Thijs de Rooij

Minimally Invasive Versus Open Pancreatoduodenectomy: Systematic Review and Meta-analysis of Comparative Cohort and Registry Studies.

Objective: This study aimed to appraise and to evaluate the current evidence on minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy only in comparative cohort and registry studies. Background: Outcomes after MIPD seem promising, but most data come from single-center, noncomparative series. Methods: Comparative cohort and registry studies on MIPD versus open pancreatoduodenectomy published before August 23, 2015 were identified systematically and meta-analyses were performed. Primary endpoints were mortality and International Study Group on Pancreatic Fistula grade B/C postoperative pancreatic fistula (POPF). Results: After screening 2293 studies, 19 comparative cohort studies (1833 patients) with moderate methodological quality and 2 original registry studies (19,996 patients) were included. For cohort studies, the median annual hospital MIPD volume was 14. Selection bias was present for cancer diagnosis. No differences were found in mortality [odds ratio (OR) = 1.1, 95% confidence interval (CI) = 0.6–1.9] or POPF [(OR) = 1.0, 95% CI = 0.8 to 1.3]. Publication bias was present for POPF. MIPD was associated with prolonged operative times [weighted mean difference (WMD) = 74 minutes, 95% CI = 29–118], but lower intraoperative blood loss (WMD = −385 mL, 95% CI = −616 to −154), less delayed gastric emptying (OR = 0.6, 95% = CI 0.5–0.8), and shorter hospital stay (WMD = −3 days, 95% CI = −5 to −2). For registry studies, the median annual hospital MIPD volume was 2.5. Mortality after MIPD was increased in low-volume hospitals (7.5% vs 3.4%; P = 0.003). Conclusions: Outcomes after MIPD seem promising in comparative cohort studies, despite the presence of bias, whereas registry studies report higher mortality in low-volume centers. The introduction of MIPD should be closely monitored and probably done only within structured training programs in high-volume centers.

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.

Pan-European survey on the implementation of minimally invasive pancreatic surgery with emphasis on cancer.

BACKGROUND Minimally invasive (MI) pancreatic surgery appears to be gaining popularity, but its implementation throughout Europe and the opinions regarding its use in pancreatic cancer patients are unknown. METHODS A 30-question survey was sent between June and December 2014 to pancreatic surgeons of the European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association and 5 European national pancreatic societies. Incomplete responses were excluded. RESULTS In total, 237 pancreatic surgeons responded. After excluding 34 incomplete responses, 203 responses from 27 European countries were included. 164 (81%) surgeons were employed at a university hospital, 184 (91%) performed advanced MI surgery and 148 (73%) performed MI distal pancreatectomy. MI pancreatoduodenectomy was performed by 42 (21%) surgeons, whereas 9 (4.4%) surgeons had performed more than 10 procedures. Robot-assisted MI pancreatic surgery was performed by 28 (14%) surgeons. 63 (31%) surgeons expected MI distal pancreatectomy for cancer to be inferior to open distal pancreatectomy concerning oncological outcomes. 151 (74%) surgeons expected to benefit from training in MI distal pancreatectomy and 149 (73%) were willing to participate in a randomized trial on this topic. CONCLUSIONS MI distal pancreatectomy is a common procedure, although its use for cancer is still disputed. MI pancreatoduodenectomy is still an uncommon procedure. Specific training and a randomized trial regarding MI pancreatic cancer surgery are welcomed.

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.

Electromagnetic-Guided Bedside Placement of Nasoenteral Feeding Tubes by Nurses Is Non-Inferior to Endoscopic Placement by Gastroenterologists: A Multicenter Randomized Controlled Trial

Objectives:Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses is limited. We aimed to compare the effectiveness of EM-guided and endoscopic nasoenteral feeding tube placement.Methods:We performed a multicenter randomized controlled non-inferiority trial in 154 adult patients who required nasoenteral feeding and were admitted to gastrointestinal surgical wards in five Dutch hospitals. Patients were randomly assigned (1:1) to undergo EM-guided or endoscopic nasoenteral feeding tube placement. The primary end point was the need for reinsertion of the feeding tube (e.g., after failed initial placement or owing to tube-related complications) with a prespecified non-inferiority margin of 10%.Results:Reinsertion was required in 29 (36%) of the 80 patients in the EM-guided group and 31 (42%) of the 74 patients in the endoscopy group (absolute risk difference −6%, upper limit of one-sided 95% confidence interval 7%; P for non-inferiority=0.022). No differences were noted in success and complication rates. In the EM-guided group, there was a reduced time to start of feeding (424 vs. 535 min, P=0.001). Although the level of discomfort was higher in the EM-guided group (Visual Analog Scale (VAS) 3.9 vs. 2.0, P=0.009), EM-guided placement received higher recommendation scores (VAS 8.2 vs. 5.5, P=0.008).Conclusions:EM-guided bedside placement of nasoenteral feeding tubes by nurses was non-inferior to endoscopic placement by gastroenterologists in surgical patients and may be considered the preferred technique for nasoenteral feeding tube placement.

Electromagnetic guided bedside or endoscopic placement of nasoenteral feeding tubes in surgical patients (CORE trial): study protocol for a randomized controlled trial

BackgroundGastroparesis is common in surgical patients and frequently leads to the need for enteral tube feeding. Nasoenteral feeding tubes are usually placed endoscopically by gastroenterologists, but this procedure is relatively cumbersome for patients and labor-intensive for hospital staff. Electromagnetic (EM) guided bedside placement of nasoenteral feeding tubes by nurses may reduce patient discomfort, workload and costs, but randomized studies are lacking, especially in surgical patients. We hypothesize that EM guided bedside placement of nasoenteral feeding tubes is at least as effective as endoscopic placement in surgical patients, at lower costs.Methods/DesignThe CORE trial is an investigator-initiated, parallel-group, pragmatic, multicenter randomized controlled non-inferiority trial. A total of 154 patients admitted to gastrointestinal surgical wards in five hospitals, requiring nasoenteral feeding, will be randomly allocated to undergo EM guided or endoscopic nasoenteral feeding tube placement. Primary outcome is reinsertion of the feeding tube, defined as the insertion of an endoscope or tube in the nose/mouth and esophagus for (re)placement of the feeding tube (e.g. after failed initial placement or dislodgement or blockage of the tube). Secondary outcomes include patient-reported outcomes, costs and tube (placement) related complications.DiscussionThe CORE trial is designed to generate evidence on the effectiveness of EM guided placement of nasoenteral feeding tubes in surgical patients and the impact on costs as compared to endoscopic placement. The trial potentially offers a strong argument for wider implementation of this technique as method of choice for placement of nasoenteral feeding tubes.Trial registrationDutch Trial Register: NTR4420, date registered 5-feb-2014

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.