Tailoring follow-up endoscopy in patients with severe oesophagitis.

Objective: We aimed to investigate the clinical utility of follow-up oesophagogastroduodenoscopy (OGD2) in patients with severe oesophagitis (Los Angeles grades C or D) through evaluating the yield of Barrett's oesophagus (BO), cancer, dysplasia and strictures. Second, we aimed to determine if the Clinical Frailty Scale (CFS) may be used to identify patients to undergo OGD2s. Design/method: Patients in NHS Lothian with an index OGD (OGD1) diagnosis of severe oesophagitis between 1 January 2014 and 31 December 2015 were identified. Univariate analysis identified factors associated with grade. Patients were stratified by frailty and a diagnosis of stricture, cancer, dysplasia and BO. Results: In total 964 patients were diagnosed with severe oesophagitis, 61.7% grade C and 38.3% grade D. The diagnostic yield of new pathology at OGD2 was 13.2% (n=51), new strictures (2.3%), dysplasia (0.5%), cancer (0.3%) and BO (10.1%). A total of 140 patients had clinical frailty (CFS score ≥5), 88.6% of which were deceased at review (median of 76 months). In total 16.4% of frail patients underwent OGD2s and five new pathologies were diagnosed, none of which were significantly associated with grade. Among non-frail patients at OGD2, BO was the only pathology more common (p=0.010) in patients with grade D. Rates of cancer, dysplasia and strictures did not vary significantly between grades. Conclusion: Our data demonstrate that OGD2s in patients with severe oesophagitis may be tailored according to clinical frailty and only be offered to non-frail patients. In non-frail patients OGD2s have similar pick-up rates of sinister pathology in both grades of severe oesophagitis.

Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro.

The gut-liver axis is defined by dietary and environmental communication between the gut, microbiome and the liver with its redox and immune systems, the overactivation of which can lead to hepatic injury. We used media preconditioning to mimic some aspects of the enterohepatic circulation by treating the human Caco-2 intestinal epithelial cell line with 5, 10 and 20 mM paracetamol (N-acetyl-para-aminophenol; APAP) for 24 h, after which cell culture supernatants were transferred to differentiated human hepatic HepaRG cells for a further 24 h. Cell viability was assessed by mitochondrial function and ATP production, while membrane integrity was monitored by cellular-based impedance. Metabolism by Caco-2 cells was determined by liquid chromatography with tandem mass spectrometry. Caco-2 cell viability was not affected by APAP, while cell membrane integrity and tight junctions were maintained and became tighter with increasing APAP concentrations, suggesting a reduction in the permeability of the intestinal epithelium. During 24 h incubation, Caco-2 cells metabolised 64-68% of APAP, leaving 32-36% of intact starting compound to be transferred to HepaRG cells. When cultured with Caco-2-preconditioned medium, HepaRG cells also showed no loss of cell viability or membrane integrity, completely in contrast to direct treatment with APAP, which resulted in a rapid loss of cell viability and membrane integrity and, ultimately, cell death. Thus, the pre-metabolism of APAP could mitigate previously observed hepatotoxicity to hepatic tight junctions caused by direct exposure to APAP. These observations could have important implications for the direct exposure of hepatic parenchyma to APAP, administered via the intravenous route.

Gastrointestinal and liver disease in patients with schizophrenia: A narrative review.

Schizophrenia is a severe mental illness which can have a devastating impact on an individual's quality of life. Comorbidities are high amongst patients and life expectancy is approximately 15 years less than the general population. Despite the well-known increased mortality, little is known about the impact of gastrointestinal and liver disease on patients with schizophrenia. We aimed to review the literature and to make recommendations regarding future care. Literature searches were performed on PubMed to identify studies related to gastrointestinal and liver disease in patients with schizophrenia. High rates of chronic liver disease were reported, with Non-Alcoholic Fatty Liver Disease being of particular concern; antipsychotics and metabolic syndrome were contributing factors. Rates of acute liver failure were low but have been associated with antipsychotic use and paracetamol overdose. Coeliac disease has historically been linked to schizophrenia; however, recent research suggests that a causal link is yet to be proven. Evidence is emerging regarding the relationships between schizophrenia and peptic ulcer disease, inflammatory bowel disease and irritable bowel syndrome; clinical vigilance regarding these conditions should be high. Patients with schizophrenia poorly engage with bowel cancer screening programmes, leading to late diagnosis and increased mortality. Clozapine induced constipation is a significant issue for many patients and requires close monitoring. There is a significant burden of gastrointestinal and liver disease amongst patients with schizophrenia. Better levels of support from all members of the medical team are essential to ensure that appropriate, timely care is provided.

Unsedated Transnasal Endoscopy: A Safe, Well-Tolerated and Accurate Alternative to Standard Diagnostic Peroral Endoscopy.

Diagnostic unsedated transnasal endoscopy (uTNE) has been proven to be a safe and well-tolerated procedure. Although its utilization in the United Kingdom (UK) is increasing, it is currently available in only a few centers. Through consideration of recent studies, we aimed to perform an updated review of the technological advances in uTNE, consider their impact on diagnostic accuracy, and to determine the role of uTNE in the COVID-19 era. Current literature has shown that the diagnostic accuracy of uTNE for identification of esophageal pathology is equivalent to conventional esophagogastroduodenoscopy (cEGD). Concerns regarding suction and biopsy size have been addressed by the introduction of TNE scopes with working channels of 2.4 mm. Advances in imaging have improved detection of early gastric cancers. The procedure is associated with less cardiac stress and reduced aerosol production; when combined with no need for sedation and improved rates of patient turnover, uTNE is an efficient and safe alternative to cEGD in the COVID-19 era. We conclude that advances in technology have improved the diagnostic accuracy of uTNE to the point where it could be considered the first line diagnostic endoscopic investigation in the majority of patients. It could also play a central role in the recovery of diagnostic endoscopic services during the COVID-19 pandemic.

Risk stratifying gastric ulcers: development and validation of a scoring system.

Objective: Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score. Design/method: All patients in National Health Service (NHS) Lothian with an index OGD and a diagnosis of gastric ulcer between 1 January 2014 and 31 December 2018 were identified. Data were analysed with logistic regression to identify factors significantly associated with a diagnosis of cancer; a risk score was derived and externally validated. Results: 778 patients were identified and 60.3% (469/778) of patients had a follow-up OGD. 8.6% (66/778) of patients were diagnosed with cancer. No cases of cancer were found on follow-up OGD of a benign appearing ulcer with negative biopsies. Macroscopic suspicion of malignancy was present at index OGD in 100% (3/3) of those diagnosed with cancer on subsequent OGDs. Older age (p=0.014), increased ulcer size (p<0.001) and non-antral location (p=0.030) were significantly associated with malignancy. A risk score (area under the curve (AUC) 0.868, p<0.001, minimum score=0, maximum score=6) was derived from these variables. 78.0% of patients with malignant ulcers scored ≥3, only 15.8% with benign ulcers scored ≥3 (negative predictive value (NPV) 97.4%). External validation yielded an AUC of 0.862 (p<0.001) and NPV of 98.6%; 84.0% of those with malignant ulcers scored ≥3. Conclusion: Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up.

Thrombin Is an Effective and Safe Therapy in the Management of Bleeding Gastric Varices. A Real-World Experience.

Variceal haemorrhage is a severe complication of liver disease with high mortality. Human recombinant thrombin has gained popularity in the management of variceal haemorrhage. We report on the use of thrombin for gastric and ectopic varices at a regional tertiary care centre. This was a retrospective observational study. Patients with portal hypertension who received endoscopic injection of recombinant thrombin were identified and data collected on haemostasis and rebleeding rates, complications and mortality. Patients were grouped by indication for thrombin injection: gastric/oesophageal/ectopic varices and endoscopic band ligation (EBL)-induced ulceration. 155 patients (96M/59F, mean age 58.3 years) received endoscopic thrombin injection. Mean volume of thrombin injected at index endoscopy was 9.5 ml/2375IU. Initial haemostasis was achieved in 144 patients (92.9%). Rebleeding occurred in a total of 53 patients (36.8%) divided as follows: early rebleeding (<5 days from index endoscopy)-26 patients (18%); rebleeding within 30 days-42 patients (29.1%); delayed rebleeding (> 30 days)-11 patients (7.6%). There was statistically significant difference in rate of initial haemostasis between Child-Pugh A/B patients vs Child-Pugh C (p = 0.046). There was no significant difference in rebleeding rates between different indication groups (p = 0.78), by presence of cirrhosis or by Child-Pugh Score. All-cause mortality at 6 weeks was 18.7%; 1-year mortality 37.4% (median follow-up 48 months). There was no significant difference in mortality between groups (p = 0.37). No significant adverse events or complications were reported. Thrombin is effective and safe for gastric varices and other portal-hypertension-related bleeding including oesophageal varices, ulcers secondary to EBL and ectopic varices.

Frontiers of Robotic Gastroscopy: A Comprehensive Review of Robotic Gastroscopes and Technologies.

Upper gastrointestinal (UGI) tract pathology is common worldwide. With recent advancements in robotics, innovative diagnostic and treatment devices have been developed and several translational attempts made. This review paper aims to provide a highly pictorial critical review of robotic gastroscopes, so that clinicians and researchers can obtain a swift and comprehensive overview of key technologies and challenges. Therefore, the paper presents robotic gastroscopes, either commercial or at a progressed technology readiness level. Among them, we show tethered and wireless gastroscopes, as well as devices aimed for UGI surgery. The technological features of these instruments, as well as their clinical adoption and performance, are described and compared. Although the existing endoscopic devices have thus far provided substantial improvements in the effectiveness of diagnosis and treatment, there are certain aspects that represent unwavering predicaments of the current gastroenterology practice. A detailed list includes difficulties and risks, such as transmission of communicable diseases (e.g., COVID-19) due to the doctor-patient proximity, unchanged learning curves, variable detection rates, procedure-related adverse events, endoscopists' and nurses' burnouts, limited human and/or material resources, and patients' preferences to choose non-invasive options that further interfere with the successful implementation and adoption of routine screening. The combination of robotics and artificial intelligence, as well as remote telehealth endoscopy services, are also discussed, as viable solutions to improve existing platforms for diagnosis and treatment are emerging.

Poor Quality of Small Bowel Capsule Endoscopy Images Has a Significant Negative Effect in the Diagnosis of Small Bowel Malignancy.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is a visual modality; hence, diagnosis relies on image quality. We studied the contribution of image parameters to visualization quality and their effect on diagnostic certainty of small bowel (SB) lesions. METHODS: Five clear CE images of common SB pathology - two vascular lesions, two inflammatory, one polyp - were processed for three image parameters to simulate poor SB conditions: opacity (color-matched to luminal content; 10-90%, 10% increments); blurriness (radius 1-10 pixels; one pixel increments); and contrast (-50-50%; 10% increments). Nine expert readers evaluated whether images were adequate for diagnosis. Points where perception of image quality changed significantly were determined for each parameter. Three further sets of SBCE images (vascular, inflammatory, and neoplastic lesions; nine images/set) were processed for four points/parameters. Twenty experienced/expert CE readers reviewed these images. RESULTS: The negative effects of opacity in diagnostic certainty were mostly evident in images of neoplasia; images of vascular and inflammatory lesions were less affected. Similar results were observed with increasing blur radius, simulating movement, and poor focus. The proportions of readers finding vascular and inflammatory images adequate for diagnosis did not drop significantly at wider blur radii, while images of neoplasia were quickly deemed inadequate. Low contrast had a greater negative effect than high, most consistently in neoplastic lesions. CONCLUSION: Poor visualization quality in all parameters affected mostly neoplastic lesions. Software to increase contrast and sharpen images can improve visualization quality; smart frame rate adaptation could improve the number of high-quality frames obtained. Thoroughness in SB cleansing is most important when there is a suspicion of neoplasia.

Balloon-Assisted Colonoscopy after Incomplete Conventional Colonoscopy-Experience from Two European Centres with A Comprehensive Review of the Literature.

BACKGROUND: Conventional colonoscopy (CC) allows access for colonic investigation and intervention; in the small group in whom CC is unsuccessful alternative imaging is often sufficient. There remains a subset, however, requiring full colonic visualisation or intervention. Balloon-assisted colonoscopy (BAC) gives a further option when access is difficult. Aims: This study aims to present the experience with BAC of two European tertiary referral centres. Methods: Procedures were carried out under local protocol over 15-years (2006-2020). Markers of procedural quality such as caecal intubation, complications and comfort were retrospectively compiled and analysed. Published evidence was summarised for comparison. Results: 122 procedures were undertaken, with polyps the most frequent indication and 90.2% having at least one previously incomplete CC. Features associated with difficult colonoscopy were common, including intraabdominal surgery (32.0%). 92.6% reached the caecum; completion was higher (96.3%) in those failing CC due to discomfort and lower in those failing due to anatomical difficulties (90.7%) or previous surgery (84.6%). Mean time to the caecum was 20.9 minutes and mean midazolam and fentanyl doses were 2.6 mg and 49.9 µg with low discomfort scores. Conclusion(s): Balloon-assisted colonoscopy is successful in >90% of patients, is well-tolerated, and is safe.

Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Analysis of volatile organic compounds (VOCs) in exhaled breath, 'volatomics', provides opportunities for non-invasive biomarker discovery and novel mechanistic insights into a variety of diseases. The purpose of this pilot study was to compare breath VOCs in an initial cohort of patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls. METHODS: Breath samples were collected from 15 participants with Child-Pugh class A NAFLD cirrhosis, 14 with non-cirrhotic NAFLD, and 14 healthy volunteers. Exhaled breath samples were collected using an established methodology and VOC profiles were analysed by gas chromatography-mass spectrometry. The levels of 19 VOCs previously associated with cirrhosis were assessed. Peaks of the VOCs were confirmed and integrated using Xcalibur® software, normalised to an internal standard. Receiver-operating characteristic (ROC) curves were used to determine the diagnostic accuracy of the candidate VOCs. RESULTS: Terpinene, dimethyl sulfide, and D-limonene provided the highest predictive accuracy to discriminate between study groups. Combining dimethyl sulfide with D-limonene led to even better discrimination of patients with NAFLD cirrhosis from healthy volunteers (AUROC 0.98; 95% CI 0.93-1.00; p <0.001) and patients with NAFLD cirrhosis from those with non-cirrhotic NAFLD (AUROC 0.91; 95% CI 0.82-1.00; p <0.001). Breath terpinene concentrations discriminated between patients with non-cirrhotic NAFLD and healthy volunteers (AUROC 0.84; 95% CI 0.68-0.99; p = 0.002). CONCLUSION: Breath terpinene, dimethyl sulfide, and D-limonene are potentially useful volatomic markers for stratifying NAFLD; in addition, a 2-stage approach enables the differentiation of patients with cirrhosis from those without. However, these observations require validation in a larger NAFLD population. (ClinicalTrials.gov Identifier: NCT02950610). LAY SUMMARY: Breath malodour has been associated with a failing liver since the ancient Greeks. Analytical chemistry has provided us an insight into ubiquitous volatile organic compounds associated with liver (and other) diseases. This has vastly improved our understanding of the mechanistic processes of liver damage. Our study aims to identify volatile organic compounds which are specific to non-alcoholic fatty liver disease and that can be exploited for rapid diagnostics.

Small bowel angioectasia as a marker of frailty and poor prognosis.

Background and study aims This study aimed to establish 5-year survival of patients diagnosed with bleeding small bowel (SB) angioectasia, with the hypothesis that many will suffer deaths relating to comorbidity rather than gastrointestinaI bleeding. Patients and methods SB capsule endoscopy (SBCE) procedures, performed for suspected SB bleeding or iron deficiency anemia, with angioectasia isolated as the cause of SB bleeding and at least 5 years of follow-up data were isolated (n = 125) along with an age-matched group with "normal" SBCE procedures (n = 125). These were retrospectively analysed with further information on mortality and comorbidity gathered through hospital records. Results Those with angioectasia had a median age of 72.7 years and comorbidities were common. The 5-year survival was 64.0 % (80/125) compared to 70.4 % (88/125) in those with "normal" SBCE. Those with significant cardiac or vascular comorbidity had a poorer survival (52.9 % (37/70) at 5 years) but anticoagulation/antiplatelets/ number of lesions or requirement endoscopic treatment seemed to make little difference. In those with SB bleeding secondary to angioectasia none of the subsequent deaths were directly attributable to gastrointestinal bleeding. Conclusions In this cohort, SB angioectasia did not lead to any deaths but the 5-year survival was poor due to those diagnosed often being older and having comorbidities. This would support the hypothesis that a diagnosis of SB bleeding secondary to angioectasia suggests frailty.

SARS-CoV-2 Infection and the Liver.

A novel strain of coronoviridae (SARS-CoV-2) was reported in Wuhan China in December 2019. Initially, infection presented with a broad spectrum of symptoms which typically included muscle aches, fever, dry cough, and shortness of breath. SARS-CoV-2 enters cells via ACE2 receptors which are abundant throughout the respiratory tract. However, there is evidence that these receptors are abundant throughout the body, and just as abundant in cholangiocytes as alveolar cells, posing the question of possible direct liver injury. While liver enzymes and function tests do seem to be deranged in some patients, it is questionable if the injury is due to direct viral damage, drug-induced liver injury, hypoxia, or microthromboses. Likely, the injury is multifactoral, and management of infected patients with pre-existing liver disease should be taken into consideration. Ultimately, a vaccine is needed to aid in reducing cases of SARS-CoV-2 and providing immunity to the general population. However, while considering the types of vaccines available, safety concerns, particularly of RNA- or DNA-based vaccines, need to be addressed.

Oxygen Plasma Substrate and Specific Nanopattern Promote Early Differentiation of HepaRG Progenitors.

Fully differentiated HepaRG™ cells are the hepatic cell line of choice for in vitro study in toxicology and drug trials. They are derived from a hepatoblast-like progenitor (HepaRG-P) that differentiates into a coculture of hepatocyte-like and cholangiocyte-like cells. This process that requires 2 weeks of proliferation followed by 2 weeks of differentiation using dimethyl sulfoxide (DMSO) can be time consuming and costly. Identifying a method to accelerate HepaRG-Ps toward a mature lineage would save both time and money. The ability to do this in the absence of DMSO would remove the possibility of confounding toxicology results caused by DMSO induction of CYP pathways. It has been shown that tissue culture substrates play an important role in the development and maturity of a cell line, and this is particularly important for progenitor cells, which retain some form of plasticity. Oxygen plasma treatment is used extensively to modify cell culture substrates. There is also evidence that patterned rather than planar surfaces have a positive effect on proliferation and differentiation. In this study, we compared the effect of standard tissue culture plastic (TCP), oxygen plasma coated (OPC), and nanopatterned substrates (NPS) on early differentiation and function of HepaRG-P cells. Since NPS were OPC we initially compared the effect of TCP and OPC to enable comparison between all three culture surfaces using OPC as control to asses if patterning further enhanced early differentiation and functionality. The results show that HepaRG-P's grown on OPC substrate exhibited earlier differentiation, proliferation, and function compared with TCP. Culturing HepaRG-P's on OPC with the addition of NPS did not confer any additional advantage. In conclusion, OPC surface appeared to enhance hepatic differentiation and functionality and could replace traditional methods of differentiating HepaRG-P cells into fully differentiated and functional HepaRGs earlier than standard methods. Impact statement We show significantly earlier differentiation and function of HepaRG progenitor cells when grown in dimethyl sulfoxide-free medium on oxygen plasma substrates versus standard tissue culture plastic. Further investigation showed that nanopatterning of oxygen plasma substrates did not confer any additional advantage over smooth oxygen plasma, although one pattern (DSQ120) showed comparable early differentiation and function.

Validation of Reference Genes for Gene Expression Studies by RT-qPCR in HepaRG Cells during Toxicity Testing and Disease Modelling.

Gene expression analysis by quantitative real-time polymerase chain reaction (RT-qPCR) is routinely used in biomedical studies. The reproducibility and reliability of the data fundamentally depends on experimental design and data interpretation. Despite the wide application of this assay, there is significant variation in the validation process of gene expression data from research laboratories. Since the validity of results depends on appropriate normalisation, it is crucial to select appropriate reference gene(s), where transcription of the selected gene is unaffected by experimental setting. In this study we have applied geNorm technology to investigate the transcription of 12 'housekeeping' genes for use in the normalisation of RT-qPCR data acquired using a widely accepted HepaRG hepatic cell line in studies examining models of pre-clinical drug testing. geNorm data identified a number of genes unaffected by specific drug treatments and showed that different genes remained invariant in response to different drug treatments, whereas the transcription of 'classical' reference genes such as GAPDH (glyceralde- hyde-3-phosphate dehydrogenase) was altered by drug treatment. Comparing data normalised using the reference genes identified by geNorm with normalisation using classical housekeeping genes demonstrated substantial differences in the final results. In light of cell therapy application, RT-qPCR analyses has to be carefully evaluated to accurately interpret data obtained from dynamic cellular models undergoing sequential stages of phenotypic change.

Nomenclature and semantic descriptions of ulcerative and inflammatory lesions seen in Crohn's disease in small bowel capsule endoscopy: An international Delphi consensus statement.

BACKGROUND: In the medical literature, the nomenclature and descriptions (ND) of small bowel (SB) ulcerative and inflammatory (U-I) lesions in capsule endoscopy (CE) are scarce and inconsistent. Inter-observer variability in interpreting these findings remains a major limitation in the assessment of the severity of mucosal lesions, which can impact negatively on clinical care, training and research on SB-CE. OBJECTIVE: Focusing on SB-CE in Crohn's disease (CD), our aim is to establish a consensus on the ND of U-I lesions. METHODS: An international panel of experienced SB-CE readers was formed during the 2016 United European Gastroenterology Week meeting. A core group of five CE and inflammatory bowel disease (IBD) experts established an Internet-based, three-round Delphi consensus but did not participate in the voting process. The core group built illustrated questionnaires, including SB-CE still frames of U-I lesions from patients with documented CD. Twenty-seven other experts were asked to rate and comment on the different proposals for the ND of the most frequent SB U-I lesions. For each round, we used a 6-point rating scale (varying from 'strongly disagree' to 'strongly agree'). The consensus was reached when at least 80 % of the voting members scored the statement within the 'agree' or 'strongly agree' categories. RESULTS: A 100% participation rate was obtained for all the rounds. Consensual ND were reached for the following seven U-I lesions: aphthoid erosion, deep ulceration, superficial ulceration, stenosis, edema, hyperemia and denudation. CONCLUSION: Considering the most frequent SB U-I lesions seen in CE in CD, a consensual ND was reached by the international group of experts. These descriptions and names are useful not only for daily practice and medical education, but also for medical research.

Application of Impedance-Based Techniques in Hepatology Research.

There are a variety of end-point assays and techniques available to monitor hepatic cell cultures and study toxicity within in vitro models. These commonly focus on one aspect of cell metabolism and are often destructive to cells. Impedance-based cellular assays (IBCAs) assess biological functions of cell populations in real-time by measuring electrical impedance, which is the resistance to alternating current caused by the dielectric properties of proliferating of cells. While the uses of IBCA have been widely reported for a number of tissues, specific uses in the study of hepatic cell cultures have not been reported to date. IBCA monitors cellular behaviour throughout experimentation non-invasively without labelling or damage to cell cultures. The data extrapolated from IBCA can be correlated to biological events happening within the cell and therefore may inform drug toxicity studies or other applications within hepatic research. Because tight junctions comprise the blood/biliary barrier in hepatocytes, there are major consequences when these junctions are disrupted, as many pathologies centre around the bile canaliculi and flow of bile out of the liver. The application of IBCA in hepatology provides a unique opportunity to assess cellular polarity and patency of tight junctions, vital to maintaining normal hepatic function. Here, we describe how IBCAs have been applied to measuring the effect of viral infection, drug toxicity /IC50, cholangiopathies, cancer metastasis and monitoring of the gut-liver axis. We also highlight key areas of research where IBCAs could be used in future applications within the field of hepatology.

Cancer Risk in Collagenous Colitis.

Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 ± 11 and 66 ± 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).

Aortoenteric fistula: a rare but critical cause of small bowel bleeding discovered on capsule endoscopy.

A 78-year-old man attended for outpatient capsule endoscopy, to investigate a recent history of unexplained small bowel bleeding. His previous medical history included an abdominal aortic aneurysm repair 6 years ago. Soon after capsule ingestion, he experienced sudden onset abdominal pain and collapsed on hospital grounds. He was rapidly transferred to the emergency department as he was haemodynamically unstable, and a significant per rectum (PR) bleed was found on examination. The patient was quickly stabilised following fluid resuscitation. CT angiography was performed which did not show active bleeding. However, use of the real-time capsule viewer indicated a profuse active jejunal bleed originating from the aortic graft, suggestive of an aortoenteric fistula. The patient underwent emergency endovascular cuff placement, and subsequent endovascular abdominal aortic stent grafting, to good effect.

Mapping the distribution of small bowel angioectasias.

Background: Angioectasias are a prominent cause of small bowel (SB) bleeding frequently identified during capsule endoscopy (CE). Subsequent management depends upon grade/severity and location. There is increasing evidence that the location of SB angioectasias is not random. We aimed to map the distribution of SB angioectasias, and assess whether this impacted clinical outcomes. Materials and methods: Retrospective study examining CEs performed over a 10-year period at a tertiary referral centre. Information regarding number, location, and Saurin classification (P0-2) of SB angioectasias was collected. Clinically significant angioectasias (P1/P2) and active SB bleeding were analysed further. Outcomes of patients with P2 angioectasias or active SB bleeding were recorded. Results: 164 SBCE examinations reported angioectasias. 554 P1-2 angioectasias and active bleeds were seen, 435 (78.52%) within the first tertile of SB transit time (SBTT). 277 (50%) angioectasias were identified within the first 10% of SBTT. 40/75 (53.3%) patients with >1 P2 angioectasia and/or active bleed were referred for intervention. Of initial interventions, 24 patients underwent upper GI endoscopy; 13 underwent double balloon enteroscopy (DBE). 9/37(24.3%) had no identifiable angioectasias on endoscopy. Of those receiving ablative therapy, 20/28 (71.4%) re-presented with iron-deficiency anaemia or bleeding. In this group, average angioectasia position was 15.6% of SBTT, compared with 7.9% in those who did not re-represent (p = 0.344). Patients who re-presented had an average 1.6 additional P1 angioectasias, compared with 7.6 amongst those who did not return (p = 0.017). Conclusions: Clinically significant angioectasias are overwhelmingly located within the proximal SB. The majority are within reach of conventional endoscopy. However, AEs are often multiple and many patients re-present following intervention.

Gastrointestinal diagnosis using non-white light imaging capsule endoscopy.

Capsule endoscopy (CE) has proved to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present, and therefore, CE is limited to mucosal inspection, with diagnosis remaining reliant on visible manifestations of disease. The introduction of WLI CE has motivated a wide range of research to improve its diagnostic capabilities through integration with other sensing modalities. These developments have the potential to overcome the limitations of WLI through enhanced detection of subtle mucosal microlesions and submucosal and/or transmural pathology, providing novel diagnostic avenues. Other research aims to utilize a range of sensors to measure physiological parameters or to discover new biomarkers to improve the sensitivity, specificity and thus the clinical utility of CE. This multidisciplinary Review summarizes research into non-WLI CE devices by organizing them into a taxonomic structure on the basis of their sensing modality. The potential of these capsules to realize clinically useful virtual biopsy and computer-aided diagnosis (CADx) is also reported.