Jony van Hilst

Impact of a Nationwide Training Program in Minimally Invasive Distal Pancreatectomy (LAELAPS)

Objective: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). Summary of Background Data: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. Methods: From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005–2013) were compared with outcomes after training (2014–2015). Results: In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7–12] vs 7 [5–8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). Conclusion: A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.

Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial

BackgroundObservational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting.MethodsLEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs.DiscussionThe LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting.Trial registrationDutch Trial Register, NTR5188. Registered on 9 April 2015

Minimally invasive pancreatoduodenectomy

BACKGROUND Minimally invasive pancreatoduodenectomy (MIPD) is increasingly performed with several institutional series and comparative studies reported. The aim was to conduct an assessment of the best-evidence and expert opinion on the current status and future challenges of MIPD. METHODS A systematic review of the literature was performed and best-evidence presented at a State-of-the-Art conference on Minimally Invasive Pancreatic Resection. Expert panel discussion and audience response activity was used to assess perceived value and future direction. RESULTS From 582 studies, 26 comparative trials of MIPD and open pancreatoduodenectomy (OPD) were assessed for perioperative outcomes. There were no randomized controlled trials and all available comparative studies were determined of low quality. Several observational and case-matched studies demonstrate longer operative times, but less estimated blood loss and shorter length of hospital stay for MIPD. Registry-based studies demonstrate increased mortality rates after MIPD in low-volume centers. Oncologic assessment demonstrates comparable outcomes of MIPD. Expert opinion supports ongoing evaluation of MIPD. CONCLUSION MIPD appears to provide similar perioperative and oncologic outcomes in selected patients, when performed at experienced, high-volume centers. Its overall role in pancreatoduodenectomy needs to be better defined. Improved training opportunities, registry participation and prospective evaluation are needed.

Minimally invasive pancreatic resections: cost and value perspectives

BACKGROUND The number of minimally invasive pancreatic resections (MIPR) performed for benign or malignant disease, have increased in recent years. However, there is limited information regarding cost/value implications. METHODS An international conference evaluating MIPR was held during the 12th Bi-Annual International Hepato-Pancreato-Biliary Association (IHPBA) World Congress in Sao Paulo, Brazil, on April 20th, 2016. This manuscript summarizes the presentations that reviewed current topics in cost and value as they pertain to MIPR. RESULTS Compared to the open approach, MIPRs are associated with higher operative costs but lower postoperative costs. However, measurements of patient value (defined as improvement in both quantity and quality of life) and financial value (using incremental cost-effectiveness ratio) are required to determine the true value at societal level. CONCLUSION Challenges remain as to how the potential benefits, both to the patient and the healthcare system as a whole, are measured. Research comparing MIPR versus other techniques for pancreatectomy will require appropriate and valid measurement tools, some of which are yet to be refined. Nonetheless, the experience to date would support the continued development of MIPR by experienced surgeons in high-volume pancreatic centers, married with appropriate review and recalibration.

Worldwide survey on opinions and use of minimally invasive pancreatic resection

BACKGROUND The introduction of minimally invasive pancreatic resection (MIPR) into surgical practice has been slow. The worldwide utilization of MIPR and attitude towards future perspectives of MIPR remains unknown. METHODS An anonymous survey on MIPR was sent to the members of six international associations of Hepato-Pancreato-Biliary (HPB) surgery. RESULTS The survey was completed by 435 surgeons from 50 countries, with each surgeon performing a median of 22 (IQR 12-40) pancreatic resections annually. Minimally invasive distal pancreatectomy (MIDP) was performed by 345 (79%) surgeons and minimally invasive pancreatoduodenectomy (MIPD) by 124 (29%). The median total personal experience was 20 (IQR 10-50) MIDPs and 12 (IQR 4-40) MIPDs. Current superiority for MIDP was claimed by 304 (70%) and for MIPD by 44 (10%) surgeons. The most frequently mentioned reason for not performing MIDP (54/90 (60%)) and MIPD (193/311 (62%)) was lack of specific training. Most surgeons (394/435 (90%)) would consider participating in an international registry on MIPR. DISCUSSION This worldwide survey showed that most participating HPB surgeons value MIPR as a useful development, especially for MIDP, but the role and implementation of MIPD requires further assessment. Most HPB surgeons would welcome specific training in MIPR and the establishment of an international registry.

Minimally invasive versus open pancreatoduodenectomy (LEOPARD-2): study protocol for a randomized controlled trial

BackgroundData from observational studies suggest that minimally invasive pancreatoduodenectomy (MIPD) is superior to open pancreatoduodenectomy regarding intraoperative blood loss, postoperative morbidity, and length of hospital stay, without increasing total costs. However, several case-matched studies failed to demonstrate superiority of MIPD, and large registry studies from the USA even suggested increased mortality for MIPDs performed in low-volume (<10 MIPDs annually) centers. Randomized controlled multicenter trials are lacking but clearly required. We hypothesize that time to functional recovery is shorter after MIPD compared with open pancreatoduodenectomy, even in an enhanced recovery setting.Methods/designLEOPARD-2 is a randomized controlled, parallel-group, patient-blinded, multicenter, phase 2/3, superiority trial in centers that completed the Dutch Pancreatic Cancer Group LAELAPS-2 training program for laparoscopic pancreatoduodenectomy or LAELAPS-3 training program for robot-assisted pancreatoduodenectomy and have performed ≥ 20 MIPDs. A total of 136 patients with symptomatic benign, premalignant, or malignant disease will be randomly assigned to undergo minimally invasive or open pancreatoduodenectomy in an enhanced recovery setting. After the first 40 patients (phase 2), the data safety monitoring board will assess safety outcomes (not blinded for treatment allocation) and decide on continuation to phase 3. Patients from phase 2 will then be included in phase 3. The primary outcome measure is time (days) to functional recovery. All patients will be blinded for the surgical approach, at least until postoperative day 5, but preferably until functional recovery has been attained. Secondary outcome measures are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life, and costs.DiscussionThe LEOPARD-2 trial is designed to assess whether MIPD reduces time to functional recovery, as compared with open pancreatoduodenectomy in an enhanced recovery setting.Trial registrationNetherlands Trial Register, NTR5689. Registered on 2 March 2016.

Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study

Objective: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). Background: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. Methods: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. Results: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60–400) vs 300 mL (150–500), P = 0.001] and hospital stay [8 (6–12) vs 9 (7–14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerotas fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8–22) vs 22 (14–31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22–34] versus 31 (95% CI, 26–36) months (P = 0.929). Conclusions: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerotas fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

The Dutch Pancreas Biobank Within the Parelsnoer Institute: A Nationwide Biobank of Pancreatic and Periampullary Diseases

Objectives Large biobanks with uniform collection of biomaterials and associated clinical data are essential for translational research. The Netherlands has traditionally been well organized in multicenter clinical research on pancreatic diseases, including the nationwide multidisciplinary Dutch Pancreatic Cancer Group and Dutch Pancreatitis Study Group. To enable high-quality translational research on pancreatic and periampullary diseases, these groups established the Dutch Pancreas Biobank. Methods The Dutch Pancreas Biobank is part of the Parelsnoer Institute and involves all 8 Dutch university medical centers and 5 nonacademic hospitals. Adult patients undergoing pancreatic surgery (all indications) are eligible for inclusion. Preoperative blood samples, tumor tissue from resected specimens, pancreatic cyst fluid, and follow-up blood samples are collected. Clinical parameters are collected in conjunction with the mandatory Dutch Pancreatic Cancer Audit. Results Between January 2015 and May 2017, 488 patients were included in the first 5 participating centers: 4 university medical centers and 1 nonacademic hospital. Over 2500 samples were collected: 1308 preoperative blood samples, 864 tissue samples, and 366 follow-up blood samples. Conclusions Prospective collection of biomaterials and associated clinical data has started in the Dutch Pancreas Biobank. Subsequent translational research will aim to improve treatment decisions based on disease characteristics.

Laparoscopic Pancreatoduodenectomy With Modified Blumgart Pancreaticojejunostomy

Minimally invasive pancreatic resections are technically demanding but rapidly increasing in popularity. In contrast to laparoscopic distal pancreatectomy, laparoscopic pancreatoduodenectomy (LPD) has not yet obtained wide acceptance, probably due to technical challenges, especially regarding the pancreatic anastomosis. The study describes and demonstrates all steps of LPD, including the modified Blumgart pancreaticojejunostomy. Indications for LPD are all pancreatic and peri-ampullary tumors without vascular involvement. Relative contra-indications are body mass index >35 kg/m2, chronic pancreatitis, mid-cholangiocarcinomas and large duodenal cancers. The patient is in French position, 6 trocars are placed, and dissection is performed using an (articulating) sealing device. A modified Blumgart end-to-side pancreaticojejunostomy is performed with 4 large needles (3/0) barbed trans-pancreatic sutures and 4 to 6 duct-to-mucosa sutures using 5/0 absorbable multifilament combined with a 12 cm, 6 or 8 Fr internal stent using 3D laparoscopy. Two surgical drains are placed alongside the pancreaticojejunostomy. The described technique for LPD including a modified Blumgart pancreatico-jejunostomy is well standardized, and its merits are currently studied in the randomized controlled multicenter trial. This complex operation should be performed at high-volume centers where surgeons have extensive experience in both open pancreatic surgery and advanced laparoscopic gastro-intestinal surgery.