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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). [ABSTRACT FROM AUTHOR]

Background: We tested the added value of 3D-vision on procedure time and surgical performance during robotic pancreatoduodenectomy anastomoses in biotissue. Robotic surgery has the advantage of articulating instruments and 3D-vision. Consensus is lacking on the added value of 3D-vision during laparoscopic surgery. Given the improved dexterity with robotic surgery, the added value of 3D-vision may be even less with robotic surgery. Methods: In this experimental randomized controlled cross-over trial, 20 surgeons and surgical residents from 5 countries performed robotic pancreaticojejunostomy and hepaticojejunostomy anastomoses in a biotissue organ model using the da Vinci® system and were randomized to start with either 3D- or 2D-vision. Primary endpoint was the time required to complete both anastomoses. Secondary endpoint was the objective structured assessment of technical skill (OSATS; range 12–60) rating; scored by two observers blinded to 3D/2D. Results: Robotic 3D-vision reduced the combined operative time from 78.1 to 57.3 min (24.6% reduction, p < 0.001; 20.8 min reduction, 95% confidence intervals 12.8–28.8 min). This reduction was consistent for both anastomoses and between surgeons and residents, p < 0.001. Robotic 3D-vision improved OSATS performance by 6.1 points (20.8% improvement, p = 0.003) compared to 2D (39.4 to 45.1 points, ± 5.5). Conclusion: 3D-vision has a considerable added value during robotic pancreatoduodenectomy anastomoses in biotissue in both time reduction and improved surgical performance as compared to 2D-vision. [ABSTRACT FROM AUTHOR]

Importance: Postoperative pancreatic fistulas (POPF) are the biggest contributor to surgical morbidity and mortality after pancreatoduodenectomy. The impact of POPF could be influenced by the surgical approach., Objective: To assess the clinical impact of POPF in patients undergoing minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD)., Design, Setting, and Participants: This cohort study was conducted from 2007 to 2020 in 36 referral centers in Europe, South America, and Asia. Participants were patients with POPF (grade B/C as defined by the International Study Group of Pancreatic Surgery [ISGPS]) after MIPD and OPD (MIPD-POPF, OPD-POPF). Propensity score matching was performed in a 1:1 ratio based on the variables age (continuous), sex, body mass index (continuous), American Society of Anesthesiologists score (dichotomous), vascular involvement, neoadjuvant therapy, tumor size, malignancy, and POPF grade C. Data analysis was performed from July to October 2023., Exposure: MIPD and OPD., Main Outcomes and Measures: The primary outcome was the presence of a second clinically relevant (ISGPS grade B/C) complication (postpancreatic hemorrhage [PPH], delayed gastric emptying [DGE], bile leak, and chyle leak) besides POPF., Results: Overall, 1130 patients with POPF were included (558 MIPD and 572 OPD), of whom 336 patients after MIPD were matched to 336 patients after OPD. The median (IQR) age was 65 (58-73) years; there were 703 males (62.2%) and 427 females (37.8%). Among patients who had MIPD-POPF, 129 patients (55%) experienced a second complication compared with 95 patients (36%) with OPD-POPF (P < .001). The rate of PPH was higher with MIPD-POPF (71 patients [21%] vs 22 patients [8.0%]; P < .001), without significant differences for DGE (65 patients [19%] vs 45 patients [16%]; P = .40), bile leak (43 patients [13%] vs 52 patients [19%]; P = .06), and chyle leak (1 patient [0.5%] vs 5 patients [1.9%]; P = .39). MIPD-POPF was associated with a longer hospital stay (median [IQR], 27 [18-38] days vs 22 [15-30] days; P < .001) and more reoperations (67 patients [21%] vs 21 patients [7%]; P < .001) but comparable in-hospital/30-day mortality (25 patients [7%] vs 7 patients [5%]; P = .31) with OPD-POPF, respectively., Conclusions and Relevance: This study found that for patients after MIPD, the presence of POPF is more frequently associated with other clinically relevant complications compared with OPD. This underscores the importance of perioperative mitigation strategies for POPF and the resulting PPH in high-risk patients.

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%; p non-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., Competing Interests: Tobias Keck is a member of the advisory board for Olympus, Medtronic, and Dexter. Daan Lips received a proctoring grant by 10.13039/100010477Intuitive Surgical. Marc Besselink and Mohammad Abu Hilal received Investigator Initiated Research grants by Medtronic (DIPLOMA trial), Ethicon (DIPLOMA trial and E-MIPS registry), and Intuitive Surgical (E-MIPS registry) and proctoring grants for Dutch and European training programs in robotic pancreatoduodenectomy by Intuitive Surgical. The other authors have no conflicts of interest., (© 2023 The Authors.)

The expression of six transmembrane epithelial antigen of the prostate (STEAP2) is increased in prostate cancer when compared to normal tissue, suggesting a role for STEAP2 in disease progression. This study aimed to determine whether targeting STEAP2 with an anti-STEAP2 polyclonal antibody (pAb) or CRISPR/Cas9 knockout influenced aggressive prostate cancer traits. Gene expression analysis of the STEAP gene family was performed in a panel of prostate cancer cell lines; C4-2B, DU145, LNCaP and PC3. The highest increases in STEAP2 gene expression were observed in C4-2B and LNCaP cells (p<0.001 and p<0.0001 respectively) when compared to normal prostate epithelial PNT2 cells. These cell lines were treated with an anti-STEAP2 pAb and their viability assessed. CRISPR/Cas9 technology was used to knockout STEAP2 from C4-2B and LNCaP cells and viability, proliferation, migration and invasion assessed. When exposed to an anti-STEAP2 pAb, cell viability significantly decreased (p<0.05). When STEAP2 was knocked out, cell viability and proliferation was significantly decreased when compared to wild-type cells (p<0.001). The migratory and invasive potential of knockout cells were also decreased. These data suggest that STEAP2 has a functional role in driving aggressive prostate cancer traits and could provide a novel therapeutic target for the treatment of prostate cancer.