BACKGROUND:Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. PATIENTS AND METHODS:This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. RESULTS:Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. CONCLUSIONS:Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Objectives/background: High-output stoma is one of the most common major morbidities in young children with an enterostomy that could lead to intestinal failure. Management of high-output enterostomy in children is mostly based on personal experience. This systematic review aims to clarify the evidence-based therapeutic approach of high-output enterostomy in children. Methods: A systematic review was performed using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published until March 20, 2023, following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The study population comprised children (i.e., age <18 years) with high-output enterostomy (i.e., jejuno-, ileo-, and/or colostomy), regardless of underlying aetiology. Interventions comprised any (non)pharmacological and/or surgical treatment. Interventions were compared with each other, placebos, and/or no interventions. Primary outcome was reduction of enterostomy output. Secondary outcomes were morbidity, mortality, quality of life, associated healthcare costs, and adverse events. Results: The literature search identified 4278 original articles of which 366 were screened on full text, revealing that none of the articles met the inclusion criteria. Conclusion: This first systematic review on management of high-output enterostomy in children revealed that any evidence on the primary and secondary outcomes is lacking. There is an urgent need for evidence on conservative treatment strategies including fluid restrictions, dietary advices, oral rehydration solution, chyme re-infusion, and pharmacological and surgical treatments of high-output enterostomy in children, aiming to reduce the risk for short- and long-term complications. Till more evidence is available, a systematic and multidisciplinary step-up approach is needed. Therefore, a therapeutic work-up is proposed that could guide the care.

Background Prophylactic passive abdominal drainage is standard practice after distal pancreatectomy. This approach aims to mitigate the consequences of postoperative pancreatic fistula (POPF) but its added value, especially in patients at low risk of POPF, is currently being debated. We aimed to assess the non-inferiority of a no-drain policy in patients after distal pancreatectomy. Methods In this international, multicentre, open-label, randomised controlled, non-inferiority trial, we recruited patients aged 18 years or older undergoing open or minimally invasive elective distal pancreatectomy for all indications in 12 centres in the Netherlands and Italy. We excluded patients with an American Society of Anesthesiology (ASA) physical status of 4-5 or WHO performance status of 3-4, added by amendment following the death of a patient with ASA 4 due to a pre-existing cardiac condition. Patients were randomly assigned (1:1) intraoperatively by permuted blocks (size four to eight) to either no drain or prophylactic passive drain placement, stratified by annual centre volume (<40 or >= 40 distal pancreatectomies) and low risk or high risk of grade B or C POPF. High-risk was defined as a pancreatic duct of more than 3 mm in diameter, a pancreatic thickness at the neck of more than 19 mm, or both, based on the Distal Pancreatectomy Fistula Risk Score. Other patients were considered low-risk. The primary outcome was the rate of major morbidity (Clavien-Dindo score >= III), and the most relevant secondary outcome was grade B or C POPF, grading per the International Study Group for Pancreatic Surgery. Outcomes were assessed up to 90 days postoperatively and analysed in the intention-to-treat population and per-protocol population, which only included patients who received the allocated treatment. A prespecified non-inferiority margin of 8% was compared with the upper limit of the two-sided 95% CI (Wald) of unadjusted risk difference to assess non-inferiority. This trial is closed and registered in the Netherlands Trial Registry, NL9116. Findings Between Oct 3, 2020, and April 28, 2023, 376 patients were screened for eligibility and 282 patients were randomly assigned to the no-drain group (n=138; 75 [54%] women and 63 [46%] men) or the drain group (n=144; 73 [51%] women and 71 [49%] men). Seven patients in the no-drain group received a drain intraoperatively; consequently, the per-protocol population included 131 patients in the no-drain group and 144 patients in the drain group. The rate of major morbidity was non-inferior in the no-drain group compared with the drain group in the intention-to-treat analysis (21 [15%] vs 29 [20%]; risk difference -49 percentage points [95% CI -138 to 40]; p(non-inferiority)=00022) and the per-protocol analysis (21 [16%] vs 29 [20%]; risk difference -41 percentage points [-132 to 50]; p(non-inferiority)=00045). Grade B or C POPF was observed in 16 (12%) patients in the no-drain group and in 39 (27%) patients in the drain group (risk difference -155 percentage points [95% CI -245 to -65]; p(non-inferiority)<00001) in the intention-to-treat analysis. Three patients in the no-drain group died within 90 days; the cause of death in two was not considered related to the trial. The third death was a patient with an ASA score of 4 who died after sepsis and a watershed cerebral infarction at second admission, leading to multiple organ failure. No patients in the drain group died within 90 days. Interpretation A no-drain policy is safe in terms of major morbidity and reduced the detection of grade B or C POPF, and should be the new standard approach in eligible patients undergoing distal pancreatectomy.

Objective:To develop a prediction model for major morbidity and endocrine dysfunction after central pancreatectomy (CP) which could help in tailoring the use of this procedure.Background:CP is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and premalignant tumors in the body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared with distal pancreatectomy but it is thought to increase the risk of short-term complications, including postoperative pancreatic fistula (POPF).Methods:International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010-2021). The primary endpoint was major morbidity. Secondary endpoints included POPF grade B/C, endocrine dysfunction, and the use of pancreatic enzymes. Two risk models were designed for major morbidity and endocrine dysfunction utilizing multivariable logistic regression and internal and external validation.Results:A total of 838 patients after CP were included [301 (36%) minimally invasive] and major morbidity occurred in 248 (30%) patients, POPF B/C in 365 (44%), and 30-day mortality in 4 (1%). Endocrine dysfunction in 91 patients (11%) and use of pancreatic enzymes in 108 (12%). The risk model for major morbidity included male sex, age, Body Mass Index, and American Society of Anesthesiologists score >= 3. The model performed acceptably with an area under the curve of 0.72 (CI: 0.68-0.76). The risk model for endocrine dysfunction included higher Body Mass Index and male sex and performed well [area under the curve: 0.83 (CI: 0.77-0.89)].Conclusions:The proposed risk models help in tailoring the use of CP in patients with symptomatic benign and premalignant lesions in the body and neck of the pancreas (readily available through www.pancreascalculator.com).

Background: International guidelines recommend monitoring the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. Patients and methods: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and high-risk groups. Results: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% (P<0.001). RDP was associated with fewer grade 2 intraoperative events compared with LDP (9.6% vs. 16.8%, P<0.001), with longer operating time (238 vs. 201 min, P<0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P=0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P=0.344). Three high-risk groups were identified; BMI greater than 25 kg/m(2), previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. Conclusion: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with fewer conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.

Background: International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN.Methods: An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy.Results: Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504).Conclusion: This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS.

OBJECTIVE:The incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants significantly reduce CR-POPF. A new biodegradable sealant patch was able to reduce POPF and to achieve bleeding control in a preclinical porcine DP model. The aim of this first-in-human study was to assess the safety and performance of the sealant patch. METHODS:In this multicenter, single-arm study, 40 patients undergoing distal pancreatectomy were prospectively enrolled from 8 centers. Following surgical resection, the transection plane was closed according to the standard of care and manually covered with the sealant patch. As primary endpoint the incidence of CR-POPF up to 30-days postoperatively was evaluated. The secondary endpoints included the assessment of complications and device usability. RESULTS:Among 40 patients after distal pancreatectomy, CR-POPF occurred in 7 (17.5%) up to postoperative day 30. No type C POPF was observed. There was no intraoperative bleeding observed after patch application. CONCLUSION:The results of this international phase II study demonstrate promising results of a new sealant patch regarding the rate of CR-POPF. Randomized studies are now needed to confirm the superiority of the current patch as compared to the best current practice.

BACKGROUND/AIM:The validity of laparoscopic distal pancreatectomy in left-sided pancreatic adenocarcinoma (PDAC) is still unclear. However, a meticulous surgical dissection through a "no-touch" technique might allow a radical oncological resection with minimal risk of tumor dissemination and seeding. This study aimed to evaluate the oncological outcomes of the laparoscopic "no touch" technique versus the "touch" technique.PATIENTS AND METHODS:From 2001 to 2020, we retrospectively analyzed 45 patients undergoing laparoscopic distal pancreatectomy (LDP) for PDAC in two centers. Factors associated with overall (OS), disease-free survival (DFS) and time to recurrence (TTR) were identified.RESULTS:The OS rates in the 'no-touch' and 'touch' groups were 95% vs. 78% (1-year OS); 50% vs. 50% (3-year OS), respectively (p=0.60). The DFS rates in the 'no-touch' and 'touch' groups were 72 % vs. 57% (1-year DFS); 32% vs. 28% (3-year DFS), respectively (p=0.11). The TTR rates in the 'no-touch' and 'touch' groups were 77% vs. 61% (1-year TTR); 54% vs. 30% (3-year TTR); 46% vs. 11% (5-year TTR); respectively (p=0.02) In multivariate analysis the only factors were Touch technique [odds ratio (OR)=2.62, p=0.02] and lymphovascular emboli (OR=4.8; p=0.002).CONCLUSION:We advise the 'no-touch' technique in patients with resectable PDAC in the pancreatic body and tail. Although this study does not provide definitive proof of superiority, no apparent downsides are present for the 'no-touch' technique in this setting although there could be oncological benefits.

Purpose: Central pancreatectomy (CP) is a parenchyma-sparing procedure performed for benign or pre-malignant tumors in the pancreatic body and neck. Most surgeons are reluctant to perform CP as it has been associated with high rates of postoperative pancreatic fistula (POPF) and morbidity. Current study reveals numbers and a risk model for severe morbidity and postoperative diabetes in the largest international study on CP to date. Method: International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010 - 2021). Primary endpoint was severe morbidity defined as Clavien-Dindo≥III. Secondary endpoints were POPF, exocrine dysfunction and postoperative diabetes. A prediction model was designed for severe morbidity and postoperative diabetes utilizing multivariable logistic regression and internally-externally validation. Results: 838 patients were included of which most common indications were pNET(24%) and IPMN(24%). Severe morbidity occurred in 248(30%) patients and POPF in 365(44%). Exocrine dysfunction occurred in 12% (n=108). The risk model to predict severe morbidity included four variables: male sex(OR:1.446 CI:1.004-2.192), Age(OR:1.013 CI:1.002-1.092), BMI(OR:1.060 CI:1.011-1.112) and ASA score ≥ 3(OR:1.714 CI:1.045-3.075). The model performed acceptable with an area under curve(AUC) of 0.72(CI:0.68-0.76). Postoperative diabetes occurred in 11%(n=91) and higher BMI(OR:1.258 CI:1.133–1.397) and male sex(OR:5.268 CI:2.080 – 13.340) were risk factors in the model that performed well(AUC:0.83 (CI: 0.77 – 0.89)). Conclusion: CP should be considered in patients with benign or low-grade lesions in the body of tail of the pancreas since it lowers the risk of endocrine and exocrine insufficiency. With current risk model for severe morbidity and postoperative diabetes, patient selection is now possible.

PURPOSE:Distal pancreatectomy (DP) is associated with a high complication rate of 30-50% with postoperative pancreatic fistula (POPF) as a dominant contributor. Adequate risk estimation for POPF enables surgeons to use a tailor-made approach. Assessment of the risk of POPF prior to DP can lead to the application of preventive strategies. The current study aims to validate the recently published preoperative and intraoperative distal fistula risk score (D-FRS) in a nationwide cohort.METHODS:This nationwide retrospective Dutch cohort study included all patients after DP for any indication, all of whom were registered in the Dutch Pancreatic Cancer Audit (DPCA) database between 2013 and 2021. The D-FRS was validated by filling in the probability equations with data from this cohort. The predictive capacity of the models was represented by an area under the receiver operating characteristic (AUROC) curve.RESULTS:A total of 896 patients underwent DP of which 152 (17%) developed POPF of whom 144 grade B (95%) and 8 grade C (5%). The preoperative D-FRS, consisting of the variables pancreatic neck thickness and pancreatic duct diameter, showed an AUROC of 0.73 (95%CI 0.68-0.78). The intraoperative D-FRS, comprising pancreatic neck, duct diameter, BMI, operating time, and soft pancreatic aspect, showed an AUROC of 0.69 (95%CI 0.64-0.74).CONCLUSION:The current study is the first nationwide validation of the preoperative and intraoperative D-FRS showing acceptable distinguishing capacity for only the preoperative D-FRS for POPF. Therefore, the preoperative score could improve prevention and mitigation strategies such as drain management, which is currently investigated in the multicenter PANDORINA trial.

Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

Background Robot-assisted distal pancreatectomy (RDP) has been suggested to hold some benefits over laparoscopic distal pancreatectomy (LDP) but consensus and data on specific subgroups are lacking. This systematic review and meta-analysis reports the surgical and oncological outcome and costs between RDP and LDP including subgroups with intended spleen preservation and pancreatic ductal adenocarcinoma (PDAC). Methods Studies comparing RDP and LDP were included from PubMed, Cochrane Central Register, and Embase (inception-July 2022). Primary outcomes were conversion and unplanned splenectomy. Secondary outcomes were R0 resection, lymph node yield, major morbidity, operative time, intraoperative blood loss, in-hospital mortality, operative costs, total costs and hospital stay. Results Overall, 43 studies with 6757 patients were included, 2514 after RDP and 4243 after LDP. RDP was associated with a longer operative time (MD = 18.21, 95% CI 2.18–34.24), less blood loss (MD = 54.50, 95% CI − 84.49–24.50), and a lower conversion rate (OR = 0.44, 95% CI 0.36–0.55) compared to LDP. In spleen-preserving procedures, RDP was associated with more Kimura procedures (OR = 2.23, 95% CI 1.37–3.64) and a lower rate of unplanned splenectomies (OR = 0.32, 95% CI 0.24–0.42). In patients with PDAC, RDP was associated with a higher lymph node yield (MD = 3.95, 95% CI 1.67–6.23), but showed no difference in the rate of R0 resection (OR = 0.96, 95% CI 0.67–1.37). RDP was associated with higher total (MD = 3009.31, 95% CI 1776.37–4242.24) and operative costs (MD = 3390.40, 95% CI 1981.79–4799.00). Conclusions RDP was associated with a lower conversion rate, a higher spleen preservation rate and, in patients with PDAC, a higher lymph node yield and similar R0 resection rate, as compared to LDP. The potential benefits of RDP need to be weighed against the higher total and operative costs in future randomized trials.

Objective: To develop 2 distinct preoperative and intraoperative risk scores to predict postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) to improve preventive and mitigation strategies, respectively. Background: POPF remains the most common complication after DP. Despite several known risk factors, an adequate risk model has not been developed yet. Methods: Two prediction risk scores were designed using data of patients undergoing DP in 2 Italian centers (2014–2016) utilizing multivariable logistic regression. The preoperative score (calculated before surgery) aims to facilitate preventive strategies and the intraoperative score (calculated at the end of surgery) aims to facilitate mitigation strategies. Internal validation was achieved using bootstrapping. These data were pooled with data from 5 centers from the United States and the Netherlands (2007–2016) to assess discrimination and calibration in an internal-external validation procedure. Results: Overall, 1336 patients after DP were included, of whom 291 (22%) developed POPF. The preoperative distal fistula risk score (preoperative D-FRS) included 2 variables: pancreatic neck thickness [odds ratio: 1.14; 95% confidence interval (CI): 1.11–1.17 per mm increase] and pancreatic duct diameter (OR: 1.46; 95% CI: 1.32–1.65 per mm increase). The model performed well with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.78–0.88) and 0.73 (95% CI: 0.70–0.76) upon internal-external validation. Three risk groups were identified: low risk (<10%), intermediate risk (10%–25%), and high risk (>25%) for POPF with 238 (18%), 684 (51%), and 414 (31%) patients, respectively. The intraoperative risk score (intraoperative D-FRS) added body mass index, pancreatic texture, and operative time as variables with an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.74–0.85). Conclusions: The preoperative and the intraoperative D-FRS are the first validated risk scores for POPF after DP and are readily available at: http://www.pancreascalculator.com. The 3 distinct risk groups allow for personalized treatment and benchmarking.

BACKGROUND:Postoperative complications following distal pancreatectomy (DP) are common, especially postoperative pancreatic fistula (POPF). In order to design adequate prophylactic strategies, it is of relevance to determine the costs of these complications. An overview of the literature on the costs of complications following DP is lacking.METHODS:A systematic literature search was performed in PubMed, Embase, and Cochrane Library (inception until 1 August 2022). The primary outcome was the costs (i.e. cost differential) of major morbidity, individual complications and prolonged hospital stay. Quality of non-RCTs were assessed using the Newcastle-Ottawa scale. Costs were compared with the use of Purchasing Power parity. This systematic review was registered with PROSPERO (CRD42021223019).RESULTS:Overall, seven studies were included with 854 patients after DP. The rate POPF grade B/C varied between 13% and 27% (based on five studies) with a corresponding cost differential of EUR 18,389 (based on two studies). The rate of severe morbidity varied between 13% and 38% (based on five studies) with a corresponding cost differential of EUR 19,281 (based on five studies).CONCLUSION:This systematic review reported considerable costs for POPF grade B/C and severe morbidity after DP. Prospective databases and studies should report on all complications in a uniform matter to better display the economic burden of complications of DP.

Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands Department of Surgery, Poliambulanza Hospital Brescia, Brescia, Italy Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy DepartmentofSurgery,RegionalAcademicCancerCentreUtrecht,UniversityMedicalCentreUtrecht, andStAntoniusZiekenhuisNieuwegein,Utrecht, theNetherlands Department of Surgery, Erasmus MC, Rotterdam, the Netherlands

Introduction: Central pancreatectomy (CP) is an alternative to distal pancreatectomy (DP) for low potential malignant diseases and is associated with lower risk of new onset diabetes (<5%) but higher morbidity (POPF and bleeding), reserving its use to young patients at lower risk of complications. The open approach (OCP) has been the standard but minimally invasive CP (MICP) is becoming more popular. The aim of this study was to compare the short- and long-term surgical results of MICP versus OCP. Method: A search in PubMed, Cochrane Central Register of Controlled Trials, and Embase until 1 July 2021 identified studies describing open, laparoscopic or robot-assisted CP. Primary endpoint was the rate of major morbidity (Clavien-Dindo ≥3). Secondary endpoints included in-hospital mortality, overall morbidity, POPF (B/C), and pancreatic function. Results: Overall, 41 studies were included with 1004 patients (766 open, 158 laparoscopic and 80 robot-assisted). No significant differences were seen between MICP and OCP for major morbidity (17%vs14%), mortality (1%vs0%), POPF (17%vs24%), overall morbidity (50%vs52%), and new onset diabetes (3%vs6%). A meta-regression was performed with the random-effects model (REM) and showed no significant difference between MICP and OCP for major morbidity (REM 0.20[0.15;0.26] with p=0.388), POPF (REM 0.16[0.10;0.24] with p=0.953), overall morbidity (REM 0.48[0.41;0.54] with p=0.446), and new onset diabetes (REM 0.04[0.02;0.07] with p=0.651). Conclusions: MICP seems to be non-inferior to OCP regarding major morbidity and pancreatic function preservation. MICP may be promoted in experienced centers because of good outcomes added to the general and esthetical advantages in these young patients without malignancy.

Postoperative pancreatic fistula (POPF) remains a major complication after distal pancreatectomy (DP) with a significant impact on patients' quality of life. There is limited evidence that preservation of the spleen reduces the risk of POPF. Therefore, we aimed to investigate the impact of splenectomy on perioperative outcome.Data from patients who underwent DP for malignant and benign disease at our institution between 2004 and 2021 were reviewed. Patients were grouped according to spleen preservation (SP-DP) and splenectomy (DPS). Intraoperative parameters and postoperative outcomes were compared between groups. Univariable and multivariable analyses were used to investigate factors that influence the occurrence of clinically relevant (cr)POPF.A total of 199 patients were included, of whom 61 (30.7%) patients underwent SP-DP. Patients who underwent SP-DP had a significantly lower rate of crPOPF (p = 0.022), shorter hospital stay (p = 0.003), and less readmissions (p = 0.012). On multivariate analysis, obesity (OR 2.88, p = 0.021), benign lesions (OR 2.35, p = 0.018), postoperative acute pancreatitis (OR 2.53, p = 0.028), and splenectomy (OR 2.83, p = 0.011) were independent risk factors associated with the onset of crPOPF.Preservation of the spleen reduces the risk of crPOPF in patients undergoing distal pancreatectomy for benign and malignant disease.