Explore the vast range of titles available.

IntroductionIn pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk.MethodsA prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT’s plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed.Results53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients’ characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%.ConclusionsFor PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated.Trial registration number:Dutch Trial Registry (NTR3142).

Background Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. Methods This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , irinotecan 150 mg/m 2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m 2 ). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Discussion The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. Trial registration Clinical Trials: NCT04927780. Registered June 16, 2021.

Background Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). Patients and Methods All patients who underwent PD for NF-PanNETs (2007–2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. Results Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p  = 0.013], a minimally invasive approach (OR 12.896; p  = 0.001), and surgical volume (OR 2.062; p  = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free ( p  = 0.487) and overall survival ( p  = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm ( p  = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates ( p  = 0.766) Conclusions TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

Background Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. Methods This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the “Trials within Cohorts” (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19–9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. Discussion The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients’ quality of life will be obtained. Trial registration Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.

BackgroundMany centers worldwide are shifting from laparoscopic to robotic minimally invasive hepato-pancreato-biliary resections (MIS-HPB) but large single center series assessing this process are lacking. We hypothesized that the introduction of robot-assisted surgery was safe and feasible in a high-volume center.MethodsSingle center, post-hoc assessment of prospectively collected data including all consecutive MIS-HPB resections (January 2010–February 2022). As of December 2018, all MIS pancreatoduodenectomy and liver resections were robot-assisted. All surgeons had participated in dedicated training programs for laparoscopic and robotic MIS-HPB. Primary outcomes were in-hospital/30-day mortality and Clavien-Dindo ≥ 3 complications.ResultsAmong 1875 pancreatic and liver resections, 600 (32%) were MIS-HPB resections. The overall rate of conversion was 4.3%, Clavien-Dindo ≥ 3 complications 25.7%, and in-hospital/30-day mortality 1.8% (n = 11). When comparing the period before and after the introduction of robotic MIS-HPB (Dec 2018), the overall use of MIS-HPB increased from 25.3 to 43.8% (P < 0.001) and blood loss decreased from 250 ml [IQR 100–500] to 150 ml [IQR 50–300] (P < 0.001). The 291 MIS pancreatic resections included 163 MIS pancreatoduodenectomies (52 laparoscopic, 111 robotic) with 4.3% conversion rate. The implementation of robotic pancreatoduodenectomy was associated with reduced operation time (450 vs 361 min; P < 0.001), reduced blood loss (350 vs 200 ml; P < 0.001), and a decreased rate of delayed gastric emptying (28.8% vs 9.9%; P = 0.009). The 309 MIS liver resections included 198 laparoscopic and 111 robotic procedures with a 3.6% conversion rate. The implementation of robotic liver resection was associated with less overall complications (24.7% vs 10.8%; P = 0.003) and shorter hospital stay (4 vs 3 days; P < 0.001).ConclusionThe introduction of robotic surgery was associated with greater implementation of MIS-HPB in up to nearly half of all pancreatic and liver resections. Although mortality and major morbidity were not affected, robotic surgery was associated with improvements in some selected outcomes. Ultimately, randomized studies and high-quality registries should determine its added value.

Background Disease recurrence is the main cause of mortality after resection of pancreatic ductal adenocarcinoma (PDAC). In 20–30% of resected patients, isolated local PDAC recurrence occurs. Retrospective studies have suggested that stereotactic body radiation therapy (SBRT) might lead to improved local control in these patients, potentially having a beneficial effect on both survival and quality of life. The “nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy” (ARCADE) will investigate the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence compared to standard of care alone, regarding both survival and quality of life outcomes. Methods The ARCADE trial is nested within a prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the ‘Trials within Cohorts’ design. All PACAP participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies are eligible. Patients will be randomized for local therapy (5 fractions of 8 Gy SBRT) in addition to standard of care or standard of care alone. In total, 174 patients will be included. The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. Discussion It is hypothesized that additional SBRT, compared to standard of care alone, improves survival and quality of life in patients with isolated local recurrence after PDAC resection. Trial registration ClinicalTrials.gov registration NCT04881487 . Registered on May 11, 2021.

Rationale Preoperative biliary drainage (PBD) has been introduced to improve outcome after surgery in patients suffering from obstructive jaundice due to a potentially resectable proximal or distal bile duct/pancreatic head lesion. In experimental models, PBD is almost exclusively associated with beneficial results: improved liver function and nutritional status; reduction of systemic endotoxemia; cytokine release; and, as a result, an improved immune response. Mortality was significantly reduced in these animal models. Human studies show conflicting results. Findings For distal obstruction, currently the “best-evidence” available clearly shows that routine PBD does not yield the appreciated improvement in postoperative morbidity and mortality in patients undergoing resection. Moreover, PBD harbors its own complications. However, most of the available data are outdated or suffer from methodological deficits. Conclusion The highest level of evidence for PBD to be performed in proximal obstruction, as well as over the preferred mode, is lacking but, nevertheless, assimilated in the treatment algorithm for many centers. Logistics and waiting lists, although sometimes inevitable, could be factors that might influence the decision to opt for PBD, as well as an extended diagnostic workup with laparoscopy (on indication) or scheduled preoperative chemotherapy.