von Ujwal Mukund Mahajan ; Bettina Oehrle ; Elisabetta Goni ; Oliver Strobel ; Jörg Kaiser ; Robert Grützmann ; Jens Werner ; Helmut Friess ; Thomas M Gress ; Thomas W Seufferlein ; Waldemar Uhl ; Uwe Will ; John P. Neoptolemos ; Uwe A Wittel ; Marlies Vornhülz ; Simon Sirtl ; Georg Beyer ; Ivonne Regel ; Stefan Boeck ; Volker Heinemann ; Fabian Frost ; Antje Steveling ; Henry Völzke ; Astrid Petersmann ; Matthias Nauck ; Eckhard Weber ; Beate Kamlage ; Markus M Lerch ; Julia Mayerle
Online verfügbar: 16. Mai 2025, Artikelversion: 4. Juni 2025 ; Gesehen am 21.01.2026
Background - Earlier diagnosis of pancreatic ductal adenocarcinoma is key to improving overall survival in patients with this hard-to-treat cancer. We independently validated two previously identified plasma-based metabolic signatures for exclusion of pancreatic ductal adenocarcinoma in cohorts with an increased annual risk. - Methods - The METAPAC study was a prospective, multicentre, investigator-masked, enrichment design, phase 4 trial done in 23 centres in Germany. Patients with pancreatic lesions identified by diagnostic imaging that required further diagnostic assessment were recruited and followed up for 24 months. Targeted quantitative plasma metabolite analysis was done on a liquid chromatography-tandem mass spectrometry platform. The improved metabolic (i-Metabolic) signature consisted of 12 analytes plus carbohydrate antigen (CA) 19-9, and the minimalistic metabolic (m-Metabolic) signature consisted of four analytes plus CA 19-9. The primary endpoint of the study was the exclusion of pancreatic ductal adenocarcinoma with an 85% specificity and the highest possible diagnostic accuracy. All statistical analyses were done per protocol. This study is registered with the German Clinical Trials Register (DRKS00010866). - Findings - Between Sept 9, 2016, and April 8, 2022, 1370 patients with CT-identified pancreatic lesions necessitating further diagnostic assessment were screened, of whom 1129 patients (489 with pancreatic ductal adenocarcinoma, 640 controls) were included in the primary analysis (median age 67 years [IQR 58-75]; 556 [49%] female, 572 [51%] male). The control group consisted of high-risk individuals with acute pancreatitis (11 [1%] of 1129 participants), chronic pancreatitis (113 [10%]), intraductal papillary mucinous neoplasms (232 [21%]), cystic lesions other than intraductal papillary mucinous neoplasms (271 [24%]), and metastases of extrapancreatic origin (13 [1%]). The i-Metabolic signature detected pancreatic ductal adenocarcinoma with an area under the curve (AUC) of 0·846 (95% CI 0·842-0·849), specificity of 90·4% (89·8-91·1), sensitivity of 67·5% (66·9-68·0), and balanced accuracy of 80·5% (80·2-80·8), compared with CA 19-9 alone (AUC 0·799 [0·797-0·802], p<0·0001; specificity 79·1% [78·7-79·4]; sensitivity 81·8% [81·5-82·0]; balanced accuracy 80·6% [80·4-80·9]). The m-Metabolic signature detected pancreatic ductal adenocarcinoma with an AUC of 0·846 (95% CI 0·842-0·849; p<0·0001 vs CA 19-9 alone), specificity of 93·6% (93·1-94·0), sensitivity of 59·9% (59·3-60·4), and accuracy of 79·0% (78·8-79·2). In a population of 242 individuals with new-onset diabetes (three cases of incident pancreatic ductal adenocarcinoma), the m-Metabolic signature (without CA 19-9) significantly discriminated patients with pancreatic ductal adenocarcinoma from those without (p=0·038). AUC, specificity, and sensitivity remained constant after random bootstrapping for a prevalence of pancreatic ductal adenocarcinoma between 1% and 20%. - Interpretation - Two plasma-based metabolic signatures showed significant improvement in performance compared with CA 19-9 alone in excluding pancreatic ductal adenocarcinoma in a prospective real-world cohort. These findings could offer a surveillance tool in patients with an annual risk of pancreatic ductal adenocarcinoma of 1% to reduce unnecessary invasive procedures and facilitate earlier detection of resectable disease. - Funding - Federal Ministry of Education and Research (BMBF, Germany).
The lancet. Gastroenterology & Hepatology London : Elsevier, 2016 10(2025), 7 vom: Juli, Seite 634-647 Online-Ressource
von Jürgen Beck ; Christian Fung ; Daniel Strbian ; Lukas Bütikofer ; Werner J. Z'Graggen ; Matthias F. Lang ; Seraina Beyeler ; Jan Gralla ; Florian Ringel ; Karl Schaller ; Nikolaus Plesnila ; Marcel Arnold ; Werner Hacke ; Peter Jüni ; Alexander David Mendelow ; Christian Stapf ; Rustam Al-Shahi Salman ; Jenny Bressan ; Stefanie Lerch ; Arsany Hakim ; Nicolas Martinez-Majander ; Anna Piippo-Karjalainen ; Peter Vajkoczy ; Stefan Wolf ; Gerrit A. Schubert ; Anke Höllig ; Michael Veldeman ; Roland Rölz ; Andreas Gruber ; Philip Rauch ; Dorothee Wachter ; Veit Rohde ; Thomas Kerz ; Eberhard Uhl ; Enea Thanasi ; Hagen B. Huttner ; Bernd Kallmünzer ; L. Jaap Kappelle ; Wolfgang Deinsberger ; Christian Roth ; Robin Lemmens ; Jan Leppert ; Jose L. Sanmillan ; Jonathan M. Coutinho ; Katharina Hackenberg ; Gernot Reimann ; Mikael Mazighi ; Claudio L. A. Bassetti ; Heinrich P. Mattle ; Andreas Raabe ; Urs Fischer ; Renán Sánchez-Porras
BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.
The lancet London [u.a.] : Elsevier, 1823 403(2024), 10442 vom: Juni, Seite 2395-2404 Online-Ressource
