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.

Distal Pancreatectomy Fistula Risk Score (D-FRS): Development and International Validation.

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.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

Learning curve of three European centers in laparoscopic, hybrid laparoscopic, and robotic pancreatoduodenectomy.

INTRODUCTION: There are limited numbers of high-volume centers performing minimally invasive pancreatoduodenectomy (MIPD) routinely. Several approaches to MIPD have been described. Aim of this analysis was to show the learning curve of three different approaches to MIPD. Focus was on determining the number of cases necessary to obtain proficient level in MIPD. PATIENTS AND METHODS: Retrospective study wherein outcomes of 300 consecutive patients at three centers-at each center the initial 100 consecutive patients undergoing MIPD for malignant and benign tumors of the head of the pancreas and perimpullary area, performed by three experienced surgeons were collected and analyzed. RESULTS: Overall, 300 patients after MIPD were included: the three different cohorts (laparoscopic n = 100, hybrid n = 100, robotic n = 100). CUSUM analysis of operating time in each center demonstrated that the plateau for laparoscopic PD was n = 61, for hybrid PDes was n = 32 and for robotic PD was n = 68. Median operative time for laparoscopic, hybrid, and robotic approaches was 395 min, 404 min, 510 min, respectively. Intraoperative blood loss for laparoscopic PD, hybrid PD, and robotic PD was 250 ml, 250 ml, and 413 ml, respectively. Delayed gastric emptying occurred 12% in laparoscopic cohort, 10% in hybrid, and 53% in robotic cohort. Major complications (Clavien-Dindo III/IV) rate for laparoscopic PD, hybrid PD, and robotic PD was 32%, 37%, and 22% with 5% death in each cohorts, respectively. CONCLUSION: This analysis of the learning curve of three European centers found a shorter learning curve with hybrid PD as compared to laparoscopic and robotic PD. In implementation of a MIPD program, a stepwise approach might be beneficial.

International Validation of Reduced Major Morbidity After Minimally Invasive Distal Pancreatectomy Compared With Open Pancreatectomy.

OBJECTIVE: To quantify the nationwide impact of minimally invasive distal pancreatectomy (MIDP) on major morbidity as compared with open distal pancreatectomy (ODP). BACKGROUND: A recent randomized controlled trial (RCT) demonstrated significant reduction in time to functional recovery after MIDP compared with ODP, but was not powered to assess potential risk reductions in major morbidity. METHODS: International cohort study using the American College of Surgeons' National Quality Improvement Program (ACS-NSQIP) (88 centers; 2014-2016) to evaluate the association between surgical approach (MIDP vs ODP) and 30-day composite major morbidity (CMM; death or severe complications) with external model validation using Dutch Pancreatic Cancer Group data (17 centers; 2005-2016). Multivariable logistic regression assessed the impact of nationwide MIDP rates between 0% and 100% on postoperative CMM at conversion rates between 0% and 25%, using estimated marginal effects. A sensitivity analysis tested the impact at various scenarios and patient populations. RESULTS: Of 2921 ACS-NSQIP patients, 1562 (53%) underwent MIDP with 18% conversion, and 1359 (47%) underwent ODP. MIDP was independently associated with reduced CMM [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.42-0.60, P < 0.001], confirmed by external model validation (n = 637, P < 0.003). The association between rising MIDP implementation rates and falling postoperative morbidity was linear between 0% (all ODP) and 100% (all MIDP). The absolute risk reduction for CMM was 11% (95% CI 7.3%-15%) at observed conversion rates and improved to 14% (95% CI 11%-18%) as conversion approached 0%. Similar effects were seen across subgroups. CONCLUSION: This international study predicted a nationwide 11% risk reduction for CMM after MIDP versus ODP, which is likely to improve as conversion rates decrease. These findings confirm secondary outcomes of the recent LEOPARD RCT.

Updated Alternative Fistula Risk Score (ua-FRS) to Include Minimally Invasive Pancreatoduodenectomy: Pan-European Validation.

OBJECTIVE: The aim of the study was to validate and optimize the alternative Fistula Risk Score (a-FRS) for patients undergoing minimally invasive pancreatoduodenectomy (MIPD) in a large pan-European cohort. BACKGROUND: MIPD may be associated with an increased risk of postoperative pancreatic fistula (POPF). The a-FRS could allow for risk-adjusted comparisons in research and improve preventive strategies for high-risk patients. The a-FRS, however, has not yet been validated specifically for laparoscopic, robot-assisted, and hybrid MIPD. METHODS: A validation study was performed in a pan-European cohort of 952 consecutive patients undergoing MIPD (543 laparoscopic, 258 robot-assisted, 151 hybrid) in 26 centers from 7 countries between 2007 and 2017. The primary outcome was POPF (International Study Group on Pancreatic Surgery grade B/C). Model performance was assessed using the area under the receiver operating curve (AUC; discrimination) and calibration plots. Validation included univariable screening for clinical variables that could improve performance. RESULTS: Overall, 202 of 952 patients (21%) developed POPF after MIPD. Before adjustment, the original a-FRS performed moderately (AUC 0.68) and calibration was inadequate with systematic underestimation of the POPF risk. Single-row pancreatojejunostomy (odds ratio 4.6, 95 confidence interval [CI] 2.8-7.6) and male sex (odds ratio 1.9, 95 CI 1.4-2.7) were identified as important risk factors for POPF in MIPD. The updated a-FRS, consisting of body mass index, pancreatic texture, duct size, and male sex, showed good discrimination (AUC 0.75, 95 CI 0.71-0.79) and adequate calibration. Performance was adequate for laparoscopic, robot-assisted, and hybrid MIPD and open pancreatoduodenectomy. CONCLUSIONS: The updated a-FRS (www.pancreascalculator.com) now includes male sex as a risk factor and is validated for both MIPD and open pancreatoduodenectomy. The increased risk of POPF in laparoscopic MIPD was associated with single-row pancreatojejunostomy, which should therefore be discouraged.

Procedure-specific Training for Robot-assisted Distal Pancreatectomy.

OBJECTIVE: To train practicing surgeons in robot-assisted distal pancreatectomy (RADP) and assess the impact on 5 domains of healthcare quality. BACKGROUND: RADP may reduce the treatment burden compared with open distal pancreatectomy (ODP), but studies on institutional training and implementation programs are scarce. METHODS: A retrospective, single-center, cohort study evaluating surgical performance during a procedure-specific training program for RADP (January 2006 to September 2017). Baseline and unadjusted outcomes were compared "before training" (ODP only; June 2012). Exclusion criteria were neoadjuvant therapy, vascular- and unrelated organ resection. Run charts evaluated index length of stay (LOS) and 90-day comprehensive complication index. Cumulative sum charts of operating time (OT) assessed institutional learning. Adjusted outcomes after RADP versus ODP were compared using a secondary propensity-score-matched (1:1) analysis to determine clinical efficacy. RESULTS: After screening, 237 patients were included in the before-training (133 ODP) and after-training (24 ODP, 80 RADP) groups. After initiation of training, mean perioperative blood loss decreased (-255 mL, P<0.001), OT increased (+65 min, P < 0.001), and median LOS decreased (-1 day, P < 0.001). All other outcomes remained similar (P>0.05). Over time, there were nonrandom (P < 0.05) downward shifts in LOS, while comprehensive complication index was unaffected. We observed 3 learning curve phases in OT: accumulation (<31 cases), optimization (case 31-65), and a steady-state (>65 cases). Propensity-score-matching confirmed reductions in index and 90-day LOS and blood loss with similar morbidity between RADP and ODP. CONCLUSION: Supervised procedure-specific training enabled successful implementation of RADP by practicing surgeons with immediate improvements in length of stay, without adverse effects on safety.

Outcomes After Minimally-invasive Versus Open Pancreatoduodenectomy: A Pan-European Propensity Score Matched Study.

OBJECTIVE: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers. BACKGROUND: Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking. METHODS: Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing ≥10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing ≥10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo ≥3). RESULTS: Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%, P = 0.526), mortality (4.0% vs 3.3%, P = 0.576), percutaneous drainage (12% vs 12%, P = 0.809), reoperation (11% vs 13%, P = 0.329), and hospital stay (mean 17 vs 17 days, P > 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%, P < 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95, P < 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF (24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%, P < 0.001). CONCLUSIONS: In the early experience of 14 European centers performing ≥10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed.

External validation and comparison of the original, alternative and updated-alternative fistula risk scores for the prediction of postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Many postoperative pancreatic fistula (POPF) predictions models were developed and validated in western populations. Direct use of these models in the large Indian/Asian population, however, requires proper validation. OBJECTIVE: To validate the original, alternative and updated alternative fistula risk score (FRS) models. METHODS: A validation study was performed in consecutive patients undergoing pancreatoduodenectomy (PD) from January 2011 to March 2018. The area under the receiver operating curve (ROC) and calibration plots were used to assess the performance of original-FRS (o-FRS), alternative FRS (a-FRS) and updated alternative FRS (ua-FRS) models. RESULTS: This cohort consisted of 825 patients of which 66% were males with a median age of 55 years and mean body mass index of 22.6. The majority of tumors (61.8%) were of periampullary origin. Clinically relevant POPF was observed in 16.8% patients. Area under curve (AUC) of ROC for the o-FRS was 0.65, 0.69 for a-FRS and 0.70 for ua-FRS, respectively (p = 0.006). CONCLUSIONS: In this large Indian cohort of predominantly periampullary tumors, the ua-FRS performed better than the a-FRS and o-FRS, although differences were small. Since the AUC value of the ua-FRS is at the accepted threshold there might be room for improvement for a FRS.

Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS): Design and International External Validation.

OBJECTIVE: The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor. BACKGROUND: Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations. METHODS: The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS. RESULTS: For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80-3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61-0.76), and high body mass index (BMI) (per kg/m increase, OR: 1.07, 95% CI: 1.04-1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71-0.78) after internal validation, and 0.78 (0.74-0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05). CONCLUSION: The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.

Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study.

OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60-400) vs 300 mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

Outcomes and Risk Score for Distal Pancreatectomy with Celiac Axis Resection (DP-CAR): An International Multicenter Analysis.

BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. METHODS: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. RESULTS: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15-25 months). CONCLUSIONS: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor.

Does surgical approach affect outcomes of enucleation for benign and low-grade pancreatic tumors? An ACS-NSQIP evaluation.

BACKGROUND: Enucleation of low-grade pancreatic tumors achieves oncological outcomes equivalent to resection but conserves parenchyma. Given strict selection criteria, we hypothesized that minimally-invasive (MI) enucleation is associated with decreased composite major morbidity (CMM) compared to open. METHODS: Pancreas-targeted ACS NSQIP (2014 -2016) was queried for enucleation (CPT code: 48120) and analyzed by intended surgical approach regardless of conversion. The primary outcome was CMM, a validated 30-day composite metric of adverse events. RESULTS: Enucleation was performed using an open (n = 71; 62.3%) or MI (n = 43; 37.7%) approach with 7 conversions (16.2%). Both cohorts had interchangeable baseline characteristics. No selection factors governing MI were identified. MI-enucleation reduced median length of stay (4 vs. 5 days; p = 0.003), whereas rates of CMM after open (24; 34%) and MIenucleation (12; 28%) were equivalent (p = 0.541). Multivariable analysis demonstrated an association between CMM and prolonged operative time (OR 2.7, 95% CI 1.14 -6.74), female sex (OR 0.38, 95% CI 0.16 -0.94), and ASA score <3 (OR 0.39, 95% CI 0.16 -0.96) but not surgical approach. CONCLUSION: MI-enucleation was not associated with reduced 30-day CMM compared to open, whereas prolonged operating time and unmodifiable patient factors were correlated with adverse outcomes.

Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study.

BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes.

Correction to: Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study.

In the original article, the institutional author the E-AHPBA DP-CAR study group was misspelled. It is correct as reflected here. The original article has also been corrected.

Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy.

BACKGROUND: Determining the resectability of locally advanced pancreatic cancer (LAPC) after induction chemotherapy is complex since CT-imaging cannot accurately portray tumor response. We hypothesized that CA19-9 response adds to RECIST-staging in predicting resectability of LAPC. METHODS: Post-hoc analysis within a prospective study on LAPC (>90° arterial or >270° venous involvement). CA19-9 response was determined after induction chemotherapy. Surgical exploration was performed in RECIST-stable or -regressive disease. The relation between CA19-9 response, resectability and survival was assessed. RESULTS: Restaging in 54 patients with LAPC after induction chemotherapy (mostly FOLFIRINOX) identified 6 RECIST-regressive, 32 RECIST-stable, and 16 patients with RECIST-progressive disease. The resection rate was 20.3% (11/54 patients). Sensitivity and specificity of RECIST-regression for resection were 40% and 87% whereas the positive predictive value (PPV) and negative predictive value (NPV) were 67% and 68%. Using a 30% decrease of CA19-9 as cut-off, 9/10 patients were correctly classified as resectable (90% sensitivity, PPV 43%) and 3/15 as unresectable (20% specificity, NPV 75%). In the total cohort, a CA19-9 decrease ≥30% was associated with improved survival (22.4 vs. 12.7 months, p = 0.02). CONCLUSION: Adding CA19-9 response after induction chemotherapy seems useful in determining which patients with RECIST non-progressive LAPC should undergo exploratory surgery.

Nationwide Evaluation of Patient Selection for Minimally Invasive Distal Pancreatectomy Using American College of Surgeons' National Quality Improvement Program.

OBJECTIVE: To assess current nationwide case selection factors for minimally invasive distal pancreatectomy (MIDP) and identify actual risk factors for adverse outcomes compared with open distal pancreatectomy (ODP). BACKGROUND: Patient selection criteria that predict outcomes after MIDP remain unknown. As a result, widespread adoption of this surgical technique may have been delayed and its potential benefits possibly under-exploited. METHODS: Retrospective cohort study of elective ODP and MIDP performed at 106 centers in 2014, using the pancreas-targeted American College of Surgeons' National Quality Improvement Program (ACS-NSQIP) database. Exclusion criteria were neoadjuvant treatment or pancreatitis as only diagnosis. Primary outcome includes a composite major morbidity metric, reflecting adverse events including mortality and reoperation. Multivariable modeling was used to detect current selection factors and to identify actual risk factors of composite major morbidity. RESULTS: A total of 928 patients underwent ODP (n = 472) or MIDP (n = 456) using a laparoscopic or robot-assisted approach, 24% for pancreatic ductal adenocarcinoma (PDAC). Current selection factors for MIDP were benign disease (odds ratio: OR: 1.56, CI: 1.10-2.21) and body mass index (BMI) 30-40 (OR: 1.41, CI: 1.04-1.91). Current selection factors for ODP were PDAC (OR: 0.45, CI: 0.31-0.64), benign tumor size >5 centimeters (OR: 0.40, CI: 0.23-0.67), and multivisceral procedures (OR: 0.39, CI: 0.26-0.59). Risk factors for composite major morbidity did not differ between ODP and MIDP. A trend was observed between MIDP and a lower risk of composite major morbidity compared with ODP (OR: 0.43, CI: 0.17-1.07). CONCLUSIONS: Current selection factors for ODP or MIDP (benign disease, tumor size, and BMI) do not mitigate the risk of major morbidity. We found no evidence that MIDP should be avoided based on tumor etiology or size, BMI, or patient physical status.