Gastroenterology

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Effects of pancreatic fistula after minimally invasive and open pancreatoduodenectomy
(American Medical Association, 2024-12-04) Bruna, Caro L; Emmen, Anouk M L H; Wei, Kongyuan; Sutcliffe, Robert P; Shen, Baiyong; Fusai, Guiseppe K; Shyr, Yi-Ming; Khatkov, Igor; White, Steve; Jones, Leia R; Manzoni, Alberto; Kerem, Mustafa; Groot Koerkamp, Bas; Ferrari, Clarissa; Saint-Marc, Olivier; Molenaar, I Quintus; Bnà, Claudio; Dokmak, Safi; Boggi, Ugo; Liu, Rong; Jang, Jin-Young; Besselink, Marc G; Abu Hilal, Mohammad; Liver; Medical and Dental; Sutcliffe, Robert
Importance: Postoperative pancreatic fistulas (POPF) are the biggest contributor to surgical morbidity and mortality after pancreatoduodenectomy. The impact of POPF could be influenced by the surgical approach. Objective: To assess the clinical impact of POPF in patients undergoing minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD). Design, setting, and participants: This cohort study was conducted from 2007 to 2020 in 36 referral centers in Europe, South America, and Asia. Participants were patients with POPF (grade B/C as defined by the International Study Group of Pancreatic Surgery [ISGPS]) after MIPD and OPD (MIPD-POPF, OPD-POPF). Propensity score matching was performed in a 1:1 ratio based on the variables age (continuous), sex, body mass index (continuous), American Society of Anesthesiologists score (dichotomous), vascular involvement, neoadjuvant therapy, tumor size, malignancy, and POPF grade C. Data analysis was performed from July to October 2023. Exposure: MIPD and OPD. Main outcomes and measures: The primary outcome was the presence of a second clinically relevant (ISGPS grade B/C) complication (postpancreatic hemorrhage [PPH], delayed gastric emptying [DGE], bile leak, and chyle leak) besides POPF. Results: Overall, 1130 patients with POPF were included (558 MIPD and 572 OPD), of whom 336 patients after MIPD were matched to 336 patients after OPD. The median (IQR) age was 65 (58-73) years; there were 703 males (62.2%) and 427 females (37.8%). Among patients who had MIPD-POPF, 129 patients (55%) experienced a second complication compared with 95 patients (36%) with OPD-POPF (P < .001). The rate of PPH was higher with MIPD-POPF (71 patients [21%] vs 22 patients [8.0%]; P < .001), without significant differences for DGE (65 patients [19%] vs 45 patients [16%]; P = .40), bile leak (43 patients [13%] vs 52 patients [19%]; P = .06), and chyle leak (1 patient [0.5%] vs 5 patients [1.9%]; P = .39). MIPD-POPF was associated with a longer hospital stay (median [IQR], 27 [18-38] days vs 22 [15-30] days; P < .001) and more reoperations (67 patients [21%] vs 21 patients [7%]; P < .001) but comparable in-hospital/30-day mortality (25 patients [7%] vs 7 patients [5%]; P = .31) with OPD-POPF, respectively. Conclusions and relevance: This study found that for patients after MIPD, the presence of POPF is more frequently associated with other clinically relevant complications compared with OPD. This underscores the importance of perioperative mitigation strategies for POPF and the resulting PPH in high-risk patients.
Efficacy of Upadacitinib in a randomized trial of patients with active ulcerative colitis.
(W.B. Saunders, 2020-02-22) Sandborn, William J; Ghosh, Subrata; Panes, Julian; Schreiber, Stefan; D'Haens, Geert; Tanida, Satoshi; Siffledeen, Jesse; Enejosa, Jeffrey; Zhou, Wen; Othman, Ahmed A; Huang, Bidan; Higgins, Peter D R
Background & aims: We evaluated the efficacy and safety of upadacitinib, an oral selective inhibitor of Janus kinase 1, as induction therapy for ulcerative colitis (UC). Methods: We performed a multicenter, double-blind, phase 2b study of 250 adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressive agents, and/or biologic therapies. Patients were randomly assigned to groups that received placebo or induction therapy with upadacitinib (7.5 mg, 15 mg, 30 mg, or 45 mg, extended release), once daily for 8 weeks. The primary endpoint was the proportion of participants who achieve clinical remission according to the adapted Mayo score at week 8. No multiplicity adjustments were applied. Results: At week 8, 8.5%, 14.3%, 13.5%, and 19.6% of patients receiving 7.5 mg, 15 mg, 30 mg, or 45 mg upadacitinib, respectively, achieved clinical remission compared with none of the patients receiving placebo (P = .052, P = .013, P = .011, and P = .002 compared with placebo, respectively). Endoscopic improvement at week 8, defined as endoscopic subscore of ≤ 1, was achieved in 14.9%, 30.6%, 26.9%, and 35.7% of patients receiving upadacitinib 7.5 mg, 15 mg, 30 mg, or 45 mg, respectively, compared with 2.2% receiving placebo (P = .033, P < .001, P < .001, and P < .001 compared with placebo, respectively). One event of herpes zoster and 1 participant with pulmonary embolism and deep venous thrombosis (diagnosed 26 days after treatment discontinuation) were reported in the group that received upadacitinib 45 mg once daily. Increases in serum lipid levels and creatine phosphokinase with upadacitinib were observed. Conclusion: In a phase 2b trial, 8 weeks of treatment with upadacitinib was more effective than placebo for inducing remission in patients with moderately to severely active UC. (ClinicalTrials.gov, Number: NCT02819635).
Emerging therapeutic targets for NASH: key innovations at the preclinical level.
(Informa Healthcare, 2020-02-13) Horn, Paul; Newsome, Phlip N
Introduction: nonalcoholic steatohepatitis (NASH) is a globally emerging health problem, mainly caused by increasing trends in the prevalence of obesity and metabolic syndrome. Patients with NASH are mainly affected by cardiovascular risk and extrahepatic cancer, but a significant proportion of patients will develop advanced liver disease, eventually resulting in liver failure or hepatocellular carcinoma. Recent research has yielded a better understanding of the underlying mechanisms and potential targetability for drug development.Areas covered: This review focuses on the role of fructose metabolism, de novo lipogenesis (DNL), endoplasmic reticulum (ER) stress, NLRP3 inflammasome, bone morphogenetic protein (BMP) signaling and platelets in the pathophysiology of NASH. We discuss the suitability of these substrates for targeting liver disease as well as cardiovascular health in patients with NASH. A non-systematic literature search was performed on PubMed and ClinicalTrials.gov.Expert opinion: Targeting fructose metabolism, DNL, ER stress, NLRP3 inflammasome, BMP signaling and platelets are promising therapeutic strategies, warranting further preclinical and clinical investigation. The discussed approaches might not only benefit liver-related outcomes but improve cardiovascular disease as well. Amidst the euphoria of advances in drug development for NASH, parallel endeavors need to address the underlying causes of obesity and metabolic syndrome to prevent NASH.
Differences in the on- and off tumor microbiota between right- and left-sided colorectal cancer.
(MDPI Publishing, 2021-05-20) Phipps, Oliver; Quraishi, Mohammed N; Dickson, Edward A; Steed, Helen; Kumar, Aditi; Acheson, Austin G; Beggs, Andrew D; Brookes, Matthew J; Al-Hassi, Hafid Omar; Surgery; Medical and Dental; Beggs, Andrew
This study aims to determine differences in the on- and off-tumor microbiota between patients with right- and left-sided colorectal cancer. Microbiome profiling of tumor and tumor-adjacent biopsies from patients with right-sided (n = 17) and left-sided (n = 7) colorectal adenocarcinoma was performed using 16S ribosomal RNA sequencing. Off-tumor alpha and beta diversity were significantly different between right- and left-sided colorectal cancer patients. However, no differences in on-tumor diversity were observed between tumor locations. Comparing the off-tumor microbiota showed the right colon to be enriched with species of the Lachnoclostridium, Selenomonas, and Ruminococcus genera. Whereas the left colon is enriched with Epsilonbacteraeota phylum, Campylobacteria class, and Pasteurellales and Campylobacterales orders, in contrast, the on-tumor microbiota showed relatively fewer differences in bacterial taxonomy between tumor sites, with left tumors being enriched with Methylophilaceae and Vadin BE97 families and Alloprevotella, Intestinibacter, Romboutsia, and Ruminococcus 2 genera. Patients with left-sided colorectal cancer had large taxonomic differences between their paired on- and off-tumor microbiota, while patients with right-sided colorectal cancer showed relatively fewer taxonomic differences. Collectively, this suggests that the right and left colon show distinctive bacterial populations; however, the presence of a colonic tumor leads to a more consistent microbiota between locations.
Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018.
(Springer-Verlag, 2021-03-22) Morgan, Alice; Hartmanis, Sally; Tsochatzis, Emmanuel; Newsome, Philip N; Ryder, Stephen D; Elliott, Rachel; Floros, Lefteris; Hall, Richard; Higgins, Victoria; Stanley, George; Cure, Sandrine; Vasudevan, Sharad; Pezzullo, Lynne
Background and aims: Non-alcoholic steatohepatitis (NASH) - a progressive subset of non-alcoholic fatty liver disease (NAFLD) - is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018. Methods: The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups. Results: Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion. Conclusion: The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing.
Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis in five European countries in 2018: A cost-of-illness analysis.
(Wiley-Blackwell, 2021-03-18) Schattenberg, Jörn M; Lazarus, Jeffrey V; Newsome, Philip N; Serfaty, Lawrence; Aghemo, Alessio; Augustin, Salvador; Tsochatzis, Emmanuel; De Ledinghen, Victor; Bugianesi, Elisabetta; Romero-Gomez, Manuel; Bantel, Heike; Ryder, Stephen D; Boursier, Jerome; Leroy, Vincent; Crespo, Javier; Castera, Laurent; Floros, Lefteris; Atella, Vincenzo; Mestre-Ferrandiz, Jorge; Elliott, Rachel; Kautz, Achim; Morgan, Alice; Hartmanis, Sally; Vasudevan, Sharad; Pezzullo, Lynne; Trylesinski, Aldo; Cure, Sandrine; Higgins, Victoria; Ratziu, Vlad
Background and aims: Non-alcoholic steatohepatitis (NASH) is a chronic disease that can progress to end-stage liver disease (ESLD). A large proportion of early-stage NASH patients remain undiagnosed compared to those with advanced fibrosis, who are more likely to receive disease management interventions. This study estimated the disease burden and economic impact of diagnosed NASH in the adult population of France, Germany, Italy, Spain and the United Kingdom in 2018. Methods: The socioeconomic burden of diagnosed NASH was estimated using cost-of-illness methodology applying a prevalence approach to estimate the number of adults with NASH and the attributable economic and wellbeing costs. Given undiagnosed patients do not incur costs in the study, the probability of diagnosis is central to cost estimation. The analysis was based on a literature review, databases and consultation with clinical experts, economists and patient groups. Results: The proportion of adult NASH patients with a diagnosis ranged from 11.9% to 12.7% across countries, which increased to 38.8%-39.1% for advanced fibrosis (F3-F4 compensated cirrhosis). Total economic costs were €8548-19 546M. Of these, health system costs were €619-1292M. Total wellbeing costs were €41 536-90 379M. The majority of the undiagnosed population (87.3%-88.2% of total prevalence) was found to have early-stage NASH, which, left untreated, may progress to more resource consuming ESLD over time. Conclusions: This study found that the majority of economic and wellbeing costs of NASH are experienced in late disease stages. Earlier diagnosis and care of NASH patients could reduce future healthcare costs.
Defining true impact of anastomotic leaks after oesophagogastric cancer surgery.
(Oxford University Press, 2020-04) Kamarajah, S K; Griffiths, E A; Phillips, A W; Surgery; Medical and Dental; Griffiths, Ewen
No abstract available
Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study.
(Elsevier, 2021-02-02) Sebastian, Shaji; Walker, Gareth J; Kennedy, Nicholas A; Conley, Thomas E; Patel, Kamal V; Subramanian, Sreedhar; Kent, Alexandra J; Segal, Jonathan P; Brookes, Matthew J; Bhala, Neeraj; Gonzalez, Haidee A; Hicks, Lucy C; Mehta, Shameer J; Lamb, Christopher A
Abstract Background: There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods: The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov, NCT04411784. Findings: We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation: The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding: None.
Appraisal of the current guidelines for management of cholangiocarcinoma-using the Appraisal of Guidelines Research and Evaluation II (AGREE II) Instrument.
(AME Publishing Company, 2020-04) Gavriilidis, Paschalis; Askari, Alan; Roberts, Keith J; Sutcliffe, Robert P; Liver Surgery; Liver; Medical and Dental; Roberts, Keith; Sutcliffe, Robert
Cholangiocarcinoma (CC) is the second most common primary liver tumour. High-quality guidelines are essential for effective patient stratification and individualised treatment. This study aimed to appraise the methodological quality of existing guidelines for the resection of CC using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. A systematic search of the literature in Cochrane, PubMed, Google Scholar, and Embase was performed. Assessment of the clinical practice guidelines (CPGs) and consensuses was performed using the AGREE II instrument by four clinicians experienced in surgical practice and the AGREE II appraisal method. Literature searches identified 13 guidelines of highly variable quality according to the AGREE II criteria. The guidelines scored well in certain domains such as scope & purpose (median score across all guidelines; 65%), clarity of presentation (76%), and editorial independence (56%). However, they scored poorly for applicability (13%), rigour of development (30%), and stakeholder involvement (39%). None of the 13 guidelines was recommended universally for use without modification. Overall, the methodological quality of guidelines on the surgical management of CC is poor. Future updates should address and modify shortcomings detected by the AGREE II instrument, thereby facilitating better patient stratification and individualised treatment strategies.
Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.
(British Medical Association, 2021-03-22) Kennedy, Nicholas A; Goodhand, James R; Bewshea, Claire; Nice, Rachel; Chee, Desmond; Lin, Simeng; Chanchlani, Neil; Butterworth, Jeffrey; Cooney, Rachel; Croft, Nicholas M; Hart, Ailsa L; Irving, Peter M; Kok, Klaartje B; Lamb, Christopher A; Limdi, Jimmy K; MacDonald, Jonathan; McGovern, Dermot Pb; Mehta, Shameer J; Murray, Charles D; Patel, Kamal V; Pollok, Richard Cg; Raine, Timothy; Russell, Richard K; Selinger, Christian P; Smith, Philip J; Bowden, Jack; McDonald, Timothy J; Lees, Charlie W; Sebastian, Shaji; Powell, Nicholas; Ahmad, Tariq; GI Medicine; Medical and Dental; Cooney, Rachel
Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. Results: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). Conclusions: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. Trial registration number: ISRCTN45176516.
Anastomotic techniques for oesophagectomy for malignancy: systematic review and network meta-analysis.
(Oxford University Press, 2020-05-23) Kamarajah, S K; Bundred, J R; Singh, P; Pasquali, S; Griffiths, E A; Surgery; Medical and Dental; Griffiths, Ewen
ackground: Current evidence on the benefits of different anastomotic techniques (hand-sewn (HS), circular stapled (CS), triangulating stapled (TS) or linear stapled/semimechanical (LSSM) techniques) after oesophagectomy is conflicting. The aim of this study was to evaluate the evidence for the techniques for oesophagogastric anastomosis and their impact on perioperative outcomes. Methods: This was a systematic review and network meta-analysis. PubMed, EMBASE and Cochrane Library databases were searched systematically for randomized and non-randomized studies reporting techniques for the oesophagogastric anastomosis. Network meta-analysis of postoperative anastomotic leaks and strictures was performed. Results: Of 4192 articles screened, 15 randomized and 22 non-randomized studies comprising 8618 patients were included. LSSM (odds ratio (OR) 0·50, 95 per cent c.i. 0·33 to 0·74; P = 0·001) and CS (OR 0·68, 0·48 to 0·95; P = 0·027) anastomoses were associated with lower anastomotic leak rates than HS anastomoses. LSSM anastomoses were associated with lower stricture rates than HS anastomoses (OR 0·32, 0·19 to 0·54; P < 0·001). Conclusion: LSSM anastomoses after oesophagectomy are superior with regard to anastomotic leak and stricture rates.
An international multicenter real life prospective study of electronic chromoendoscopy score PICaSSO in ulcerative colitis.
(W.B. Saunders, 2021-02-06) Iacucci, Marietta; Smith, Samuel C L; Bazarova, Alina; Shivaji, Uday N; Bhandari, Pradeep; Cannatelli, Rosanna; Daperno, Marco; Ferraz, Jose; Goetz, Martin; Gui, Xianyong; Hayee, Bu; De Hertogh, Gert; Lazarev, Mark; Li, Jim; Nardone, Olga M; Parra-Blanco, Adolfo; Pastorelli, Luca; Panaccione, Remo; Occhipinti, Vincenzo; Rath, Timo; Tontini, Gian Eugenio; Vieth, Michael; Villanacci, Vincenzo; Zardo, Davide; Bisschops, Raf; Kiesslich, Ralf; Ghosh, Subrata
Background & aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes. Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy. Results: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission. Conclusion: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC.
Associations between angiotensin-converting enzyme inhibitors and angiotensin II receptor blocker use, gastrointestinal symptoms, and mortality among patients With COVID-19.
(W.B. Saunders, 2020-05-16) Tan, Nian-Di; Qiu, Yun; Xing, Xiang-Bin; Ghosh, Subrata; Chen, Min-Hu; Mao, Ren
No abstract available
Alcoholic hepatitis and metabolic disturbance in female mice: a more tractable model than animals.
(Company of Biologists Ltd, 2020-12-29) Sheriff, Lozan; Khan, Reenam S; Saborano, Raquel; Wilkin, Richard; Luu, Nguyet-Thin; Gunther, Ulrich L; Hubscher, Stefan G; Newsome, Philip N; Lalor, Patricia F
Alcoholic hepatitis (AH) is the dramatic acute presentation of alcoholic liver disease, with a 15% mortality rate within 28 days in severe cases. Research into AH has been hampered by the lack of effective and reproducible murine models that can be operated under different regulatory frameworks internationally. The liquid Lieber-deCarli (LdC) diet has been used as a means of ad libitum delivery of alcohol but without any additional insult, and is associated with relatively mild liver injury. The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) protects against oxidative stress, and mice deficient in this molecule are suggested to be more sensitive to alcohol-induced injury. We have established a novel model of AH in mice and compared the nature of liver injury in C57/BL6 wild-type (WT) versus Nrf2-/- mice. Our data showed that both WT and Nrf2-/- mice demonstrate robust weight loss, and an increase in serum transaminase, steatosis and hepatic inflammation when exposed to diet and ethanol. This is accompanied by an increase in peripheral blood and hepatic myeloid cell populations, fibrogenic response and compensatory hepatocyte regeneration. We also noted characteristic disturbances in hepatic carbohydrate and lipid metabolism. Importantly, use of Nrf2-/- mice did not increase hepatic injury responses in our hands, and female WT mice exhibited a more-reproducible response. Thus, we have demonstrated that this simple murine model of AH can be used to induce an injury that recreates many of the key human features of AH - without the need for challenging surgical procedures to administer ethanol. This will be valuable for understanding of the pathogenesis of AH, for testing new therapeutic treatments or devising metabolic approaches to manage patients whilst in medical care.This article has an associated First Person interview with the joint first authors of the paper.
Administration of human MSC-derived extracellular vesicles for the treatment of primary sclerosing cholangitis: preclinical data in MDR2 knockout mice.
(MDPI, 2020-11-23) Angioni, Roberta; Calì, Bianca; Vigneswara, Vasanthy; Crescenzi, Marika; Merino, Ana; Sánchez-Rodríguez, Ricardo; Liboni, Cristina; Hoogduijn, Martin J; Newsome, Philip Noel; Muraca, Maurizio; Russo, Francesco Paolo; Viola, Antonella
Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.
Adaptations to the British Society of Gastroenterology guidelines on the management of acute severe UC in the context of the COVID-19 pandemic: a RAND appropriateness panel.
(British Medical Association, 2020-06-08) Din, Shahida; Kent, Alexandra; Pollok, Richard C; Meade, Susanna; Kennedy, Nicholas A; Arnott, Ian; Beattie, R Mark; Chua, Felix; Cooney, Rachel; Dart, Robin J; Galloway, James; Gaya, Daniel R; Ghosh, Subrata; Griffiths, Mark; Hancock, Laura; Hansen, Richard; Hart, Ailsa; Lamb, Christopher Andrew; Lees, Charlie W; Limdi, Jimmy K; Lindsay, James O; Patel, Kamal; Powell, Nick; Murray, Charles D; Probert, Chris; Raine, Tim; Selinger, Christian; Sebastian, Shaji; Smith, Philip J; Tozer, Phil; Ustianowski, Andrew; Younge, Lisa; Samaan, Mark A; Irving, Peter M; GI Medicine; Medical and Dental; Cooney, Rachel
Objective: Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point. Design: We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey. Results: Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4-6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab. Conclusion: We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel.
Abdominal ultrasound and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease.
(Wiley, 2021-04-15) Colli, Agostino; Nadarevic, Tin; Miletic, Damir; Giljaca, Vanja; Fraquelli, Mirella; Štimac, Davor; Casazza, Giovanni; Endoscopy; Medical and Dental; Giljaca, Vanja
Background: Hepatocellular carcinoma (HCC) occurs mostly in people with chronic liver disease and ranks sixth in terms of global instances of cancer, and fourth in terms of cancer deaths for men. Despite that abdominal ultrasound (US) is used as an initial test to exclude the presence of focal liver lesions and serum alpha-foetoprotein (AFP) measurement may raise suspicion of HCC occurrence, further testing to confirm diagnosis as well as staging of HCC is required. Current guidelines recommend surveillance programme using US, with or without AFP, to detect HCC in high-risk populations despite the lack of clear benefits on overall survival. Assessing the diagnostic accuracy of US and AFP may clarify whether the absence of benefit in surveillance programmes could be related to under-diagnosis. Therefore, assessment of the accuracy of these two tests for diagnosing HCC in people with chronic liver disease, not included in surveillance programmes, is needed. Objectives: Primary: the diagnostic accuracy of US and AFP, alone or in combination, for the diagnosis of HCC of any size and at any stage in adults with chronic liver disease, either in a surveillance programme or in a clinical setting. Secondary: to assess the diagnostic accuracy of abdominal US and AFP, alone or in combination, for the diagnosis of resectable HCC; to compare the diagnostic accuracy of the individual tests versus the combination of both tests; to investigate sources of heterogeneity in the results. Search methods: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic-Test-Accuracy Studies Register, Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, until 5 June 2020. We applied no language or document-type restrictions. Selection criteria: Studies assessing the diagnostic accuracy of US and AFP, independently or in combination, for the diagnosis of HCC in adults with chronic liver disease, with cross-sectional and case-control designs, using one of the acceptable reference standards, such as pathology of the explanted liver, histology of resected or biopsied focal liver lesion, or typical characteristics on computed tomography, or magnetic resonance imaging, all with a six-months follow-up. Data collection and analysis: We independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest-plots, and tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses. Main results: We included 373 studies. The index-test was AFP (326 studies, 144,570 participants); US (39 studies, 18,792 participants); and a combination of AFP and US (eight studies, 5454 participants). We judged at high-risk of bias all but one study. Most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time-interval between the index test and the reference standard was rarely defined. Most studies with AFP had a case-control design. We also had major concerns for the applicability due to the characteristics of the participants. As the primary studies with AFP used different cut-offs, we performed a meta-analysis using the hierarchical-summary-receiver-operating-characteristic model, then we carried out two meta-analyses including only studies reporting the most used cut-offs: around 20 ng/mL or 200 ng/mL. AFP cut-off 20 ng/mL: for HCC (147 studies) sensitivity 60% (95% CI 58% to 62%), specificity 84% (95% CI 82% to 86%); for resectable HCC (six studies) sensitivity 65% (95% CI 62% to 68%), specificity 80% (95% CI 59% to 91%). AFP cut-off 200 ng/mL: for HCC (56 studies) sensitivity 36% (95% CI 31% to 41%), specificity 99% (95% CI 98% to 99%); for resectable HCC (two studies) one with sensitivity 4% (95% CI 0% to 19%), specificity 100% (95% CI 96% to 100%), and one with sensitivity 8% (95% CI 3% to 18%), specificity 100% (95% CI 97% to 100%). US: for HCC (39 studies) sensitivity 72% (95% CI 63% to 79%), specificity 94% (95% CI 91% to 96%); for resectable HCC (seven studies) sensitivity 53% (95% CI 38% to 67%), specificity 96% (95% CI 94% to 97%). Combination of AFP (cut-off of 20 ng/mL) and US: for HCC (six studies) sensitivity 96% (95% CI 88% to 98%), specificity 85% (95% CI 73% to 93%); for resectable HCC (two studies) one with sensitivity 89% (95% CI 73% to 97%), specificity of 83% (95% CI 76% to 88%), and one with sensitivity 79% (95% CI 54% to 94%), specificity 87% (95% CI 79% to 94%). The observed heterogeneity in the results remains mostly unexplained, and only in part referable to different cut-offs or settings (surveillance programme compared to clinical series). The sensitivity analyses, excluding studies published as abstracts, or with case-control design, showed no variation in the results. We compared the accuracy obtained from studies with AFP (cut-off around 20 ng/mL) and US: a direct comparison in 11 studies (6674 participants) showed a higher sensitivity of US (81%, 95% CI 66% to 90%) versus AFP (64%, 95% CI 56% to 71%) with similar specificity: US 92% (95% CI 83% to 97%) versus AFP 89% (95% CI 79% to 94%). A direct comparison of six studies (5044 participants) showed a higher sensitivity (96%, 95% CI 88% to 98%) of the combination of AFP and US versus US (76%, 95% CI 56% to 89%) with similar specificity: AFP and US 85% (95% CI 73% to 92%) versus US 93% (95% CI 80% to 98%). Authors' conclusions: In the clinical pathway for the diagnosis of HCC in adults, AFP and US, singularly or in combination, have the role of triage-tests. We found that using AFP, with 20 ng/mL as a cut-off, about 40% of HCC occurrences would be missed, and with US alone, more than a quarter. The combination of the two tests showed the highest sensitivity and less than 5% of HCC occurrences would be missed with about 15% of false-positive results. The uncertainty resulting from the poor study quality and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results.
Improving 30-day mortality after radiologically inserted gastrostomy tube from 2007 to 2019 : a population-based study of 15,605 patients
(Elsevier, 2025-02-05) Hussain, Syed Shezal; Umar, Nosheen; Kamran, Umair; Coupland, Benjamin; Varyani, Fumi; Trudgill, Nigel; Birmingham Heartlands Hospital; Sandwell and West Birmingham NHS Trust; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Gastroenterology; Doctors; Research and Development; Medical and Dental; Umar, Nosheen; Kamran, Umair; Varyani, Fumi; Trudgill, Nigel; Hussain, Syed; Coupland, Benjamin
Background and aims: Radiologically inserted gastrostomy (RIG) allows long-term enteral nutrition when percutaneous endoscopic gastrostomy (PEG) tube insertion is not feasible either due to technical difficulty or a higher risk of complications. The aims of this study were to examine mortality associated with RIG insertion. Methods: Adult patients with RIG insertion from 2007 to 2019 were identified in the Hospital Episode Statistics database. Indications and adverse events were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Provider nutrition support data were available from the Getting It Right First Time in Gastroenterology Report 2021. Multivariable logistic regression analysis examined factors associated with 30-day mortality following a RIG. Results: 15,605 patients were studied (68.0 % male; age 64(Interquartile range (IQR) 56-73)). There was a steady increase in the number of RIGs inserted from 510 per year in 2007 to 1787 per year in 2019. 59.9 % of RIGs were inserted as an outpatient. 63.3 % of RIGs were inserted in head and neck cancer patients. Of the patients who had a RIG insertion, 4.7 % had pneumonia within 7 days and 6.9 % died within 30 days of RIG insertion. Thirty-day mortality fell from 12.2 % in 2007 to 5.8 % in 2019. Higher 30-day mortality rates were observed in patients with Dementia (16.4 %) and in NHS providers without a nutrition support nurse (11.5 %). Factors associated with 30 day mortality included: increasing age (>81 years odds ratio (OR) 13.67 (95 % confidence interval (CI) 4.99-37.48), p < 0.001); increasing NHS provider volume of RIG insertion >12 per year (OR 0.69 (95 % CI (0.55-0.88), p = 0.003); RIG insertion during an emergency admission (OR 2.53 (95 % CI 2.19-2.93), p < 0.001); increasing comorbidity Charlson score >5 (OR 1.38 (95 % CI 1.10-1.75), p = 0.006); NHS provider without a nutrition support nurse (OR 1.38 (95%CI 1.09-1.75), p = 0.007) and other neurological conditions than stroke as indication for RIG (OR 1.55 (95%CI 1.24-1.95), p < 0.001). Conclusions: Despite an increase in RIG insertion over the study period, 30-day mortality has fallen by 52 %. Providers without a nutrition support nurse and providers with a lower volume of RIG insertions were associated with higher mortality.
A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.
(Massachusetts Medical Society, 2020-11-13) Newsome, Philip N; Buchholtz, Kristine; Cusi, Kenneth; Linder, Martin; Okanoue, Takeshi; Ratziu, Vlad; Sanyal, Arun J; Sejling, Anne-Sophie; Harrison, Stephen A
Background: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known. Methods: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients. Results: In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed. Conclusions: This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).
An urgent need to institute COVID-19 testing in patients with IBD experiencing flares.
(BMJ, 2020-03-27) Quraishi, Mohammed Nabil; Cooney, Rachel; Brookes, Matthew James; Sharma, Naveen; GI Medicine; Medical and Dental; Cooney, Rachel; Sharma, Naveen
No abstract available

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