Novel blood-based protein biomarkers may be of value for efficient, accurate, and non-invasive diagnosis of pancreatic cancer. This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer, and investigates their added value to CA19-9, the common blood-based biomarker in clinical use for pancreatic cancer. PubMed, Embase, Web of Science, and the Wiley/Cochrane Library were systematically searched from inception until June 2022. A meta-analysis of aggregate and individual participant data was conducted using frequentist and Bayesian hierarchical random-effects models. The added clinical utility of protein biomarkers was investigated using bootstrap bias-corrected decision curve analyses. Aggregate data from 28 primary studies (6127 participants) were included, of which 8 studies (1790 participants) provided individual participant data. CA19-9 was significantly more accurate than MIC-1 for distinguishing pancreatic cancer from benign disease (AUC, 0.83 vs 0.74; relative diagnostic odds ratio [rDOR], 2.10 [95% CI, 0.98–4.48]; p = 0.002), THBS2 (AUC, 0.87 vs 0.69; rDOR, 4.53 [2.16–9.39]; p < 0.0001), TIMP-1 (AUC, 0.91 vs 0.70; rDOR, 8.00 [3.81–16.9]; p < 0.0001), OPN (AUC, 0.89 vs 0.74; rDOR, 4.22 [1.13–15.6]; p < 0.0001), ICAM-1 (AUC, 0.91 vs 0.68; rDOR 9.30 [0.87–99.5]; p < 0.0001), and IGFBP2 (AUC, 0.91 vs 0.68; rDOR, 4.48 [0.78–24.3]; p < 0.0001). The addition of these novel protein biomarkers to CA19-9 did not significantly improve the AUC, and resulted in minor increases or limited decreases in clinical utility. Novel protein biomarkers have moderate diagnostic accuracy, do not outperform CA19-9 in differentiating pancreatic cancer from benign disease, and show limited added clinical value to CA19-9. We propose recommendations to aid the development of minimally invasive diagnostic tests with sufficient clinical utility to improve the management of patients with suspected pancreatic cancer. Bennink Foundation, Dutch Cancer Foundation (KWF Kankerbestrijding), and AIRC.

Distinction of pancreatic ductal adenocarcinoma (PDAC) in the head of the pancreas, distal cholangiocarcinoma (dCCA), and benign periampullary conditions, is complex as they often share similar clinical symptoms. However, these diseases require specific management strategies, urging improvement of non-invasive tools for accurate diagnosis. Recent evidence has shown that the ratio between CA19-9 and bilirubin levels supports diagnostic distinction of benign or malignant hepatopancreaticobiliary diseases. Here, we investigate the diagnostic value of this ratio in PDAC, dCCA and benign diseases of the periampullary region in a novel fashion. To address this aim, we enrolled 265 patients with hepatopancreaticobiliary diseases and constructed four logistic regression models on a subset of patients (n = 232) based on CA19-9, bilirubin and the ratio of both values: CA19-9/(bilirubin⁻¹). Non-linearity was investigated using restricted cubic splines and a final model, the ‘Model Ratio’, based on these three variables was fitted using multivariable fractional polynomials. The performance of this model was consistently superior in terms of discrimination and calibration compared to models based on CA19-9 combined with bilirubin and CA19-9 or bilirubin alone. The ‘Model Ratio’ accurately distinguished between malignant and benign disease (AUC [95% CI], 0.91 [0.86–0.95]), PDAC and benign disease (AUC 0.91 [0.87–0.96]) and PDAC and dCCA (AUC 0.83 [0.74–0.92]) which was confirmed by internal validation using 1000 bootstrap replicates. These findings provide a foundation to improve minimally-invasive diagnostic procedures, ultimately ameliorating effective therapy for PDAC and dCCA.

BACKGROUND: Differences in clinical presentation of acute ischemic stroke between men and women may affect prehospital identification of anterior circulation large vessel occlusion (aLVO). We assessed sex differences in diagnostic performance of 8 prehospital scales to detect aLVO. METHODS: We analyzed pooled individual patient data from 2 prospective cohort studies (LPSS [Leiden Prehospital Stroke Study] and PRESTO [Prehospital Triage of Patients With Suspected Stroke Study]) conducted in the Netherlands between 2018 and 2019, including consecutive patients ≥18 years suspected of acute stroke who presented within 6 hours after symptom onset. Ambulance paramedics assessed clinical items from 8 prehospital aLVO detection scales: Los Angeles Motor Scale, Rapid Arterial Occlusion Evaluation, Cincinnati Stroke Triage Assessment Tool, Cincinnati Prehospital Stroke Scale, Prehospital Acute Stroke Severity, gaze-face-arm-speech-time, Conveniently Grasped Field Assessment Stroke Triage, and Face-Arm-Speech-Time Plus Severe Arm or Leg Motor Deficit. We assessed the diagnostic performance of these scales for identifying aLVO at prespecified cut points for men and women. RESULTS: Of 2358 patients with suspected stroke (median age, 73 years; 47% women), 231 (10%) had aLVO (100/1114 [9%] women and 131/1244 [11%] men). The area under the curve of the scales ranged from 0.70 (95% CI, 0.65–0.75) to 0.77 (95% CI, 0.73–0.82) in women versus 0.69 (95% CI, 0.64–0.73) to 0.75 (95% CI, 0.71–0.79) in men. Positive predictive values ranged from 0.23 (95% CI, 0.20–0.27) to 0.29 (95% CI, 0.26–0.31) in women versus 0.29 (95% CI, 0.24–0.33) to 0.37 (95% CI, 0.32–0.43) in men. Negative predictive values were similar (0.95 [95% CI, 0.94–0.96] to 0.98 [95% CI, 0.97–0.98] in women versus 0.94 [95% CI, 0.93–0.95] to 0.96 [95% CI, 0.94–0.97] in men). Sensitivity of the scales was slightly higher in women than in men (0.53 [95% CI, 0.43–0.63] to 0.76 [95% CI, 0.68–0.84] versus 0.49 [95% CI, 0.40–0.57] to 0.63 [95% CI, 0.55–0.73]), whereas specificity was lower (0.79 [95% CI, 0.76–0.81] to 0.87 [95% CI, 0.84–0.89] versus 0.82 [95% CI, 0.79–0.84] to 0.90 [95% CI, 0.88–0.91]). Rapid arterial occlusion evaluation showed the highest positive predictive values in both sexes (0.29 in women and 0.37 in men), reflecting the different event rates. CONCLUSIONS: aLVO scales show similar diagnostic performance in both sexes. The rapid arterial occlusion evaluation scale may help optimize prehospital transport decision-making in men as well as in women with suspected stroke.

Background/Objectives: The effect of thoracic duct (TD) management—resection, ligation, or preservation—during esophagectomy for cancer remains controversial. This systematic review and meta-analysis aimed to assess the impact of TD management strategies on oncological outcomes and surgical morbidity. Methods: A systematic review and meta-analysis were performed following PRISMA reporting guidelines. Searches of OVID, Embase, and Web of Science identified studies comparing thoracic duct resection or TD ligation with TD preservation in esophagectomy for cancer. Outcomes included 5-year overall survival (OS), postoperative morbidity, postoperative chyle leakage, lymph node yield, and length of stay. Random-effects meta-analyses using the Hartung-Knapp-Sidik-Jonkman variance correction were conducted. Results: A total of 17 studies involving 4200 patients were included. TD resection was associated with a significantly higher lymph node yield (mean difference [MD]: 4, 95% CI: 0 to 8, p = 0.043), but also increased risk of chyle leakage (odds ratio [OR]: 2.41, 95% CI: 1.04–5.61, p = 0.044). There was no significant improvement in 5-year OS with TD resection compared to TD preservation (hazard ratio [HR]: 0.94, 95% CI: 0.76–1.17, p = 0.48). TD ligation showed no significant differences in 5-year OS (HR: 1.15, 95% CI: 0.81–1.63, p = 0.33) or morbidity compared to TD preservation. Certainty of evidence was low across outcomes. Conclusions: TD resection increases lymph node yield but is associated with higher rates of chyle leakage, without a significantly improved overall survival. TD ligation does not significantly affect oncological or surgical outcomes compared to TD preservation. A higher grade of evidence is needed to determine the definitive oncological and surgical impact of TD management strategies.

Background: Postoperative pancreatic fistula represents the leading cause of morbidity and mortality after robotic pancreatoduodenectomy. Various scores have been proposed to stratify patients based on their postoperative pancreatic fistula risk, including three fistula risk scores, and two International Study Group for Pancreatic Surgery scores. This study compares the performance of these scores in patients undergoing robotic pancreatoduodenectomy. Methods: This is a multicentre European retrospective study in consecutive patients receiving robotic pancreatoduodenectomy for all indications (April 2014 to December 2021). The performance of the International Study Group for Pancreatic Surgery 4-tier (A–D) risk score, and its 3-tier (A–C) modification (International Study Group for Pancreatic Surgery 3-tier), fistula risk scores, alternative-fistula risk scores and the updated alternative-fistula risk scores in postoperative pancreatic fistula grade B/C prediction were compared based on their discrimination (area under the curve), calibration and clinical utility, evaluated through decision curve analyses. Results: Overall, 919 patients undergoing robotic pancreatoduodenectomy were included. The rate of grade B/C postoperative pancreatic fistula was 22.2% (n = 204). The area under the curve for the five scores differed only slightly: International Study Group for Pancreatic Surgery 0.63 (95% confidence interval (c.i.) 0.58 to 0.67), International Study Group for Pancreatic Surgery 3-tier 0.63 (95% c.i. 0.58 to 0.67), fistula risk scores 0.65 (95% c.i. 0.61 to 0.69), alternative-fistula risk scores 0.64 (95% c.i. 0.60 to 0.68) and updated alternative-fistula risk scores 0.65 (95% c.i. 0.60 to 0.69). The International Study Group for Pancreatic Surgery, International Study Group for Pancreatic Surgery 3-tier, fistula risk scores and alternative-fistula risk scores underestimated the risk of postoperative pancreatic fistula. In contrast, the updated alternative-fistula risk score was well-calibrated at low predicted risks, but overestimated postoperative pancreatic fistula risk for high-risk patients. In decision curve analyses, the updated alternative-fistula risk score showed a higher clinical utility compared with the four other risk scores. Conclusion: The clinical utility of the updated alternative-fistula risk score for robotic pancreatoduodenectomy slightly outperformed the four other fistula risk scores, and might be used for patient counselling and patient stratification in clinical practice and research.