Objective: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival. Summary of Background data: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence. Methods: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014)(2015)(2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence. Results: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001]. Conclusions: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.
Resection of soft tissue sarcomas (STS) is accompanied by a high rate of tumor-positive surgical margins (14-34%), which potentially leads to decreased disease-free survival. Vascular Endothelial Growth Factor-A (VEGF-A) is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety and optimal dose of bevacizumab-800CW for fluorescence-guided surgery (FGS) in STS for in-and ex vivo tumor detection. Materials and MethodsPatients with a histopathologically diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 days prior to surgery (10, 25 and 50 mg, n=8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab-800CW at the optimal dose. Fluorescence images in-and ex vivo were obtained during all stages of standard of care. The optimal dose was determined by calculating in-and ex vivo Tumor-to-Background ratios (TBR) and correlating these results with histopathology. ResultsFifteen patients with STS completed this study. All tumors could be visualized during in-and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg with a median in vivo TBR of 2.0 (0.58) and an ex vivo TBR of 2.67 (1.6). All seven tumor-positive margins could be observed real-time after surgical resection. Conclusion 4FGS using 10 mg bevacizumab-800CW is feasible and safe for intra-operative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase II study is needed to confirm the diagnostic accuracy.
Background Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. Methods This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005–2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. Results From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel–Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). Conclusion Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.
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