To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation.
Good results for ...RPD have been reported from single center studies. However, data on feasibility and safety of implementation through a multicenter training program in RPD are lacking.
A multicenter training program in RPD was designed together with the University of Pittsburgh Medical Center, including an online video bank, robot simulation exercises, biotissue drills, and on-site proctoring. Benchmark patients were based on the criteria of Clavien. Outcomes were collected prospectively (March 2016-October 2019). Cumulative sum analysis of operative time was performed to distinguish the first and second phase of the learning curve. Outcomes were compared between both phases of the learning curve. Trends in nationwide use of robotic and laparoscopic PD were assessed in the Dutch Pancreatic Cancer Audit.
Overall, 275 RPD procedures were performed in seven centers by 15 trained surgeons. The recent benchmark criteria for low-risk PD were met by 125 (45.5%) patients. The conversion rate was 6.5% (n = 18) and median blood loss 250ml interquartile range (IQR) 150-500. The rate of Clavien-Dindo grade ≥III complications was 44.4% (n = 122), postoperative pancreatic fistula (grade B/C) rate 23.6% (n = 65), 90-day complication-related mortality 2.5% (n = 7) and 90-day cancer-related mortality 2.2.% (n = 6). Median postoperative hospital stay was 12 days (IQR 8-20). In the subgroup of patients with pancreatic cancer (n = 80), the major complication rate was 31.3% and POPF rate was 10%. Cumulative sum analysis for operative time found a learning curve inflection point at 22 RPDs (IQR 10-35) with similar rates of Clavien-Dindo grade ≥III complications in the first and second phase (43.4% vs 43.8%, P = 0.956, respectively). During the study period the nationwide use of laparoscopic PD reduced from 15% to 1%, whereas the use of RPD increased from 0% to 25%.
This multicenter RPD training program in centers with sufficient surgical volume was found to be feasible without a negative impact of the learning curve on clinical outcomes.
Minimally invasive distal pancreatectomy (MIDP) has been suggested to reduce postoperative outcomes as compared to open distal pancreatectomy (ODP). Recently, the first randomized controlled trials ...(RCTs) comparing MIDP to ODP were published. This individual patient data meta-analysis compared outcomes after MIDP versus ODP combining data from both RCTs.
A systematic literature search was performed to identify RCTs on MIDP vs. ODP, and individual patient data were harmonized. Primary endpoint was the rate of major (Clavien-Dindo ≥ III) complications. Sensitivity analyses were performed in high-risk subgroups.
A total of 166 patients from the LEOPARD and LAPOP RCTs were included. The rate of major complications was 21% after MIDP vs. 35% after ODP (adjusted odds ratio 0.54; p = 0.148). MIDP significantly reduced length of hospital stay (6 vs. 8 days, p = 0.036), and delayed gastric emptying (4% vs. 16%, p = 0.049), as compared to ODP. A trend towards higher rates of postoperative pancreatic fistula was observed after MIDP (36% vs. 28%, p = 0.067). Outcomes were comparable in high-risk subgroups.
This individual patient data meta-analysis showed that MIDP, when performed by trained surgeons, may be regarded as the preferred approach for distal pancreatectomy. Outcomes are improved after MIDP as compared to ODP, without obvious downsides in high-risk subgroups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Robotic surgery may improve surgical performance during minimally invasive pancreatoduodenectomy as compared to 3D- and 2D-laparoscopy but comparative studies are lacking. This study ...assessed the impact of robotic surgery versus 3D- and 2D-laparoscopy on surgical performance and operative time using a standardized biotissue model for pancreatico- and hepatico-jejunostomy using pooled data from two randomized controlled crossover trials (RCTs).
Methods
Pooled analysis of data from two RCTs with 60 participants (36 surgeons, 24 residents) from 11 countries (December 2017–July 2019) was conducted. Each included participant completed two pancreatico- and two hepatico-jejunostomies in biotissue using 3D-robotic surgery, 3D-laparoscopy, or 2D-laparoscopy. Primary outcomes were the objective structured assessment of technical skills (OSATS: 12–60) rating, scored by observers blinded for 3D/2D and the operative time required to complete both anastomoses. Sensitivity analysis excluded participants with excess experience compared to others.
Results
A total of 220 anastomoses were completed (robotic 80, 3D-laparoscopy 70, 2Dlaparoscopy 70). Participants in the robotic group had less surgical experience median 1 (0–2) versus 6 years (4–12),
p
< 0.001, as compared to the laparoscopic group. Robotic surgery resulted in higher OSATS ratings (50, 43, 39 points,
p
= .021 and
p
< .001) and shorter operative time (56.5, 65.0, 81.5 min,
p
= .055 and
p
< .001), as compared to 3D- and 2Dlaparoscopy, respectively, which remained in the sensitivity analysis.
Conclusion
In a pooled analysis of two RCTs in a biotissue model, robotic surgery resulted in better surgical performance scores and shorter operative time for biotissue pancreatic and biliary anastomoses, as compared to 3D- and 2D-laparoscopy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Randomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD ...and OPD, and could identify high-risk subgroups.
A systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.
Data from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference −6.97 days). Outcomes remained stable in the high-risk subgroups.
LPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Data 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.
LEOPARD-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.
The LEOPARD-2 trial is designed to assess whether MIPD reduces time to functional recovery, as compared with open pancreatoduodenectomy in an enhanced recovery setting.
Netherlands Trial Register, NTR5689 . Registered on 2 March 2016.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract only
LBA4002
Background: Standard of care for patients with (borderline) resectable pancreatic adenocarcinoma is resection followed by adjuvant chemotherapy. Previous studies suggest a ...benefit of neoadjuvant treatment. We conducted a multicenter phase III randomized controlled trial to evaluate the effect of preoperative chemoradiotherapy. Methods: Patients with (borderline) resectable pancreatic cancer, pathologically confirmed, were randomized between immediate surgery (arm A) and preoperative chemoradiotherapy (arm B), both followed by adjuvant chemotherapy. The preoperative chemoradiotherapy consisted of 15 times of 2.4 Gray (Gy) combined with gemcitabine, 1,000 mg/m
2
on days 1, 8 and 15, preceded and followed by a cycle of gemcitabine. Primary endpoint was overall survival (OS), secondary endpoints were (R0) resection rate, disease free survival (DFS), distant metastases free interval (DMFI), locoregional recurrence free interval (LRFI) and toxicity. Accrual was completed between April 23, 2013 and July 25, 2017. Results: In total, 246 patients were included in the intention-to-treat analysis (127 patients in arm A and 119 in arm B). Currently, 142 of the 176 needed events for the primary outcome are observed. OS was significantly better in arm B (median 13.5 vs. 17.1 months; HR 0.71; p = 0.047). This was also the case for R0 resection rate (31% vs. 65%, p = < 0.001), DFS (median 7.9 vs. 11.2 months; HR 0.67; p = 0.010), DMFI (median 10.2 vs 17.1 months; HR 0.63; p = 0.012) and LRFI (median 11.8 vs not reached; HR 0.47; p < 0.001). Resection rates were 72% (91/127) in arm A vs. 62% (74/119) in arm B (p = 0.15). No significant difference was observed in grade ≥ 3 adverse events between both groups (p = 0.17). A subgroup analysis of patients who actually underwent a resection was performed which showed a median OS of 16.8 and 29.9 months respectively (p < 0.001). Conclusion: Our preliminary data show that preoperative chemoradiotherapy significantly improves outcome in (borderline) resectable pancreatic cancer compared to immediate surgery. Updated results will be presented at the meeting. Clinical trial information: NTR3709.
Observational 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.
LEOPARD 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.
The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting.
Dutch Trial Register, NTR5188 . Registered on 9 April 2015.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A potential downside of robotic pancreatoduodenectomy (RPD) is the lack of tactile feedback when tying sutures, which could be especially perilous during pancreatic anastomosis. Near-infrared ...fluorescence imaging with indocyanine green (NIRF-ICG) could detect transpancreatic-suture-induced hypoperfusion of the pancreatic stump during RPD, which may be related to postoperative pancreatic fistula (POPF) grade B/C, but studies are lacking.
This prospective study included 37 patients undergoing RPD to assess the relation between pancreatic stump hypoperfusion as objectified with NIRF-ICG using Firefly and the rate of POPF grade B/C. In 27 patients, NIRF-ICG was performed after tying down the transpancreatic U-sutures. In 10 'negative control' patients, NIRF-ICG was performed before tying these sutures.
Pancreatic stump hypoperfusion was detected using NIRF-ICG in 9/27 patients (33%) during RPD. Hypoperfusion was associated with POPF grade B/C (67% 6/9 patients versus 17% 3/18 patients,
= 0.026). No hypoperfusion was objectified in 10 'negative controls'.
Transpancreatic-suture-induced pancreatic stump hypoperfusion can be detected using NIRF-ICG during RPD and was associated with POPF grade B/C. Surgeons could use NIRF-ICG to adapt their suturing approach during robotic pancreatico-jejunostomy. Further larger prospective studies are needed to validate the association between transpancreatic-suture-induced hypoperfusion and POPF.
OBJECTIVE:This trial followed a structured nationwide training program in minimally invasive distal pancreatectomy (MIDP), according to the IDEAL framework for surgical innovation, and aimed to ...compare time to functional recovery after minimally invasive and open distal pancreatectomy (ODP).
BACKGROUND:MIDP is increasingly used and may enhance postoperative recovery as compared with ODP, but randomized studies are lacking.
METHODS:A multicenter patient-blinded randomized controlled superiority trial was performed in 14 centers between April 2015 and March 2017. Adult patients with left-sided pancreatic tumors confined to the pancreas without vascular involvement were randomly assigned (1:1) to undergo MIDP or ODP. Patients were blinded for type of surgery using a large abdominal dressing. The primary endpoint was time to functional recovery. Analysis was by intention to treat. This trial was registered with the Netherlands Trial Register (NTR5689).
RESULTS:Time to functional recovery was 4 days interquartile range (IQR) 3–6) in 51 patients after MIDP versus 6 days (IQR 5–8) in 57 patients after ODP (P < 0.001). The conversion rate of MIDP was 8%. Operative blood loss was less after MIDP (150 vs 400 mL; P < 0.001), whereas operative time was longer (217 vs 179 minutes; P = 0.005). The Clavien–Dindo grade ≥III complication rate was 25% versus 38% (P = 0.21). Delayed gastric emptying grade B/C was seen less often after MIDP (6% vs 20%; P = 0.04). Postoperative pancreatic fistulas grade B/C were seen in 39% after MIDP versus 23% after ODP (P = 0.07), without difference in percutaneous catheter drainage (22% vs 20%; P = 0.77). Quality of life (day 3–30) was better after MIDP as compared with ODP, and overall costs were non-significantly less after MIDP. No 90-day mortality was seen after MIDP versus 2% (n = 1) after ODP.
CONCLUSIONS:In patients with left-sided pancreatic tumors confined to the pancreas, MIDP reduces time to functional recovery compared with ODP. Although the overall rate of complications was not reduced, MIDP was associated with less delayed gastric emptying and better quality of life without increasing costs.
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