Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.

BACKGROUND: Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. METHODS: All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. RESULTS: Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CONCLUSION: CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.

Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study.

OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.

Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. BACKGROUND: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. METHODS: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. RESULTS: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. CONCLUSION: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.

Life expectancy and likelihood of surgery in multiple endocrine neoplasia type 1: AFCE and GTE cohort study.

BACKGROUND: The overall natural history, risk of death and surgical burden of patients with multiple endocrine neoplasia type 1 (MEN1) is not well known. METHODS: Patients with MEN1 from a nationwide cohort were included. The survival of patients with MEN1 was compared with that of the general population using simulated controls. The cumulative probabilities of MEN1-specific operations and postoperative mortality were assessed, and surgical sequences were analysed using sunburst charts and Venn diagrams. RESULTS: A total of 1386 patients with MEN1 were included. Life expectancy was significantly reduced in patients with MEN1 compared with simulated controls from the general population, with a lifetime difference of 15 years. Mutations affecting the JunD interaction domain had a significant negative impact on survival. Survival for patients with MEN1 compared with the general population improved over time. The probability of experiencing at least one specific MEN1 operation was above 95 per cent after 75 years, and most patients had surgery at least twice during their lifetime. Time to a 50 per cent risk of MEN1 surgery was 30.5 years for patients born after 1960, compared with 47.9 years for those born before 1960. Sex and mutations affecting the JunD interacting domain had no impact on time to first surgery. There was considerable heterogeneity in surgical sequences, with no specific clinical pathway. CONCLUSION: Life expectancy was significantly lower among patients with MEN1 compared with the general population, and further decreased in patients with mutations affecting the JunD interacting domain. Almost all patients underwent at least one MEN1-specific operation during their lifetime, but there was no standardized sequence of surgery.

Associations between the severity of medical and surgical complications and perception of surgeon empathy in esophageal and gastric cancer patients.

OBJECTIVE: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients. METHODS: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses. RESULTS: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR = .95, 95% CI = [.91-.99], p = .029). Among the three dimensions, only "establishing rapport" (OR = .84, 95% CI = [.73-.98], p = .019) and the "emotional process" (OR = .85, 95% CI = [.74-.98], p = .022) predicted major complications. CONCLUSIONS: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period.

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate.

BACKGROUND: The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. OBJECTIVE: The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. METHODS: Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). RESULTS: Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). CONCLUSION: Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort.

BACKGROUND: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. PATIENTS AND METHODS: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). RESULTS: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007). CONCLUSIONS: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.

First pancreatic perivascular epithelioid cell tumor (PEComa) treated by mTOR inhibitor.

BACKGROUND: Perivascular epithelioid cell tumor, an extremely rare mesenchymal tumor, could be ubiquitous but rarely arises from pancreas. Surgery is considered the most appropriate treatment. Nevertheless, activation of mTOR pathway seems to be a common pathogenic event in PEComas paving the way to chemotherapy by mTOR inhibitor. METHOD: A 17 year-old man presented a hypervascular tumor of 55 mm, located in the head of pancreas without bile duct or pancreatic duct compression. RESULTS: Histopathology showed epithelioid cells with clear or focally granular eosinophilic cytoplasm with melanocytic (HMB-45, Melan-A) and myoid markers which confirmed diagnosis of PEComa. Given the absence of worrisome feature, we ruled out surgery and decided to initiate treatment with Sirolimus, an mTOR inhibitor. After 3.5 years, we showed a significant reduction in size of the tumor. CONCLUSION: This first case of pancreatic PEComa treated by mTOR inhibitor without surgery suggests a good efficiency of this therapy.

Effect of endoscopic failure on the results of internal surgical drainage in pancreatic pseudocyst.

BACKGROUND: The treatment of pancreatic pseudocysts has evolved during the past two decades. Endoscopic treatment (ET) has gradually become used as a first-line management even though it showed no significant superiority to surgical internal drainages (SIDs) in a recent randomized trial. The objective of the present work was to analyze the effect of ET failure on the results of SID in the global management of pancreatic pseudocysts. METHODS: A multicenter retrospective study (Clichy, Bordeaux, Nantes, and Rennes) was conducted between January 2000 and December 2012. The main criteria were as follows: (i) major postoperative complications (MPCs) (Clavien ≥ 3) and (ii) treatment failure in the first 12 mo. All factors that may affect these two parameters were tested in univariate and multivariate analyses, when necessary. RESULTS: One hundred nineteen patients, with a median age of 52 y (22-83) underwent SID, including 45 procedures (37.8%) performed after ET failure. Mortality and overall morbidity rates were 1.7% and 30.2%, respectively. Eighteen patients (15.1%) presented an MPC. Multivariate analysis revealed that failure of ET (odds ratio 3.04, confidence interval [1.04 to 9.5], P = 0.046) and BMI ≤20 (odds ratio 4.5, confidence interval [1.50; 15.5], P = 0.010) were independent risk factors of MPCs. The success of SID was 92.5% in the first year. In univariate analysis, the occurrence of an MPC was the only factor linked to the failure of SID (P = 0.029). CONCLUSIONS: Performing an SID after ET failure is associated with an increased risk of MPC. Close postoperative monitoring is recommended for these patients.

Impact of adjuvant chemotherapy after pancreaticoduodenectomy for distal cholangiocarcinoma: a propensity score analysis from a French multicentric cohort.

BACKGROUND: The benefit of adjuvant chemotherapy (AC) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains controversial. The study aimed to evaluate the impact of AC after PD for DCC in a large multicentric cohort. METHODS: Patients from five French centers who underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or surgery only (AC- group) were included in the analysis. Variables associated with AC administration were analyzed by univariate analysis. The Cox regression identified covariates associated with overall survival (OS) and disease-free survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a propensity score (PS) based on the likelihood of AC administration and independent factors associated with decreased OS and DFS. RESULTS: Of the 178 patients included, 56 (31.5%) received AC. In the whole cohort, no difference on OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07, respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC- group (n = 49) on factors associated with AC administration and on factors associated with a decreased survival in the large cohort. After matching, the medians of OS and DFS in the AC+ group and in the AC- group were comparable (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79, respectively). CONCLUSION: Our study did not demonstrate a survival benefit of adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even after propensity score matching. New trial specially designed for DCC is urgently needed to improve survival after surgical resection.

Multicentre study of the impact of factors that may affect long-term survival following pancreaticoduodenectomy for distal cholangiocarcinoma.

BACKGROUND: Although the peri-operative mortality following pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) has decreased, the post-operative morbidity remains high. The aim of this study was to evaluate the impact of factors that may affect the long term survival for patients with DCC following PD. METHODS: All patients who underwent PD for DCC between January 2000 and December 2015 in 5 tertiary referral centers underwent retrospective medical record review. Factors likely to influence overall (OS) and disease-free (DFS) survivals were assessed by univariate and multivariate analysis. RESULTS: A total of 201 on 217 patients who underwent PD for DCC were included for further analysis. The median OS was 39 months, with actuarial survival rates at 1, 3, and 5 years of 85%, 53% and 39%. Recurrence occurred in 123 (61%) patients. The median DFS was 16 months, with actuarial survival rates at 1, 3 and 5 years of 60%, 37% and 28%. Following multivariate analysis, peri-operative blood transfusions (PBT) were associated to worse OS (HR = 2.25 [1.31-3.85], P = 0.003) and DFS (HR = 2.08 [1.24-3.5], P = 0.005). CONCLUSION: This study confirms the negative impact of PBT on the oncologic result following PD for DCC.

Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study.

BACKGROUND: Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

Prognostic Value of Resection Margin Involvement After Pancreaticoduodenectomy for Ductal Adenocarcinoma: Updates From a French Prospective Multicenter Study.

OBJECTIVE: The aim of the study was to assess the relevance of resection margin status for survival after resection of pancreatic-head ductal adenocarcinoma. SUMMARY BACKGROUND DATA: The definition and prognostic value of incomplete microscopic resection (R1) remain controversial. METHODS: Prognostic factors were analyzed in 147 patients included in a prospective multicenter study on the impact of tumor clearance evaluated using a standardized pathology protocol. RESULTS: Thirty patients received neoadjuvant treatment (NAT = 20%); 41 had venous resection (VR = 28%), and 70% received adjuvant chemotherapy. In-hospital mortality was 3% (5/147). Follow-up was 83 months. Tumor clearance was 0, <1.0, <1.5, and <2.0 mm in 35 (25%), 92 (65%), 95 (67%), and 109 (77%) patients, respectively. R0-resection rates decreased from 75% to 35% when changing the definition of R1 status from R1-direct invasion (0 mm) to R1 <1.0 mm. On univariate analysis, clearance <1.0 or <1.5 mm, pT stage, pN stage, LNR ≥0.2, tumor grade 3, and lymphovascular invasion were significantly associated with 5-year survival. On multivariate analysis, pN was the most powerful independent predictor (P = 0.004). Clearance <1.0 or <1.5 mm had borderline significance for the entire cohort, but was relevant in certain subgroups (upfront pancreatectomy (n = 117; P = 0.049); without VR or NAT (n = 87; P = 0.003); N+ without VR or NAT (n = 50; P = 0.004). No N0-patient had R1-0 mm. Additional independent risk predictors were (1) R1 <1.0 mm for the SMA-margin in specific subgroups (upfront pancreatectomy, N0 patients without NAT, N+ patients without NAT or VR; (2) R1-0 mm posterior-margin for the NAT group (P = 0.004). CONCLUSION: Tumor clearance <1.0 or <1.5 mm was an independent determinants of postresection survival in certain subgroups. To avoid misinterpretation, future trials should specify the clearance margin in millimeter. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00918853.

Chylous Ascites Management After Pancreatic Surgery.

BACKGROUND: Postoperative chylous ascites (CA) following pancreatic surgery is uncommon. If left untreated, it leads to malnutrition, immunodeficiency and increased postoperative morbidity and mortality. The aim of this study was to seek out risk factors associated with CA onset and conservative treatment (CT) failure in order to determine better management of CA following pancreatic resection. MATERIALS AND METHODS: All consecutive patients who underwent pancreatic surgery between 2004 and 2014 were reviewed retrospectively. Main demographic, clinical and pathological data were searched for CA risk factors. Patients with CA successfully treated with CT alone were compared to those requiring additional bipedal lymphangiography (BPLAG) in order to seek out risk factors associated with CT failure. RESULTS: Fifteen patients (2.4 %) developed CA after pancreatic surgery. Para-aortic lymph node sampling and early enteral feeding were found to be independent risk factors for postoperative CA (OR 6.36, p = 0.024 and OR 12.18, p = 0.02, respectively). CT was successful in ten patients, and five patients required additional BPLAG to achieve CA resolution. Statistical analysis revealed no significant risk factors for CT failure, including total lymph node count (p = 0.196), para-aortic lymph node sampling (p = 0.661) or maximum chyle loss per day (p = 0.758). CONCLUSIONS: Owing to postoperative CA rarity, there is no consensus in treatment. Early on, CT should be attempted in all patients with CA. BPLAG is a safe and efficient procedure that should be discussed earlier in the step-up therapeutic management.

Laparoscopic Versus Open Surgery for Gastric Gastrointestinal Stromal Tumors: What Is the Impact on Postoperative Outcome and Oncologic Results?

OBJECTIVES: The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs). BACKGROUND: The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5 cm, remains unknown. METHODS: Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20 cm (N = 666), by either laparoscopy (group L, n = 282) or open surgery (group O, n = 384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. RESULTS: In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P = 0.086) and 11.3% vs 19.5% (P = 0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P = 0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P = 0.103). After 1:1 propensity score matching (n = 224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P = 0.005), surgical morbidity (4.9% vs 9.8%; P = 0.048), and medical morbidity (6.2% vs 13.4%; P = 0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P = 0.011). In tumors greater than 5 cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P = 0.255 and P = 0.423, respectively). CONCLUSIONS: Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results.

Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO-FRENCH, Prospective, Multicentric Cohort.

PURPOSE: In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy. METHODS: We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review. RESULTS: Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1-30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035). CONCLUSIONS: Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies.

Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens.

OBJECTIVES: This study aimed to determine the impact of a standardized pathological protocol on resection margin status after pancreaticoduodenectomy (PD) for ductal adenocarcinoma. METHODS: A total of 150 patients operated during 2008-2010 were included in a prospective multicentre study using a 'quality protocol'. Multicolour inking by the surgeon identified three resection margins: the portal vein-superior mesenteric vein margin (PV-SMVm) or mesenterico-portal vein groove; the superior mesenteric artery margin (SMAm), and the posterior margin. Resection margins were stratified by 0.5-mm increments (range: 0-2.0 mm). Pancreatic neck, bile duct and intestinal margins were also analysed. Correlations between histopathological factors and survival in the 0-mm resection margin group were analysed. RESULTS: Thirty-six patients (24%) had a PV-SMV resection (PV-SMVR). An analysis of resections categorized according to margin distances of 0 mm, <1.0 mm, <1.5 mm and <2.0 mm confirmed R1 resections in 35 (23%), 91 (61%), 94 (63%) and 107 (71%) patients, respectively. The most frequently invaded resection margin was the PV-SMVm (35% of all patients) and PV-SMVR was the only factor correlated with a higher risk for at least one 0-mm positive resection margin on multivariate analysis (P < 0.001). Two-year progression-free survival (PFS) and median PFS time in patients with R0 and R1 resections (at 0 mm), respectively, were 42.0% and 26.5%, and 19.5 months and 10.5 months, respectively (P = 0.02). A positive PV-SMVm and SMAm had significant impact on PFS, whereas a positive posterior margin had no impact. CONCLUSIONS: Pancreaticoduodenectomy requiring PV-SMVR was associated with a higher risk for R1 resection. The standardization of histopathological analysis has a clinically relevant impact on PFS data.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: A propensity score matched multicentric comparative French study.

BACKGROUND: Minimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. METHODS: This retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. RESULTS: During the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of "textbook" outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. CONCLUSION: Minimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.