GutPub Date : 2024-10-15DOI: 10.1136/gutjnl-2024-332820
Giulio Antonelli, Diogo Libanio, Albert Jeroen De Groof, Fons van der Sommen, Pietro Mascagni, Pieter Sinonquel, Mohamed Abdelrahim, Omer Ahmad, Tyler Berzin, Pradeep Bhandari, Michael Bretthauer, Miguel Coimbra, Evelien Dekker, Alanna Ebigbo, Tom Eelbode, Leonardo Frazzoni, Seth A Gross, Ryu Ishihara, Michal Filip Kaminski, Helmut Messmann, Yuichi Mori, Nicolas Padoy, Sravanthi Parasa, Nastazja Dagny Pilonis, Francesco Renna, Alessandro Repici, Cem Simsek, Marco Spadaccini, Raf Bisschops, Jacques J G H M Bergman, Cesare Hassan, Mario Dinis Ribeiro
{"title":"QUAIDE - Quality assessment of AI preclinical studies in diagnostic endoscopy","authors":"Giulio Antonelli, Diogo Libanio, Albert Jeroen De Groof, Fons van der Sommen, Pietro Mascagni, Pieter Sinonquel, Mohamed Abdelrahim, Omer Ahmad, Tyler Berzin, Pradeep Bhandari, Michael Bretthauer, Miguel Coimbra, Evelien Dekker, Alanna Ebigbo, Tom Eelbode, Leonardo Frazzoni, Seth A Gross, Ryu Ishihara, Michal Filip Kaminski, Helmut Messmann, Yuichi Mori, Nicolas Padoy, Sravanthi Parasa, Nastazja Dagny Pilonis, Francesco Renna, Alessandro Repici, Cem Simsek, Marco Spadaccini, Raf Bisschops, Jacques J G H M Bergman, Cesare Hassan, Mario Dinis Ribeiro","doi":"10.1136/gutjnl-2024-332820","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332820","url":null,"abstract":"Artificial intelligence (AI) holds significant potential for enhancing quality of gastrointestinal (GI) endoscopy, but the adoption of AI in clinical practice is hampered by the lack of rigorous standardisation and development methodology ensuring generalisability. The aim of the Quality Assessment of pre-clinical AI studies in Diagnostic Endoscopy (QUAIDE) Explanation and Checklist was to develop recommendations for standardised design and reporting of preclinical AI studies in GI endoscopy. The recommendations were developed based on a formal consensus approach with an international multidisciplinary panel of 32 experts among endoscopists and computer scientists. The Delphi methodology was employed to achieve consensus on statements, with a predetermined threshold of 80% agreement. A maximum three rounds of voting were permitted. Consensus was reached on 18 key recommendations, covering 6 key domains: data acquisition and annotation (6 statements), outcome reporting (3 statements), experimental setup and algorithm architecture (4 statements) and result presentation and interpretation (5 statements). QUAIDE provides recommendations on how to properly design (1. Methods, statements 1–14), present results (2. Results, statements 15–16) and integrate and interpret the obtained results (3. Discussion, statements 17–18). The QUAIDE framework offers practical guidance for authors, readers, editors and reviewers involved in AI preclinical studies in GI endoscopy, aiming at improving design and reporting, thereby promoting research standardisation and accelerating the translation of AI innovations into clinical practice.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"29 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-14DOI: 10.1136/gutjnl-2024-332837
Henrike Salié, Lara Wischer, Antonio D'Alessio, Ira Godbole, Yuan Suo, Patricia Otto-Mora, Juergen Beck, Olaf Neumann, Albrecht Stenzinger, Peter Schirmacher, Claudia A M Fulgenzi, Andreas Blaumeiser, Melanie Boerries, Natascha Roehlen, Michael Schultheiß, Maike Hofmann, Robert Thimme, David J Pinato, Thomas Longerich, Bertram Bengsch
{"title":"Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma.","authors":"Henrike Salié, Lara Wischer, Antonio D'Alessio, Ira Godbole, Yuan Suo, Patricia Otto-Mora, Juergen Beck, Olaf Neumann, Albrecht Stenzinger, Peter Schirmacher, Claudia A M Fulgenzi, Andreas Blaumeiser, Melanie Boerries, Natascha Roehlen, Michael Schultheiß, Maike Hofmann, Robert Thimme, David J Pinato, Thomas Longerich, Bertram Bengsch","doi":"10.1136/gutjnl-2024-332837","DOIUrl":"10.1136/gutjnl-2024-332837","url":null,"abstract":"<p><strong>Background: </strong>The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.</p><p><strong>Objective: </strong>We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.</p><p><strong>Design: </strong>We conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy.</p><p><strong>Results: </strong>Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-14DOI: 10.1136/gutjnl-2024-333611
Yiwen Yuan, Xi Fu, Yiqun Deng, Yu Sun
{"title":"Exploring the role of genetics, gut microbiota and blood metabolites in IBD.","authors":"Yiwen Yuan, Xi Fu, Yiqun Deng, Yu Sun","doi":"10.1136/gutjnl-2024-333611","DOIUrl":"10.1136/gutjnl-2024-333611","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-10DOI: 10.1136/gutjnl-2024-332695
Anke M Onnekink, Myrte Gorris, Noor Lh Bekkali, Philip Bos, Paul Didden, J Enrique Dominguez-Muñoz, Pieter Friederich, Emo E van Halsema, Wouter L Hazen, Nadine C van Huijgevoort, Akin Inderson, Maarten Ajm Jacobs, Jan J Koornstra, Sjoerd Kuiken, Bob Ch Scheffer, Hilbert Sloterdijk, Ellert J van Soest, Niels G Venneman, Rogier P Voermans, Thomas R de Wijkerslooth, Janneke Wonders, Roeland Zoutendijk, Serge Jlb Zweers, Paul Fockens, Robert C Verdonk, Roy L J van Wanrooij, Jeanin E Van Hooft
{"title":"Endoscopic sphincterotomy to prevent post-ERCP pancreatitis after self-expandable metal stent placement for distal malignant biliary obstruction (SPHINX): a multicentre, randomised controlled trial.","authors":"Anke M Onnekink, Myrte Gorris, Noor Lh Bekkali, Philip Bos, Paul Didden, J Enrique Dominguez-Muñoz, Pieter Friederich, Emo E van Halsema, Wouter L Hazen, Nadine C van Huijgevoort, Akin Inderson, Maarten Ajm Jacobs, Jan J Koornstra, Sjoerd Kuiken, Bob Ch Scheffer, Hilbert Sloterdijk, Ellert J van Soest, Niels G Venneman, Rogier P Voermans, Thomas R de Wijkerslooth, Janneke Wonders, Roeland Zoutendijk, Serge Jlb Zweers, Paul Fockens, Robert C Verdonk, Roy L J van Wanrooij, Jeanin E Van Hooft","doi":"10.1136/gutjnl-2024-332695","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332695","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic retrograde cholangiopancreatography (ERCP) with fully covered self-expandable metal stent (FCSEMS) placement is the preferred approach for biliary drainage in patients with suspected distal malignant biliary obstruction (MBO). However, FCSEMS placement is associated with a high risk of post-ERCP pancreatitis (PEP). Endoscopic sphincterotomy prior to FCSEMS placement may reduce PEP risk.</p><p><strong>Objective: </strong>To compare endoscopic sphincterotomy to no sphincterotomy prior to FCSEMS placement.</p><p><strong>Design: </strong>This multicentre, randomised, superiority trial was conducted in 17 hospitals and included patients with suspected distal MBO. Patients were randomised during ERCP to receive either endoscopic sphincterotomy (sphincterotomy group) or no sphincterotomy (control group) prior to FCSEMS placement. The primary outcome was PEP within 30 days. Secondary outcomes included procedure-related complications and 30-day mortality. An interim analysis was performed after 50% of patients (n=259) had completed follow-up.</p><p><strong>Results: </strong>Between May 2016 and June 2023, 297 patients were included in the intention-to-treat analysis, with 156 in the sphincterotomy group and 141 in the control group. After the interim analysis, the study was terminated prematurely due to futility. PEP did not differ between groups, occurring in 26 patients (17%) in the sphincterotomy group compared with 30 patients (21%) in the control group (relative risk 0.78, 95% CI 0.49 to 1.26, p=0.37). There were no significant differences in bleeding, perforation, cholangitis, cholecystitis or 30-day mortality.</p><p><strong>Conclusion: </strong>This trial found that endoscopic sphincterotomy was not superior to no sphincterotomy in reducing PEP in patients with distal MBO. Therefore, there was insufficient evidence to recommend routine endoscopic sphincterotomy prior to FCEMS placement.</p><p><strong>Trial registration number: </strong>NL5130.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-08DOI: 10.1136/gutjnl-2024-332526
David Z Pan, Cameron M Soulette, Abhishek Aggarwal, Dong Han, Nicholas van Buuren, Peiwen Wu, Becket Feierbach, Jaw-Town Lin, Cheng-Hao Tseng, Chi-Yi Chen, Bryan Downie, Hongmei Mo, Lauri Diehl, Li Li, Simon P Fletcher, Scott Balsitis, Ricardo Ramirez, Vithika Suri, Yao-Chun Hsu
{"title":"Effects of tenofovir disoproxil fumarate on intrahepatic viral burden and liver immune microenvironment in patients with chronic hepatitis B","authors":"David Z Pan, Cameron M Soulette, Abhishek Aggarwal, Dong Han, Nicholas van Buuren, Peiwen Wu, Becket Feierbach, Jaw-Town Lin, Cheng-Hao Tseng, Chi-Yi Chen, Bryan Downie, Hongmei Mo, Lauri Diehl, Li Li, Simon P Fletcher, Scott Balsitis, Ricardo Ramirez, Vithika Suri, Yao-Chun Hsu","doi":"10.1136/gutjnl-2024-332526","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332526","url":null,"abstract":"Background The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear. Objective We aimed to characterise the effects of tenofovir disoproxil fumarate (TDF) on intrahepatic viral burden and the liver immune microenvironment in patients with CHB. Design Core liver biopsies were collected at baseline and year 3 from patients with CHB with minimally raised serum alanine aminotransferase in a double-blind placebo-controlled trial ([NCT01522625][1]). Paired biopsies were analysed by RNA-sequencing (n=119 pairs), a custom multiplex immunofluorescence assay (n=30 pairs), and HBV-targeted long-read DNA sequencing (n=49 pairs). Results Both non-integrated and integrated HBV DNA were present in all patients at baseline, with >65% having interchromosomal translocations. Treatment significantly reduced the frequency of HBV core+ hepatocytes and intrahepatic (integrated and non-integrated) HBV DNA, but had no effect on HBsAg+ hepatocytes. Clonally expanded integrations were enriched for HBsAg coding regions and showed dysregulation of nearby genes. At baseline, there was significant enrichment of intrahepatic CD8+ T cell proximity to HBV core+ hepatocytes, but not to HBsAg+ cells. The densities of T cells and B cells were significantly reduced by TDF. Transcriptomic analyses found TDF induced widespread downregulation of immune-related genes including inhibitory and regulatory genes. Conclusion TDF significantly reduced intrahepatic integrated and non-integrated HBV DNA, exerting disparate effects on HBV core+ and HBsAg+ cells and on different immune cell subsets. Our data suggest there may be differential cytotoxic T cell-mediated killing of HBV core+ versus HBsAg+ hepatocytes, providing insights for HBV cure strategies. Data are available upon reasonable request. Data collected for this study, including deidentified individual participant data and data dictionaries defining fields in the datasets, will be made available on request to with qualified external researchers based on submitted curriculum vitae and reflecting non conflict of interest as well as laws and regulations regarding patient privacy. Approval of such requests is dependent on the nature of the request, the merit of the research proposed, the availability of the data and the intended use of the data. Data requests should be sent to the corresponding author at holdenhsu@gmail.com. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01522625&atom=%2Fgutjnl%2Fearly%2F2024%2F10%2F08%2Fgutjnl-2024-332526.atom","PeriodicalId":12825,"journal":{"name":"Gut","volume":"12 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-07DOI: 10.1136/gutjnl-2024-332807
Timothy O'Sullivan, Oliver Cronin, W Arnout van Hattem, Francesco Vito Mandarino, Julia L Gauci, Clarence Kerrison, Anthony Whitfield, Sunil Gupta, Eric Lee, Stephen J Williams, Nicholas Burgess, Michael J Bourke
{"title":"Cold versus hot snare endoscopic mucosal resection for large (≥15 mm) flat non-pedunculated colorectal polyps: a randomised controlled trial.","authors":"Timothy O'Sullivan, Oliver Cronin, W Arnout van Hattem, Francesco Vito Mandarino, Julia L Gauci, Clarence Kerrison, Anthony Whitfield, Sunil Gupta, Eric Lee, Stephen J Williams, Nicholas Burgess, Michael J Bourke","doi":"10.1136/gutjnl-2024-332807","DOIUrl":"10.1136/gutjnl-2024-332807","url":null,"abstract":"<p><strong>Background and aims: </strong>Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR.</p><p><strong>Methods: </strong>Flat, 15-50 mm adenomatous LNPCPs were prospectively enrolled and randomly assigned to C-EMR or H-EMR with margin thermal ablation at a single tertiary centre. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at 6 months surveillance colonoscopy. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success.</p><p><strong>Results: </strong>177 LNPCPs in 177 patients were randomised to C-EMR arm (n=87) or H-EMR (n=90). Treatment groups were equivalent for technical success 86/87 (98.9%) C-EMR versus H-EMR 90/90 (100%); p=0.31. Recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; relative risk (RR) 16.6, 95% CI 2.24 to 122; p<0.001).Delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB was significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); RR 6.77, 95% CI 0.85 to 53.9; p=0.034).</p><p><strong>Conclusion: </strong>Compared with H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique.</p><p><strong>Trial registration number: </strong>NCT04138030.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1823-1830"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.","authors":"Xiao-Bo Huang, Qiang Huang, Mei-Chen Jiang, Qing Zhong, Hua-Long Zheng, Jia-Bin Wang, Ze-Ning Huang, Hua-Gen Wang, Zhi-Yu Liu, Yi-Fan Li, Kai-Xiang Xu, Mi Lin, Ping Li, Zhi-Hong Huang, Jian-Wei Xie, Jian-Xian Lin, Jun Lu, Jian-Wen Que, Chao-Hui Zheng, Qi-Yue Chen, Chang-Ming Huang","doi":"10.1136/gutjnl-2023-331111","DOIUrl":"10.1136/gutjnl-2023-331111","url":null,"abstract":"<p><strong>Objective: </strong>Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood.</p><p><strong>Design: </strong>An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout <i>Klhl21</i>-floxed mice, were generated to investigate the role of <i>Klhl21</i> deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms.</p><p><strong>Results: </strong>Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of <i>Klhl21</i> enhances the rapid proliferation of <i>Mist1<sup>+</sup></i> cells and their descendant cells. <i>Klhl21</i> loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes <i>PIK3CB</i> mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy.</p><p><strong>Conclusions: </strong>Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1785-1798"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-07DOI: 10.1136/gutjnl-2024-331956
Claudia Campani, Sandrine Imbeaud, Gabrielle Couchy, Marianne Ziol, Theo Z Hirsch, Sandra Rebouissou, Bénédicte Noblet, Pierre Nahon, Katia Hormigos, Sabrina Sidali, Olivier Seror, Valerie Taly, Nathalie Ganne Carrie, Pierre Laurent-Puig, Jessica Zucman-Rossi, Jean-Charles Nault
{"title":"Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments.","authors":"Claudia Campani, Sandrine Imbeaud, Gabrielle Couchy, Marianne Ziol, Theo Z Hirsch, Sandra Rebouissou, Bénédicte Noblet, Pierre Nahon, Katia Hormigos, Sabrina Sidali, Olivier Seror, Valerie Taly, Nathalie Ganne Carrie, Pierre Laurent-Puig, Jessica Zucman-Rossi, Jean-Charles Nault","doi":"10.1136/gutjnl-2024-331956","DOIUrl":"10.1136/gutjnl-2024-331956","url":null,"abstract":"<p><strong>Objective: </strong>Circulating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).</p><p><strong>Design: </strong>We analysed 772 plasmas from 173 patients with HCC collected at the time of diagnosis or treatment (n=502), 24 hours after locoregional treatment (n=154) and during follow-up (n=116). For controls, 56 plasmas from patients with chronic liver disease without HCC were analysed. All samples were analysed for cell free DNA (cfDNA) concentration, and for mutations in <i>TERT</i> promoter, <i>CTNNB1</i>, <i>TP53</i>, <i>PIK3CA</i> and <i>NFE2L2</i> by sequencing and droplet-based digital PCR. Results were compared with 232 corresponding tumour samples.</p><p><strong>Results: </strong>In patients with active HCC, 40.2% of the ctDNA was mutated vs 14.6% in patients with inactive HCC and 1.8% in controls (p<0.001). In active HCC, we identified 27.5% of mutations in <i>TERT</i> promoter, 21.3% in <i>TP53</i>, 13.1% in <i>CTNNB1</i>, 0.4% in <i>PIK3CA</i> and 0.2% in <i>NFE2L2,</i> most of the times similar to those identified in the corresponding tumour. CtDNA mutation rate increased with advanced tumour stages (p<0.001). In 103 patients treated by percutaneous ablation, the presence and number of mutations in the ctDNA before treatment were associated with higher risk of death (p=0.001) and recurrence (p<0.001). Interestingly, cfDNA concentration and detectable mutations increased 24 hours after a locoregional treatment. Among 356 plasmas collected in 53 patients treated by systemic treatments, we detected mutations at baseline in 60.4% of the cases. In patients treated by atezolizumab-bevacizumab, persistence of mutation in ctDNA was associated with radiological progression (63.6% vs 36.4% for disappearance, p=0.019). In two patients progressing under systemic treatments, we detected the occurrence of mutations in <i>CTNNB1</i> in the plasma that was subclonal in the tumour for one patient and not detectable in the tumour for the other one.</p><p><strong>Conclusion: </strong>ctDNA offers dynamic information reflecting tumour biology. It represents a non-invasive tool useful to guide HCC clinical management.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1870-1882"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GutPub Date : 2024-10-07DOI: 10.1136/gutjnl-2023-331331
Ying Shang, Camilla Akbari, Maja Dodd, Patrik Nasr, Johan Vessby, Fredrik Rorsman, Stergios Kechagias, Per Stål, Mattias Ekstedt, Hannes Hagström
{"title":"Cause of death by fibrosis stage in 959 patients with biopsy-proven NAFLD.","authors":"Ying Shang, Camilla Akbari, Maja Dodd, Patrik Nasr, Johan Vessby, Fredrik Rorsman, Stergios Kechagias, Per Stål, Mattias Ekstedt, Hannes Hagström","doi":"10.1136/gutjnl-2023-331331","DOIUrl":"10.1136/gutjnl-2023-331331","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e30"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}