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.

Long-term quality of life is better after laparoscopic compared to open pancreatoduodenectomy.

BACKGROUND: Three randomized controlled trials have reported improved functional recovery after Laparoscopic pancreatoduodenectomy (LPD), as compared to open pancreatoduodenectomy (OPD). Long-term results regarding quality of life (QoL) are lacking. The aim of this study was to compare long-term QoL of LPD versus OPD. METHODS AND PATIENTS: A monocentric retrospective cross-sectional study was performed among patients < 75 years old who underwent LPD or OPD for a benign or premalignant pathology in a high-volume center (2011-2021). An electronic three-part questionnaire was sent to eligible patients, including two diseases specific QoL questionnaires (the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire for cancer (QLQ-C30) and a pancreatic cancer module (PAN26) and a body image questionnaire. Patient demographics and postoperative data were collected and compared between LPD and OPD. RESULTS: Among 948 patients who underwent PD (137 LPD, 811 OPD), 170 were eligible and 111 responded (58 LPD and 53 OPD). LPD versus OPD showed no difference in mean age (51 vs. 55 years, p = 0.199) and female gender (40% vs. 45%, p = 0.631), but LPD showed lower BMI (24 vs 26; p = 0.028) and higher preoperative pancreatitis (29% vs 13%; p = 0.041). The postoperative outcome showed similar Clavien-Dindo ≥ III morbidity (19% vs. 23%; p = 0.343) and length of stay (24 vs. 21 days, p = 0.963). After a similar median follow-up (3 vs. 3 years; p = 0.122), LPD vs OPD patients reported higher QoL (QLQ-C30: 49.6 vs 56.3; p = 0.07), better pancreas specific health status score (PAN20: 50.5 vs 55.5; p = 0.002), physical functioning (p = 0.002), and activities limitations (p = 0.02). Scar scores were better after LPD regarding esthetics (p = 0.001), satisfaction (p = 0.04), chronic pain at rest (p = 0.036), moving (p = 0.011) or in daily activities (p = 0.02). There was no difference in digestive symptoms (p = 0.995). CONCLUSION: This monocentric study found improved long-term QoL in patients undergoing LPD, as compared to OPD, for benign and premalignant diseases. These results could be considered when choosing the surgical approach in these patients.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial.

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, ≥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.

Development of biotissue training models for anastomotic suturing in pancreatic surgery.

BACKGROUND: Anastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be trained outside the operating room. Realistic training models are therefore needed. METHODS: Models of the pancreas, small bowel, stomach, bile duct, and a realistic training torso were developed for training of anastomoses in pancreatic surgery. Pancreas models with soft and hard textures, small and large ducts were incrementally developed and evaluated. Experienced pancreatic surgeons (n = 44) evaluated haptic realism, rigidity, fragility of tissues, and realism of suturing and knot tying. RESULTS: In the iterative development process the pancreas models showed high haptic realism and highest realism in suturing (4.6 ± 0.7 and 4.9 ± 0.5 on 1-5 Likert scale, soft pancreas). The small bowel model showed highest haptic realism (4.8 ± 0.4) and optimal wall thickness (0.1 ± 0.4 on -2 to +2 Likert scale) and suturing behavior (0.1 ± 0.4). The bile duct models showed optimal wall thickness (0.3 ± 0.8 and 0.4 ± 0.8 on -2 to +2 Likert scale) and optimal tissue fragility (0 ± 0.9 and 0.3 ± 0.7). CONCLUSION: The biotissue training models showed high haptic realism and realistic suturing behavior. They are suitable for realistic training of anastomoses in pancreatic surgery which may improve patient outcomes.

Short-term Outcomes After Spleen-preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels: A Pan-European Retrospective Study in High-volume Centers.

OBJECTIVE: To compare short-term clinical outcomes after Kimura and Warshaw MIDP. BACKGROUND: Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce. METHODS: Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in 8 European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding ("rescue") Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP. RESULTS: Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs 1.6%, P = 0.127) and major complications (11.5% vs 14.4%, P = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs 1.2%, P = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, P = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 minutes, P = 0.033) and less blood loss (100 vs 150 mL, P < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, P < 0.001). CONCLUSIONS: Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.

Framework for Training in Minimally Invasive Pancreatic Surgery: An International Delphi Consensus Study.

BACKGROUND: Previous reports suggest that structured training in minimally invasive pancreatic surgery (MIPS) can ensure a safe implementation into standard practice. Although some training programs have been constructed, worldwide consensus on fundamental items of these training programs is lacking. This study aimed to determine items for a structured MIPS training program using the Delphi consensus methodology. STUDY DESIGN: The study process consisted of 2 Delphi rounds among international experts in MIPS, identified by a literature review. The study committee developed a list of items for 3 key domains of MIPS training: (1) framework, (2) centers and surgeons eligible for training, and (3) surgeons eligible as proctor. The experts rated these items on a scale from 1 (not important) to 5 (very important). A Cronbach's α of 0.70 or greater was defined as the cut-off value to achieve consensus. Each item that achieved 80% or greater of expert votes was considered as fundamental for a training program in MIPS. RESULTS: Both Delphi study rounds were completed by all invited experts in MIPS, with a median experience of 20 years in MIPS. Experts included surgeons from 31 cities in 13 countries across 4 continents. Consensus was reached on 38 fundamental items for the framework of training (16 of 35 items, Cronbach's α = 0.72), centers and surgeons eligible for training (19 of 30 items, Cronbach's α = 0.87), and surgeons eligible as proctor (3 of 10 items, Cronbach's α = 0.89). Center eligibility for MIPS included a minimum annual volume of 10 distal pancreatectomies and 50 pancreatoduodenectomies. CONCLUSION: Consensus among worldwide experts in MIPS was reached on fundamental items for the framework of training and criteria for participating surgeons and centers. These items act as a guideline and intend to improve training, proctoring, and safe worldwide dissemination of MIPS.

Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): study protocol for a randomized controlled trial.

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 (α), 80% power (1-ß), 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. TRIAL REGISTRATION: ISRCTN registry ISRCTN44897265 . Prospectively registered on 16 April 2018.

Long-Term Quality of Life after Minimally Invasive vs Open Distal Pancreatectomy in the LEOPARD Randomized Trial.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) shortens time to functional recovery and improves 30-day quality of life (QoL), as compared with open distal pancreatectomy (ODP) for nonmalignant disease. The impact of MIDP on QoL, cosmetic satisfaction, and overall major complications beyond 1-year follow-up is currently unknown. STUDY DESIGN: The Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD) trial randomized 108 patients to MIDP (laparoscopic or robotic) or ODP in 14 Dutch centers (April 2015 to March 2017). The primary outcome measure of this study was quality-adjusted life years (QALYs), as assessed with the EQ-5D. QoL was assessed using subscales of the EORTC QLQ-C30, PAN-26, and a body image questionnaire. The latter included a cosmetic satisfaction score (range 3-24), and a body image score (range 5-20). Differences between MIDP and ODP for QALYs, generic, and disease-specific QoL and body image were analyzed. Missing QoL data were imputed using multiple imputation. RESULTS: In total, 84 patients were alive, with a median follow-up of 44 months; 62 of these patients (74%) completed the questionnaires (27 MIDP, 35 ODP). There was no significant difference in QALYs between the 2 groups (mean score 2.34 vs 2.46 years, p = 0.63), nor on the QoL subscales. Significant overall change in EQ-5D health utilities were found for both groups over time (p < 0.001). Patients in the MIDP group scored higher on cosmetic satisfaction (21 vs 14, p = 0.049). No differences between the 2 groups were observed for clinical outcomes such as major complications, readmissions, and incisional hernias. CONCLUSIONS: More than 3 years after distal pancreatectomy, no improvement in QALYs and overall QoL was seen after MIDP, whereas cosmetic satisfaction was higher after MIDP as compared with ODP.

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.

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.

Laparoscopic Radical Left Pancreatectomy for Pancreatic Cancer: Surgical Strategy and Technique Video.

Radical resection margins, resection of Gerota's (perirenal) fascia, and adequate lymph node dissection are crucial for an adequate oncological resection of left-sided pancreatic cancer. Several surgical techniques have been described in recent years, but few were specifically designed for minimally invasive approaches. This study describes and demonstrates a standardized and reproducible technique for an adequate oncological resection of pancreatic cancer: laparoscopic radical left pancreatectomy (LRLP). A 61-year-old woman presented with an incidental finding of a 3 cm mass in the left pancreas suspect for malignancy. Imaging did not reveal distant metastases, central vascular involvement, or morbid obesity, hence the patient was suitable for LRLP. This study describes the main steps of LRLP for pancreatic cancer. First, the lesser sac is opened by transecting the gastrocolic ligament. The splenic flexure of the colon is mobilized and the inferior border of the pancreas including Gerota's fascia is dissected down to the inferior border of the spleen. The pancreas is tunneled and hung, including Gerota's fascia with a vessel loop. At the pancreatic neck, a tunnel is created between the pancreas and the portal vein, likewise a vessel loop is passed. The pancreas is then transected using the graded compression technique with an endostapler. Both the splenic vein and artery are transected before completing the resection. The entire specimen is extracted in a retrieval bag via a small Pfannenstiel incision. Duration of the surgery was 210 min with 250 mL blood loss. Pathology revealed a R0-resection (>1 mm) of a well-to-moderately differentiated adenocarcinoma originating from an intraductal papillary mucinous neoplasm. A total of 15 tumor-negative lymph nodes were resected. This is a detailed description of LRLP for left-sided pancreatic cancer as is currently being used within the international, multicenter randomized DIPLOMA (Distal Pancreatectomy Minimally Invasive or Open for PDAC) trial.

DIPLOMA Approach for Standardized Pathology Assessment of Distal Pancreatectomy Specimens.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant cancers. A minority (20%) of PDACs are found in the pancreatic body and tail. Accurate pathology assessment of the pancreatic specimen is essential for providing prognostic information and it may guide further treatment strategies. The recent 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system for pancreatic tumors has incorporated significant changes to tumor (pT) stage, which is predominantly based on tumor size. This change emphasizes the importance of careful block selection. Owing to the greater prevalence of tumors in the head of the pancreas, efforts are made to standardize the assessment of pancreatoduodenectomy specimens. However, consensus regarding the macroscopic assessment of distal (i.e., left) pancreatectomy specimens is lacking. The DIPLOMA approach includes the standardized measurement of pancreas and other resected organs, inking of relevant surgical margins and anatomical surfaces without removing covering layers of fat, measurement of tumor size (for T-stage), together with assessment of splenic vessel involvement (and other organs if present). All relevant margins are assessed, and relevant blocks are selected to confirm these parameters microscopically. The current protocol describes a standardized approach to the macroscopic assessment of distal pancreatectomy specimens. This approach was developed during several meetings with pathologists and surgeons during the preparation phase for an international multicenter trial (DIPLOMA, ISRCTN44897265), which focuses on radicality of distal pancreatectomy for pancreatic ductal adenocarcinoma. This standardized approach can be instrumental in the design of studies and will uniform reporting on the outcomes of distal pancreatectomy. The described technique is used in the DIPLOMA trial for pancreatic ductal adenocarcinoma but may also be useful for other indications.

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.

Long term outcome after minimally invasive and open Warshaw and Kimura techniques for spleen-preserving distal pancreatectomy: International multicenter retrospective study.

BACKGROUND: The Warshaw (WT) and the Kimura (KT) techniques are both used for open or minimally invasive (MI) spleen preserving distal pancreatectomy (SPDP). Multicenter studies on long-term outcome of WT and KT are lacking. METHODS: Multicenter retrospective study with transversal follow-up moment, including patients who underwent SPDP from 2000 to 2017 at three high-volume centers in Italy and the Netherlands. Primary endpoint was the incidence of short and long term complications. Patients without regular follow-up were interviewed about symptoms and complications. RESULTS: In total, 164 patients were enrolled, 55 WT (33.5%) and 109 kT (66.5%), of which 95 (57.9%) MI. There was no 30-day mortality (0%).The only significant difference in short-term outcome was more delayed gastric emptying (DGE) after WT (9.1% vs 1.8%, p = 0.043). MI-SPDP was associated with less blood loss (median 150 vs 250 ml, respectively, p < 0.001), less DGE (0% vs 10%, p = 0.002), less abdominal abscesses (8.4% vs 18.4%, p = 0.03) and less splenic infarctions (3.2% vs. 13%, p = 0.042), than open SPDP. Long-term follow-up (median 41 months) was available for 111 patients (67.7%) of whom 18 (16.2%) had an SPDP-related long-term sequela, mostly perigastric varices (n = 11, 9%) but without differences between WT and KT. Less long-term sequelae were reported after MI as compared to open SPDP (12.5% vs 21.2%, p = 0.032). CONCLUSIONS: In this international retrospective study, the WT and KT had comparable short- and long-term outcomes. If a KT does not seem feasible during SPDP, a WT is recommended, rather than performing a splenectomy. MI-SPDP was associated with less short- and long term complications as compared to an open SPDP.

Oncologic outcomes of minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

In the absence of randomized trials, uncertainty regarding the oncologic efficacy of minimally invasive distal pancreatectomy (MIDP) remains. This systematic review aimed to compare oncologic outcomes after MIDP (laparoscopic or robot-assisted) and open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). Matched and non-matched studies were included. Pooled analyses were performed for pathology (e.g., microscopically radical (R0) resection and lymph node retrieval) and oncologic outcomes (e.g., overall survival). After screening 1760 studies, 21 studies with 11,246 patients were included. Overall survival (hazard ratio 0.86; 95% confidence interval (CI) 0.73 to 1.01; p = 0.06), R0 resection rate (odds ratio (OR) 1.24; 95%CI 0.97 to 1.58; p = 0.09) and use of adjuvant chemotherapy (OR 1.07; 95%CI 0.89 to 1.30; p = 0.46) were comparable for MIDP and ODP. The lymph node yield (weighted mean difference (WMD) -1.3 lymph nodes; 95%CI -2.46 to -0.15; p = 0.03) was lower after MIDP. Patients undergoing MIDP were more likely to have smaller tumors (WMD -0.46 cm; 95%CI -0.67 to -0.24; p < 0.001), less perineural (OR 0.48; 95%CI 0.33 to 0.70; p < 0.001) and less lymphovascular invasion (OR 0.53; 95%CI 0.38 to 0.74; p < 0.001) reflecting earlier staged disease as a result of treatment allocation bias. Based on these results we can conclude that in patients with PDAC, MIDP is associated with comparable survival, R0 resection, and use of adjuvant chemotherapy, but a lower lymph node yield, as compared to ODP. Due to treatment allocation bias and lower lymph node yield the oncologic efficacy of MIDP remains uncertain.