The Diagnostic Utility of Volatile Organic Compounds in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Volatile organic compounds [VOCs] show promise as potential biomarkers of for ulcerative colitis and Crohn's disease, two chronic, idiopathic, gastrointestinal disorders with diagnostic and management challenges. Non-invasive biomarkers aid early diagnosis and management. In this study we review studies of diagnostic accuracy of VOCs in inflammatory bowel disease. METHODS: A systematic search was carried out on the Pubmed and Scopus databases; with 16 studies reviewed and meta-analysis carried out on 10. RESULTS: Meta-analysis of 696 inflammatory bowel disease [IBD] cases against 605 controls revealed a pooled sensitivity and specificity of 87% (95% confidence interval [CI], 0.79 - 0.92) and 83% [95% CI, 0.73 - 0.90], respectively. Area under the curve [AUC] was 0.92. CONCLUSION: VOCs perform very well as non-invasive biomarkers of IBD, with much scope for future improvement and research.

Gut microbiota signatures in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affect millions of people worldwide with increasing incidence. OBJECTIVES: Several studies have shown a link between gut microbiota composition and IBD, but results are often limited by small sample sizes. We aimed to re-analyze publicly available fecal microbiota data from IBD patients. METHODS: We extracted original fecal 16S rRNA amplicon sequencing data from 45 cohorts of IBD patients and healthy individuals using the BioProject database at the National Center for Biotechnology Information. Unlike previous meta-analyses, we merged all study cohorts into a single dataset, including sex, age, geography, and disease information, based on which microbiota signatures were analyzed, while accounting for varying technical platforms. RESULTS: Among 2518 individuals in the combined dataset, we discovered a hitherto unseen number of genera associated with IBD. A total of 77 genera associated with CD, of which 38 were novel associations, and a total of 64 genera associated with UC, of which 28 represented novel associations. Signatures were robust across different technical platforms and geographic locations. Reduced alpha diversity in IBD compared to healthy individuals, in CD compared to UC, and altered microbiota composition (beta diversity) in UC and especially in CD as compared to healthy individuals were found. CONCLUSIONS: Combining original microbiota data from 45 cohorts, we identified a hitherto unseen large number of genera associated with IBD. Identification of microbiota features robustly associated with CD and UC may pave the way for the identification of new treatment targets.

Human gut microbiota and endocrinology: paradigm shift from genome to its regulation.

Over the last two decades, it has become clear that the human gut microbiota, a complex community of bacteria, archaea, fungi and viruses, are a critical determinant of human health and disease. Microbiota-derived metabolites provide the host with energy, protect against pathogens, modulate immune and endocrine systems as well as the level of reactive oxygen species in the gut. It has come with no surprise that the human gut microbiota is also linked to the production, utilisation and regulation of host hormones. This implies that the gut microbiota is capable of influencing human behaviour, appetite regulation and metabolism as well as development and immunity. Many of the advances in the field of crosstalk between the gut microbiota and host health, disease and behaviours are generally based on DNA analyses of microbial populations and transplantation of monocultured commensal species to germ-free animals. Recent reports on the activity of the gut microbiota in gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer have highlighted two important points. First, microbial DNA-based abundance does not always correlate with their level of activity and secondly, that metabolism of the complex gut microbiota is regulated by host health status, including the production and metabolism of several human hormones. In this review, we will discuss the lessons learnt from studying the activity and metabolism of the human gut microbiota in health and across gastrointestinal diseases, and how these findings can shape future research on the microbiome-gut-endocrine axis.

Clinical utility of colon capsule endoscopy: a moving target?

The purpose of this article is to provide an overview of white light colon capsule endoscopy's current clinical application, concentrating on its most recent developments. Second-generation colon capsule endoscopy (CCE2) is approved by the FDA for use as an adjunctive test in patients with incomplete colonoscopy and within Europe in patients at average risk, those with incomplete colonoscopies or those unwilling to undergo conventional colonoscopies. Since the publication of European Society of GI Endoscopy guidelines on the use of CCE, there has been a significant increase in comparative studies on the diagnostic yield of CCE. This paper discusses CCE2 in further detail. It explains newly developed colon capsule system and the current status on the use of CCE, it also provides a comprehensive summary of systematic reviews on the implementation of CCE in colorectal cancer screening from a methodological perspective. Patients with ulcerative colitis can benefit from CCE2 in terms of assessing mucosal inflammation. As part of this review, performance of CCE2 for assessing disease severity in ulcerative colitis is compared with colonoscopy. Finally, an assessment if CCE can become a cost-effective clinical service overall.

Study of capsule endoscopy delivery at scale through enhanced artificial intelligence-enabled analysis (the CESCAIL study).

AIM: Lower gastrointestinal (GI) diagnostics have been facing relentless capacity constraints for many years, even before the COVID-19 era. Restrictions from the COVID pandemic have resulted in a significant backlog in lower GI diagnostics. Given recent developments in deep neural networks (DNNs) and the application of artificial intelligence (AI) in endoscopy, automating capsule video analysis is now within reach. Comparable to the efficiency and accuracy of AI applications in small bowel capsule endoscopy, AI in colon capsule analysis will also improve the efficiency of video reading and address the relentless demand on lower GI services. The aim of the CESCAIL study is to determine the feasibility, accuracy and productivity of AI-enabled analysis tools (AiSPEED) for polyp detection compared with the 'gold standard': a conventional care pathway with clinician analysis. METHOD: This multi-centre, diagnostic accuracy study aims to recruit 674 participants retrospectively and prospectively from centres conducting colon capsule endoscopy (CCE) as part of their standard care pathway. After the study participants have undergone CCE, the colon capsule videos will be uploaded onto two different pathways: AI-enabled video analysis and the gold standard conventional clinician analysis pathway. The reports generated from both pathways will be compared for accuracy (sensitivity and specificity). The reading time can only be compared in the prospective cohort. In addition to validating the AI tool, this study will also provide observational data concerning its use to assess the pathway execution in real-world performance. RESULTS: The study is currently recruiting participants at multiple centres within the United Kingdom and is at the stage of collecting data. CONCLUSION: This standard diagnostic accuracy study carries no additional risk to patients as it does not affect the standard care pathway, and hence patient care remains unaffected.

A Systematic Review and Meta-Analysis: Volatile Organic Compound Analysis in the Detection of Hepatobiliary and Pancreatic Cancers.

BACKGROUND: Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The currently used biomarkers such as AFP (alpha-fetoprotein) and CA19.9 lack sensitivity and specificity. Hence, there is an unmet need for an alternative biomarker. AIM: To evaluate the diagnostic accuracy of volatile organic compounds (VOCs) for the detection of hepatobiliary and pancreatic cancers. METHODS: A systematic review of VOCs' use in the detection of hepatobiliary and pancreatic cancers was performed. A meta-analysis was performed using the software R. Heterogeneity was explored through meta-regression analysis. RESULTS: A total of 18 studies looking at 2296 patients were evaluated. Pooled sensitivity and specificity of VOCs for the detection of hepatobiliary and pancreatic cancer were 0.79 (95% CI, 0.72-0.85) and 0.81 (97.5% CI, 0.76-0.85), respectively. The area under the curve was 0.86. Meta-regression analysis showed that the sample media used contributed to heterogeneity. Bile-based VOCs showed the highest precision values, although urine and breath are preferred for their feasibility. CONCLUSIONS: Volatile organic compounds have the potential to be used as an adjunct tool to aid in the early diagnosis of hepatobiliary cancers.

The Fatty Liver, Cirrhosis, and Liver Cancer Study (TENDENCY): Protocol for a Multicenter Case-Control Study.

BACKGROUND: Hepatocellular cancer (HCC) is associated with high mortality, and early diagnosis leads to better survival. Patients with cirrhosis, especially due to nonalcoholic fatty liver disease and viral hepatitis, are at higher risk of developing HCC and form the main screening group. The current screening methods for HCC (6-monthly screening with serum alpha fetoprotein and ultrasound liver) have low sensitivity; hence, there is a need for better screening markers for HCC. OBJECTIVE: Our study, TENDENCY, aims to validate the novel screening markers (methylated septin 9, urinary volatile organic compounds, and urinary peptides) for HCC diagnosis and study these noninvasive biomarkers in liver disease. METHODS: This is a multicenter, nested case-control study, which involves comparing the plasma levels of methylated septin 9 between confirmed HCC cases and patients with cirrhosis (control group). It also includes the comparison of urine samples for the detection of HCC-specific volatile organic compounds and peptides. Based on the findings of a pilot study carried out at University Hospital Coventry & Warwickshire, we estimated our sample size to be 308 (n=88, 29% patients with HCC; n=220, 71% patients with cirrhosis). Urine and plasma samples will be collected from all participants and will be frozen at -80 °C until the end of recruitment. Gas chromatography-mass spectrometry will be used for urinary volatile organic compounds detection, and capillary electrophoresis-mass spectrometry will be used for urinary peptide identification. Real-time polymerase chain reaction will be used for the qualitative detection of plasma methylated septin 9. The study will be monitored by the Research and Development department at University Hospital Coventry & Warwickshire. RESULTS: The recruitment stage was completed in March 2023. The TENDENCY study is currently in the analysis stage, which is expected to finish by November 2023. CONCLUSIONS: There is lack of effective screening tests for hepatocellular cancer despite higher mortality rates. The application of more sensitive plasma and urinary biomarkers for hepatocellular cancer screening in clinical practice will allow us to detect the disease at earlier stages and hence, overall, improve HCC outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44264.

The Influence of Mechanical Bowel Preparation on Volatile Organic Compounds for the Detection of Gastrointestinal Disease-A Systematic Review.

(1) Background: Colorectal cancer is the second commonest cause of cancer deaths worldwide; recently, volatile organic compounds (VOCs) have been proposed as potential biomarkers of this disease. In this paper, we aim to identify and review the available literature on the influence of mechanical bowel preparation on VOC production and measurement. (2) Methods: A systematic search for studies was carried out for articles relevant to mechanical bowel preparation and its effects on volatile organic compounds. A total of 4 of 1349 papers initially derived from the search were selected. (3) Results: Two studies with a total of 134 patients found no difference in measured breath VOC profiles after bowel preparation; one other study found an increase in breath acetone in 61 patients after bowel preparation, but no other compounds were affected. Finally, the last study showed the alteration of urinary VOC profiles. (4) Conclusions: There is limited data on the effect of bowel preparation on VOC production in the body. As further studies of VOCs are conducted in patients with symptoms of gastrointestinal disease, the quantification of the effect of bowel preparation on their abundance is required.

A Multi-Centre Study to Risk Stratify Colorectal Polyp Surveillance Patients Utilising Volatile Organic Compounds and Faecal Immunochemical Test.

(1) Background: The service capacity for colonoscopy remains constrained, and while efforts are being made to recover elective services, polyp surveillance remains a challenge. (2) Methods: This is a multi-centre study recruiting patients already on polyp surveillance. Stool and urine samples were collected for the faecal immunochemical test (FIT) and volatile organic compounds (VOC) analysis, and all participants then underwent surveillance colonoscopy. (3) Results: The sensitivity and specificity of VOC for the detection of a high-risk finding ((≥2 premalignant polyps including ≥1 advanced polyp or ≥5 premalignant polyps) were 0.94 (95% CI, 0.88 to 0.98) and 0.69 (95% CI, 0.64 to 0.75) respectively. For FIT, the sensitivity was (≥10 µg of haemoglobin (Hb) / g faeces) 0.54 (95% CI, 0.43 to 0.65) and the specificity was 0.79 (95% CI, 0.73 to 0.84). The probability reduction for having a high-risk finding following both negative VOC and FIT will be 24% if both tests are applied sequentially. (4) Conclusion: The diagnostic performance of VOC is superior to FIT for the detection of a high-risk finding. The performance further improves when VOC is applied together with FIT sequentially (VOC first and then FIT). VOC alone or the combination of VOC and FIT can be used as a triage tool for patients awaiting colonoscopy within a polyp surveillance population, especially in resource-constrained healthcare systems.

Efficacy and Safety of Maintenance Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension.

BACKGROUND AND AIMS: The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy. METHODS: Patients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab]. RESULTS: Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes. CONCLUSIONS: Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

REducing Colonoscopies in patients without significant bowEl DiseasE: the RECEDE Study - protocol for a prospective diagnostic accuracy study.

INTRODUCTION: Demand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs. METHODS AND ANALYSIS: This is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy. ETHICS AND DISSEMINATION: Ethical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346). TRIAL REGISTRATION NUMBER: RECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.

A systematic review and meta-analysis: the diagnostic accuracy of methylated SEPTIN9 for the detection of hepatocellular carcinoma and the clinical evaluation of its use in combination with other surveillance modalities.

BACKGROUND: Hepatocellular carcinoma (HCC) lacks a suitable biomarker for minimally-invasive disease detection. Methylated SEPTIN9 (mSEPT9) is an emerging liquid biopsy test. We aimed to investigate recent studies that applied mSEPT9 for HCC diagnosis. Furthermore, we evaluated the combinations of other surveillance modalities for the detection of HCC. METHODS: A systematic review was performed on the diagnostic accuracy of mSEPT9 for the detection of HCC. Using a bivariate model, the pooled sensitivity and specificity were calculated. Additionally, Fagan's nomograms were used to calculate the pre-test and post-test probabilities of HCC for various combinations of surveillance modalities. RESULTS: Six full texts were included in the meta-analysis. The pooled sensitivity and specificity of mSEPT9 for the detection of HCC, were 0.80 (95% CI, 0.67-0.89) and 0.90 (95% CI, 0.84-0.94). The area under the receiver operating curve was 0.92. The probability of having HCC for the combinations of mSEPT9+ ultrasound scan (USS) and mSEPT9+ Alpha fetoprotein (AFP) were 0.7% and 1.2% respectively if both tests were negative (in a population with 10% HCC prevalence). The combination of USS and AFP would miss relatively fewer cancers for 1000 patients in comparison to other combinations of two surveillance modalities. CONCLUSION: Test combinations have superior performance for the detection of HCC than any individual test. mSEPT9 has shown promise in the detection of HCC with higher estimates of performance accuracy. mSEPT9 has potential for use as an HCC surveillance modality in adjunct with other tests to improve detection rates. However, cost effectiveness of this approach needs further evaluation.

Urinary Volatiles and Chemical Characterisation for the Non-Invasive Detection of Prostate and Bladder Cancers.

Bladder cancer (BCa) and prostate cancer (PCa) are some of the most common cancers in the world. In both BCa and PCa, the diagnosis is often confirmed with an invasive technique that carries a risk to the patient. Consequently, a non-invasive diagnostic approach would be medically desirable and beneficial to the patient. The use of volatile organic compounds (VOCs) for disease diagnosis, including cancer, is a promising research area that could support the diagnosis process. In this study, we investigated the urinary VOC profiles in BCa, PCa patients and non-cancerous controls by using gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to analyse patient samples. GC-IMS separated BCa from PCa (area under the curve: AUC: 0.97 (0.93-1.00)), BCa vs. non-cancerous (AUC: 0.95 (0.90-0.99)) and PCa vs. non-cancerous (AUC: 0.89 (0.83-0.94)) whereas GC-TOF-MS differentiated BCa from PCa (AUC: 0.84 (0.73-0.93)), BCa vs. non-cancerous (AUC: 0.81 (0.70-0.90)) and PCa vs. non-cancerous (AUC: 0.94 (0.90-0.97)). According to our study, a total of 34 biomarkers were found using GC-TOF-MS data, of which 13 VOCs were associated with BCa, seven were associated with PCa, and 14 VOCs were found in the comparison of BCa and PCa.

Pathophysiological Implications of Urinary Peptides in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is known to be associated with protein alterations and extracellular fibrous deposition. We investigated the urinary proteomic profiles of HCC patients in this prospective cross sectional multicentre study. 195 patients were recruited from the UK (Coventry) and Germany (Hannover) between 1 January 2013 and 30 June 2019. Out of these, 57 were HCC patients with a background of liver cirrhosis (LC) and 138 were non-HCC controls; 72 patients with LC, 57 with non-cirrhotic liver disease and 9 with normal liver function. Analysis of the urine samples was performed by capillary electrophoresis (CE) coupled to mass spectrometry (MS). Peptide sequences were obtained and 31 specific peptide markers for HCC were identified and further integrated into a multivariate classification model. The peptide model demonstrated 79.5% sensitivity and 85.1% specificity (95% CI: 0.81-0.93, p < 0.0001) for HCC and 4.1-fold increased risk of death (95% CI: 1.7-9.8, p = 0.0005). Proteases potentially involved in HCC progression were mapped to the N- and C-terminal sequence motifs of the CE-MS peptide markers. In silico protease prediction revealed that kallikrein-6 (KLK6) elicits increased activity, whilst Meprin A subunit α (MEP1A) has reduced activity in HCC compared to the controls. Tissue expression of KLK6 and MEP1A was subsequently verified by immunohistochemistry.

Non-Invasive Detection and Staging of Colorectal Cancer Using a Portable Electronic Nose.

Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy-to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). For diseases such as cancer with a high mortality, a technology that can provide fast results for use in routine clinical applications is important. Colorectal cancer (CRC) is among the highest occurring cancers and has high mortality rates, if diagnosed late. In our study, we investigated the use of portable electronic nose (PEN3), with further analysis using GC-TOF-MS, for the analysis of gases and volatile organic compounds (VOCs) to profile the urinary metabolome of colorectal cancer. We also compared the different cancer stages with non-cancers using the PEN3 and GC-TOF-MS. Results obtained from PEN3, and GC-TOF-MS demonstrated high accuracy for the separation of CRC and non-cancer. PEN3 separated CRC from non-cancerous group with 0.81 AUC (Area Under the Curve). We used data from GC-TOF-MS to obtain a VOC profile for CRC, which identified 23 potential biomarker VOCs for CRC. Thus, the PEN3 and GC-TOF-MS were found to successfully separate the cancer group from the non-cancer group.

Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy.

AIM: The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy. METHOD: Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results. RESULTS: A total of 667 participants were eligible for the final analysis. At a cut-off of 10 µg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT. CONCLUSION: FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.

Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit.

INTRODUCTION: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1-57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices. METHODS: A retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05). RESULTS: A total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days). DISCUSSION/CONCLUSION: Only a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

Role of methylated septin 9 as an adjunct diagnostic and prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Methylated septin 9 (mSEPT9) has a role in hepatocarcinogenesis. We evaluated mSEPT9 performance in patients with hepatocellular carcinoma (HCC) and those at risk of HCC METHODS: Using Epi-proColon® V2.0 assay adapted for 1 mL plasma, we investigated mSEPT9 sensitivity, specificity, associations with influential covariates and relation to death. RESULTS: Of 141 participants included, 136 had liver disease, 38 with HCC (mean-age 71 years) and 103 without HCC (mean-age 56.8 years), with further five without liver disease. 41 patients died (23 HCC) by the end of the study follow-up period. In HCC, mSEPT9 sensitivity and specificity were 89.47% (CI:75.20%-97.06%) and 81.55% (CI:72.70%-88.51%), whilst alpha fetoprotein (AFP) sensitivity and specificity were 50% (CI:33.38%-66.62%) and 97.09% (CI:91.72%-99.40%), respectively. Age-adjusted logistic regression showed mSEPT9 was associated with age, body mass index, HCC, liver cirrhosis, AFP, platelets, neutrophil-to-lymphocyte-ratio, albumin-bilirubin grade and fibrosis-4 index (p < 0.05). Odds for HCC patients to have positive mSEPT9 were 27.4 times more than those without HCC. Time-to-death was associated with mSEPT9 positivity (p < 0.05). Kaplan-Meier curves showed higher HCC survival with mSEPT9 compared to AFP. CONCLUSIONS: The mSEPT9 offers potential diagnostic and prognostic biomarker for HCC. After adjusting for age, mSEPT9 remained associated with liver function, liver fibrosis and inflammatory surrogate markers.