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The promise of indocyanine green in colorectal surgery. 吲哚菁绿在结直肠手术中的应用前景。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1016/S2468-1253(24)00235-8
Zoe Garoufalia
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引用次数: 0
Polyp detection with colonoscopy assisted by the GI Genius artificial intelligence endoscopy module compared with standard colonoscopy in routine colonoscopy practice (COLO-DETECT): a multicentre, open-label, parallel-arm, pragmatic randomised controlled trial. 在常规结肠镜检查实践中,使用 GI Genius 人工智能内镜检查模块辅助结肠镜检查与标准结肠镜检查进行息肉检测比较(COLO-DETECT):一项多中心、开放标签、平行臂、实用随机对照试验。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-14 DOI: 10.1016/S2468-1253(24)00161-4
Alexander Seager, Linda Sharp, Laura J Neilson, Andrew Brand, James S Hampton, Tom J W Lee, Rachel Evans, Luke Vale, John Whelpton, Nathania Bestwick, Colin J Rees
<p><strong>Background: </strong>Increased polyp detection during colonoscopy is associated with decreased post-colonoscopy colorectal cancer incidence and mortality. The COLO-DETECT trial aimed to assess the clinical effectiveness of the GI Genius intelligent endoscopy module for polyp detection, comparing colonoscopy assisted by GI Genius (computer-aided detection [CADe]-assisted colonoscopy) with standard colonoscopy in routine practice.</p><p><strong>Methods: </strong>We did a multicentre, open-label, parallel-arm, pragmatic randomised controlled trial in 12 National Health Service (NHS) hospitals (ten NHS Trusts) in England, among adults (aged ≥18 years) undergoing planned colonoscopy for gastrointestinal symptoms or for surveillance due to personal or family history (ie, symptomatic indications), or colorectal cancer screening. Randomisation (1:1) to CADe-assisted colonoscopy or standard colonoscopy was done with a web-based dynamic adaptive algorithm, immediately before colonoscopy, with stratification by age group, sex, colonoscopy indication (screening or symptomatic), and NHS Trust. Recruiting staff, participants, and colonoscopists were unmasked to trial allocation; histopathologists, co-chief investigators, and trial statisticians were masked. CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal. The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures); the key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma). Analysis was by intention to treat (ITT), with outcomes compared between groups by mixed-effects regression modelling, in which effect estimates were adjusted for randomisation stratification variables. Data were imputed for outcome measures with more than 5% missing values. All participants who underwent colonoscopy were assessed for safety. The trial is registered on ISRCTN (ISRCTN10451355) and ClinicalTrials.gov (NCT04723758), and is complete.</p><p><strong>Findings: </strong>Between March 29, 2021, and April 6, 2023, 2032 participants (1132 [55·7%] male, 900 [44·3%] female; mean age 62·4 years [SD 10·8]) were recruited and randomly assigned: 1015 to CADe-assisted colonoscopy and 1017 to standard colonoscopy. 1231 (60·6%) participants were undergoing screening and 801 (39·4%) had symptomatic indications. Mean adenomas per procedure was 1·56 (SD 2·82; n=1001 participants with available data) in the CADe-assisted colonoscopy group versus 1·21 (1·91; n=1009) in the standard colonoscopy group, representing an adjusted mean difference of 0·36 (95% CI 0·14-0·57; adjusted incidence rate ratio 1·30 [95% CI 1·15-1·47], p<0·0001). Adenomas were detected in 555 (56·6%) of 980 participants in the CADe-assisted colonoscopy group versus 477 (48·4%) of 986 in the standard colonoscopy group, representing a proportion d
背景:结肠镜检查中息肉检测率的提高与结肠镜检查后结直肠癌发病率和死亡率的降低有关。COLO-DETECT 试验旨在评估 GI Genius 智能内窥镜检查模块在息肉检测方面的临床效果,并将 GI Genius 辅助结肠镜检查(计算机辅助检测[CADe]辅助结肠镜检查)与常规做法中的标准结肠镜检查进行比较:我们在英格兰的 12 家国民健康服务(NHS)医院(10 个 NHS 信托基金会)开展了一项多中心、开放标签、平行臂、实用随机对照试验,对象是因胃肠道症状或因个人或家族病史(即症状适应症)或结直肠癌筛查而计划接受结肠镜检查的成年人(年龄≥18 岁)。在结肠镜检查前,通过网络动态自适应算法随机分配(1:1)CADe 辅助结肠镜检查或标准结肠镜检查,并根据年龄组、性别、结肠镜检查适应症(筛查或症状)和 NHS 信托基金会进行分层。招募人员、参与者和结肠镜医师均未蒙面,不参与试验分配;组织病理学家、联合首席研究员和试验统计人员均蒙面。CADe辅助结肠镜检查包括标准结肠镜检查和至少在结肠镜退出的整个检查阶段都在使用的GI Genius模块。主要结果是每次手术的平均腺瘤数(检测到的腺瘤总数除以手术总数);次要结果是腺瘤检测率(至少有一个腺瘤的结肠镜检查比例)。分析采用意向治疗(ITT)法,通过混合效应回归模型对各组间的结果进行比较,其中效应估计值根据随机分层变量进行了调整。对于缺失值超过5%的结果指标,将对数据进行估算。对所有接受结肠镜检查的参与者进行了安全性评估。该试验已在ISRCTN(ISRCTN10451355)和ClinicalTrials.gov(NCT04723758)上注册,并已完成:2021年3月29日至2023年4月6日期间,共招募并随机分配了2032名参与者(男性1132人[55-7%],女性900人[44-3%];平均年龄62-4岁[SD 10-8]):其中 1015 人接受 CADe 辅助结肠镜检查,1017 人接受标准结肠镜检查。1231人(60-6%)正在接受筛查,801人(39-4%)有症状指征。CADe辅助结肠镜检查组每次检查的平均腺瘤数为1-56(标度2-82;人数=1001,有可用数据),而标准结肠镜检查组为1-21(1-91;人数=1009),调整后的平均差异为0-36(95% CI 0-14-0-57;调整后的发病率比为1-30 [95% CI 1-15-1-47],p解释:COLO-DETECT试验结果支持在常规结肠镜检查中使用消化道天才来提高恶性前大肠息肉的检出率:资金来源:美敦力公司。
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引用次数: 0
Metastatic pancreatic cancer: a new standardised dose-reduction regimen? 转移性胰腺癌:新的标准化剂量减少方案?
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-16 DOI: 10.1016/S2468-1253(24)00227-9
Paula Ghaneh, Daniel Palmer
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引用次数: 0
Breaking down barriers between liver, addiction, and mental health services for people with alcohol-related liver disease. 打破为酒精相关肝病患者提供的肝脏、成瘾和心理健康服务之间的障碍。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-06-25 DOI: 10.1016/S2468-1253(24)00189-4
Ashwin D Dhanda, Victoria Allgar, Neeraj Bhala, Lynne Callaghan, Joana Castro, Shilpa Chokshi, Amanda Clements, Colin Drummond, Ewan H Forrest, Lesle Manning, Richard Parker, Debbie L Shawcross, Jennifer Towey
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引用次数: 0
The need for affordable, pragmatic, investigator-led clinical trials of treatment strategies in inflammatory bowel disease. 需要对炎症性肠病的治疗策略进行负担得起的、务实的、由研究者主导的临床试验。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1016/S2468-1253(24)00225-5
Nurulamin M Noor, Shaji Sebastian, Miles Parkes, Tim Raine
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引用次数: 0
Indocyanine green near-infrared fluorescence bowel perfusion assessment to prevent anastomotic leakage in minimally invasive colorectal surgery (AVOID): a multicentre, randomised, controlled, phase 3 trial. 吲哚菁绿近红外荧光肠道灌注评估以预防微创结直肠手术中的吻合口漏(AVOID):一项多中心、随机对照的 3 期试验。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1016/S2468-1253(24)00198-5
Robin A Faber, Ruben P J Meijer, Daphne H M Droogh, Jasmijn J Jongbloed, Okker D Bijlstra, Fran Boersma, Jeffrey P B M Braak, Elma Meershoek-Klein Kranenbarg, Hein Putter, Fabian A Holman, J Sven D Mieog, Peter A Neijenhuis, Esther van Staveren, Johanne G Bloemen, Jacobus W A Burger, Tjeerd S Aukema, Mark A M Brouwers, Andreas W K S Marinelli, Marinke Westerterp, Pascal G Doornebosch, Annelies van der Weijde, Koop Bosscha, Henricus J M Handgraaf, Esther C J Consten, Daan J Sikkenk, Jacobus Burggraaf, Stijn Keereweer, Joost R van der Vorst, Merlijn Hutteman, Koen C M J Peeters, Alexander L Vahrmeijer, Denise E Hilling
<p><strong>Background: </strong>Anastomotic leakage is a severe postoperative complication in colorectal surgery and compromised bowel perfusion is considered a major contributing factor. Conventional methods to assess bowel perfusion have a low predictive value for anastomotic leakage. We therefore aimed to evaluate the efficacy of real-time assessment with near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in the prevention of anastomotic leakage.</p><p><strong>Methods: </strong>This multicentre, randomised, controlled, phase 3 trial was done in eight hospitals in the Netherlands. We included adults (aged >18 years) who were scheduled for laparoscopic or robotic colorectal surgery (with planned primary anastomosis) for benign and malignant diseases. Preoperatively, patients were randomly assigned (1:1) to fluorescence-guided bowel anastomosis (FGBA) or conventional bowel anastomosis (CBA) by variable block randomisation (block sizes 4, 6, and 8) and stratified by site. The operating surgeon and investigators analysing the data were not masked to group assignment. Patients were unmasked after the surgical procedure or after study end. In the FGBA group, surgeons marked anastomosis levels per conventional perfusion assessment and then administered 5 mg of ICG by 2 mL intravenous bolus. They assessed bowel perfusion using NIR fluorescence imaging and adjusted (or kept) transection lines accordingly. Only conventional methods for bowel perfusion assessment were used in the CBA group. The primary outcome was the difference in the rate of clinically relevant anastomotic leakage (ie, requiring active therapeutic intervention but manageable without reoperation [grade B] or requiring reoperation [grade C], per the International Study Group of Rectal Cancer) between the FGBA group and the CBA group within 90 days post-surgery. The primary outcome and safety were assessed in the intention-to-treat population. This study was registered with ToetsingOnline.nl (NL7502) and ClinicalTrials.gov (NCT04712032) and is complete.</p><p><strong>Findings: </strong>Between July 2, 2020, and Feb 21, 2023, 982 patients were enrolled, of whom 490 were assigned to FGBA and 492 were assigned to CBA. After excluding 51 patients, the intention-to-treat population comprised 931 (463 assigned FGBA and 468 assigned CBA). Patients had a median age of 68·0 years (IQR 59·0-75·0) and 485 (52%) were male and 446 (48%) were female. Ethnicity data were not available. The overall 90-day rate of clinically relevant anastomotic leakage was not significantly different between the FGBA group (32 [7%] of 463 patients) and the CBA group (42 [9%] of 468 patients; relative risk 0·77 [95% CI 0·50-1·20]; p=0·24). No adverse events related to ICG use were observed. 313 serious adverse events in 229 (25%) patients were at 90-day follow-up (159 serious adverse events in 113 [24%] patients in the FGBA group and 154 serious adverse events in 116 [25%] patients in the CBA group). 18
背景:吻合口漏是结直肠手术中一种严重的术后并发症,而肠道灌注受损被认为是导致吻合口漏的主要因素。传统的肠道灌注评估方法对吻合口漏的预测价值较低。因此,我们旨在评估吲哚青绿(ICG)近红外(NIR)荧光成像实时评估在预防吻合口漏方面的功效:这项多中心、随机对照的 3 期试验在荷兰的 8 家医院进行。我们纳入了因良性和恶性疾病而计划接受腹腔镜或机器人结直肠手术(计划进行主吻合)的成人(年龄大于 18 岁)。术前,患者通过可变区块随机分配(区块大小为 4、6 和 8)被随机分配(1:1)到荧光引导肠吻合术(FGBA)或传统肠吻合术(CBA),并按部位进行分层。手术医生和分析数据的研究人员不对分组分配进行蒙蔽。患者在手术后或研究结束后才会被揭去面具。在 FGBA 组,外科医生根据常规灌注评估标记吻合口水平,然后通过 2 毫升静脉注射 5 毫克 ICG。他们使用近红外荧光成像技术评估肠道灌注情况,并相应调整(或保留)横切线。CBA组仅使用传统方法评估肠道灌注。主要结果是 FGBA 组和 CBA 组在术后 90 天内发生临床相关吻合口漏(即需要积极治疗干预,但无需再次手术即可控制[B 级]或需要再次手术[C 级],根据国际直肠癌研究小组的标准)的比率差异。主要结果和安全性在意向治疗人群中进行评估。该研究已在ToetsingOnline.nl(NL7502)和ClinicalTrials.gov(NCT04712032)注册,研究结果已完成:2020年7月2日至2023年2月21日期间,982名患者入组,其中490人被分配到FGBA,492人被分配到CBA。排除51名患者后,意向治疗人群为931人(463人分配到FGBA,468人分配到CBA)。患者的中位年龄为68-0岁(IQR为59-0-75-0),男性485人(52%),女性446人(48%)。种族数据不详。FGBA 组(463 例患者中的 32 [7%] 例)和 CBA 组(468 例患者中的 42 [9%] 例;相对风险 0-77 [95% CI 0-50-1-20];P=0-24)的 90 天临床相关吻合口漏总发生率无显著差异。未观察到与使用 ICG 相关的不良事件。229例(25%)患者中的313例严重不良事件发生在90天的随访中(FGBA组113例[24%]患者中发生了159例严重不良事件,CBA组116例[25%]患者中发生了154例严重不良事件)。18人(2%)在90天内死亡(FGBA组10人,CBA组8人):ICG近红外荧光成像并没有降低该试验中所有类型结直肠手术的 90 天吻合口漏率。有证据表明ICG近红外荧光成像可能对直肠乙状结肠切除术等亚组有益,因此应针对这些亚组开展进一步研究:资金来源:奥林巴斯医疗、Diagnostic Green 和 Intuitive Foundation。
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引用次数: 0
Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. GLP-1 受体激动剂的胃肠道效应:机制、管理和未来方向。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-01 DOI: 10.1016/S2468-1253(24)00188-2
Ryan J Jalleh, Chris K Rayner, Trygve Hausken, Karen L Jones, Michael Camilleri, Michael Horowitz

The availability of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) such as liraglutide and semaglutide, and a GLP-1 and glucose dependent insulinotropic polypeptide coagonist (tirzepatide) represents a paradigm shift in the management of both type 2 diabetes and obesity. There is now considerable attention, including in the public media, on the effect of both long-acting and short-acting GLP-1RAs to delay gastric emptying. Although slowed gastric emptying is integral to reducing post-prandial blood glucose responses in type 2 diabetes, marked slowing of gastric emptying might also increase the propensity for longer intragastric retention of food, with a consequent increased risk of aspiration at the time of surgery or upper gastrointestinal endoscopy. This Personal View summarises current knowledge of the effects of GLP-1 and GLP-1RAs on gastrointestinal physiology, particularly gastric emptying, and discusses the implications for the development of sound pre-operative or pre-procedural guidelines. The development of pre-procedural guidelines is currently compromised by the poor evidence base, particularly in relation to the effect of long-acting GLP-1RAs on gastric emptying. We suggest pre-procedural management pathways for individuals on GLP-1RA-based therapy and discuss priorities for future research.

胰高血糖素样肽-1(GLP-1)受体激动剂(RA),如利拉鲁肽和赛马鲁肽,以及 GLP-1 和葡萄糖依赖性胰岛素促泌多肽协同剂(替泽帕肽)的出现,代表着 2 型糖尿病和肥胖症治疗模式的转变。目前,长效和短效 GLP-1RA 均可延缓胃排空,这引起了包括公共媒体在内的广泛关注。虽然胃排空减慢是降低 2 型糖尿病患者餐后血糖反应不可或缺的因素,但胃排空明显减慢也可能会延长食物在胃内滞留的时间,从而增加手术或上消化道内镜检查时误吸的风险。本个人观点总结了目前有关 GLP-1 和 GLP-1RA 对胃肠道生理学(尤其是胃排空)影响的知识,并讨论了对制定合理的术前或术前指南的影响。目前,由于证据基础薄弱,尤其是长效 GLP-1RA 对胃排空的影响,术前指南的制定受到了影响。我们为接受 GLP-1RA 治疗的患者提出了术前管理路径,并讨论了未来研究的重点。
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引用次数: 0
Alternating gemcitabine plus nab-paclitaxel and gemcitabine alone versus continuous gemcitabine plus nab-paclitaxel after induction treatment of metastatic pancreatic cancer (ALPACA): a multicentre, randomised, open-label, phase 2 trial. 转移性胰腺癌诱导治疗(ALPACA)后吉西他滨加纳布-紫杉醇和吉西他滨单药交替治疗与吉西他滨加纳布-紫杉醇连续治疗:一项多中心、随机、开放标签的 2 期试验。
IF 30.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-16 DOI: 10.1016/S2468-1253(24)00197-3
Klara Dorman, Stefan Boeck, Karel Caca, Maximilian Reichert, Thomas J Ettrich, Helmut Oettle, Oliver Waidmann, Dominik P Modest, Lothar Müller, Patrick Michl, Stephan Kanzler, Daniel Pink, Anke Reinacher-Schick, Michael Geißler, Henning Pelz, Volker Kunzmann, Swantje Held, Thomas Schichtl, Volker Heinemann, Frank Kullmann
<p><strong>Background: </strong>A standardised dose-reduction strategy has not been established for the widely used gemcitabine plus nab-paclitaxel regimen in patients with metastatic pancreatic ductal adenocarcinoma. We aimed to investigate the efficacy and tolerability of alternating treatment cycles of nab-paclitaxel-gemcitabine combination therapy and gemcitabine alone versus continuous treatment with the nab-paclitaxel-gemcitabine combination.</p><p><strong>Methods: </strong>ALPACA was a randomised, open-label, phase 2 trial conducted at 29 study centres across Germany. Patients aged 18 years or older with a histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma who had not been previously treated for advanced disease were enrolled. After an induction phase with three cycles of nab-paclitaxel-gemcitabine combination therapy (nab-paclitaxel 125 mg/m<sup>2</sup> and gemcitabine 1000 mg/m<sup>2</sup> administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients were randomly assigned (1:1) by stratified permuted block randomisation either to continue treatment with standard nab-paclitaxel-gemcitabine or to receive alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone. Patients and investigators were not masked to treatment allocation. Randomisation was done centrally by the study statistician using a computer-generated randomisation list, and was stratified by Karnofsky Performance Status and presence of liver metastases. The primary endpoint was the derivation of an unbiased point estimate and an associated confidence interval with a confidence coefficient of 80% for the hazard ratio (HR) for overall survival after randomisation, without testing a specific hypothesis, analysed by intention to treat in all patients who started randomised treatment. Safety was analysed according to treatment received. This trial is registered with ClinicalTrials.gov, NCT02564146, and is completed.</p><p><strong>Findings: </strong>Between May 27, 2016, and May 27, 2021, 325 patients were enrolled. Following three cycles of induction treatment, 174 patients were randomly assigned: 85 to continue receiving standard nab-paclitaxel-gemcitabine, of whom 79 started treatment, and 89 to the alternating treatment schedule, of whom 88 started treatment. Of the 167 patients who started randomised treatment, 88 (53%) were female and 79 (47%) were male. Median overall survival after randomisation was 10·4 months (80% CI 9·2-12·0) in the group that received standard treatment and 10·5 months (10·2-11·1) in the group that received alternating treatment (HR 0·90, 80% CI 0·72-1·13; p=0·56). The most common adverse events of any grade were peripheral neuropathy (59 [74%] of 80 patients in the continuous treatment group vs 53 [62%] of 85 patients in the alternating treatment group) and fatigue (43 [54%] vs 44 [52%]). Treatment-emergent serious adverse events after randomisation occurred in 40 (50%) pati
背景:对于转移性胰腺导管腺癌患者广泛使用的吉西他滨加纳布-紫杉醇方案,尚未建立标准化的剂量减少策略。我们旨在研究纳布-紫杉醇-吉西他滨联合疗法和吉西他滨单药交替治疗周期与纳布-紫杉醇-吉西他滨联合疗法连续治疗的疗效和耐受性:ALPACA是一项随机、开放标签的2期试验,在德国的29个研究中心进行。年龄在18岁或18岁以上、组织学或细胞学确诊为转移性胰腺导管腺癌、既往未接受过晚期治疗的患者均被纳入其中。经过三个周期的纳布-紫杉醇-吉西他滨联合疗法(纳布-紫杉醇 125 毫克/平方米和吉西他滨 1000 毫克/平方米,在每个 28 天周期的第 1、8 和 15 天静脉给药)诱导阶段后,患者被随机分配(1:通过分层包块随机分配(1:1),患者要么继续接受标准的纳布-紫杉醇-吉西他滨治疗,要么交替接受纳布-紫杉醇-吉西他滨和吉西他滨单药治疗。患者和研究人员不对治疗分配进行蒙蔽。随机分配由研究统计人员使用计算机生成的随机名单集中进行,并根据卡诺夫斯基表现状态和是否存在肝转移进行分层。主要终点是得出随机化后总生存期危险比(HR)的无偏点估计值和相关置信区间(置信系数为80%),无需测试特定假设,对所有开始随机治疗的患者进行意向治疗分析。安全性根据所接受的治疗进行分析。该试验已在ClinicalTrials.gov(NCT02564146)注册,并已完成:2016年5月27日至2021年5月27日期间,共有325名患者入组。经过三个周期的诱导治疗后,174 名患者被随机分配:85人继续接受标准纳布-紫杉醇-吉西他滨治疗,其中79人开始治疗;89人接受交替治疗方案,其中88人开始治疗。在开始接受随机治疗的167名患者中,88人(53%)为女性,79人(47%)为男性。随机分组后,接受标准治疗组的中位总生存期为10-4个月(80% CI 9-2-12-0),接受交替治疗组的中位总生存期为10-5个月(10-2-11-1)(HR 0-90,80% CI 0-72-1-13;P=0-56)。最常见的任何级别的不良事件是周围神经病变(持续治疗组 80 名患者中的 59 [74%] 对交替治疗组 85 名患者中的 53 [62%] )和疲劳(43 [54%] 对 44 [52%])。随机分组后,连续治疗组有 40 例(50%)患者发生了治疗突发严重不良事件,交替治疗组有 28 例(33%)患者发生了治疗突发严重不良事件。与接受标准疗法的患者相比,接受交替周期疗法的患者发生的3级或以上治疗突发不良事件较少,尤其是周围神经病变(连续治疗组17例[21%],交替治疗组12例[14%])和感染(16例[20%],交替治疗组9例[11%])。随机分组后有两例与治疗相关的死亡,均发生在连续治疗组(一例为多器官功能障碍综合征,随机分组后未接受治疗;一例为间质性肺病):我们的研究结果表明,在三个诱导周期后交替使用纳布-紫杉醇-吉西他滨和吉西他滨单药的剂量递减方案与纳布-紫杉醇-吉西他滨标准治疗的总生存期相似,但耐受性更好。因此,我们建议临床上可以考虑对经过纳布-紫杉醇-吉西他滨三个周期治疗后病情至少稳定的转移性胰腺癌患者改用交替疗法:资金来源:Celgene/Bristol Myers Squibb。
{"title":"Alternating gemcitabine plus nab-paclitaxel and gemcitabine alone versus continuous gemcitabine plus nab-paclitaxel after induction treatment of metastatic pancreatic cancer (ALPACA): a multicentre, randomised, open-label, phase 2 trial.","authors":"Klara Dorman, Stefan Boeck, Karel Caca, Maximilian Reichert, Thomas J Ettrich, Helmut Oettle, Oliver Waidmann, Dominik P Modest, Lothar Müller, Patrick Michl, Stephan Kanzler, Daniel Pink, Anke Reinacher-Schick, Michael Geißler, Henning Pelz, Volker Kunzmann, Swantje Held, Thomas Schichtl, Volker Heinemann, Frank Kullmann","doi":"10.1016/S2468-1253(24)00197-3","DOIUrl":"10.1016/S2468-1253(24)00197-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;A standardised dose-reduction strategy has not been established for the widely used gemcitabine plus nab-paclitaxel regimen in patients with metastatic pancreatic ductal adenocarcinoma. We aimed to investigate the efficacy and tolerability of alternating treatment cycles of nab-paclitaxel-gemcitabine combination therapy and gemcitabine alone versus continuous treatment with the nab-paclitaxel-gemcitabine combination.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;ALPACA was a randomised, open-label, phase 2 trial conducted at 29 study centres across Germany. Patients aged 18 years or older with a histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma who had not been previously treated for advanced disease were enrolled. After an induction phase with three cycles of nab-paclitaxel-gemcitabine combination therapy (nab-paclitaxel 125 mg/m&lt;sup&gt;2&lt;/sup&gt; and gemcitabine 1000 mg/m&lt;sup&gt;2&lt;/sup&gt; administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients were randomly assigned (1:1) by stratified permuted block randomisation either to continue treatment with standard nab-paclitaxel-gemcitabine or to receive alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone. Patients and investigators were not masked to treatment allocation. Randomisation was done centrally by the study statistician using a computer-generated randomisation list, and was stratified by Karnofsky Performance Status and presence of liver metastases. The primary endpoint was the derivation of an unbiased point estimate and an associated confidence interval with a confidence coefficient of 80% for the hazard ratio (HR) for overall survival after randomisation, without testing a specific hypothesis, analysed by intention to treat in all patients who started randomised treatment. Safety was analysed according to treatment received. This trial is registered with ClinicalTrials.gov, NCT02564146, and is completed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between May 27, 2016, and May 27, 2021, 325 patients were enrolled. Following three cycles of induction treatment, 174 patients were randomly assigned: 85 to continue receiving standard nab-paclitaxel-gemcitabine, of whom 79 started treatment, and 89 to the alternating treatment schedule, of whom 88 started treatment. Of the 167 patients who started randomised treatment, 88 (53%) were female and 79 (47%) were male. Median overall survival after randomisation was 10·4 months (80% CI 9·2-12·0) in the group that received standard treatment and 10·5 months (10·2-11·1) in the group that received alternating treatment (HR 0·90, 80% CI 0·72-1·13; p=0·56). The most common adverse events of any grade were peripheral neuropathy (59 [74%] of 80 patients in the continuous treatment group vs 53 [62%] of 85 patients in the alternating treatment group) and fatigue (43 [54%] vs 44 [52%]). Treatment-emergent serious adverse events after randomisation occurred in 40 (50%) pati","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006003","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}
引用次数: 0
Spleen stiffness measurement by vibration-controlled transient elastography at 100 Hz for non-invasive predicted diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a modelling study. 通过 100 Hz 振动控制瞬态弹性成像技术测量脾脏硬度,用于无创预测诊断代偿期晚期慢性肝病患者具有临床意义的门静脉高压症:一项模型研究。
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-23 DOI: 10.1016/s2468-1253(24)00234-6
Mathias Jachs,Aitor Odriozola,Fanny Turon,Lucile Moga,Luis Téllez,Petra Fischer,Dario Saltini,Wilhelmus J Kwanten,Maria Grasso,Elba Llop,Yuly P Mendoza,Angelo Armandi,Julia Thalhammer,Carlos Pardo,Antonio Colecchia,Federico Ravaioli,Benjamin Maasoumy,Wim Laleman,José Presa,Jörn M Schattenberg,Annalisa Berzigotti,José L Calleja,Vincenza Calvaruso,Sven Francque,Filippo Schepis,Bogdan Procopet,Agustín Albillos,Pierre-Emmanuel Rautou,Juan C García-Pagán,Ángela Puente,José I Fortea,Thomas Reiberger,Mattias Mandorfer,,
BACKGROUNDIn patients with compensated advanced chronic liver disease (cACLD), risk of clinically significant portal hypertension (CSPH) can be estimated by applying non-invasive tests such as liver stiffness measurement (LSM), platelet count, and, in some cases, BMI. We aimed to assess the diagnostic utility of spleen stiffness measurement (SSM) at 100 Hz as a standalone non-invasive test for CSPH and to evaluate its incremental value compared with the ANTICIPATE±NASH model in patients with cACLD.METHODSFor this modelling study, patients were recruited from 16 expert centres in Europe. Patients who underwent characterisation by hepatic venous pressure gradient (HVPG) and non-invasive tests (ie, LSM, platelet count, and SSM at 100 Hz) at one of the participating centres between Jan 1, 2020, and Dec 31, 2023, were considered for inclusion. Only patients aged 18 years or older with Child-Pugh class A cACLD, shown by LSM 10 kPa or more or F3 or F4 fibrosis on liver histology, were included. The overall cohort was split into the derivation cohort (patients recruited between Jan 1, 2020, and Dec 31, 2022) and the temporal validation cohort (patients recruited between Jan 1, 2023, and Dec 31, 2023). The ANTICIPATE±NASH model was applied to assess individual CSPH probability and SSM was investigated as a standalone non-invasive test for CPSH; in combination with platelet count and BMI; and in a full model of SSM, LSM, platelet count, and BMI (ie, the Non-Invasive CSPH Estimated Risk [NICER] model). All models were binary logistic regression models. The primary outcome was CSPH. We evaluated the discriminative utility of the models by calculating the area under the receiver operating characteristics curve (AUC) and creating calibration plots and calibration of intercept, slope, and integrated calibration index.FINDINGS407 patients with cACLD were included, 202 (50%) in the derivation cohort and 205 (50%) in the validation cohort. Median age was 60·0 years (IQR 55·0-66·8); 275 (68%) of 407 patients were male and 132 (32%) were female. 164 (40%) of 407 patients had metabolic dysfunction-associated steatotic liver disease (MASLD), 133 (33%) had MASLD with increased alcohol intake or alcohol-related liver disease, 75 (18%) had viral hepatitis (61 [81%] of whom had sustained virologic response of hepatitis C virus or suppression of hepatitis B virus DNA), and 35 (9%) had other chronic liver diseases. 241 (59%) patients had CSPH. Median SSM was 45·0 kPa (32·1-65·4) and LSM was 21·4 kPa (14·1-31·6). SSM and LSM had similar AUCs for prediction of CSPH in the derivation cohort (0·779 [95% CI 0·717-0·842] vs 0·781 [0·718-0·844]; p=0·97) and in the validation cohort (0·830 [0·772-0·887] vs 0·804 [0·743-0·864]; p=0·50). The SSM-based model comprising platelet count and BMI had a similar AUC as the ANTICIPATE±NASH model in both the derivation cohort (0·849 [0·794-0·903] vs 0·849 [0·794-0·903]; p=0·999) and in the validation cohort (0·873 [0·819-0·922] vs 0·863 [0·810
背景在代偿性晚期慢性肝病(cACLD)患者中,临床意义门静脉高压症(CSPH)的风险可通过肝脏僵硬度测量(LSM)、血小板计数等无创检验进行估计,在某些情况下还可通过体重指数(BMI)进行估计。我们的目的是评估 100 Hz 脾脏僵硬度测量 (SSM) 作为 CSPH 独立无创检验的诊断效用,并评估其在 cACLD 患者中与 ANTICIPATE±NASH 模型相比的增量价值。在 2020 年 1 月 1 日至 2023 年 12 月 31 日期间,在其中一个参与中心通过肝静脉压力梯度(HVPG)和非侵入性测试(即 LSM、血小板计数和 100 Hz 的 SSM)对患者进行特征描述的患者被视为纳入对象。只有年龄在18岁或18岁以上、Child-Pugh A级cACLD(LSM 10 kPa或以上或肝组织学显示F3或F4纤维化)患者才被纳入。总体队列分为衍生队列(2020 年 1 月 1 日至 2022 年 12 月 31 日期间招募的患者)和时间验证队列(2023 年 1 月 1 日至 2023 年 12 月 31 日期间招募的患者)。ANTICIPATE±NASH 模型用于评估个体 CSPH 概率,SSM 作为 CPSH 的独立无创检验;与血小板计数和 BMI 结合;以及在 SSM、LSM、血小板计数和 BMI 的完整模型(即无创 CSPH 估计风险 [NICER] 模型)中进行了研究。所有模型均为二元逻辑回归模型。主要结果是 CSPH。我们通过计算接收者操作特征曲线下面积(AUC)和创建校准图以及校准截距、斜率和综合校准指数来评估模型的判别效用。中位年龄为60-0岁(IQR 55-0-66-8);407名患者中有275名(68%)为男性,132名(32%)为女性。407名患者中有164人(40%)患有代谢功能障碍相关性脂肪性肝病(MASLD),133人(33%)患有代谢功能障碍相关性脂肪性肝病并伴有酒精摄入量增加或酒精相关性肝病,75人(18%)患有病毒性肝炎(其中61人[81%]具有丙型肝炎病毒持续病毒学应答或乙型肝炎病毒DNA抑制),35人(9%)患有其他慢性肝病。241(59%)名患者患有 CSPH。中位 SSM 为 45-0 kPa(32-1-65-4),LSM 为 21-4 kPa(14-1-31-6)。在衍生队列(0-779 [95% CI 0-717-0-842] vs 0-781 [0-718-0-844]; p=0-97)和验证队列(0-830 [0-772-0-887] vs 0-804 [0-743-0-864]; p=0-50)中,SSM 和 LSM 预测 CSPH 的 AUC 相似。在衍生队列(0-849 [0-794-0-903] vs 0-849 [0-794-0-903];p=0-999)和验证队列(0-873 [0-819-0-922] vs 0-863 [0-810-0-916];p=0-75)中,由血小板计数和体重指数组成的基于 SSM 的模型的 AUC 与 ANTICIPATE±NASH 模型相似。在衍生队列(0-889 [0-843-0-934] vs 0-849 [0-794-0-903];p=0-022)和验证队列(0-906 [0-864-0-946] vs 0-863 [0-810-0-916];p=0-012)中,NICER 模型预测 CSPH 的 AUC 明显高于 ANTICIPATE±NASH 模型。在我们的当代 cACLD 患者队列中,在 LSM、BMI 和血小板计数的基础上增加 SSM 进行 CSPH 风险分层的效果优于 ANTICIPATE±NASH 模型。SSM改进了CSPH的无创诊断,支持将其应用于临床实践。
{"title":"Spleen stiffness measurement by vibration-controlled transient elastography at 100 Hz for non-invasive predicted diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a modelling study.","authors":"Mathias Jachs,Aitor Odriozola,Fanny Turon,Lucile Moga,Luis Téllez,Petra Fischer,Dario Saltini,Wilhelmus J Kwanten,Maria Grasso,Elba Llop,Yuly P Mendoza,Angelo Armandi,Julia Thalhammer,Carlos Pardo,Antonio Colecchia,Federico Ravaioli,Benjamin Maasoumy,Wim Laleman,José Presa,Jörn M Schattenberg,Annalisa Berzigotti,José L Calleja,Vincenza Calvaruso,Sven Francque,Filippo Schepis,Bogdan Procopet,Agustín Albillos,Pierre-Emmanuel Rautou,Juan C García-Pagán,Ángela Puente,José I Fortea,Thomas Reiberger,Mattias Mandorfer,,","doi":"10.1016/s2468-1253(24)00234-6","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00234-6","url":null,"abstract":"BACKGROUNDIn patients with compensated advanced chronic liver disease (cACLD), risk of clinically significant portal hypertension (CSPH) can be estimated by applying non-invasive tests such as liver stiffness measurement (LSM), platelet count, and, in some cases, BMI. We aimed to assess the diagnostic utility of spleen stiffness measurement (SSM) at 100 Hz as a standalone non-invasive test for CSPH and to evaluate its incremental value compared with the ANTICIPATE±NASH model in patients with cACLD.METHODSFor this modelling study, patients were recruited from 16 expert centres in Europe. Patients who underwent characterisation by hepatic venous pressure gradient (HVPG) and non-invasive tests (ie, LSM, platelet count, and SSM at 100 Hz) at one of the participating centres between Jan 1, 2020, and Dec 31, 2023, were considered for inclusion. Only patients aged 18 years or older with Child-Pugh class A cACLD, shown by LSM 10 kPa or more or F3 or F4 fibrosis on liver histology, were included. The overall cohort was split into the derivation cohort (patients recruited between Jan 1, 2020, and Dec 31, 2022) and the temporal validation cohort (patients recruited between Jan 1, 2023, and Dec 31, 2023). The ANTICIPATE±NASH model was applied to assess individual CSPH probability and SSM was investigated as a standalone non-invasive test for CPSH; in combination with platelet count and BMI; and in a full model of SSM, LSM, platelet count, and BMI (ie, the Non-Invasive CSPH Estimated Risk [NICER] model). All models were binary logistic regression models. The primary outcome was CSPH. We evaluated the discriminative utility of the models by calculating the area under the receiver operating characteristics curve (AUC) and creating calibration plots and calibration of intercept, slope, and integrated calibration index.FINDINGS407 patients with cACLD were included, 202 (50%) in the derivation cohort and 205 (50%) in the validation cohort. Median age was 60·0 years (IQR 55·0-66·8); 275 (68%) of 407 patients were male and 132 (32%) were female. 164 (40%) of 407 patients had metabolic dysfunction-associated steatotic liver disease (MASLD), 133 (33%) had MASLD with increased alcohol intake or alcohol-related liver disease, 75 (18%) had viral hepatitis (61 [81%] of whom had sustained virologic response of hepatitis C virus or suppression of hepatitis B virus DNA), and 35 (9%) had other chronic liver diseases. 241 (59%) patients had CSPH. Median SSM was 45·0 kPa (32·1-65·4) and LSM was 21·4 kPa (14·1-31·6). SSM and LSM had similar AUCs for prediction of CSPH in the derivation cohort (0·779 [95% CI 0·717-0·842] vs 0·781 [0·718-0·844]; p=0·97) and in the validation cohort (0·830 [0·772-0·887] vs 0·804 [0·743-0·864]; p=0·50). The SSM-based model comprising platelet count and BMI had a similar AUC as the ANTICIPATE±NASH model in both the derivation cohort (0·849 [0·794-0·903] vs 0·849 [0·794-0·903]; p=0·999) and in the validation cohort (0·873 [0·819-0·922] vs 0·863 [0·810","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":35.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328669","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}
引用次数: 0
Spleen stiffness in portal hypertension algorithms: the next advance. 门静脉高压算法中的脾脏硬度:下一个进步。
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-23 DOI: 10.1016/s2468-1253(24)00249-8
Cristina Rigamonti
{"title":"Spleen stiffness in portal hypertension algorithms: the next advance.","authors":"Cristina Rigamonti","doi":"10.1016/s2468-1253(24)00249-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00249-8","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":35.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328758","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}
引用次数: 0
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Lancet Gastroenterology & Hepatology
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