Nationwide use and Outcome of Minimally Invasive Distal Pancreatectomy in IDEAL Stage IV following a Training Program and Randomized Trial.

OBJECTIVE: To assess the nationwide long-term uptake and outcomes of minimally invasive distal pancreatectomy (MIDP) after a nationwide training program and randomized trial. BACKGROUND: Two randomized trials demonstrated the superiority of MIDP over open distal pancreatectomy (ODP) in terms of functional recovery and hospital stay. Data on implementation of MIDP on a nationwide level are lacking. METHODS: Nationwide audit-based study including consecutive patients after MIDP and ODP in 16 centers in the Dutch Pancreatic Cancer Audit (2014 to 2021). The cohort was divided into three periods: early implementation, during the LEOPARD randomized trial, and late implementation. Primary endpoints were MIDP implementation rate and textbook outcome. RESULTS: Overall, 1496 patients were included with 848 MIDP (56.5%) and 648 ODP (43.5%). From the early to the late implementation period, the use of MIDP increased from 48.6% to 63.0% and of robotic MIDP from 5.5% to 29.7% ( P <0.001). The overall use of MIDP (45% to 75%) and robotic MIDP (1% to 84%) varied widely between centers ( P <0.001). In the late implementation period, 5/16 centers performed >75% of procedures as MIDP. After MIDP, in-hospital mortality and textbook outcome remained stable over time. In the late implementation period, ODP was more often performed in ASA score III-IV (24.9% vs. 35.7%, P =0.001), pancreatic cancer (24.2% vs. 45.9%, P <0.001), vascular involvement (4.6% vs. 21.9%, P <0.001), and multivisceral involvement (10.5% vs. 25.3%, P <0.001). After MIDP, shorter hospital stay (median 7 vs. 8 d, P <0.001) and less blood loss (median 150 vs. 500 mL, P <0.001), but more grade B/C postoperative pancreatic fistula (24.4% vs. 17.2%, P =0.008) occurred as compared to ODP. CONCLUSION: A sustained nationwide implementation of MIDP after a successful training program and randomized trial was obtained with satisfactory outcomes. Future studies should assess the considerable variation in the use of MIDP between centers and, especially, robotic MIDP.

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy: nationwide propensity-score-matched analysis.

BACKGROUND: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. METHODS: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. RESULTS: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P < 0.001), less intraoperative blood loss (200 ml versus 500 ml; P < 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P < 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). CONCLUSION: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.

International survey on opinions and use of robot-assisted and laparoscopic minimally invasive pancreatic surgery: 5-year follow up.

BACKGROUND: Evidence on the value of minimally invasive pancreatic surgery (MIPS) has been increasing but it is unclear how this has influenced the view of pancreatic surgeons on MIPS. METHODS: An anonymous survey was sent to members of eight international Hepato-Pancreato-Biliary Associations. Outcomes were compared with the 2016 international survey. RESULTS: Overall, 315 surgeons from 47 countries participated. The median volume of pancreatic resections per center was 70 (IQR 40-120). Most surgeons considered minimally invasive distal pancreatectomy (MIDP) superior to open (ODP) (94.6%) and open pancreatoduodenectomy (OPD) superior to minimally invasive (MIPD) (67.9%). Since 2016, there has been an increase in the number of surgeons performing both MIDP (79%-85.7%, p = 0.024) and MIPD (29%-45.7%, p < 0.001), and an increase in the use of the robot-assisted approach for both MIDP (16%-45.6%, p < 0.001) and MIPD (23%-47.9%, p < 0.001). The use of laparoscopy remained stable for MIDP (91% vs. 88.1%, p = 0.245) and decreased for MIPD (51%-36.8%, p = 0.024). CONCLUSION: This survey showed considerable changes of MIPS since 2016 with most surgeons considering MIDP superior to ODP and an increased use of robot-assisted MIPS. Surgeons prefer OPD and therefore the value of MIPD remains to be determined in randomized trials.

Outcomes After Minimally Invasive Versus Open Total Pancreatectomy: A Pan-European Propensity Score Matched Study.

OBJECTIVE: To assess postoperative 90-day outcomes after minimally invasive (laparoscopic/robot-assisted) total pancreatectomy (MITP) in selected patients versus open total pancreatectomy (OTP) among European centers. BACKGROUND: Minimally invasive pancreatic surgery is becoming increasingly popular but data on MITP are scarce and multicenter studies comparing outcomes versus OTP are lacking. It therefore remains unclear if MITP is a valid alternative. METHODS: Multicenter retrospective propensity-score matched study including consecutive adult patients undergoing MITP or OTP for all indications at 16 European centers in 7 countries (2008-2017). Patients after MITP were matched (1:1, caliper 0.02) to OTP controls. Missing data were imputed. The primary outcome was 90-day major morbidity (Clavien-Dindo ≥3a). Secondary outcomes included 90-day mortality, length of hospital stay, and survival. RESULTS: Of 361 patients (99MITP/262 OTP), 70 MITP procedures (50 laparoscopic, 15 robotic, 5 hybrid) could be matched to 70 OTP controls. After matching, MITP was associated with a lower rate of major morbidity (17% MITP vs. 31% OTP, P = 0.022). The 90-day mortality (1.4% MITP vs. 7.1% OTP, P = 0.209) and median hospital stay (17 [IQR 11-24] MITP vs. 12 [10-23] days OTP, P = 0.876) did not differ significantly. Among 81 patients with PDAC, overall survival was 3.7 (IQR 1.7-N/A) versus 0.9 (IQR 0.5-N/ A) years, for MITP versus OTP, which was nonsignificant after stratification by T-stage. CONCLUSION: This international propensity score matched study showed that MITP may be a valuable alternative to OTP in selected patients, given the associated lower rate of major morbidity.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

Outcomes of a Multicenter Training Program in Robotic Pancreatoduodenectomy (LAELAPS-3).

OBJECTIVE: To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation. BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Routine prophylactic abdominal drainage versus no-drain strategy after distal pancreatectomy: A multicenter propensity score matched analysis.

BACKGROUND: /Objectives Postoperative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). Traditionally, surgical drains are placed routinely after DP, but some question its efficacy and postulate that the use of drains may convert a self-limiting postoperative collection into a POPF. This study aimed to compare outcomes between three institutions with varying drainage strategies. METHODS: The study is a retrospective propensity score-matched analysis of intraoperative prophylactic drain placement during DP (2010-2019). The primary outcome is major morbidity. Propensity score matching was used to obtain comparable groups. RESULTS: Overall, 963 patients after DP were included. One center did not place a surgical drain routinely, but decided to place a drain when unsatisfactory pancreatic closure occurred. Prophylactic abdominal drains were placed in 805 patients (84%) of which 74 could be matched to 74 patients without a drain. The rate of major morbidity (8% vs 19%, p = 0.054) and radiological interventions (5% vs 12%, p = 0.147) were non-significantly lower in the no-drain group as compared to the prophylactic drain group, respectively. The rates of POPF (4% vs 16%, p = 0.014) were lower in the no-drain group. CONCLUSION: In this international retrospective multicenter study, a selective no-drain strategy after DP was not associated with higher rates major morbidity or radiological interventions as compared to routine prophylactic abdominal drainage. Although the rate of POPF was lower in the no-drain group, randomized trials should confirm the safety and outcome of a no-drain strategy after DP.

Performance with robotic surgery versus 3D- and 2D-laparoscopy during pancreatic and biliary anastomoses in a biotissue model: pooled analysis of two randomized trials.

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, 2D-laparoscopy 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 2D-laparoscopy, 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.

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Outcomes of Elective and Emergency Conversion in Minimally Invasive Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma: An International Multicenter Propensity Score-matched Study.

OBJECTIVE: The aim of this study was to investigate the impact of conversion during minimally invasive distal pancreatectomy (MIDP) for pancreatic ductal adenocarcinoma (PDAC) on outcome by a propensity-matched comparison with open distal pancreatectomy (ODP). BACKGROUND: MIDP is associated with faster recovery as compared with ODP. The high conversion rate (15%-25%) in patients with PDAC, however, is worrisome and may negatively influence outcome. METHODS: A post hoc analysis of a retrospective cohort including distal pancreatectomies for PDAC from 34 centers in 11 countries. Patients requiring conversion were matched, using propensity scores, to ODP procedures (1:2 ratio). Indications for conversion were classified as elective conversions (eg, vascular involvement) or emergency conversions (eg, bleeding). RESULTS: Among 1212 distal pancreatectomies for PDAC, 345 patients underwent MIDP, with 68 (19.7%) conversions, mostly elective (n = 46, 67.6%). Vascular resection (other than splenic vessels) was required in 19.1% of the converted procedures. After matching (61 MIDP-converted vs 122 ODP), conversion did not affect R-status, recurrence of cancer, nor overall survival. However, emergency conversion was associated with increased overall morbidity (61.9% vs 31.1%, P= 0.007) and a trend to worse oncological outcome compared with ODP. Elective conversion was associated with comparable overall morbidity. CONCLUSIONS: Elective conversion in MIDP for PDAC was associated with comparable short-term and oncological outcomes in comparison with ODP. However, emergency conversions were associated with worse both short- and long-term outcomes, and should be prevented by careful patient selection, awareness of surgeons' learning curve, and consideration of early conversion when unexpected intraoperative findings are encountered.

The Landmark Series: Minimally Invasive Pancreatic Resection.

BACKGROUND: Pancreatic resections are among the most technically demanding procedures, including a high risk of potentially life-threatening complications and outcomes strongly correlated to hospital volume and individual surgeon experience. Minimally invasive pancreatic resections (MIPRs) have become a part of standard surgical practice worldwide over the last decade; however, in comparison with other surgical procedures, the implementation of minimally invasive approaches into clinical practice has been rather slow. OBJECTIVE: The aim of this study was to highlight and summarize the available randomized controlled trials (RCTs) evaluating the role of minimally invasive approaches in pancreatic surgery. METHODS: A WHO trial registry and Pubmed database literature search was performed to identify all RCTs comparing MIPRs (robot-assisted and/or laparoscopic distal pancreatectomy [DP] or pancreatoduodenectomy [PD]) with open pancreatic resections (OPRs). RESULTS: Overall, five RCTs on MIPR versus OPR have been published and seven RCTs are currently recruiting. For DP, the results of two RCTs were in favor of minimally invasive distal pancreatectomy (MIDP) in terms of shorter hospital stay and less intraoperative blood loss, with comparable morbidity and mortality. Regarding PD, two RCTs showed similar advantages for MIPD. However, concerns were raised after the early termination of the third multicenter RCT on MIPD versus open PD due to higher complication-related mortality in the laparoscopic group and no clear other demonstrable advantages. No RCTs on robot-assisted pancreatic procedures are available as yet. CONCLUSION: At the current level of evidence, MIDP is thought to be safe and feasible, although oncological safety should be further evaluated. Based on the results of the RCTs conducted for PD, MIPD cannot be proclaimed as the superior alternative to open PD, although promising outcomes have been demonstrated by experienced centers. Future studies should provide answers to the role of robotic approaches in pancreatic surgery and aim to identity the subgroups of patients or indications with the greatest benefit of MIPRs.

Minimally invasive versus open distal pancreatectomy: an individual patient data meta-analysis of two randomized controlled trials.

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.

Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer.

BACKGROUND: We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers. METHODS: Materials were derived from the prospective nationwide Dutch Pancreas Biobank (2015-2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed. RESULTS: Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87). CONCLUSION: High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.

Outcomes After Minimally-invasive Versus Open Pancreatoduodenectomy: A Pan-European Propensity Score Matched Study.

OBJECTIVE: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers. BACKGROUND: Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking. METHODS: Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing ≥10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing ≥10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo ≥3). RESULTS: Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%, P = 0.526), mortality (4.0% vs 3.3%, P = 0.576), percutaneous drainage (12% vs 12%, P = 0.809), reoperation (11% vs 13%, P = 0.329), and hospital stay (mean 17 vs 17 days, P > 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%, P < 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95, P < 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF (24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%, P < 0.001). CONCLUSIONS: In the early experience of 14 European centers performing ≥10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed.

The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection.

OBJECTIVE: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). SUMMARY BACKGROUND DATA: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. METHODS: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. RESULTS: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. CONCLUSION: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

Impact of Neoadjuvant Therapy in Resected Pancreatic Ductal Adenocarcinoma of the Pancreatic Body or Tail on Surgical and Oncological Outcome: A Propensity-Score Matched Multicenter Study.

BACKGROUND: Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. METHODS: Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007-2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. RESULTS: Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien-Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14-39) versus 31 months (95% CI 19-42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18-53) versus 20 months (95% CI 15-24), P = 0.049], as compared with upfront resection. CONCLUSION: In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.

Technique and audited outcomes of laparoscopic distal pancreatectomy combining the clockwise approach, progressive stepwise compression technique, and staple line reinforcement.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) has proven advantages over its open counterpart and is becoming more frequently performed around the world. It still remains a difficult operation due to the retroperitoneal location of the pancreas and limited experience and training with the procedure. In addition, complications such as bleeding or postoperative pancreatic fistula (POPF) remain a problem. A standardized approach to LDP with stepwise graded compression technique for pancreatic transection has been utilized at a single center, and we sought to describe the technique and determine the outcomes. METHODS: A review of all patients undergoing LDP by a clockwise approach including the graded compression technique from August 1, 2008 to December 31, 2017 was performed. An external audit was performed by the Dutch Pancreatic Cancer Group. RESULTS: Overall, 260 patients with a mean age and a BMI of 62.3 and 28, respectively, underwent LDP using this technique. Mean operative time and blood loss were 183 min and 248 mL, respectively,. Hand-assisted method and conversion to open were both 5%. Major morbidity and mortality were 9.2% and 0.4%, respectively,. POPF was noted in 8.1%. The technical steps include (1) mobilization of the splenic flexure of the colon and exposure of the pancreas, (2) dissection along the inferior edge of the pancreas and choosing the site for pancreatic division, (3) pancreatic parenchymal division using a progressive stepwise compression technique with staple line reinforcement, (4) ligation of the splenic vein and artery, (5) dissection along the superior edge of the pancreas and residual posterior attachments, and (6) mobilization of the spleen and specimen removal. CONCLUSION: LDP with a clockwise approach for dissection, combined with the progressive stepwise compression technique for pancreatic transection, resulted in excellent outcomes including a very low POPF rate.

Outcomes of a Multicenter Training Program in Laparoscopic Pancreatoduodenectomy (LAELAPS-2).

OBJECTIVE: The aim of the study was to assess feasibility and outcomes of a multicenter training program in laparoscopic pancreatoduodenectomy (LPD). BACKGROUND: Whereas expert centers have reported promising outcomes of LPD, nationwide analyses have raised concerns on its safety, especially during the learning curve. Multicenter, structured LPD training programs reporting outcomes including the first procedures are lacking. No LPD had been performed in the Netherlands before this study. METHODS: During 2014-2016, 8 surgeons from 4 high-volume centers completed the Longitudinal Assessment and Realization of Laparoscopic Pancreatic Surgery (LAELAPS-2) training program in LPD, including detailed technique description, video training, and proctoring. In all centers, LPD was performed by 2 surgeons with extensive experience in pancreatic and laparoscopic surgery. Outcomes of all LPDs were prospectively collected. RESULTS: In total, 114 patients underwent LPD. Median pancreatic duct diameter was 3 mm [interquartile range (IQR = 2-4)] and pancreatic texture was soft in 74% of patients. The conversion rate was 11% (n = 12), median blood loss 350 mL (IQR = 200-700), and operative time 375 minutes (IQR = 320-431). Grade B/C postoperative pancreatic fistula occurred in 34% of patients, requiring catheter drainage in 22% and re-operation in 2%. A Clavien-Dindo grade ≥ III complication occurred in 43% of patients. Median length of hospital stay was 15 days (IQR = 9-25). Overall, 30-day and 90-day mortality were both 3.5%. Outcomes were similar for the first and second part of procedures. CONCLUSIONS: This LPD training program was feasible and ensured acceptable outcomes during the learning curve in all centers. Future studies should determine whether such a training program is applicable in other settings and assess the added value of LPD.

Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD): A Multicenter Patient-blinded Randomized Controlled Trial.

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.

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 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.