cochrane Library (2005 Issue 2) and contact with authors of published reports.