Radical antegrade modular pancreatosplenectomy: Myth or reality? A systematic review and trial sequential meta-analysis

Background: The superiority of radical antegrade modular pancreatosplenectomy versus standard distal pancreatectomy has never been demonstrated. Methods: A systematic review was performed to identify all comparative studies about radical antegrade modular pancreatosplenectomy versus standard distal pancreatectomy. Random-effects analysis was performed, and hazard ratios, odds ratios, and mean differences were calculated. Using trial sequential analysis, type I and II errors were evaluated by comparing the accrued sample size with the required sample size. When the required sample size is superior to the accrued sample size, type I or II errors can be hypothesized. The critical endpoint was overall survival. Secondary endpoints were disease-free survival, R0 resection rate, major morbidity and mortality rate, clinically relevant postoperative pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, length of stay, and operative time. Results: The accrued sample size and required sample size were 1,172 and 176 for the primary endpoint, respectively. The overall survival was similar between the 2 groups, with a hazard ratio of 1.33 (95% confidence interval: 0.89-2.0 0). The required sample size reached, and false-negative equivalence can be excluded. Disease-free survival, R0 resection rate, major morbidity and mortality rate, clinically relevant postoperative pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, and operative time are similar and reached required sample sizes, suggesting that false equivalence can be excluded. Length of stay was shorter in radical antegrade modular pancreatosplenectomy than in standard distal pancreatectomy (-3.48 days; -6.66 to -0.31 days). The accrued sample size was 826, and the required sample size was not reached. False-positive results cannot be excluded. Conclusion: Radical antegrade modular pancreatosplenectomy was not superior in guaranteeing a better overall survival and disease-free survival. The data are robust, and further retrospective comparative studies are unnecessary. (c) 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Surgical and oncological implications of the presence of hepatic artery anatomical variations in patients undergoing pancreaticoduodenectomy: a single center experience

The presence of an aberrant right hepatic artery (a-RHA) could influence the oncological and postoperative outcomes after pancreaticoduodenectomy (PD). A comparative study was conducted, including patients who underwent PD with a-RHA or with normal RHA anatomy. The primary endpoints were R1 resection in all margins (pancreatic, anterior, posterior, superior mesenteric artery, and portal groove), overall survival (OS), and disease-free survival (DFS). The secondary endpoints were morbidity, mortality, biliary leak (BL), postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post pancreatectomy hemorrhage (PPH), length of stay (LOS), and operative time (OT). The selection bias was measured using the d-value and limited using entropy balancing analysis. Patients with arterial variants were 84 (37.5%), 39 (17.4%) of whom had a-RHA from SMA. The patients with a-RHA were more frequently symptomatic (d = 0.652), often affected by PDAC (d = 0.369), and judged borderline resectable (d = 0.588). Neoadjuvant therapy was more frequently proposed for patients with a-RHA (d = 0.465). The patients with a-RHA often had the Wirsung dilated compared to those without a-RHA (d = 0.336). After bias correction, the R1 resection rate on the superior mesenteric artery (SMA) margin was higher in the a-RHA group than in patients with normal RHA anatomy (OR 2.3; 1.1-5.2; P = 0.045). OS, DFS, morbidity, mortality, biliary leak (BL), postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post pancreatectomy hemorrhage (PPH), length of stay (LOS), and operative time (OT) were similar in unmatched and matched population. The presence of a-RHA seems to increase the risk of R1 resection in the SMA margin

Converted laparoscopic distal pancreatectomy: is there an impact on patient outcome and total cost?

Purpose: Recent studies have reported worse outcomes of converted laparoscopic distal pancreatectomy (CLDP) with respect to total laparoscopic (TLDP) and open (ODP). The aim of the study was to evaluate the impact of conversion on patient outcome and on total cost. Methods: Patients requiring a conversion (CLDP) were compared with both TLDP and ODP patients. The relevant patient- and tumour-related variables were collected for each patient. Both intra and postoperative data were extracted. Propensity score matching (PSM) analysis was carried out to equate the groups compared. Results: Two hundred and five patients underwent DP, 105 (51.2%) ODPs, 81 (39.5%) TLDPs, and 19 (9.3%) CLDPs. After PSM, 19 CLDPs, 38 TLDPs, and 38 ODPs were compared. Patients who underwent CLDP showed a significantly longer operative time (P < 0.001), and an increase in blood loss (P = 0.032) and total cost (P = 0.034) with respect to TLDP, and a significantly longer operative time (P < 0.001), less frequent postoperative morbidity (P = 0.050), and a higher readmission rate (P = 0.035) with respect to ODP. Conclusion: Total laparoscopic pancreatectomy was superior regarding operative findings and total costs with respect to CLDP; ODP showed a higher postoperative morbidity rate and a lower readmission rate with respect to CLDP. However, the reasons for the readmission of patients who underwent CLDP were mainly related to postoperative pancreatic fistula (POPF) grade B which is usually due to pancreas texture. Thus, the majority of distal pancreatectomies can be started using a minimally invasive approach, performing an early conversion if necessary

Blumgart Anastomosis After Pancreaticoduodenectomy. A Comprehensive Systematic Review, Meta-Analysis, and Meta-Regression

Background: The superiority of Blumgart anastomosis (BA) over non-BA duct to mucosa (non-BA DtoM) still remains under debate. Methods: We performed a systematic search of studies comparing BA to non-BA DtoM. The primary endpoint was CR-POPF. Postoperative morbidity and mortality, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), reoperation rate, and length of stay (LOS) were evaluated as secondary endpoints. The meta-analysis was carried out using random effect. The results were reported as odds ratio (OR), risk difference (RD), weighted mean difference (WMD), and number needed to treat (NNT). Results: Twelve papers involving 2368 patients: 1075 BA and 1193 non-BA DtoM were included. Regarding the primary endpoint, BA was superior to non-BA DtoM (RD = 0.10; 95% CI: −0.16 to −0.04; NNT = 9). The multivariate ORs' meta-analysis confirmed BA's protective role (OR 0.26; 95% CI: 0.09 to 0.79). BA was superior to DtoM regarding overall morbidity (RD = −0.10; 95% CI: −0.18 to −0.02; NNT = 25), PPH (RD = −0.03; 95% CI −0.06 to −0.01; NNT = 33), and LOS (− 4.2 days; −7.1 to −1.2 95% CI). Conclusion: BA seems to be superior to non-BA DtoM in avoiding CR-POPF

Trial sequential meta-analysis of laparoscopic versus open pancreaticoduodenectomy: is it the time to stop the randomization?

Background: The advantages of LPD compared with OPD remain debatable. The study aimed to compare the laparoscopic (LPD) versus open (OPD) for pancreaticoduodenectomy. Methods: A meta-analysis of randomized studies (RCTs) comparing LPD and OPD was made. The results were reported as relative risk (RRs) or mean differences (MDs). The trial sequential analysis was used to test the type I and type II errors defining the required information size (RIS). The primary outcome was mortality, major morbidity, and postoperative pancreatic fistula (POPF). R1 resection, post-pancreatectomy hemorrhage, delayed gastric emptying, biliary fistula, reoperation, readmission, operative time (OT), lymph nodes harvested, and length of stay (LOS) were also studied. Results: Four RCTs, counting 818 patients, were found. The RRs for mortality, major morbidity, and POPF were 1.16, 1.04, and 0.86, without significant differences. The RISs were 35,672, 16,548, and 8206. To confirm this equivalence, at least 34,854, 15,730, and 7338 should be randomized. OT was significantly longer in LPD than OPD, with an MD of 63.22. The LOS was significantly shorter in LPD than in OPD, with − 1.76 days. The RISs were 1297 and 1273, excluding a false-positive result. No significant differences were observed for the remaining endpoints, and RISs suggested that more than 3000 patients should be randomized to confirm the equivalence. Conclusion: The equivalence of LPD and OPD for mortality, major morbidity, and POPF is affected by type II error. The RISs to demonstrate a superiority of one of the two techniques seem unrealistic to obtain

Early Versus Late Drainage Removal in Patients Who Underwent Pancreaticoduodenectomy: A Comprehensive Systematic Review and Meta-analysis of Randomized Controlled Trials Using Trial Sequential Analysis

Background. The superiority of early drain removal (EDR) versus late (LDR) after pancreaticoduodenectomy (PD) has been demonstrated only in RCTs.Methods. A meta-analysis was conducted using a random-effects model and trial sequential analysis. The critical endpoints were morbidity, redrainage, relaparotomy, and postoperative pancreatic fistula (CR-POPF). Hemorrhage (PPH), delayed gastric emptying (DGE), length of stay (LOS), and readmission rates were also evaluated. Risk ratios (RRs) and mean differences (MDs) with a 95% confidence interval (CI) were calculated. Type I and type II errors were excluded, comparing the accrued sample size (ASS) with the required sample size (RIS). When RIS is superior to ASS, type I or II errors can be hypothesized.Results. ASS was 632 for all endpoints except DGE and PPH (557 patients). The major morbidity (RR 0.55; 95% CI 0.32-0.97) was lower in the EDR group. The CR-POPF rate was lower in the EDR than in the LDR group (RR 0.50), but this difference is not statistically significant (95% CI 0.24-1.03). The RIS to confirm or exclude these results can be reached by randomizing 5959 patients. The need for percutaneous drainage, relaparotomy, PPH, DGE, and readmission rates was similar. The related RISs were higher than ASS, and type II errors cannot be excluded. LOS was shorter in the EDR than the LDR group (MD - 2.25; 95% CI - 3.23 to - 1.28). The RIS was 567, and type I errors can be excluded.Conclusions. EDR, compared with LDR, is associated with lower major morbidity and shorter LOS

Physical Prehabilitation in Patients who Underwent Major Abdominal Surgery: A Comprehensive Systematic Review and Component Network Meta-Analysis Using GRADE and CINeMA Approach

Background: Physical prehabilitation is recommended before major abdominal surgery to ameliorate short-term outcomes. Methods: A frequentist, random-effects network meta-analysis (NMA) was performed to clarify which type of preoperative physical activity among aerobic exercise (AE), inspiratory muscle training (IMT), and resistance training produces benefits in patients who underwent major abdominal surgery. The surface under the P-score, odds ratio (OR), or mean difference (MD) with a 95% confidence interval (CI) were reported. The results were adjusted by using the component network approach. The critical endpoints were overall and major morbidity rate and mortality rate. The important but not critical endpoints were the length of stay (LOS) and pneumonia. Results: The meta-analysis included 25 studies. The best approaches for overall morbidity rate were AE and AE + IMT (OR = 0.61, p-score = 0.76, and OR = 0.66, p-score = 0.68). The best approaches for pneumonia were AE + IMT and AE (OR = 0.21, p-score = 0.91, and OR = 0.52, p-score = 0.68). The component analysis confirmed that the best incremental OR (0.30; 95% CI 0.12–0.74) could be obtained using AE + IMT. The best approach for LOS was AE alone (MD − 1.63 days; 95% CI − 3.43 to 0.18). The best combination of components was AE + IMT (MD − 1.70; 95% CI − 2.06 to − 1.27). Conclusions: Physical prehabilitation reduces the overall morbidity rate, pneumonia, and length of stay. The most relevant effect of prehabilitation requires the simultaneous use of AE and IMT

Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis

Background and aims: Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy. Methods: Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay. Results: One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of −7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome. Conclusion: Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome

The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program

Background:Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. Methods: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months.Results: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p &lt; 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1–13, p = 0.03). Conclusions: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.</p

Discharge protocol in acute pancreatitis: an international survey and cohort analysis

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p &lt; 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients’ care