Acute Pancreatitis as the Initial Presentation of Pancreatic Adenocarcinoma does not Impact Short- and Long-term Outcomes of Curative Intent Surgery: A Study of the French Surgical Association.

BACKGROUND: Acute 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 METHODS: From 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. RESULTS: There 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. CONCLUSION: AP before PDAC resection did not impact postoperative morbidity and mortality, as well as recurrence rate and survival.

Peritoneal Carcinomatosis Risk and Long-Term Survival Following Hepatectomy for Spontaneous Hepatocellular Carcinoma Rupture: Results of a Multicenter French Study (FRENCH-AFC).

BACKGROUND: Spontaneous rupture of hepatocellular carcinoma (HCC) remains a life-threatening complication, with a reported mortality rate of between 16 and 30% and an incidence rate of approximately 3% in Europe. Survival data and risk factors after ruptured HCC are lacking, especially for peritoneal metastasis (PM). OBJECTIVES: The aims of this study were to evaluate the pattern of recurrence and mortality after hepatectomy for ruptured HCC, and to focus on PM. METHODS: We retrospectively reviewed the files of patients admitted to 14 French surgical centers for spontaneous rupture of HCC between May 2000 and May 2012. RESULTS: Overall, 135 patients were included in this study. The median disease-free survival and overall survival (OS) rates were 16.1 (11.0-21.1) and 28.7 (26.0-31.5) months, respectively, and the median follow-up period was 29 months. At last follow-up, recurrences were observed in 65.1% of patients (n = 88). The overall rate of PM following ruptured HCC was 12% (n = 16). Surgical management of PM was performed for six patients, with a median OS of 36.6 months. An α-fetoprotein level > 30 ng/mL (p = 0.0009), tumor size at rupture > 70 mm (p = 0.0009), and vascular involvement (p < 0.0001) were found to be independently associated with an increased likelihood of recurrence. No risk factor for PM was observed. CONCLUSION: This large-cohort French study confirmed that 12% of patients had PM after ruptured HCC. A curative approach may be an option for highly selected patients with exclusive PD because of the survival benefit it could provide.

Short-term outcomes after major hepatic resection in patients with cirrhosis: a 75-case unicentric western experience.

BACKGROUND: The benefit of performing major hepatic resection (MHR) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial because of its high risk of posthepatectomy liver failure (PHLF). This study was conducted to assess the risk of MHR for HCC in patients with cirrhosis. METHODS: Patients with Child-Pugh A or B cirrhosis and HCC who underwent MHR from January 2000 to June 2014 were retrospectively identified. Risk factors for postoperative morbidity and mortality using univariate and multivariate analyses were evaluated. RESULTS: Seventy patients with Child-Pugh A (93%) and 5 (7%) with Child-Pugh B cirrhosis underwent MHR for HCC. Thirteen (17%) had Barcelona Clinic Liver Cancer (BCLC) stage A, 39 (50%) had BCLC B, and 23 (32%) had BCLC C disease. A perioperative blood transfusion was performed in 18 patients (24%). Ninety-day postoperative mortality was 9% (n=7). Major complications occurred in 16 patients (21%), including PHLF in 9 patients (12%). A multivariate analysis showed that perioperative blood transfusion was the main independent factor associated with mortality (OR= 6.5) and major morbidity (OR=10). CONCLUSION: In selected patients with HCC and cirrhosis, MHR is feasible and has acceptable mortality, but careful perioperative management and limiting blood loss are required.

Half of Postoperative Deaths After Hepatectomy may be Preventable: A Root-cause Analysis of a Prospective Multicenter Cohort Study.

OBJECTIVE: To perform a retrospective root-cause analysis of the causes of postoperative mortality after hepatectomy. BACKGROUND: Mortality after liver resection has not decreased over the past decade. METHODS: The study population was a prospective cohort of hepatectomies performed at hepatic, pancreatic, and biliary (HPB) centers between October 2012 and December 2014. Of the 1906 included patients, 90 (5%) died within 90 days of surgery. Perioperative data were retrieved from the original medical records. The root-cause analysis was performed independently by a senior HBP-surgeon and a surgical HBP-fellow. The objectives were to record the cause of death and then assess whether (1) the attending surgeon had identified the cause of death and what was it?, (2) the intra- and postoperative management had been appropriate, (3) the patient had been managed according to international guidelines, and (4) death was preventable. A typical root cause of death was defined. RESULTS: The cause of death was identified by the index surgeon and by the root-cause analysis in 84% and 88% of cases, respectively. Intra- and postoperative management procedures were inadequate in 33% and 23% of the cases, respectively. Guidelines were not followed in 57% of cases. Overall, 47% of the deaths were preventable. The typical root cause of death was insufficient evaluation of the tumor stage or tumor progression in a patient with malignant disease resulting in a more invasive procedure than expected. CONCLUSION: Measures to ensure compliance with guidelines and (in the event of unexpected operative findings) better within-team communication should be implemented systematically.

Indocyanine Green Retention Rates at 15 min Predicted Hepatic Decompensation in a Western Population.

BACKGROUND: ICGR15 is widely used in Asia to evaluate the liver reserve before hepatectomy, but not in Western countries where patients are selected using the MELD score and/or platelet count. Postoperative liver failure is rare nowadays, but hepatic decompensation (HD), defined by 3-month postoperative ascites, impairs quality of life and survival. The aim of this study was to evaluate the relevance of indocyanine green retention rate at 15 min (ICGR15) before liver resection in Western countries, in order to predict HD. METHODS: This prospectively designed study included consecutive adult patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in three French HPB centres. RESULTS: Between 2012 and 2014, 147 patients were included (80% of HCC and 20% of ICC). The Child-Pugh status was grade A for all patients. In the overall population and in F3/F4 patients (n = 83), ICGR15 (P = 0.02) and platelet counts (P = 0.02) were predictive of HD under multivariate analysis. Among F3/F4 patients undergoing minor hepatectomy with preoperative ICGR15 > 15%, the rate of HD was 36%. In the overall population, ICGR15 was predictive of HD (P = 0.02) and postoperative ascites (P = 0.03). The ROC curve identified a cut-off point of 15% as being associated with increased HD, with good accuracy for ICGR15 in the study population (AUROC 0.73), mainly before minor hepatectomy (AUROC 0.79). CONCLUSIONS: In patients with HCC and ICC selected using the MELD score and platelet rate, an ICGR15 > 15% is a relevant, non-invasive and clearly accurate method to predict HD specially before minor hepatectomy.

Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: the Achilles' Heel?

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is technically demanding, and its impact on postoperative outcomes remains controversial. OBJECTIVE: To compare short-term outcomes between laparoscopic versus open pancreaticoduodenectomy (OPD) in order to assess the safety of LPD. METHODS: From 2002 to 2014, all consecutive patients undergoing LPD or OPD at two tertiary centers were retrospectively analyzed. Patients were matched for demographics, comorbidities, pathological diagnosis, and pancreatic texture. Results for the two groups were compared for postoperative outcomes. RESULTS: Sixty-five LPD were performed and compared to 290 OPD. In the whole population, postoperative pancreatic fistula (PF) was higher in the LPD group, but the proportion of ampullary adénocarcinoma (25 vs. 10%, p = 0.004) and soft pancreatic parenchyma (52 vs. 38%, p = 0.001) were higher in the LDP group. After matching (n = 65), LPD was associated with longer operative time (429 vs. 328 min, p < 0.001) and lower blood loss (370 vs. 515 mL, p = 0.047). The PF rate and its severity were similar (33 vs. 27%, p = 0.439, p = 0.083) in the two groups. However, both complications (78 vs. 71%, p = 0.030) and major complications (40 vs. 23%, p = 0.033) were more frequent in the LPD group. LPD patients experience more postoperative bleeding (21 vs. 14%, p = 0.025) compared to their open counterparts. In multivariate analysis, perioperative transfusion (OR = 5 IC 95% (1.5-16), p = 0.008), soft pancreas (OR = 2.5 IC 95% (1.4-4.6), p = 0.001), and ampullary adenocarcinoma (OR = 2.6 IC 95% (1.2-5.6), p = 0.015) were independent risks factors of major complications. CONCLUSION: Despite lower blood loss and lower intraoperative transfusion, LPD leads to higher rate of postoperative complications with postoperative bleeding in particular.

Bleeding Recurrence and Mortality Following Interventional Management of Spontaneous HCC Rupture: Results of a Multicenter European Study.

BACKGROUND: The incidence of spontaneous rupture of hepatocellular carcinoma (HCC) is low in Europe, at less than 3%. HCC rupture remains a life-threatening complication, with mortality reported between 16 and 30%. The risk of bleeding recurrence has never been clearly evaluated in such clinical situation. The objectives of this study were to evaluate the current risk of mortality related to HCC rupture and to focus on the risk of bleeding recurrence following interventional management. METHODS: All patients admitted to 14 French-Italian surgical centers for spontaneous rupture of HCC between May 2000 and May 2012 were retrospectively included. Clinical data, imaging features, relevant laboratory data, treatment strategies, and prognoses were analyzed. RESULTS: Overall, 58 of the 138 included patients (42%) had cirrhosis. Thirty-five patients (25%) presented with hemorrhagic shock, and 19% with organ(s) dysfunction. Bleeding control was obtained by interventional hemostasis, emergency liver resection, and conservative medical management in 86 (62%), 24 (18%), and 21 (15%) patients, respectively. Best supportive care was chosen for 7 (5%) patients. The mortality rate following rupture was 24%. The bleeding recurrence rate was 22% with related mortality of 52%. In multivariate analysis, a bilirubin level >17 micromol/L (HR 3.768; p = 0.006), bleeding recurrence (HR 5.400; p < 0.0001), and ICU admission after initial management (HR 8.199; p < 0.0001) were associated with in-hospital mortality. CONCLUSION: This European, multicenter, large-cohort study confirmed that the prognosis of ruptured HCC is poor with an overall mortality rate of 24%, despite important advances in endovascular techniques. Overall, the rate of bleeding recurrence was more than 20%, with a related high risk of mortality.

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.

Predictive factors of severe complications for ampullary, bile duct and duodenal cancers following pancreaticoduodenectomy: Multivariate analysis of a 10-year multicentre retrospective series.

BACKGROUND: Postoperative outcomes following pancreaticoduodenectomy are well described for pancreatic cancers. Due to a lower incidence rate, complication rates and relative predictive factors are less detailed for ampullary, bile duct and duodenal cancers. METHODS: Medical charts of patients operated on between 2001 and 2011 for an ampullary, bile duct or duodenal cancer were reviewed. Data were retrospectively studied with respect to demographics, surgical management, postoperative complications and histological findings. Specific complication rates were reported, and predictive factors for severe morbidity and mortality were determined by multivariate analysis. RESULTS: 135 patients were identified: 55 ampullary, 55 bile duct and 25 duodenal cancers. Twelve patients (8.9%) deceased postoperatively, and 36 others (26.7%) presented severe complications. Sixty-seven percent of the pancreas was soft, and pancreatic hardness was found to be the main protective factor against severe morbidity (HR = 0.36, 95% CI = 0.14-0.94, P = 0.037). Age and postpancreatectomy haemorrhage were independent predictors for death (HR = 14.63, 95% CI = 1.57-135.77, P = 0.018, and HR = 14.71, 95% CI = 2.86-75.62, P = 0.001, respectively). Only the use of an external transanastomotic duct stent significantly reduced both the morbidity (HR = 0.37, 95% CI = 0.16-0.83, P = 0.016), and the mortality (HR = 0.12, 95% CI = 0.02-0.69, P = 0.017). CONCLUSIONS: Pancreaticoduodenectomy for ampullary, bile duct and duodenal cancers is a high-risk procedure. The systematic use of transanastomotic duct stents would significantly decrease the complication rate. Older patients should beneficiate from specific preoperative evaluation using an adapted index. Omental flap techniques to prevent a postpancreatectomy haemorrhage should be efficient. Effects of preoperative octreotid to harden the pancreas should be clarified.

Liver transplantation for adenomatosis: European experience.

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

BACKGROUND: Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation. METHODS: A retrospective cross-sectional study, from 27 European high-volume HPB units. RESULTS: 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients. DISCUSSION: Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.

Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria.

In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance.

Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study.

BACKGROUND: The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined. METHODS: Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients). RESULTS: The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01). CONCLUSIONS: An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.

Pancreatic adenocarcinoma with venous involvement: is up-front synchronous portal-superior mesenteric vein resection still justified? A survey of the Association Française de Chirurgie.

BACKGROUND: Venous resection (VR) during pancreatectomy has been reported to neither increase mortality nor morbidity and to provide similar survival outcomes in same stage tumors. However, controversy remains regarding the indications for up-front surgery according to the degree of venous involvement. METHODS: From 2004 to 2009, 1,399 patients included in a French multicenter survey underwent pancreaticoduodenectomy or total pancreatectomy for pancreatic adenocarcinoma, either without VR (997 standard resections [SR]) or with VR (402 patients; 29 %). Postoperative and long-term outcomes were compared in both groups. RESULTS: VR was associated with the following factors: larger tumors (p < 0.001), poorly differentiated tumors (p = 0.004), higher numbers of positive lymph nodes (p = 0.042), and positive resection margins (R1; p < 0.001). Overall, VR increased neither postoperative morbidity nor postoperative mortality (5 vs. 3 % in SR patients; p = 0.16). The median and 3-year survival rates in VR patients versus SR patients were 21 months and 31 % vs. 29 months and 44 %, respectively (p = 0.0002). In the entire cohort, multivariate analysis identified VR as a significant poor prognostic factor for long-term survival (hazard ratio [HR] 1.75, 95 % confidence interval [CI] 1.28-2.40; p = 0.0005). In the VR patients, lymph node ratio, whatever the cutoff (<0.3: p = 0.093; ≥ 0.3: p = 0.0098), R1 resection (p = 0.010), and segmental resection (p = 0.016) were independent risk factors; neoadjuvant treatment (HR 0.52, 95 % CI 0.29-0.94; p = 0.031) and adjuvant treatment (HR 0.55, 95 % CI 0.35-0.85; p = 0.006) were significantly associated with improved long-term survival. CONCLUSIONS: Long-term survival after pancreatectomy was significantly altered when up-front VR was performed. Neoadjuvant treatment may be a better strategy than up-front resection in patients with preoperative suspicion of venous involvement.

Liver transplantation for neuroendocrine tumour liver metastases.

OBJECTIVE: Search and review of available literature were made to define the indications for and timing of liver transplantation for neuroendocrine tumour (NET) liver metastases. METHODS: Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case-controlled studies were used for qualitative and quantitative synthesis of the systematic review. Reports of patients with liver transplantation alone for NET liver metastases of any origin or combined with resection of extrahepatic tumour deposits were recruited. RESULTS: The number of patients who have undergone liver transplantation for NET liver metastases is 706. The post-transplant 5-year survival rate from the time of diagnosis was approximately 70%. NET patients with metastases confined to the liver and not poorly differentiated are favourable candidates for liver transplantation. Selection of patients based on evolution of tumours over 6 months is not recommended. CONCLUSION: Non-resectable NET liver metastasis resistant to medical treatment and confined to the liver is an accepted indication for liver transplantation.

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group.

INTRODUCTION: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection. METHODS: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection. RESULTS: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis. CONCLUSION: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.

Relevance of postoperative peak transaminase after elective hepatectomy.

OBJECTIVES: Determine whether inflow occlusion is correlated with peak-postoperative serum-transaminases (PSTs) and whether PST is predictive of outcome after liver resections. BACKGROUND: PST is used as the surrogate of ischemia reperfusion and as the main endpoint in prospective trials of inflow occlusion. This assumption has, however, not been validated. Furthermore, the impact of PST on the postoperative course is unknown. METHODS: This prospectively designed registered study included consecutive adult patients undergoing elective hepatectomy in 9 HPB centers. Primary outcome was PST of aspartate-amino-transferase (AST) and alanine-amino-transferase (ALT). Secondary outcome was 90-day morbidity (Dindo-Clavien grades) and length of stay. Explanatory variables were preoperative (including age, sex, body mass index, comorbidities, cirrhosis, and chemotherapy), and intraoperative variables (including procedure performed, inflow occlusion and its duration, length of surgery, vasoactive drugs used, blood loss, and transfusion) were collected prospectively on a dedicated Web site. Multivariable regression models were used to identify independent predictors of PST and of morbidity. RESULTS: Between January 2013 and September 2013, 651 hepatectomies were included. Inflow occlusion was performed in 58% (intermittent in 32%, continuous in 24%) and was not performed in 42%. PST-AST (336 IU/L; interquartile range: 204-573) and PST-ALT (336 IU/L; interquartile range: 205-557) occurred on postoperative day 1. PST was not correlated with the duration of inflow occlusion (ρ-AST=0.20, P<0.01; ρ-ALT=0.18, P<0.01). PST was not independently associated with morbidity. Receiver operating characteristic curve identified a cutoff of 450 IU/L but this prediction's accuracy was low: area under the receiver operating characteristic curve for PST-AST: 0.61, confidence interval: 0.56-0.66, P<0.01, and area under the receiver operating characteristic curve for PST-ALT: 0.57, confidence interval: 0.52-0.62, P=0.01. CONCLUSIONS: PST is not correlated with ischemia time and should not be used as a surrogate of postoperative outcome.

"Surgeons' intuition" versus "prognostic models": predicting the risk of liver resections.

OBJECTIVES: Analyze surgeons' anticipation of the risk of hepatectomy. BACKGROUND: Risk prediction enables adequate counseling and improves safety. Models are available that predict postoperative morbidity and length of stay (LOS), but their performance is ill-defined. Surgeons' ability to predict these endpoints is unknown. METHODS: This prospectively designed, multicenter trial included all adult patients undergoing elective hepatectomy. Primary endpoints were 90-day morbidity and mortality and LOS. Explanatory variables included (i) "surgeons' intuition" (surgeons' anticipation) of the difficulty of the procedure, postoperative morbidity, and LOS and (ii) "prognostic models" (models based on objective clinic-biological variables) available at the time of anticipation. The performance of "surgeons' intuition" and "prognostic models" was assessed by area under the receiver operating characteristic curve and its accuracy by the diagnostic odd ratios. RESULTS: Between October 2012 and September 2013, 946 patients operated on in hepato-pancreatico-biliary units in 9 teaching hospitals by 26 surgeons were enrolled. Mortality, morbidity, and median LOS were 3.3%, 49.4%, and 8 days, respectively. Preoperative surgeons' intuition of difficulty correlated with actual difficulty (Kendall τ=0.97; P=0.0001) but not with morbidity (Kendall τ=0.01; P=0.0006) or LOS (Kendall τ=0.10; P=0.004). Morbidity was predicted accurately in 38.8% of patients and underestimated in 38.2%. Anticipation of LOS was accurate (±2 days) in 30.0% and underestimated in 47.1%. The accuracies and performance of preoperative and postoperative "surgeons' intuition" were not different and were not different between centers or surgeons' experience. The accuracy of "prognostic models" was significantly greater than that of anticipations and not improved by adding "anticipations" to the model. CONCLUSIONS: Surgeons should be aware of the limited accuracy of their intuition.

Pancreatic fistula after a pancreaticoduodenectomy for ductal adenocarcinoma and its association with morbidity: a multicentre study of the French Surgical Association.

BACKGROUNDS: A pancreatic fistula (PF) is the most relevant complication after a pancreaticoduodenectomy (PD). This retrospective multicentric study attempts to elucidate the risk factors and complications of a PF in a large cohort of patients undergoing a PD for ductal adenocarcinoma. METHODS: Using a survey tool, clinical data of 1325 patients undergoing a PD for ductal adenocarcinoma at 37 institutions, between January 2004 and December 2009, were collected. Peri-operative risk factors associated with PF and its association with morbidity and mortality were assessed. Morbidity and PF were graded according to the ISGPF (International Study group for pancreatic fistula) definition and the Dindo-Clavien classification. RESULTS: Overall PF, mortality, morbidity and relaparotomy rates were 14.3%, 3.8%, 54.4% and 11.7%, respectively. PF occurred more frequently after a pancreaticojejunostomy (PJ) compared with a pancreaticogastrostomy (PG) (16.8% vs. 10.4%; P = 0.0012). Independent risk factors for PF by multivariate analysis were absence of pre-operative diabetes (P = 0.0014), PJ reconstruction (P = 0.0035), soft pancreatic parenchyma (P < 0.0001) and low-volume centre (P = 0.0286). Clinically relevant PF (grade B and C) and severe complications (Dindo-Clavien grade IIIB, IV, V) were significantly more frequent after PJ than PG (71.6% vs. 28.3%; P = 0.030 and 24.8% vs. 19.1%; P = 0.015, respectively). Overall mortality and relaparotomy rates were similar after PG and PJ. CONCLUSIONS: A soft pancreatic parenchyma, the absence of pre-operative diabetes, PJ and low-volume centre are independent risk factors for PF after PD for ductal adenocarcinoma. A significantly higher incidence and clinical severity of PF are associated with PJ.

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.