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Purpose: Aberrant activation of the hedgehog (Hh) pathway is implicated in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis. We investigated the prognostic and predictive value of four Hh signaling proteins and of the tumor stromal density.Experimental Design: Using tissue microarray and immunohistochemistry, the expression of Shh, Gli1, SMO, and PTCH1 was assessed in 567 patients from three independent cohorts who underwent surgical resection for PDAC. In 82 patients, the tumor stromal index (SI) was calculated, and its association with overall survival (OS) and disease-free survival (DFS) was investigated.Results: Shh and Gli1 protein abundance were independent prognostic factors in resected PDACs; low expressors for those proteins experiencing a better OS and DFS. The combination of Shh and Gli1 levels was the most significant predictor for OS and defined 3 clinically relevant subgroups of patients with different prognosis (Gli1 and Shh low; HR set at 1 vs. 3.08 for Shh or Gli1 high vs. 5.69 for Shh and Gli1 high; P < 0.001). The two validating cohorts recapitulated the findings of the training cohort. After further stratification by lymph node status, the prognostic significance of combined Shh and Gli1 was maintained. The tumor SI was correlated with Shh levels and was significantly associated with OS (P = 0.023).Conclusions: Shh and Gli1 are prognostic biomarkers for patients with resected PDAC. Clin Cancer Res; 21(5); 1215–24. ©2014 AACR.

Supplementary Tables 1-6. Table 1 shows the correlation between immunohistochemical factors and clinicopathological data, Table 2: Univariate analyses of patients characteristics and IHC factors to disease-free survival, Table 3: Multivariate analysis for training and validation sets: clinicopathological variables, Table 4: Multivariate Analyses: OS for patients according to the nodal status, Table 5: Interaction between adjuvant therapy and biomarkers, Table 6: Stromal index and patients' outcomes

Background Factors excluding postoperative pancreatic fistula (POPF), facilitating early drain removal and hospital discharge represent a novel approach in patients undergoing enhanced recovery after pancreatic surgery. This study aimed to establish the relevance of neutrophil-to-lymphocyte ratio (NLR) in excluding POPF after pancreatoduodenectomy (PD). Methods A prospectively maintained database of patients who underwent PD at two high-volume centres was used. Patients were divided into three cohorts (training, internal, and external validation). The primary endpoints of this study were accuracy, optimal timing, and cutoff values of NLR for excluding POPF after PD. Results From 2012 to 2020, in a 2:1 ratio, 451 consecutive patients were randomly sampled as training (n = 301) and validation (n = 150) cohorts. Additionally, the external validation cohort included 197 patients between 2018 and 2020. POPF was diagnosed in 135 (20.8 per cent) patients. The 90-day mortality rate was 4.1 per cent. NLR less than 8.5 on postoperative day 3 (OR, 95 per cent c.i.) was significantly associated with the absence of POPF in the training (2.41, 1.19 to 4.88; P = 0.015), internal validation (5.59, 2.02 to 15.43; P = 0.001), and external validation (5.13, 1.67 to 15.76; P = 0.004) cohorts when adjusted for relevant clinical factors. Postoperative outcomes significantly differed using this threshold. Conclusion NLR less than 8.5 on postoperative day 3 may be a simple, independent, cost-effective, and easy-to-use criterion for excluding POPF.

PURPOSE The double purse-string telescoped pancreaticogastrostomy (PG) technique has been suggested as an alternative approach to reduce the risk of postoperative pancreatic fistula (POPF). Its efficacity in high-risk situations has not yet been explored. This study compared the incidence of clinically relevant POPF (CR-POPF) between patients with high-risk anastomosis undergoing PG and those undergoing pancreaticojejunostomy (PJ). METHODS From 2013 to 2019, 198 consecutive patients with high-risk anastomosis, an updated alternative fistula risk score > 20%, and who underwent pancreatoduodenectomy with the PJ (165) or PG (33) technique were included. Optimal mitigation strategy (external stenting/octreotide omission) was applied for all patients. The primary endpoint was the incidence of CR-POPF. RESULTS The mean ua-FRS was 33%. CR-POPF (grade B/C) was found in 42 patients (21%) and postoperative hemorrhage in 30 (15%); the mortality rate was 4%. CR-POPF rates were comparable between the PJ (19%) and PG (33%) groups (P = 0.062). The PG group had a higher rate of POPF grade C (24% vs. 10%; P = 0.036), longer operative time (P = 0.019), and a higher transfusion rate (P

Background Emergency completion pancreatectomy (CP) after pancreatoduodenectomy (PD) is a technically demanding procedure. We report our experiences with a four-step standardized technique used at our center since 2012. Methods In the first step, the gastrojejunostomy is divided with a stapler to quickly access the pancreatic anastomosis and permit adequate exposure, especially in cases of active bleeding. Second, the bowel loops connected to the pancreatic anastomosis is divided in cases of pancreaticojejunostomy. Third, the pancreatectomy is completed with or without the splenic vessels and spleen conservation according to the local conditions. Finally, the fourth step reconstructs in a Roux-en-Y fashion and ensures drainage. Results From January 2012 to December 2019, 450 patients underwent PD at our center. Reintervention for grade C postoperative pancreatic fistula was decided for 30 patients, and CP was performed in 21 patients. The mean intraoperative blood loss and operative duration were relatively low (600 ml and 240 min, respectively). During the perioperative period, three patients died from multiple organ failure, and two patients died intraoperatively from a cataclysmic hemorrhage originating from the superior mesenteric artery. Discussion Our standardized procedure appears to be relatively safe, reproducible, and could be particularly useful for young surgeons.

International audience; BackgroundAcute pancreatitis (AP) can be one of the earliest clinical presentation of pancreatic ductal adenocarcinoma (PDAC). Information about the impact of AP on postoperative outcomes as well as its influences on PDAC survival is scarce. This study aimed to determine whether AP as initial clinical presentation of PDAC impact the short- and long-term outcomes of curative intent pancreatic resection.Patients and methodsFrom 2004 to 2009, 1449 patients with PDAC underwent pancreatic resection in 37 institutions (France, Belgium and Switzerland). We used univariate and multivariate analysis to identify factors associated with severe complications and pancreatic fistula as well as overall and disease-free survivals.ResultsThere were 764 males (52,7%), and the median age was 64 years. A total of 781 patients (53.9%) developed at least one complication, among whom 317 (21.8%) were classified as Clavien–Dindo ≥ 3. A total of 114 (8.5%) patients had AP as the initial clinical manifestation of PDAC. This situation was not associated with any increase in the rates of postoperative fistula (21.2% vs 16.4%, P = 0.19), postoperative complications (57% vs 54.2%, P = 0.56), and 30 day mortality (2.6% vs 3.4%, P = 1). In multivariate analysis, AP did not correlate with postoperative complications or pancreatic fistula. The median length of follow-up was 22.4 months. The median overall survival after surgery was 29.9 months in the AP group and 30.5 months in the control group. Overall recurrence rate and local recurrence rate did not differ between groups.ConclusionAP before PDAC resection did not impact postoperative morbidity and mortality, as well as recurrence rate and survival.

The Birmingham score predicts the risk of hospital readmission after pancreaticoduodenectomy (PD). This study aimed to validate the risk score in a different healthcare cohort.From 2017 to 2021, 301 patients underwent PD. The Birmingham score was applied to 276 patients. Postoperative deceased patients (n = 7) or those requiring a completion of pancreatectomy (n = 18) were excluded.Forty-seven (17%) patients were readmitted after a median delay of 9 (range 1-49) days and stayed for 5 (range 1-27) days; 4 (8.5%) died during the hospital stay. The leading cause of readmission was a septic condition (53%), mostly resolved by medical treatment (77%). A multivariate analysis identified the occurrence of a clinically relevant postoperative pancreatic fistula, the score criteria, and the score itself as independent factors favouring readmission. Readmission rates in patients with low [n = 97 (35%)], intermediate [n = 98 (36%)], and high [n = 81 (29%)] scores were 5%, 17%, and 31%, respectively (P 0.01).This study confirmed the relevance and robustness of the Birmingham risk score. Patients with a high risk of readmission after PD, identified based on the score, were discharged to a partnership medical centre close to the pancreatic centre to plan readmission and avoid futile unplanned hospitalisation.

International audience; Background: Experienced pancreatic surgeons, for whom complexity is not an issue, must decide at the end of neoadjuvant therapy whether to continue or discontinue surgery, when pancreatectomy with vascular resection is planned in patients with pancreatic ductal adenocarcinoma (PDAC). Objective: Our study aimed to determine preoperative factors that can predict short postoperative survival in such situations. Methods: Overall, 105 patients with borderline or locally advanced PDAC received neoadjuvant FOLFIRINOX (followed by chemoradiation in 22% of patients) and underwent pancreatectomy with segmental venous and/or arterial resection at two high-volume centers. The primary endpoint was overall survival (OS) of < 1 year after surgery for patients who did not die from the surgery. Results: Tumors were classified as borderline in 78% of cases and locally advanced in 22% of cases. Mean CA19-9 at diagnosis was 934 U/mL, which significantly decreased to 213 U/mL (p < 0.01) after a median of six cycles of FOLFIRINOX. Pancreaticoduodenectomy was performed most often (76%). The vast majority of patients underwent venous resection (92%), and a simultaneous arterial resection was performed in 16 patients (15%). The severe morbidity rate and 30- and 90-day mortality rates were 21%, 8.5%, and 10.4%, respectively. The median OS after surgery was 23 months. In the multivariate analysis, preoperative CA19-9 ≥ 450 U/mL was the only preoperative factor independently associated with OS of < 1 year (p = 0.044). Conclusion: The preoperative CA19-9 value should be considered in the clinical decision-making process when complex vascular resection is required. © 2021, Society of Surgical Oncology.

This study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.From 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.The 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3-16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P 0.001). In resected patients, the ASA 3 score (P 0.01), venous resection (P 0.01), hemorrhage (P 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P 0.001).Neoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.

Background Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs according to the cystic component and confirm the accuracy of preoperative staging. Methods From 1997 to 2016, 106 patients underwent resection of PNETs, including 73 purely solid (S-PNETs, 69%), 21 mixed (M-PNETs, 20%), and 12 purely cystic lesions (C-PNETs, 11%). To ensure consistent comparisons of overall (OS) and disease-free (DFS) survival outcomes between the 3 groups, the patients were matched according to the World Health Organization (WHO) grade and tumor height. Results Overall, the rate of correlation between the preoperative and pathological diagnoses was low in the C-PNET group (33%, P = 0.03). None of the 24 patients (23%) with metastatic disease at the time of surgery were in the C-PNET group. Furthermore, significantly more parenchyma-sparing resections (P = 0.039) and fewer enlarged resections (P = 0.019) were achieved in the C-PNET group. C-PNET group had a significantly lower node invasion rate than the S-PNET and M-PNET groups (8% vs. 41% and 24%, P = 0.004). Although median OS was comparable in all 3 groups before (P = 0.3) and after (P = 0.18) matching, higher median DFS was observed in the C-PNET group than in the other groups after matching (P = 0.038). Conclusion C-PNET was associated with a better prognosis than PNET with a solid component. The results support a wait-and-see policy in cases wherein a reliable preoperative diagnosis remains challenging.

Purpose To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC). Methods From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a dual energy spectral computed tomography (CT) scanner and liver diffusion weighted magnetic resonance imaging (DW-MRI) was included in the imaging workup. We consequently considered 2 periods of inclusion: period #1 (February 2000–March 2011) and period #2 (April 2011–August 2019). Results All patients underwent a preoperative CT scan with a median delay to surgery of 18 days. Liver DW-MRI was performed among 407 patients (54%). Median delay between CT and surgery decreased (21 days to 16 days, P P P P P P Conclusions Due to changes in our therapeutic strategies, the NRR did not decrease during two decades despite imaging improvement.

Postoperative pancreatic fistula (POPF) is the most serious complication following pancreaticoduodenectomy (PD). Identifying patients at high or low risk of developing POPF is important in perioperative management. This study aimed to determine a predictive risk score for POPF following PD, and compare it to preexisting scores. All patients who underwent open PD from 2012 to 2017 in two high-volume centers were included. The training dataset was used for the development of the POPF predictive risk score (using the 2016 ISGPS definition), while the testing dataset was used for external validation. The proposed score was compared to the fistula risk score (FRS), the NSQIP-modified FRS (mFRS), and the alternative FRS (aFRS). Overall, 448 and 213 patients were included in the training and testing datasets, respectively. A probabilistic predictive risk score was developed using four independent POPF risk factors (increasing age, no preoperative radiation therapy, soft pancreatic stump, and decreasing main pancreatic duct diameter). The discriminative capacities of the new score, FRS, mFRS, and aFRS were similar (AUC ranging from 0.73 to 0.79 in the training cohort and from 0.73 to 0.76 in the testing cohort). However, the new score identified more specifically patients at low risk of POPF compared with other scores, in both cohorts, with a 6% false-negative rate. Preoperative radiation therapy is an independent protective factor of POPF following PD. It should be included in the risk score of POPF to identify more precisely patients at low risk for this complication.

We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B).From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 500 U/mL and/or regional lymph node metastasis; n = 53) groups.The 3 groups were comparable according to patient characteristics (except for back pain (P .01) and CA 19-9 (P .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P.001), respectively.The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.

Background: We aimed to evaluate the outcomes of resections for liver metastases (LMs) originating from pancreatic ductal adenocarci-noma (PDAC), non-small cell lung cancer (NSCLC), and esophagus/ gastric cancers (EGCs), which we label as major killers (MKs; overall survival (OS) under 10%). We hypothesized that LM resection must provide the patient with almost a year of OS postoperatively that is considered beneficial. Methods: From January 2005 to December 2020, 23 patients under-went resection for isolated LM from MKs. These patients underwent surgery after a multidisciplinary discussion about their performance status, disease evolution during prolonged medical treatment, and the existence or absence of extrahepatic metastases. Results: LM originated from an PDAC, EGC, or NSCLC in 10 pa-tients (43%), nine patients (39%), and four patients (18%), respective-ly. The median delay between primary cancer and LM diagnoses was 12 months, and the median delay between LM diagnosis and liver re-section was 10 months. Most patients, who had objectively responded to medical treatment (57%), had a solitary (61%) and unilobar (70%) LM. Severe morbidity and 90-day mortality rates were 13% and 4.3%, respectively. Margin-free resection was achieved in 16 patients (70%). After liver resection, the median OS was 24 months without a statistical difference when considering the primary tumor site; 1, 3-, and 5-year OS were 70%, 23%, and 23%, respectively. Conclusion: Selection based on criteria such as good clinical condi-tion, response to treatment, and long observation period helped iden-tify patients with LM of MKs who seemed to benefit from resection.

Central hepatectomy (CH) is technically challenging and seldom-used to treat centrally located tumors. However, CH is a parenchyma-sparing resection that may decrease the risk of postoperative liver failure. This retrospective study presents our technique of CH and assesses the outcomes.All CH performed in our department over two decades (1997-2017) were identified. Indications and short-term outcomes were compared between the two decades. Long-term outcomes were assessed.Sixty-four patients underwent CH using a suprahilar approach for hepatocellular carcinoma (HCC: n = 30), metastasis (n = 23), intrahepatic cholangiocarcinoma (IHCCA: n = 9) or other diseases (n = 2). CH represented 6% of 1004 major hepatectomies, (7.4% (n = 35) before 2007 vs 5.4% (n = 29) after 2007). The mean operating time was 219 ± 56 min. A perioperative blood transfusion was required in 14 patients (22%). Intraoperative bile duct injuries occurred in 5 patients (8%), and they were repaired. One patient died postoperatively (1,5%). Ten patients (16%) experienced a major complication. Nine patients (14%) suffered from bile leakage, of which 6 healed spontaneously. Only one patient had low grade liver failure. The R0-resection rate was 69%. After 2007, there were no bile duct injuries (0/29 vs 5/35, p 0.05), and the average hospital stay was shorter but not significantly (11 vs 14 days). Actuarial 5-year survival was 56% for HCC patients and 34% for those with colorectal metastasis CONCLUSIONS: CH is associated with significant biliary morbidity and may increase positive surgical margins. Nevertheless, it should be recommended in selected patients to avoid the risk of postoperative liver failure.

Two-stage hepatectomy (TSH) strategy is used to treat patients with bilobar colorectal liver metastasis (CLM). However, many patients do not undergo the second hepatectomy owing to disease progression in the future liver remnant (FLR) after portal vein embolization (PVE). This study aimed to assess the impact of disease progression in the FLRs of patients who completed the first hepatectomy.68 consecutive patients underwent the first hepatectomy followed by PVE. Six patients (9%) dropped out after the PVE (two-stage failed [TSF] group) because of unresectable hepatic or general disease progression. Seventeen patients (25%) completed their second hepatectomy despite disease progression in the FLR (new CLM [nCLM] group) as it was considered resectable, while 45 patients (66%) underwent the second hepatectomy (control group).The 5-year overall survival rates in the TSF, nCLM, and control groups were 0%, 7%, and 60%, respectively (P 0.001). The median overall survival times between the TSF and nCLM groups were 26 months and 42 months (P = 0.005). Patients in the nCLM group whose hepatic disease progression was detected preoperatively versus intraoperatively had comparable survival rates.Resectable hepatic disease progression in the FLR after PVE should not be considered a contraindication for the second hepatectomy.

International audience

Surgical field photography is a tough exercise: surgeons dedicate the required time for photography even during complex surgeries; the intense lighting of the operating field works against photography, and the surgeon has to utilise whatever equipment is available. We selected five complex interventions and two surgeons (one with an iPhone

Purpose: Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin. Methods: From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC (n = 288) or DC (n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm, however, clearances of 0 and 1.5 mm were also evaluated. Results: Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p &lt, 0.01), and received less neoadjuvant treatment (p &lt, 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC (p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC. Conclusion: Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.

Postoperative aspiration pneumonitis (POAP) is a rare (1%) but worrying complication with a high mortality rate (up to 30%). 1 , 2 , 3 General anesthesia combined with gastrointestinal surgery induces digestive tract paralysis with the risk of delayed gastric emptying and consequent POAP. In the last two decades, efforts to decrease perioperative opioid use, 4 together with the rise of minimally invasive surgery, have reduced the surgical impact on digestive motility. In contrast, enhanced recovery after digestive surgery leads to decreased routine gastric tube feeding and increased early postoperative feeding, 5 , 6 , 7 , 8 which may induce gastric emptying and increase the risk of POAP, which remains a constant risk after digestive surgery, with various effects ranging from isolated radiologic signs to severe pneumonitis with multiorgan failure. To date, there have been no definitions or grading schemes for POAP, and it is difficult to draw realistic comparisons among perioperative drugs or procedures that could be effective in reducing POAP. Therefore, the present study seeks to develop a simple and reliable POAP classification that could facilitate relevant comparisons of preventive measures and postoperative courses.

To describe, in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the laparotomy findings, treatments and outcomes before (period 1) and after 2010 (period 2).From 2000 to 2015, patients newly diagnosed with resectable PDAC at Paoli-Calmettes Institute, France, were evaluated. Survival was examined using the Kaplan-Meier method, and statistical comparisons were conducted using log rank tests.Among 1175 patients diagnosed with pancreatic mass, 164 underwent laparotomy with an intention of pancreatic resection. Some of them did not undergo pancreatic resection due to peroperative discovery of advanced disease. For those who were finally resected (n = 119), there were fewer pancreaticoduodenectomies (p = 0.045), shorter operation times (p 0.01), lower mortality rates (p = 0.02), more advanced-stage tumors (T3), more frequent perineural invasion and R1 resection in period 2. This group had a trend of better outcomes after 2010 (51 months vs. 36 months (p = 0.065)).Improvement in surgical procedures and postoperative management led to prolonged survival of those who underwent surgery for resectable pancreatic cancer since 2010, despite a higher frequency of advanced tumors at the diagnosis in our institution.

OBJECTIVE To evaluate the influence of hospital volume on failure-to-rescue (FTR) after pancreatectomy in France. BACKGROUND There are growing evidences that FTR is an important source of postoperative mortality (POM) after pancreatectomy. However, few studies have analyzed the volume-FTR relationship following pancreatic surgery. METHODS All patients undergoing pancreatectomy between 2012 and 2015 were included. FTR is defined as the 90-day POM rate among patients with major complications. According to the spline model, the critical cutoff was 20 resections per year and hospitals were divided into low (

OBJECTIVE The aim of the current study was to assess the short and long-term outcome of total pancreatectomy (TP) for IPMN based on the largest series to date. BACKGROUND Literature data are scarce regarding TP for IPMN, though increasingly performed in this setting. METHODS Data of 888 IPMN patients operated between 2004 and 2013 were collected in a multicentric retrospective AFC database. Ninety-three patients (10.5%) who had TP entered this study. Patient demographics, indications, intraoperative data, 3-month morbi-mortality (Clavien), and long-term outcome were analyzed. RESULTS Most patients had mixed type IPMN (59%) and underwent upfront (56%) or intraoperatively-decided (33%) TP. Morbidity and mortality rates were 47.3% and 4.3%, respectively, with no lethal hypoglycemia; morbidity was higher for intraoperatively-decided TP. Misdiagnoses were frequent regarding main pancreatic duct involvement (12%), invasiveness (33%), or mural nodules (50%), resulting in 12 TPs (13%) performed for asymptomatic IPMN showing only low/moderate dysplasia (LMD). On histopathological examination, there were 54 (58%) invasive IPMN (mostly pT3/T4 (76%), N+ (60%), R0 (75%)), with a significantly worse 5-year survival (21.2%) compared to noninvasive group (85.7%; P < 0.0001). In the former, 24 (58.5%) developed recurrence showing mostly distant metastasis, within 2 years in 92%. CONCLUSION This large series of TP for IPMN reported acceptable morbi-mortality rates with no long-term death from diabetes-related complication. Morphologic assessment was imperfectly reliable with 13% of TP done for LMD only. More than half of patients were operated at an invasive carcinoma stage with poor outcome. Conversely, long-term survival was excellent after TP for noninvasive IPMN.

Positive para-aortic lymph nodes (PALN) (station 16) are commonly detected in the final pathologic examination (ranging from 15 to 26%) among patients who undergo upfront pancreatoduodenectomy for resectable pancreatic ductal adenocarcinoma. However, after neoadjuvant treatment (NAT) the role of positive PALN as a watershed for surgical resection remains unclear. We aimed to determine the incidence of intraoperative detection of PALN after NAT with FOLFIRINOX for pancreatic head adenocarcinoma and its impact on survival, as our policy was to not resect the tumor in such situations. From January 2014 to December 2020, 136 patients with non-metastatic cancer who received neoadjuvant FOLFIRINOX and underwent explorative laparotomy were included. Intraoperative positive PALN were observed in 7 patients (5%). Patients had resectable (n = 5) or locally advanced (n = 2) disease at the time of surgery, but none of them underwent surgical resection. Positive PALN were significantly associated with a lower median number of FOLFIRINOX cycles (4 vs. 6, P = 0.05). There was no significant difference in overall survival between patients with positive loco-regional lymph nodes after resection and patients with non-resection owing to positive PALN (22 versus 16 months, P = 0.16), Overall survival with positive PALN, carcinomatosis, and liver metastasis was 16, 14, and 10 months, respectively (P > 0.05). Our results suggest that NAT may lower PALN involvement. We have modified our policy, positive PALN after NAT are no longer a contraindication to resection, rather a holistic picture of the disease guides management.

Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence.Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described.During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P.001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence.The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data.

Parenchymal sparing duodenal and pancreatic resection are safe procedures in selected patients with the aim to reduce endocrine and exocrine long-term dysfunction. When the tumor is benign or borderline malignant, this appears to be a good option for the surgeon, associated with low rates of severe surgery-related early postoperative complications and low in-hospital mortality. This mini review offers comments, tips and tricks, and a review of literature concerning those different options with specific illustrations in order to clarify their indication.

Background This study aimed to investigate the short- and long-terms outcomes of patients undergoing major hepatectomy (MH) with inferior vena cava (IVC) resection for intrahepatic cholangiocarcinoma (ICC). Methods Data from all patients who underwent MH for ICC with or without IVC resection between 2010 and 2018 were analysed retrospectively. Postoperative outcomes, overall survival (OS), and recurrence-free survival (RFS) were compared in the whole population. A propensity score matching (PSM) analysis and an inverse probability weighting analysis (IPW) were performed to assess the influence of IVC resection on short- and long-terms outcomes. Results Among the 78 patients who underwent MH, 20 had IVC resection (IVC patients). Overall, the mortality and severe complication rate were 8% and 20%, respectively. IVC patients required more extended hepatectomies (p = 0.001) and had increased rates of transfusions (p = 0.001), however they did not experience increased postoperative morbidity, even after PSM. The 1-, 3- and 5-years OS and DFS were 78%, 45%, and 32% and 48%, 20%, and 16%, respectively. IVC was not associated with decreased OS (p = 0.52) and/or RFS (p = 0.85), even after IPW. Conclusion MH with IVC resection for ICC seems to provide acceptable short- and long-term results in a selected population of patients.

Background Sacrificing a replaced right hepatic artery (rRHA) from the superior mesenteric artery is occasionally necessary to obtain an R0 resection after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). Preoperative embolization (PEA) of the rRHA has been proposed to avoid the onset of postoperative biliary and ischemic liver complications. Methods Eighteen patients with cephalic PA with an rRHA underwent PEA of the rRHA from 2013 to 2019. The monitoring after embolization and PD was systematic and included a clinical-biological evaluation and a computed tomography scan. This study aimed to determine the feasibility of PEA of the rRHA, postoperative morbidity at 90 days, and quality of oncologic resection after PD. Results Feasibility of PEA was 100% without complications. A PD was performed in 16/18 patients. Mortality was 2/16 with one death after septic shock with hepatic ischemia without an arterial obstruction. Overall morbidity was 44% including one hepatic abscess after hepatic ischemia (6%). Two resections were R1 ( Conclusion PEA of the rRHA before PD was safe and reproducible. PEA of the rRHA followed by en bloc PD resection seems to limit the risk of bilio-hepatic ischemia and could facilitate oncologic resection.

Backgrounds/Aims Surgical resection remains the gold standard in the treatment of colorectal liver metastasis. However, when a patient presents with a deep solitary colorectal liver metastasis (S-CLM), the balance between the hepatic volume sacrificed and the S-CLM volume is sometimes clearly unappropriated. Thus, alternatives to surgery, such as operative and percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA), have been developed. This study aimed to identify the prognostic factors affecting survival of patients with S-CLM who undergo curative-intent liver resection or local destruction (RFA or MWA). Methods We retrospectively identified 211 patients with synchronous or metachronous S-CLM who underwent either surgical resection (n=182) or local destruction (RFA or MWA; n=29) according to the S-CLM size, location, and surrounding Glissonian structures. Results Patients who underwent RFA or MWA had S-CLM of a smaller size than those who underwent resection (mean 19.7 vs. 37.3 mm, p

This case aims to report a video of a pancreaticoduodenectomy that required both portal vein and Michels type 9 hepatic artery reconstruction using the inverted splenic artery technique in a patient with a rare condition.

Additional file 2: Supplementary Table 5. Overall Survival before and after matching.

Additional file 1: Supplementary Table 4. Matching process.

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. 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). 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

Introduction Type II AEG is now considered as oesophageal cancer in the seventh and eighth edition of TNM classification but optimal surgical approach for these tumors remains debated. The objective of the study is to assess and compare surgical and oncological outcomes of two surgical approaches: superior polar oesogastrectomy (SPO) or total gastrectomy (TG) in patients with type II adenocarcinoma of the oesophagogastric junction (AEG). Material and methods 183 patients with type II AEG treated from 1997 to 2010 in 21 French centers by SPO or TG were included in a multicenter retrospective study. The surgical and oncological outcomes were compared between these two surgical approaches. Results A TG was performed in 64 (35%) patients whereas 119 (65%) patients were treated by SPO with transthoracic approach in 100 of them (83.2%) and transhiatal approach with cervicotomy in 19 (16.8%). Surgical outcomes were comparable between the two approaches with a postoperative mortality rate of 4.9% and a severe operative morbidity rate within 30 days of 15.3%. Median survival in patients operated on by TG was of 46 months compared to 27 months in patients treated by SPO (p = 0.118). At multivariate analysis, TG appears to be an independent good prognostic factor compared to SPO (HR = 1.847; p = 0.008). However, TG was also associated with a higher rate of incomplete resection, (12.5% vs 5.9%; p = 0.120). Conclusion When TG allows obtaining tumor-free resection margins, this approach should be preferred to SPO.

The online version of this article ( https://doi.org/10.1007/s00423-018-1702-1) contains supplementary material, which is available to authorized users.; International audience; 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.

We report the case of a 56-year-old woman with pancreatic adenocarcinoma (PA) discovered during an episode of febrile jaundice. A computed tomography (CT) scan showed a mass in the head of the pancreas with circumferential infiltration of the superior mesenteric vein (SMV) and dilatation of the biliary and pancreatic ducts without metastases. The patient benefited from neoadjuvant chemotherapy (FOLFIRINOX) followed by radio-chemotherapy (45 Gy) and chemotherapy (LV5FU2). The revaluation CT revealed SMV thrombosis without portal vein (PV) thrombosis. There was no contact of the tumor with the PV. Pancreatoduodenectomy with combined resection of the SMV was performed with no reconstruction of this venous axis after confirmation of adequate PV, splenic, and left gastric venous flow and the absence of bowel ischemia. The pathological diagnosis was pT4N1R0 PA. There were no bowel angina issues during the follow-up period. At 15 mo after surgery, the patient died of metastatic recurrence.

International audience; Hepatic hemangioma is the most common benign hepatic tumor, and most of them are small in size and asymptomatic. Giant hepatic hemangiomas are uncommon, but pedunculated giant hemangiomas are even rarer and often difficult to diagnose because of their exophytic development. We report here on a 48-year-old man with a symptomatic pedunculated giant hepatic hemangioma and hepatic angiomatosis, mimicking a gastric gastrointestinal stromal tumor with liver metastases. The preoperative diagnosis was suspected on imaging including CT scan and MRI. The patient was successfully operated (left hepatic lobectomy), without any complication, and the pathological analysis confirmed the diagnosis. We reviewed the English literature, and to our knowledge, our case represents the largest case reported so far when compared with the 19 other informative cases.

International audience; BACKGROUND:Postoperative complications influence overall and disease free survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma is still a matter of debate and controversy.METHODS:The outcome of 942 consecutive patients, from the multicentric study of the French Association of Surgery, between January 2004 and December 2009 was analyzed. Perioperative data, including severe complications (grade III and above), were used in univariate and multivariate analysis to assess their influence on overall and disease free survival. Recurrence and its location were investigated as well.RESULTS:Median overall and disease free survival were 24 and 19 months respectively. Postoperative complications occurred in 444 patients (47%) with 18.3% of severe complications. On multivariate analysis, severe complications, positive lymph node status and R1-R2 resection were independent prognostic factors for both overall and disease free survival. The median overall survival decreased from 25 to 22 months (p = 0.005) and disease free survival from 21 to 16 months (p = 0.02) if severe complications occurred. Severe complications were independent prognostic factor of recurrence (p < 0.001).CONCLUSIONS:Severe complications significantly alter both overall and disease free survival and are an independent factor of recurrence.

International audience; OBJECTIVES:Multicenter studies comparing the reverse strategy (RS) with the classical strategy (CS) for the management of stage IVA liver-only colorectal cancer (CCR) are scarce. The aim of this study was to compare long-term survival and recurrence patterns following use of the CS and RS.METHOD:This retrospective multicenter review collected data from all consecutive patients with stage IVA liver-only CCR who underwent staged resection of CCR and liver metastases (LM) at 24 French hospitals between 2006 and 2013 and were retrospectively analyzed. Patients who underwent simultaneous liver and CCR resection, those with synchronous extrahepatic metastasis, and those who underwent emergent CCR resection were excluded. Overall survival (OS) and recurrence-free survival (RFS) rates and recurrence patterns were investigated before and after propensity score matching (PSM).RESULTS:A total of 653 patients were included: 587 (89.9%) in the CS group and 66 (10.1%) in the RS group. Compared with the CS patients, RS patients were more likely to have rectal cancer (43.9 vs. 24.9%; p = 0.006), larger liver tumor size (52.5 ± 38.6 vs. 39.6 ± 30 mm; p = 0.01), and more positive lymph nodes (62.1 vs. 44.8%; p = 0.009). OS was not different between the two groups (75 vs. 72% at 5 years; p = 0.77), while RFS was worse in the RS group (24 vs. 33% at 5 years; p = 0.01). Time to recurrence at any site (1.8 vs. 2.4 years, p = 0.024) and intrahepatic recurrence (1.7 vs. 2.2 years, p = 0.014) were significantly shorter in the RS group than in the CS group. After PSM (63 patients in each group), no significant difference was found between the two groups in OS (p = 0.35), RFS (p = 0.62), time to recurrence at any site (p = 0.19), or intrahepatic recurrence (p = 0.13).CONCLUSIONS:In this study, approximately 10% of patients with CCR and synchronous LM were offered surgery with the RS. Both strategies ensured similar oncological outcomes.

Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets., Pancreatic ductal adenocarcinoma (PDAC) is a complex disease and its underlying epigenomic heterogeneity is not fully understood. Here, the authors utilize patient-derived PDAC xenografts to define the epigenomic landscape of PDAC, highlighting chromatin states linked to differing disease aggressiveness and survival.

RAS mutation status is an important prognostic factor after resection of liver metastases (LiM) from colorectal cancer (CRC). The prognostic significance of RAS after resection of lung (LuM) and peritoneal (PM) metastases from CRC is unknown. Between 2005 and 2014, all consecutive patients with known RAS status who underwent potentially curative resection for LiM, LuM, or PM were evaluated. A total of 720 patients with known RAS status underwent resection of LiM (n = 468), LuM (n = 102), and PM (n = 150). RAS mutations were identified in 63 and 58% of patients with LuM and PM, respectively, compared with 41% of patients with LiM (p