Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy.

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.

A decision support tool for the detection of pancreatic cancer in general practice: A modified Delphi consensus.

BACKGROUND/OBJECTIVES: Diagnosis of pancreatic cancer is often delayed, contributing to patient and family distress and leading to worse survival. We aimed to develop a decision support tool to support primary care providers to identify patients that should undergo investigations for pancreatic cancer, and to recommend initial diagnostic pathways. METHODS: A modified Delphi process, including a series of three surveys, was undertaken to ascertain clinical expert opinion on which combinations of signs, symptoms and risk factors should be included in a tool for the early identification of pancreatic cancer. A group of clinical specialists finalised the development of the tool during a focus group meeting. RESULTS: The tool presents individual or combinations of signs, symptoms, and risk factors in three tiers which direct the urgency of investigation. Tier 1 includes 5 clinical presentation and risk factors clusters that indicate the need for urgent investigation of the pancreas. A further five clusters are included as Tier 2 aiming to elimate other causes and reduce the time to investigating the pancreas. Tier 3 includes a list of non-specific signs, symptoms and risk factors that indicate the need to consider pancreatic cancer as a potential diagnosis, but without specific recommendations for investigation. CONCLUSIONS: Prospective validation studies are now required prior to implementation in the primary care setting. Implementation into primary care practice and as an educational resource may facilitate rapid diagnosis and improve outcomes such as distress and survival.

Randomized clinical trial of intraoperative endoscopic retrograde cholangiopancreatography versus laparoscopic bile duct exploration in patients with choledocholithiasis.

BACKGROUND: Various minimally invasive approaches exist for the management of choledocholithiasis at the time of laparoscopic cholecystectomy. The aim of this study was to compare endoscopic retrograde cholangiopancreatography (ERCP) with laparoscopic bile duct exploration (LBDE) and test the hypothesis that intraoperative ERCP is no different to LBDE in terms of rate of bile duct clearance or retained stones. METHODS: Eligible patients with choledocholithiasis undergoing emergency laparoscopic cholecystectomy were randomized to intraoperative ERCP or LBDE in a 1 : 1 ratio. The primary outcomes were rates of bile duct clearance and retained stones. Secondary outcomes were postprocedure complication rate, mortality rate, postoperative length of hospital stay, conversion to open surgery rate, procedural time and total duration of surgery. RESULTS: Some 104 patients were randomized, and 52 patients in each group were included in an intention-to-treat analysis. Duct clearance rates were 87 per cent for patients who had intraoperative ERCP and 69 per cent for those in the LBDE group (P = 0·057). The rate of retained stones was lower in the ERCP group than in the LBDE group: 15 versus 42 per cent respectively (P = 0·004). Median postoperative length of stay was shorter with ERCP (2 days versus 3 days for LBDE; P = 0·015). CONCLUSION: Intraoperative ERCP is more effective than LBDE in terms of minimizing the rate of retained stones in patients with choledocholithiasis undergoing emergency laparoscopic cholecystectomy. REGISTRATION NUMBER: ACTRN12613000761763 (http://www.anzctr.org.au/).

Acute surgical unit safely reduces unnecessary after-hours cholecystectomy.

INTRODUCTION: The acute surgical model has been trialled in several institutions with mixed results. The aim of this study was to determine whether the acute surgical model provides better outcomes for patients with acute biliary presentation, compared with the traditional emergency surgery model of care. METHODS: A retrospective review was carried out of patients who were admitted for management of acute biliary presentation, before and after the establishment of an acute surgical unit (ASU). Outcomes measured were time to operation, operating time, after-hours operation (6pm - 8am), length of stay and surgical complications. RESULTS: A total of 342 patients presented with acute biliary symptoms and were managed operatively. The median time to operation was significantly reduced in the ASU group (32.4 vs 25.4 hours, p=0.047), as were the proportion of operations performed after hours (19.5% vs 2.5%, p<0.001) and the median length of stay (4 vs 3 days, p<0.001). The median operating time, rate of conversion to open cholecystectomy and wound infection rates remained similar. CONCLUSIONS: Implementation of an ASU can lead to objective differences in outcomes for patients who present with acute cholecystitis. In our study, the ASU significantly reduced time to operation, the number of operations performed after hours and length of stay.

Factors influencing outcome in patients undergoing portal vein resection for adenocarcinoma of the pancreas.

BACKGROUND: Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA. METHODS: A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival. RESULTS: Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival. CONCLUSION: In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness.

Implementation and learning of laproscopic donor nephrectomy by a non-transplant general surgeon with advanced laparoscopic skills.

INTRODUCTION: Traditionally performed by vascular surgeons or urologists, laparoscopic nephrectomy for live kidney donor transplantation has emerged as a new effective and safe technique. This study examines the implementation of this technique at our centre, as performed by a single general surgeon with expertise in advanced laparoscopic surgery. METHODS: Patient records for 78 live donor transplants performed between February 2002 and September 2008 were divided into two groups (with 39 patients each) analyzed. A variety of outcome variables were compared. The same individual surgeon performed all laparoscopic donor nephrectomy (LDN) procedures. RESULTS: A significant advantage was noted for LDN with respect to hospital stay (LDN 5.1 ± 1.1 days vs open donor nephrectomy [ODN] 6.4 ± 2.6 days, P=0.01) while ODN had a significant advantage with respect to operative time (LDN 241.1 ± 55.7 min vs ODN 152.0 ± 27.7 min, P<0.01). Within the LDN group, we noted a significant shortening in the operation time with each case as experience increased (see graph; P<0.01). The total postoperative complication rate was similar in both groups (LDN: 31% vs ODN: 44%, P=0.25). There was a trend towards more respiratory complications in ODN (ODN 11/39 [28%] vs LDN 5/39 [13%], P=0.09). CONCLUSION: While implementing a new procedure may result in longer operative times initially, these improve with time, and our data demonstrates no compromise in patient safety or outcomes. The LDN procedure proved to be a desirable alternative to ODN, with shorter hospital stay and improved operator skills with each case, and without significant compromise in allograft recovery.