REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.

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.

Minimally invasive versus open radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma: an entropy balancing analysis.

BACKGROUND: The safety and efficacy of minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS) remain to be established in pancreatic cancer (PDAC) METHODS: Eighty-five open (O)-RAMPS were compared to 93 MI-RAMPS. The entropy balance matching approach was used to compare the two cohorts, eliminating the selection bias. Three models were created. Model 1 made O-RAMPS equal to the MI-RAMPS cohort (i.e., compared the two procedures for resectable PDAC); model 2 made MI-RAMPS equal to O-RAMPS (i.e., compared the two procedures for borderline-resectable PDAC); model 3, compared robotic and laparoscopic RAMPS. RESULTS: O-RAMPS and MI-RAMPS showed "non-small" differences for BMI, comorbidity, back pain, tumor size, vascular resection, anterior or posterior RAMPS, multi-visceral resection, stump management, grading, and neoadjuvant therapy. Before reweighting, O-RAMPS had fewer clinically relevant postoperative pancreatic fistulae (CR-POPF) (20.0% vs. 40.9%; p = 0.003), while MI-RAMPS had a higher mean of lymph nodes (25.7 vs. 31.7; p = 0.011). In model 1, MI-RAMPS and O-RAMPS achieved similar results. In model 2, O-RAMPS was associated with lower comprehensive complication index scores (MD = 11.2; p = 0.038), and CR-POPF rates (OR = 0.2; p = 0.001). In model 3, robotic-RAMPS had a higher probability of negative resection margins. CONCLUSION: In patients with anatomically resectable PDAC, MI-RAMPS is feasible and as safe as O-RAMPS.

Cure Probabilities After Resection Of Pancreatic Ductal Adenocarcinoma: A Multi-Institutional Analysis Of 2554 Patients.

OBJECTIVE: To assess the probability of being cured from pancreatic ductal adenocarcinoma (PDAC) by pancreatic surgery. SUMMARY BACKGROUND DATA: Statistical cure implies that a patient treated for a specific disease will have the same life expectancy as if he/she never had that disease. METHODS: Patients who underwent pancreatic resection for PDAC between 2010 and 2021 were retrospectively identified using a multi-institutional database. A non-mixture statistical cure model was applied to compare disease-free survival to the survival expected for matched general population. RESULTS: Among 2554 patients, either in the setting of upfront (n=1691) or neoadjuvant strategy (n=863), the cure model showed that the probability that surgery would offer the same life-expectancy (and tumor-free) as the matched general population was 20.4% (95%CI: 18.3, 22.5). Cure likelihood reached the 95% of certainty (time-to-cure) after 5.3 years (95%CI: 4.7, 6.0). A preoperative model was developed based on tumor stage at diagnosis (P=0.001), radiological size (P=0.001), response to chemotherapy (P=0.007), American Society of Anesthesiology class (P=0.001) and pre-operative Ca19-9 (P=0.001). A post-operative model with the addition of surgery type (P=0.015), pathological size (P=0.001), tumour grading (P=0.001), resection margin (P=0.001), positive lymphnode ratio (P=0.001) and the receipt of adjuvant therapy (P=0.001) was also developed. CONCLUSIONS: Patients operated for PDAC can achieve a life-expectancy similar to that of general population and the likelihood of cure increases with the passage of recurrence-free time. An online calculator was developed and available at https://aicep.website/?cff-form=15.

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

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

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.

Robot-Assisted Versus Laparoscopic Distal Pancreatectomy in Patients with Resectable Pancreatic Cancer: An International, Retrospective, Cohort Study.

BACKGROUND: Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking. METHODS: An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010-2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival. RESULTS: In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively. CONCLUSIONS: In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials.

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.

The Presence of an Aberrant Right Hepatic Artery Did Not Influence Surgical and Oncological Outcomes After Pancreaticoduodenectomy: A Comprehensive Systematic Review and Meta-Analysis.

BACKGROUND: The presence of an aberrant right hepatic artery (a-RHA) could influence the oncological and postoperative results after pancreaticoduodenectomy (PD). METHODS: A systematic review and metanalysis were conducted, including all comparative studies having patients who underwent PD without (na-RHA) or with a-RHA. The results were reported as risk ratios (RRs), mean differences (MDs), or hazard ratios (HRs) with 95% confidence intervals (95 CI). The random effects model was used to calculate the effect sizes. The endpoints were distinguished as critical and important. Critical endpoints were: R1 resection, overall survival (OS), morbidity, mortality, and biliary fistula (BL). Important endpoints were: postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post pancreatectomy hemorrhage (PPH), length of stay (LOS), and operative time (OT). RESULTS: Considering the R1 rate no significant differences were observed between the two groups (RR 1.06; 0.89 to 1.27). The two groups have a similar OS (HR 0.95; 0.85 to 1.06). Postoperative morbidity and mortality were similar between the two groups, with a RR of 0.97 (0.88 to 1.06) and 0.81 (0.54 to 1.20), respectively. The biliary fistula rate was similar between the two groups (RR of 1.09; 0.72 to 1.66). No differences were observed for non-critical endpoints. CONCLUSION: The presence of a-RHA does not affect negatively the short-term and long-term clinical outcomes of PD.

Appendiceal goblet cell carcinoma has marginal advantages from perioperative chemotherapy: a population-based study with an entropy balancing analysis.

PURPOSE: The aim is to clarify the use of perioperative chemotherapy in resectable goblet cell carcinoma (GCC). METHODS: A retrospective study was carried out based on the Surveillance, Epidemiology, and End Results study. The population was divided: into patients who received only radical surgery (group A) and those who received radical surgery plus chemotherapy (group B). An entropy balancing was carried out to correct the imbalance between the two groups. Two models were generated. Model 1 contained only high-risk patients: group B and a "virtual" group A with similar characteristics. Model 2 included only low-risk patients: group A and "virtual" group B with identical attributes. The efficacy of entropy balancing was evaluated with the d value. The overall survival was compared and reported with Hazard Ratio (HR) within a confidence interval of 95% (95 CI). RESULTS: The groups A and B were imbalanced for tumor size (d = 0.392), T (d = 1.128), N (d = 1.340), M (d = 1.456), mean number of positive lymph nodes (d = 0.907), and LNR (d = 0.889). Before the balancing, the risk of death was higher in group B than in A (4.3; 2.5 to 7.4). After reweighting, all large differences were eliminated (d < 0.200). In high-risk patients, the risk of death was higher in patients who underwent surgery alone than those who received perioperative chemotherapy (HR 0.5; 0.2 to 1.3) without statistical significance (p = 0.187). In low-risk patients, the risk of death was similar (HR 1.1; 0.3 to 3.3). CONCLUSION: Perioperative chemotherapy could provide some marginal advantages to high-risk patients.

Value of immunonutrition in patients undergoing pancreatic resection: a trial sequential meta-analysis.

BACKGROUND: The benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. METHODS: A meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). RESULTS: The meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36-0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; -0.6 to -0.1). For both, the RISs were reached, excluding type I error. CONCLUSION: The IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs.

Survival after active surveillance versus upfront surgery for incidental small pancreatic neuroendocrine tumours.

BACKGROUND: The safety of observing small non-functioning pancreatic neuroendocrine tumours (NF-Pan-NETs) remains under debate. METHODS: This was a multicentre retrospective study of patients with small incidental NF-Pan-NETs. Survival of patients who underwent upfront surgery versus active surveillance was compared. The risk of death was matched with that in the healthy population. The excess hazard rate and probability of a normal lifespan (NLP) were calculated. Propensity score matching (PSM) with a 1 : 1 ratio was used to minimize the risk of selection bias. RESULTS: Some 222 patients (43.7 per cent) underwent upfront surgery and 285 (56.3 per cent) were observed. The excess hazard rate for the entire cohort was quantifiable as 0.04 (95 per cent c.i. 0 to 0.08) deaths per 1000 persons per year, and the NLP was 99.7 per cent. Patients in the active surveillance group were older (median age 65 versus 58 years; P < 0.001), and more often had co-morbidity (45.3 versus 24.8 per cent; P = 0.001), and smaller tumours (median 12 versus 13 mm; P < 0.001), less frequently located in the pancreatic body-tail (59.5 versus 69.6 per cent; P = 0.008, 59.3 versus 73.9 per cent; P = 0.001). Median follow-up was longer for patients who underwent upfront surgery (5.6 versus 2.7 years; P < 0.001). After PSM, 118 patients per group were included. The excess hazard rates were 0.2 and 0.9 deaths per 1000 persons per year (P = 0.020) for patients in the active surveillance and upfront surgery groups respectively. Corresponding NLPs were 99.9 and 99.5 per cent respectively (P = 0.011). CONCLUSION: Active surveillance of small incidental NF-Pan-NETs is a reasonable alternative to resection.

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods.

BACKGROUND: Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. METHODS: Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006-2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. RESULTS: Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. CONCLUSION: Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently.

Benchmarking of minimally invasive distal pancreatectomy with splenectomy: European multicentre study.

BACKGROUND: Benchmarking is the process to used assess the best achievable results and compare outcomes with that standard. This study aimed to assess best achievable outcomes in minimally invasive distal pancreatectomy with splenectomy (MIDPS). METHODS: This retrospective study included consecutive patients undergoing MIDPS for any indication, between 2003 and 2019, in 31 European centres. Benchmarks of the main clinical outcomes were calculated according to the Achievable Benchmark of Care (ABC™) method. After identifying independent risk factors for severe morbidity and conversion, risk-adjusted ABCs were calculated for each subgroup of patients at risk. RESULTS: A total of 1595 patients were included. The ABC was 2.5 per cent for conversion and 8.4 per cent for severe morbidity. ABC values were 160 min for duration of operation time, 8.3 per cent for POPF, 1.8 per cent for reoperation, and 0 per cent for mortality. Multivariable analysis showed that conversion was associated with male sex (OR 1.48), BMI exceeding 30 kg/m2 (OR 2.42), multivisceral resection (OR 3.04), and laparoscopy (OR 2.24). Increased risk of severe morbidity was associated with ASA fitness grade above II (OR 1.60), multivisceral resection (OR 1.88), and robotic approach (OR 1.87). CONCLUSION: The benchmark values obtained using the ABC method represent optimal outcomes from best achievable care, including low complication rates and zero mortality. These benchmarks should be used to set standards to improve patient outcomes.

Development and validation of a preoperative "difficulty score" for laparoscopic transabdominal adrenalectomy: a multicenter retrospective study.

BACKGROUND: A difficulty score for laparoscopic adrenalectomy (LA) is lacking in the literature. A retrospective cohort study was designed to develop a preoperative "difficulty score" for LA. METHODS: A multicenter study was conducted involving four Italian tertiary centers for adrenal disease. The population was randomly divided into two subsets: training group and validation one. A multicenter study was undertaken, including 964 patients. Patient, adrenal lesion, surgeon's characteristics, and the type of procedure were studied as potential predictors of target events. The operative time (pOT), conversion rate (cLA), or both were used as indicators of the difficulty in three multivariate models. All models were developed in a training cohort (70% of the sample) and validated using 30% of patients. For all models, the ability to predict complicated postoperative course was reported describing the area under the curve (AUCs). Logistic regression, reporting odds ratio (OR) with p-value, was used. RESULTS: In model A, gender (OR 2.04, p = 0.001), BMI (OR 1.07, p = 0.002), previous surgery (OR 1.29, p = 0.048), site (OR 21.8, p < 0.001) and size of the lesion (OR 1.16, p = 0.002), cumulative sum of procedures (OR 0.99, p < 0.001), extended (OR 26.72, p < 0.001) or associated procedures (OR 4.32, p = 0.015) increased the pOT. In model B, ASA (OR 2.86, p = 0.001), lesion size (OR 1.20, p = 0.005), and extended resection (OR 8.85, p = 0.007) increased the cLA risk. Model C had similar results to model A. All scores obtained predicted the target events in validation cohort (OR 1.99, p < 0.001; OR 1.37, p = 0.007; OR 1.70, p < 0.001, score A, B, and C, respectively). The AUCs in predicting complications were 0.740, 0.686, and 0.763 for model A, B, and C, respectively. CONCLUSION: A difficulty score based on both pOT and cLA (Model C) was developed using 70% of the sample. The score was validated using a second cohort. Finally, the score was tested, and its results are able to predict a complicated postoperative course.

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.

Minimally invasive adrenalectomy: a comprehensive systematic review and network meta-analysis of phase II/III randomized clinical controlled trials.

PURPOSE: The best approach for minimally invasive adrenalectomy is still under debate. METHODS: A systematic search of randomized clinical trials was carried out. A frequentist random-effects network meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded both in-hospital mortality and morbidity. The secondary endpoints were operative time (OP), blood loss (BL), length of stay (LOS), conversion, incisional hernia, and disease recurrence rate. RESULTS: Eight studies were included, involving 359 patients clustered as follows: 175 (48.7%) in the TPLA arm; 55 (15.3%) in the RPLA arm; 10 (2.8%) in the Ro-TPLA arm; 25 (7%) in the TPAA arm; 20 (5.6%) in the SILS-LA arm; and 74 (20.6%) in the RPA arm. The RPLA had the highest probability of being the safest approach (SUCRA 69.6%), followed by RPA (SUCRA 63.0%). TPAA, Ro-TPLA, SILS-LA, and TPLA have similar probability of being safe (SUCRA values 45.2%, 43.4%, 43.0%, and 38.5%, respectively). Analysis of the secondary endpoints confirmed the superiority of RPA regarding OP, BL, LOS, and incisional hernia rate. CONCLUSIONS: The best choice for patients with adrenal masses candidate for minimally invasive surgery seems to be RPA. An alternative could be RPLA. The remaining approaches could have some specific advantages but do not represent the first minimally invasive choice.

Treatment for Infected Pancreatic Necrosis Should be Delayed, Possibly Avoiding an Open Surgical Approach: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate all invasive treatments for suspected IPN. SUMMARY OF BACKGROUND DATA: The optimal invasive treatment for suspected IPN remains unclear. METHODS: A systematic search of randomized clinical trials comparing at least 2 invasive strategies for the treatment of suspected IPN was carried out. A frequentist random-effects network meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded both the in-hospital mortality and major morbidity rates. The secondary endpoints were mortality, length of stay, intensive care unit stay, the pancreatic fistula rate, and exocrine and endocrine insufficiency. RESULTS: Seven studies were included, involving 400 patients clustered as following: 64 (16%) in early surgical debridement (ED); 27 (6.7%) in peritoneal lavage (PL); 45 (11.3%) in delayed surgical debridement (DD), 169 (42.3%) in the step-up approach with minimally invasive debridement (SUA-DD) and 95 (23.7%) with endoscopic debridement (SUA-EnD). The step-up approach with endoscopic debridement had the highest probability of being the safest approach (SUCRA 87.1%), followed by SUA-DD (SUCRA 59.5%); DD, ED, and PL had the lowest probability of being safe (SUCRA values 27.6%, 31.4%, and 44.4%, respectively). Analysis of the secondary endpoints confirmed the superiority of SUA-EnD regarding length of stay, intensive care unit stay, pancreatic fistula rate, and new-onset diabetes. The SUA approaches are similar regarding exocrine function. Mortality was reduced by any delayed approaches (DD, SUA-DD, or SUA-EnD). CONCLUSIONS: The first choice for suspected IPN seemed to be SUA-EnD. An alternative could be SUA-DD. PL, ED, and DD should be avoided.