RSS 1.0Gastroenterology
Recent Submissions
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The risk of Venous Thromboembolism in children with Inflammatory Bowel DiseaseBackground: Recent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD. Methods: Hospital Episode Statistics was used to identify patients diagnosed with either IBD or VTE before reaching 18 years of age between 2001 and 2019. Populations and subgroups are described, and the risks of developing VTE in the general and IBD populations were calculated. Results: Children with VTE following a diagnosis of IBD or in the previous 6 months (n = 85) and with VTE without IBD (n = 4160) were studied. The absolute risk in children with IBD was 9.42 (95% confidence interval [CI], 7.4-11.4) per 10 000 patient-years, compared with 0.18 (95% CI, 18-0.19) in children without IBD. Between 6 months prior to and 1 year following IBD diagnosis was the highest absolute risk period for VTE (18.0; 95% CI, 13.7-22.4). The relative risk of VTE in children with IBD vs children without IBD was greatest in younger patient groups: the relative risk for the age band 0 to 8 years was 96.5 (95% CI, 51.8-179.9) and for 9 to 11 years was 153.1 (95% CI, 81.2-288.8) vs 14.3 (95% CI, 10.3-20.0) for 15 to 17 years. Cerebral venous sinus thrombosis represented 17.6% of pediatric VTE events in IBD patients compared with 4.2% in children without IBD (P = .001). Conclusions: This study confirms the increased risk of VTE in children with IBD compared with children without IBD. The time of greatest VTE risk was around diagnosis. Cerebral venous sinus thrombosis was significantly more common in children with IBD than other children.
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Bouveret syndrome managed conservatively with the insertion of a double pigtail stent between the stomach and the gallbladder.A woman in her early 90s presented to the acute surgical take with a 3-day history of worsening reflux, vomiting, epigastric pain and constipation. Subsequent imaging demonstrated two large, impacted gallstones in the pylorus and proximal jejunum secondary to a cholecystoduodenal fistula. A diagnosis of Bouveret syndrome was made, and endoscopic attempts to break down and remove the stones were unsuccessful. The stones were left in the stomach, with a pigtail stent placed through the fistula between the stomach and gallbladder to prevent the stones impacting again and to allow adequate drainage of the gallbladder to prevent further flare-ups. Due to the patient's comorbidities, it was decided to leave the stent in situ long term as opposed to surgical management. This has shown to be successful in follow-up. Our case highlights that Bouveret syndrome can potentially be managed conservatively long term in patients deemed unfit for major surgical intervention.
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Open label vancomycin in primary sclerosing cholangitis-inflammatory bowel disease: improved colonic disease activity and associations with changes in host-microbiome-metabolomic signatures.Background: We conducted a single-arm interventional study, to explore mucosal changes associated with clinical remission under oral vancomycin (OV) treatment, in primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD); NCT05376228. Method: Fifteen patients with PSC and active colitis (median faecal calprotectin 459µg/g; median total Mayo score 5) were treated with OV (125mg QID) for 4 weeks and followed-up for a further 4 weeks of treatment withdrawal (8 weeks, end-of-study). Colonic biopsies were obtained at baseline and week 4. Clinical assessments, and serum and stool samples (metagenomics, metatranscriptomics and metabolomics) were collected at weeks 0, 2, 4 and 8. The primary efficacy outcome measure was induction of clinical remission. Results: OV resulted in clinical remission in 12/15 patients and significant reductions in faecal calprotectin. OV was associated with reduced abundances of Lachnospiraceae, genera Blautia and Bacteroides; and enrichment of Enterobacteriaceae, and genera Veillonella, Akkermansia and Escherichia. OV treatment was associated with downregulation of multiple metatranscriptomic pathways (including short chain fatty acid [SCFA] metabolism and bile acid [BA] biotransformation), along with host genes and multiple pathways involved in inflammatory responses and antimicrobial defence; and an upregulation of genes associated with extracellular matrix repair. OV use resulted in loss of specific faecal SCFAs and secondary BAs, including lithocholic acid derivatives. Colitis activity relapsed following OV withdrawal, with host mucosal and microbial changes trending towards baseline. Conclusion: Four weeks of OV induces remission in PSC-IBD activity, associated with a reduction in gut bacterial diversity and compositional changes relating to BA and SCFA homeostasis.
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the long lost denture: a rare case of an acquired, non-malignant tracheo-oesophageal fistula.Background: Ingested dental prosthesis are susceptible to impaction in the gastrointestinal tract due to their sharp edges, size and contour. Delays in presentation arise from the lack of clear history of ingestion and misdiagnosis occurs due to the radiolucency of denture material on plain radiography. An acquired, non-malignant tracheo-oesophageal fistula (TOF) may develop from a chronically impacted denture. Surgical management of a TOF secondary to denture is a challenging clinical problem that is rarely reported in the literature and no previous case reports have described the two-staged reconstruction approach that we present here. Case presentation: We report a case of a male in his early 60s who presented to an acute general hospital with symptoms ongoing for over one year of dysphagia, recurrent chest infections and weight loss. Barium swallow and computed tomography identified an ingested dental prosthesis (denture) that had caused a TOF. He was transferred to our specialist thoracic surgery unit where an attempt to remove the foreign body endoscopically was abandoned due to firm impaction and risk of further injury. The subsequent multi-disciplinary management of this complex case required a two-staged reconstruction approach. The first procedure involved extracting the foreign body, repairing the underlying defects with tracheal resection and anastomosis, and creating an oesophageal diversion with cervical oesophagostomy. The second procedure achieved continuity of the gastrointestinal tract with gastric pull-up and pharyngo-gastric anastomosis. Following rehabilitation, the patient was discharged on oral intake alongside percutaneous jejunostomy feeding. Conclusions: Early recognition and removal of impacted dental prosthesis is essential to prevent morbidity and mortality. Delayed diagnosis can lead to acquired TOF with associated consequences such as recurrent pulmonary infection, mediastinitis and nutritional deficit. Challenges we encountered, such as failed attempts at endoscopic retrieval and the difficult dissection of fibrotic tissue, were directly due to the delayed identification of the denture. We highlight the importance of holding a high index of clinical suspicion of foreign body ingestion in dental prosthesis wearers who present with recurrent chest infections and ongoing dysphagia. We also promote the need for a collaborative multi-disciplinary approach in the surgical management of complex cases.
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Cecal volvulus in marfan syndrome.Gastrointestinal pathology in adult patients with Marfan Syndrome is rarely reported in literature. Nevertheless, it could be life threatening when it occurs. In our paper, we are presenting the first reported case of caecal volvulus in an adult patient with Marfan Syndrome, our findings and management. We also discuss the more common radiological findings that may enhance decision making amongst surgical clinicians. A high index of suspicion and a multidisciplinary approach is advised when encountering these group of patients.
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Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials.Aims: Weight loss mediated by glucagon-like peptide-1 (GLP-1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP-1 analogue semaglutide. Materials and methods: This was a post hoc analysis of data from three 48-72-week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy-confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre-type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations. Results: The overall mean weight change was -11.1 kg (-11.7%) and -0.7 kg (-0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (-10.2 kg; -10.8%), pre-type 2 diabetes (-9.8 kg; -10.2%) and no diabetes (-11.6 kg; -13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change. Conclusions: People with MASLD/MASH had similar semaglutide-mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters.
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Can a transition clinic bridge the gap between paediatric and adult inflammatory bowel disease care models?Transition care in inflammatory bowel disease is increasingly recognized as challenging given the inherent differences between paediatric and adult health care models, disease characteristics and treatment strategies. Transition is a dynamic process involving adolescents and young adults that are moving from a paediatric to an adult health care setting, and it should be flexible, continually updated and tailored to each patient. The implementation of a transition clinic is essential given the increasing incidence of the paediatric population with inflammatory bowel disease and the lifelong impact of this disease. The key question is when and how to structure transition according to the adolescent's clinical, psycho-social, educational needs and expectations to ensure continuity of care. In the attempt to improve the management of transition in inflammatory bowel disease and address the wide gap between adult and child care, we provide an update of the transition clinic and we propose a "treat to target" approach in transition to facilitate an effective and successful transition programme. In the changing landscape of the treatment of inflammatory bowel disease, further studies are necessary to determine the role of the transition clinic in determining the choice and strategy of therapy and its monitoring and the adoption of newer strategies such as biomarkers guided treating to target.
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Combined portal and hepatic vein embolisation in perihilar cholangiocarcinomaBackground: Major hepatectomy in perihilar cholangiocarcinoma (pCCA) patients with a small future liver remnant (FLR) risks posthepatectomy liver failure (PHLF). This study examines combined portal and hepatic vein embolisation (PVE/HVE) to increase preoperative FLR volume and potentially decrease PHLF rates. Methods: In this retrospective, multicentre, observational study, data was collected from centres affiliated with the DRAGON Trials Collaborative and the EuroLVD registry. The study included pCCA patients who underwent PVE/HVE between July 2016 and January 2023. Results: Following PVE/HVE, 28% of patients (9/32) experienced complications, with 22% (7/32) necessitating biliary interventions for cholangitis. The median degree of hypertrophy after a median of 16 days was 16% with a kinetic growth rate of 6.8% per week. 69% of patients (22/32) ultimately underwent surgical resection. Cholangitis after PVE/HVE was associated with unresectability. After resection, 55% of patients (12/22) experienced complications, of which 23% (5/22) were Clavien-Dindo grade III or higher. The 90-day mortality after resection was 0%. Conclusion: PVE/HVE quickly enhances the kinetic growth rate in pCCA patients. Cholangitis impairs chances on resection significantly. Resection after PVE/HVE is associated with low levels of 90-day mortality. The study highlights the potential of PVE/HVE in improving safety and outcomes in pCCA undergoing resection.
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British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemicThe COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.
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International consensus statement on microbiome testing in clinical practiceThere is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.
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Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modellingInflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.
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A home-based exercise programme attenuates fatigue in primary biliary cholangitis: results from the EXCITED clinical trialBackground & aims: Fatigue is a commonly reported symptom of primary biliary cholangitis (PBC). We conducted a single-arm, open-label clinical trial to assess the efficacy of a physiotherapist-led home-based exercise programme (HBEP) in patients with PBC and moderate-to-severe fatigue (NCT04265235). Methods: A 12-week individualised HBEP (aerobic + resistance based) was delivered to patients with a PBC-40 fatigue domain score ≥33. The primary efficacy outcome measure was a reduction in fatigue severity by ≥5 points. Secondary outcome measures included other domains of PBC-40, the FIS (fatigue impact scale), ESS (Epworth sleepiness score), HADS (hospital anxiety and depression scale), aerobic capacity (ISWT [incremental shuttle walk test], Duke activity status index (predicted VO₂ peak) and physical function (short physical performance battery [SPPB]). Results: A total of 31 patients were recruited, of whom 30 completed the 12-week HBEP (29 women; median age 53 years, median alkaline phosphatase value: 1.5x the upper limit of normal, median bilirubin: 12 μmol/L, and median baseline PBC-40 fatigue score 42). The primary outcome was met by 26 patients, with a median reduction in PBC-40 fatigue score of -10.5 points (IQR -9 to -13; p <0.001). Reductions were also observed in the symptom, cognition, and emotion domains of PBC-40, and in the FIS, ESS and HADS (p <0.01 for all measures). This was alongside increases in the median ISWT (+90 m; IQR 57.5-110), predicted VO₂ peak (+2.41 ml/kg/min; IQR 0.01-4.05), and SPPB (+1 point; IQR 0-1.4) (all p <0.001). 28 participants achieved the maximum SPPB score of 12/12 (vs. 13 patients at baseline; p <0.001). No significant adverse events were reported. Conclusion: This proof-of-concept study shows that a HBEP is safe, feasible, and has the potential to attenuate fatigue. Controlled trials are needed to validate the efficacy of exercise interventions in PBC. Impact and implications: Fatigue is a common symptom in primary biliary cholangitis (PBC), and is linked to cognitive dysfunction, somnolence, and reduced activity. The pathogenesis is multifactorial, and muscle bioenergetic abnormalities have been proposed to contribute. In this study, we show that a home-based exercise programme, consisting of aerobic and resistance-based sets, can be safely delivered to people living with PBC. In addition, the programme led to a reduction in fatigue severity, less daytime sleepiness and improved cognitive function.
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Plasma exchange does not improve overall survival in patients with acute liver failure in a real-world cohortBackground & aims: Therapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF. Methods: This multicentre retrospective cohort study included consecutive patients with ALF admitted to all seven tertiary liver transplant centres in the UK between June 2013 and December 2021. Changes in clinical variables following PEX treatment were assessed, while overall survival and transplant-free survival up to hospital discharge in patients receiving PEX were compared to those receiving standard medical therapy Propensity score matching was performed to control for intergroup covariates and selection bias. Results: We included 378 patients with ALF (median [IQR] age 36 (28-48), 64% [n = 242] female) of whom 120 received PEX. There was a significant improvement in most clinical variables following PEX, including median dose of noradrenaline (reduction from 0.35 μg/kg/min [0.19-0.70 μg/kg/min] to 0.16 μg/kg/min [0.08-0.49], p = 0.001). There was no significant difference between PEX and standard medical therapy groups in overall survival (51.4% vs. 62.6%, respectively, p = 0.12) or transplant-free survival (42.6% vs. 53.1%, p = 0.24). Conclusion: PEX is now frequently used in the management of patients with ALF in the UK. It is associated with significant improvement in haemodynamic parameters but not survival benefit. Impact and implications: Therapeutic plasma exchange is frequently used in the management of patients with acute liver failure in the UK. This real-world study demonstrates significant improvement in haemodynamic status but has not confirmed the survival benefit seen in previous published literature. These results should help guide the future use of plasma exchange in this patient population.
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Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis.Gremlin-1 has been implicated in liver fibrosis in metabolic dysfunction-associated steatohepatitis (MASH) via inhibition of bone morphogenetic protein (BMP) signalling and has thereby been identified as a potential therapeutic target. Using rat in vivo and human in vitro and ex vivo model systems of MASH fibrosis, we show that neutralisation of Gremlin-1 activity with monoclonal therapeutic antibodies does not reduce liver inflammation or liver fibrosis. Still, Gremlin-1 was upregulated in human and rat MASH fibrosis, but expression was restricted to a small subpopulation of COL3A1/THY1+ myofibroblasts. Lentiviral overexpression of Gremlin-1 in LX-2 cells and primary hepatic stellate cells led to changes in BMP-related gene expression, which did not translate to increased fibrogenesis. Furthermore, we show that Gremlin-1 binds to heparin with high affinity, which prevents Gremlin-1 from entering systemic circulation, prohibiting Gremlin-1-mediated organ crosstalk. Overall, our findings suggest a redundant role for Gremlin-1 in the pathogenesis of liver fibrosis, which is unamenable to therapeutic targeting.
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Role of telemedicine in inflammatory bowel disease: systematic review and meta-analysis of randomized controlled trialsBackground: Telemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. Objective: This systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. Methods: We systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. Results: A total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference -0.71, 95% CI -1.07 to -0.36; P<.001). Subgroup analysis showed that adolescents in the telemedicine group had significantly higher IBD-specific QoL than those in the standard care group (standard mean difference 0.42, 95% CI 0.15 to 0.69; I2=0; P.002), but there was no significant difference between adults in the 2 groups. There were no significant differences in disease activity, remission rate, patient satisfaction, depression, self-efficacy, generic QoL, and medication adherence outcomes between the telemedicine and standard care groups. Conclusions: Telemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine.
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Role of early transjugular intrahepatic portosystemic stent-shunt in acute variceal bleeding: An update of the evidence and future directionsVariceal bleeding is a serious complication of cirrhosis and portal hypertension. Despite the improvement in management of acute variceal bleed (AVB), it still carries significant mortality. Portal pressure is the main driver of variceal bleeding and also a main predictor of decompensation. Reduction in portal pressure has been the mainstay of management of variceal bleeding. Transjugular intrahepatic porto-systemic stent shunt (TIPSS) is a very effective modality in reducing the portal hypertension and thereby, controlling portal hypertensive bleeding. However, its use in refractory bleeding (rescue/salvage TIPSS) is still associated with high mortality. "Early" use of TIPSS as a "pre-emptive strategy" in patients with AVB at high risk of failure of treatment has shown to be superior to standard treatment in several studies. While patients with Child C cirrhosis (up to 13 points) clearly benefit from early-TIPSS strategy, it's role in less severe liver disease (Child B) and more severe disease (Child C > 13 points) remains less clear. Moreover, standard of care has improved in the last decade leading to improved 1-year survival in high-risk patients with AVB as compared to earlier "early" TIPSS studies. Lastly in the real world, only a minority of patients with AVB fulfil the stringent criteria for early TIPSS. Therefore, there is unmet need to explore role of early TIPSS in management of AVB in well-designed prospective studies. In this review, we have appraised the role of early TIPSS, patient selection and discussed future directions in the management of patients with AVB.
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Regulatory T-Cell therapy in liver transplantation and chronic liver diseaseThe constant exposure of the liver to gut derived foreign antigens has resulted in this organ attaining unique immunological characteristics, however it remains susceptible to immune mediated injury. Our understanding of this type of injury, in both the native and transplanted liver, has improved significantly in recent decades. This includes a greater awareness of the tolerance inducing CD4+ CD25+ CD127low T-cell lineage with the transcription factor FoxP3, known as regulatory T-Cells (Tregs). These cells comprise 5-10% of CD4+ T cells and are known to function as an immunological "braking" mechanism, thereby preventing immune mediated tissue damage. Therapies that aim to increase Treg frequency and function have proved beneficial in the setting of both autoimmune diseases and solid organ transplantations. The safety and efficacy of Treg therapy in liver disease is an area of intense research at present and has huge potential. Due to these cells possessing significant plasticity, and the potential for conversion towards a T-helper 1 (Th1) and 17 (Th17) subsets in the hepatic microenvironment, it is pre-requisite to modify the microenvironment to a Treg favourable atmosphere to maintain these cells' function. In addition, implementation of therapies that effectively increase Treg functional activity in the liver may result in the suppression of immune responses and will hinder those that destroy tumour cells. Thus, fine adjustment is crucial to achieve this immunological balance. This review will describe the hepatic microenvironment with relevance to Treg function, and the role these cells have in both native diseased and transplanted livers.
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Recurrence and survival following microwave, radiofrequency ablation, and hepatic resection of colorectal liver metastases: A systematic review and network meta-analysis.Background: Gold standard for colorectal liver metastases (CRLM) remains hepatic resection (HR). However, patients with severe comorbidities, unresectable or deep-situated resectable CRLM are candidates for ablation. The aim of the study was to compare recurrence rate and survival benefit of the microwave ablation (MWA), radiofrequency ablation (RFA) and HR by conducting the first network meta-analysis. Data sources: Systematic search of the literature was conducted in the electronic databases. Both updated traditional and network meta-analyses were conducted and the results were compared between them. Results: HR cohort demonstrated significantly less local recurrence rate and better 3- and 5-year disease-free (DFS) and overall survival (OS) compared to MWA and RFA cohorts. HR cohort included significantly younger patients and with significantly lower preoperative carcinoembryonic antigen (CEA) by 10.28 ng/mL compared to RFA cohort. Subgroup analysis of local recurrence and OS of solitary and ≤ 3 cm CRLMs did not demonstrate any discrepancies when compared with the whole sample. Conclusions: For resectable CRLM the treatment of choice still remains HR. MWA and RFA can be used as a single or adjunct treatment in patients with unresectable CRLM and/or prohibitive comorbidities.
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Recent advances in clinical practice: epidemiology of autoimmune liver diseasesAutoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.
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Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease.Background: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain. Aims: To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. Methods: Adults with moderately active disease (CDAI > 220-450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 μg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy. Results: Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location. Conclusion: Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study. Trial registration: ClinicalTrials.gov NCT01783106.