| 1. |
- van Hilst, Jony, et al.
(författare)
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Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA)
- 2019
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 269:1, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- 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 Gerota's 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 Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.
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| 2. |
- de Graaf, Nine, et al.
(författare)
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Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2) : study protocol for an international multicenter patient-blinded randomized controlled trial
- 2023
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Ingår i: Trials. - : BioMed Central Ltd. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023. © 2023, BioMed Central Ltd., part of Springer Nature.
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| 3. |
- van Hilst, Jony, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA) : study protocol for a randomized controlled trial
- 2021
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Ingår i: Trials. - : BMC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin >= 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (alpha), 80% power (1-beta), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.
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| 4. |
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| 5. |
- Korrel, Maarten, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy: an individual patient data meta-analysis of two randomized controlled trials
- 2021
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Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 23:3, s. 323-330
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Forskningsöversikt (refereegranskat)abstract
- Background: 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. Methods: 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. Results: 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. Conclusion: 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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| 6. |
- Korrel, Maarten, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial
- 2023
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Ingår i: The Lancet Regional Health. - : ELSEVIER. - 2666-7762. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Background The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, & GE;1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society. Copyright & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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