Publications by authors named "Yves-Patrice Le Treut"

68 Publications

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.

World J Surg 2021 10 30;45(10):3146-3156. Epub 2021 Jun 30.

Department of Surgery, Hôpital Saint Antoine, Université Paris VI, Paris, France.

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.
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October 2021

Response to Comments on "Closed Cyst Resection for Liver Hydatid Disease: a New Standard".

J Gastrointest Surg 2020 10 17;24(10):2437-2438. Epub 2020 Aug 17.

Department of Surgery and Liver Transplantation, Hôpital de la Timone, Marseille, France.

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October 2020

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

Ann Surg Oncol 2020 Sep 13;27(9):3383-3392. Epub 2020 Apr 13.

Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen University Hospital, Rouen Cedex, France.

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.
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September 2020

Closed Cyst Resection for Liver Hydatid Disease: a New Standard.

J Gastrointest Surg 2021 02 10;25(2):436-446. Epub 2020 Feb 10.

Department of Surgery and Liver Transplantation, Hôpital de la Timone, Marseille, France.

Background: Although radical resections are recommended for the surgical management of liver hydatid disease (LHD), whether closed (CCR) or opened (OCR) cyst resections should be performed remains unclear. The aim of this study was to compare the postoperative and long-term outcomes of CCR and OCR for primary and recurrent LHD.

Materials And Methods: Medical charts of patients who underwent surgery at a single centre were retrospectively reviewed and compared with respect to major postoperative complications and recurrence rates.

Results: Seventy-nine CCRs and 37 OCRs were included. The major morbidity rates were 19% and 5% in the OCR and CCR groups, respectively (P = 0.036). In multivariate analysis, OCR (P = 0.030, OR = 5.37) and the operative time (P < 0.001, OR = 18.88) were the only independent predictors of major complications. The 5-year and 10-year recurrence rates were both 0% in the CCR group compared to 18% and 27%, respectively, in the OCR group (P < 0.001). The mean time to recurrence was 10.5 (± 8) years.

Discussion: Closed cyst resection for LHD is a safe and effective approach with a low risk of recurrence. Considering that recurrence could appear more than 10 years after surgery, follow-up of patients should be adapted.
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February 2021

The technique and outcomes of central hepatectomy by the Glissonian suprahilar approach.

Eur J Surg Oncol 2019 Dec 12;45(12):2369-2374. Epub 2019 Sep 12.

Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Marseille, France; Aix-Marseille University, 27 boulevard Jean Moulin, 13385, Marseille, France.

Introduction: 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.

Methods: 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.

Results: 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.
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December 2019

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

HPB (Oxford) 2019 03 16;21(3):352-360. Epub 2018 Aug 16.

Department of Digestive Surgery, Hôpital de la Timone, Marseille, France; Université Aix-Marseille, 27 Boulevard Jean Moulin, 13385, Marseille, France.

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.
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March 2019

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

Ann Surg 2018 11;268(5):792-798

Department of Digestive Surgery, Amiens, France.

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.
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November 2018

Severe postoperative complications decrease overall and disease free survival in pancreatic ductal adenocarcinoma after pancreaticoduodenectomy.

Eur J Surg Oncol 2018 07 10;44(7):1078-1082. Epub 2018 Apr 10.

Department of Digestive Surgery, Paoli-Calmette Institution, Marseille, France.

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.
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July 2018

How to Reliably Assess Nodal Status in Distal Pancreatectomy for Adenocarcinoma.

Pancreas 2018 03;47(3):308-313

Objectives: The optimal number of lymph nodes that need to be analyzed to reliably assess nodal status in distal pancreatectomy for adenocarcinoma is still unknown.

Methods: Two hundred seventy-eight patients who underwent distal pancreatectomy for adenocarcinoma were retrieved from a retrospective French nationwide database. The relations between the number of analyzed lymph nodes and the nodal status of the tumor were studied. The beta-binomial law was used to estimate the probability of being truly node negative depending on the number of analyzed lymph nodes. Cox proportional hazard model was used for the survival analysis.

Results: The median number of analyzed lymph nodes was 15. There was a positive correlation between the number of positive lymph nodes and the number of lymph nodes analyzed. The curve reached a plateau at approximately 25 lymph nodes. The beta binomial model demonstrated that an analysis of 21 negative lymph nodes shows a probability to be truly N0 at 95%. N+ status was associated with survival, but the number of lymph node analyzed was not.

Conclusion: At least 21 lymph nodes should be analyzed to ensure a reliable assessment of the nodal status, but this number may be hard to reach in distal pancreatectomy.
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March 2018

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

World J Surg 2018 08;42(8):2570-2578

Centre Hépato-biliaire, Hôpital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94800, Villejuif, France.

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.
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August 2018

Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: the Achilles' Heel?

World J Surg 2018 04;42(4):1138-1146

Department of Digestive Disease, Institut Mutualiste Montsouris, Université Paris-Descartes, 42 Boulevard Jourdan, 75014, Paris, France.

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.
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April 2018

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

Ann Surg 2017 11;266(5):787-796

*Department of Surgery, Paoli-Calmettes Institute, Marseille, France †Department of Surgery, La Pitié-Salpêtrière - Université Pierre and Marie Curie, Paris VI, France ‡Department of Surgery, Hautepierre Hospital, University of Strasbourg, Strasbourg, France §Department of Surgery, Hotel Dieu Hospital, University of Nantes, Nantes, France ¶Department of Surgery, Hospital de la Conception, University of Aix-Marseille, Marseille, France ||Department of Surgery, Saint Antoine Hospital, University of Paris VI, Paris, France **Department of Surgery, Purpan Hospital, University of Toulouse Hospital Centre, Toulouse, France ††Department of Surgery, Beaujon Hospital, University of Paris VII, Clichy, France ‡‡Groupement Hospitalier Edouard Herriot, Université Claude Bernard Lyon 1, France §§Department of Histopathology, Paoli-Calmettes Institute, Marseille, France ¶¶Department of Biostatistics, Paoli-Calmettes Institute, Aix Marseille Univeristy, INSERM, IRD, SESSTIM, Marseille, France.

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: NCT00918853.
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November 2017

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

World J Surg 2018 01;42(1):225-232

Department of General Surgery and Liver Transplantation, APHM, Hôpital de la Conception, Marseille University Hospital, Marseille, France.

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.
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January 2018

Venous Resection in Pancreatic Ductal Adenocarcinoma: Impact of Surgical Experience on Early Postoperative Courses.

Anticancer Res 2017 08;37(8):4205-4213

Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France.

Background/aim: The aim of this study was to determine the effects of surgical experience on early postoperative courses after pancreaticoduodenectomy (PD) with venous resection.

Patients And Methods: From 2005 to 2014, 134 patients were analyzed, 62 and 72 patients were resected in periods 1 (2005-2009) and 2 (2010-2014) respectively; 115 and 19 patients underwent PD with venous resection in high- and low-volume center groups respectively.

Results: Of the entire cohort, mortality rate was 4%. There were no significant differences between the two periods. In the low-volume center group, the mortality rate was increased (21% vs. 2%, p<0.01) and the mean length of hospital stay was longer (25 (±27) days vs. 17 (±8) days, p=0.04). The high-volume center group was the only independent protective factor regarding death (OR=0.04, 95%CI (0.01-0.38), p<0.01) and length of hospital stay (OR<0.01, 95%CI (0.00-0.43), p=0.03).

Conclusion: Patients who present isolated venous invasion must be referred to high-volume centers for surgery.
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August 2017

Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort.

World J Gastroenterol 2017 Apr;23(14):2545-2555

Xavier Adhoute, Hervé Perrier, Paul Castellani, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph Marseille, 13008 Marseille, France.

Aim: To compare the performances of the Barcelona clinic liver cancer (BCLC) nomogram and others systems (BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma (HCC) French cohort.

Methods: Data were collected retrospectively from 01/2007 to 12/2013 in five French centers. Newly diagnosed HCC patients were analyzed. The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion (AIC) and C-index were compared among scoring systems.

Results: The cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis (81%), child-Pugh A (73%), alcohol-related (41%), HCV-related (27%). HCC were multinodular (59%) and vascular invasion was present in 41% of cases. At time of HCC diagnosis BCLC stages were A (17%), B (16%), C (60%) and D (7%). First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population. Median OS was 10.8 mo [4.9-28.0]. Each system distinguished different survival prognosis groups ( < 0.0001). The nomogram had the highest discriminatory ability, the highest C-index value. NIACE score had the lowest AIC value. The nomogram distinguished sixteen different prognosis groups. By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful.

Conclusion: In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.
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April 2017

Disease-free survival following resection in non-ductal periampullary cancers: A retrospective multicenter analysis.

Int J Surg 2017 Jun 28;42:103-109. Epub 2017 Apr 28.

Aix-Marseille University, APHM La Conception, Department of Surgery and Liver Transplantation, Marseille, France.

Background: Predictors of recurrence following pancreaticoduodenectomy are well described for ductal periampullary cancers but lack reliability for non-ductal tumors. The purpose of this study is to analyze the disease-free survival (DFS) and to define the predictors of recurrence following resection for ampullary (AC), bile duct (BDC) and duodenal cancers (DC).

Materials And Methods: Clinico-pathological data of patients operated on between 2001 and 2011 were retrospectively reviewed. The effect of lymphatic invasion was specified using the lymph node ratio (LNR) and the number of positive nodes (NPN), with thresholds calculated with the likelihood ratio. Kaplan-Meier disease-free survival (DFS) curves were compared for all covariates by a log-rank test. Multivariate logistic regression analyses were performed to identify predictors of recurrence.

Results: 135 patients were identified. Mean follow-up was 49 ± 35 months. Median DFS was not reached for AC and was 36 and 18 months for DC and BDC, respectively. Five-year DFS was 52%, 43% and 32% for AC, DC and BDC, respectively. Predictors of recurrence were T4 tumors, neural invasion and preoperative biliary drainage for DC, ≥3 positive nodes and ≥4% loss of BMI for AC, and T3-T4 tumors for BDC.

Conclusion: Loss of BMI ≥4% is a strong predictor of recurrence in AC, and the recurrence risk increases with the total number of lymph nodes invaded (0; 1-3; ≥4). Only T stage influences recurrence for BDC. Considering DC, the adverse effect of preoperative biliary drainage should be validated in randomized series.
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June 2017

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

HPB (Oxford) 2016 09 22;18(9):748-55. Epub 2016 Jul 22.

Department of Surgery, Hôpital de la Timone, Marseille, France.

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.
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September 2016

Emerging role of Raoultella ornithinolytica in human infections: a series of cases and review of the literature.

Int J Infect Dis 2016 Apr 24;45:65-71. Epub 2016 Feb 24.

Centre de Référence des Infections Ostéo-Articulaires (CRIOAC) Interrégional Sud Méditerranée, Service des Maladies Infectieuses, Hôpital de la Conception, 147 boulevard Baille, 13005 Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France.

Background: Raoultella ornithinolytica is known to inhabit aquatic environments. The clinical features and outcomes of human infections caused by R. ornithinolytica have been reported for only a limited number of cases.

Methods: A retrospective study of cases of infection caused by R. ornithinolytica managed at four university hospital centres during the period before and after the introduction of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed. The aim was to describe the clinical and microbiological characteristics, treatments, and outcomes.

Results: Among 187 R. ornithinolytica isolates identified for which clinical information was available, 71 were considered colonizers and 116 were pathogenic. A total of 112 cases of R. ornithinolytica infection were identified. Urinary tract infections, gastrointestinal infections, wound and skin infections, and bacteraemia were observed in 36%, 14%, 13%, and 5% of cases, respectively. Associated infections that have been poorly reported, such as respiratory infections, i.e. pneumonia and pleural effusion, were observed in 24% of cases. Additional diseases reported here for the first time included osteomyelitis, meningitis, cerebral abscess, mediastinitis, pericarditis, conjunctivitis, and otitis. The proportion of R. ornithinolytica isolates resistant to antibiotics was found to be relatively high: 4% of isolates were resistant to ceftriaxone, 6% to quinolones, and 13% to co-trimoxazole. The mortality rate related to infection was 5%.

Conclusions: R. ornithinolytica is an underreported, emerging hospital-acquired infection and is particularly associated with invasive procedures. R. ornithinolytica should never be considered simply a saprophytic bacterium that occasionally contaminates bronchial lavage or other deep respiratory samples or surgical sites. Physicians should be aware of the high rates of antimicrobial resistance of R. ornithinolytica isolates so that immediate broad-spectrum antibiotic treatment can be established before accurate microbiological results are obtained.
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April 2016

Liver transplantation for adenomatosis: European experience.

Liver Transpl 2016 Apr;22(4):516-26

Service de Pathologie, INSERM U1053, Université Bordeaux Segalen, Hôpital Pellegrin, Bordeaux, France.

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.
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April 2016

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

Surgeon 2017 Oct 17;15(5):251-258. Epub 2015 Dec 17.

Aix-Marseille University, APHM La Conception, Department of Surgery and Liver Transplantation, 147 Boulevard Baille, Marseille, France.

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.
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October 2017

Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma.

J Am Coll Surg 2015 Aug 14;221(2):380-9. Epub 2015 Apr 14.

Department of Surgical Oncology, Institut Paoli Calmettes, Marseille, France.

Background: The influence of jaundice on outcomes after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to determine, in a large multicentric series, the influence of severe jaundice (serum bilirubin level ≥250 μmol/L and 300 μmol/L) on early severe morbidity and survival after PD.

Study Design: From 2004 to 2009, twelve hundred patients (median age 66 years, 57% male) with resectable PDAC underwent PD. Patients who received preoperative biliary drainage for neoadjuvant treatment or cholangitis were excluded. Pre- and intraoperative data were collected by a standardized form. Serum bilirubin level and creatinine clearance were analyzed as categorical variables. Predictive factors of severe complications and poor survival (Kaplan-Meier method) were identified by univariate and multivariate analysis.

Results: Median follow-up was 21 months (95% CI, 19-23). Operative mortality was 3.9% (n = 47), with no predictive factors in multivariate analysis. Severe complications (Dindo-Clavien grade III to IV) occurred in 22% (n = 268), with male sex (p = 0.025), America Society of Anesthesiologists score 3 to 4 (p = 0.022), serum bilirubin level ≥300 μmol/L (p = 0.034), and creatinine clearance <60 mL/min/1.73 m(2) (p = 0.013) identified as predictive factors in multivariate analysis. Overall 3-year survival rate was 41% (95% CI, 37-45%). In multivariate analysis, serum bilirubin level ≥300 μmol/L (p = 0.048), low-volume center (p < 0.001), venous resection (p = 0.014), N1 status (p < 0.01), R1 status (p < 0.001), and absence of adjuvant treatment (p < 0.001) negatively impacted survival. There was a negative relationship between survival at 12 months or later and higher rates of bilirubin. Presence of a biliary stent did not influence early or long-term results.

Conclusions: In this multicentric study, serum bilirubin level ≥300 μmol/L increased severe morbidity and decreased long-term survival after PD for PDAC. These findings suggest that biliary stenting is appropriately indicated before PD in patients with PDAC and severe jaundice.
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August 2015

Predictors of Survival in Ampullary, Bile Duct and Duodenal Cancers Following Pancreaticoduodenectomy: a 10-Year Multicentre Analysis.

J Gastrointest Surg 2015 Jul 7;19(7):1247-55. Epub 2015 May 7.

APHM La Conception, Department of Surgery and Liver Transplantation, Aix-Marseille University, 147 Boulevard Baille, Marseille, France,

Introduction: Predictors of survival following pancreaticoduodenectomy (PD) are well described for pancreatic cancers but are less detailed in ampullary (AC), bile duct (BDC) and duodenal cancers (DC). We therefore sought to evaluate the long-term results of PD for AC, BDC and DC, and to determine for each tumour the predictive factors of survival.

Methods: Medical charts of patients operated on between 2001 and 2011 were retrospectively reviewed. Univariate and multivariate analyses were performed to determine predictors of survival.

Results: One hundred thirty-five patients were identified. Mean follow-up was 47 ± 33 months. Median survival was not reached for DC and was 66 and 24 months for AC and BDC, respectively. Two-year and five-year survival rates were 80 and 51% for DC and 69 and 51% for AC, respectively. BDC had a significantly poorer prognosis, with two-year and five-year survival rates of 51 and 34%, respectively. Predictors of survival were weight loss, N stage and International Union Against Cancer (UICC) stage for AC, T stage and resection margin status for BDC and N stage for DC.

Conclusion: AC, BDC and DC display distinctive predictors of survival related to the biological aggressiveness. Preoperative malnutrition worsens the prognosis. The effect of adapted nutritional management on the survival improvement has to be studied.
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July 2015

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

Liver Transpl 2015 Apr;21(4):512-23

Liver Intensive Care Unit, Centre Hepato-Biliaire, Hôpital Paul Brousse, AP-HP, Villejuif, France; Unite 785, Inserm, Villejuif, France; Unités Mixtes de Recherche en Santé 785, Université Paris-Sud, Villejuif, France.

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.
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April 2015

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

Ann Surg Oncol 2015 10;22(6):1874-83. Epub 2015 Feb 10.

Department of Surgical Oncology, Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France,

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.
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February 2016

Sonic hedgehog and Gli1 expression predict outcome in resected pancreatic adenocarcinoma.

Clin Cancer Res 2015 Mar 31;21(5):1215-24. Epub 2014 Dec 31.

Saint Antoine Department of Gastroenterology and Gastrointestinal Cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

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.
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March 2015

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

Ann Surg 2014 Nov;260(5):923-8; discussion 928-30

*Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique Hôpitaux de Paris, Université Paris 7, Clichy, France †Department of Hepatobiliopancreatic Surgery and Liver Transplantation Hôpital Paul Brousse, Villejuif, France ‡Department of Methodology and Statistics, Hôpital Nord, Amiens, France §Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Claude Huriez, Lille, France ¶Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital de la Conception, Marseilles, France ‖Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Saint Antoine, Paris, France **Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Saint André, Bordeaux, France ††Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Croix Rousse, Lyon, France ‡‡Department of Hepatobiliopancreatic Surgery, Hôpital Edouard Herriot, Lyon France §§Department of Methodology and Statistics, INSERM U669, Paris, France.

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.
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November 2014

Transjugular intrahepatic porto-systemic shunt is a risk factor for liver dysplasia but not hepatocellular carcinoma: a retrospective study of explanted livers.

Dig Liver Dis 2015 Jan 11;47(1):57-61. Epub 2014 Oct 11.

Department of Hepato-Gastroenterology, Hôpital de la Conception, Marseille, France; UMR 911, Université de la Méditerranée, Marseille, France.

Background: Conflicting data exist regarding the risk for hepatocellular carcinoma after transjugular intrahepatic porto-systemic shunt (TIPS) insertion in cirrhotic patients.

Methods: We retrospectively analysed histopathological data from 214 patients who were transplanted in our Institution including 68 patients who underwent TIPS placement before transplantation. Pathological lesions from explanted livers, including incidental hepatocellular carcinoma, small cell dysplasia and large cell dysplasia were recorded.

Results: Pathological lesions were found in 36.4% of explanted livers. TIPS insertion was an independent risk factor for pathological lesion (HR = 2.11, p < 0.05), concurrently with age (HR = 1.10 per year, p < 0.001) and viral aetiology of cirrhosis (HR = 3.05, p < 0.001). When considering the different type of lesions, TIPS insertion was not associated with an increased risk for hepatocellular carcinoma but was an independent risk factor for liver dysplasia (HR = 2.15, p = 0.042).

Conclusion: Although a direct relationship between TIPS insertion and hepatocellular carcinoma risk was not demonstrated in this study, the increased frequency of liver dysplasia observed in TIPS-bearing explanted livers deserves further prospective investigations with adequate follow-up.
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January 2015

Further characterization of HDAC and SIRT gene expression patterns in pancreatic cancer and their relation to disease outcome.

PLoS One 2014 2;9(9):e108520. Epub 2014 Oct 2.

Aix-Marseille University, CRO2, UMR_S 911, Marseille, France; INSERM UMR 911, Marseille, France.

Ductal adenocarcinoma of the pancreas is ranking 4 for patient' death from malignant disease in Western countries, with no satisfactory treatment. We re-examined more precisely the histone deacetylases (HDAC) and Sirtuin (SIRT) gene expression patterns in pancreatic cancer with more pancreatic tumors and normal tissues. We also examined the possible relationship between HDAC gene expression levels and long term disease outcome. Moreover, we have evaluated by using an in vitro model system of human pancreatic tumor cell line whether HDAC7 knockdown may affect the cell behavior. We analyzed 29 pancreatic adenocarcinoma (PA), 9 chronic pancreatitis (CP), 8 benign pancreatic (BP) and 11 normal pancreatic tissues. Concerning pancreatic adenocarcinoma, we were able to collect biopsies at the tumor periphery. To assess the possible involvement of HDAC7 in cell proliferation capacity, we have generated recombinant human Panc-1 tumor which underexpressed or overexpressed HDAC7. The expression of HDAC1,2,3,4,7 and Nur77 increased in PA samples at levels significantly higher than those observed in the CP group (p = 0.0160; 0.0114; 0.0227; 0.0440; 0.0136; 0.0004, respectively). The expression of HDAC7, was significantly greater in the PA compared with BP tissue samples (p = 0.05). Mean mRNA transcription levels of PA for HDAC7 and HDAC2 were higher when compared to their counterpart biopsies taken at the tumor periphery (p = 0.0346, 0.0053, respectively). Moreover, the data obtained using confocal microscopy and a quantitative method of immunofluorescence staining strongly support the HDAC7 overexpression in PA surgical specimens. The number of deaths and recurrences at the end of follow up were significantly greater in patients with overexpression of HDAC7. Interestingly, the rate of growth was significantly reduced in the case of cell carrying shRNA construct targeting HDAC7 encoding gene when compared to the parental Panc-1 tumor cells (p = 0.0015) at 48 h and 96 h (p = 0.0021). This study strongly support the notion that HDAC7play a role in pancreatic adenocarcinoma progression.
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June 2015

Relevance of postoperative peak transaminase after elective hepatectomy.

Ann Surg 2014 Nov;260(5):815-20; discussion 820-1

*Service de Chirurgie Digestive et Transplantations, Hôpital Huriez, CHU, Univ Nord-de-France, Lille, France †Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France ‡Hôpital de la Conception, Marseille, France §Hôpital Saint-Antoine, Paris, France ¶Hôpital Saint-André, Bordeaux, France ‖Hôpital de la Croix-Rousse, Lyon, France **Hôpital Nord, CHU Amiens, France ††Hôpital Edouard Herriot, Lyon, France ‡‡Department of Methodology and Statistics, Hôpital Nord, Amiens, France §§Hôpital Beaujon, Assistance-Publique Hôpitaux de Paris, Université Paris 7, Clichy, France.

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.
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November 2014