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

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

Liver stiffness-based model predicts hepatic venous pressure gradient in patients with liver disease.

BACKGROUND: The aim was to develop a model to predict clinically significant portal hypertension, hepatic venous pressure gradient (HVPG) ≥10 mmHg using pre-operative noninvasive makers. METHODS: Patients who have been programmed for liver resection/transplantation were enrolled prospectively. Preoperative liver stiffness measurement (LSM), liver function test (LFT), and intraoperative HVPG were assessed. A probability score model to predict HVPG≥10 mmHg called HVPG10 score was developed and validated. RESULTS: A total of 161 patients [66% men, median age of 63 years] were recruited for the study. Median LSM, and HVPG were 9.5 kPa, and 5 mmHg respectively. HVPG10 score was developed using independent predictors of HVPG≥10 mmHg in the training set were LSM, total bilirubin, alkaline phosphatase, and international normalized ratio. Area under receiver operating curve of HVPG10 score in the training and validation sets were 0.91 and 0.93 respectively with a cutoff of 15. In the overall cohort, HVPG10 score≥15 had 83% accuracy, 90% sensitivity, 81% specificity and 96% negative predictive value in predicting HVPG≥10 mmHg. CONCLUSION: HVPG10 score is an easy-to-use noninvasive continuous scale tool to rule out clinically significant portal hypertension in >95% patients with chronic liver disease.

Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort.

BACKGROUND: FOLFIRINOX has shown promising results in locally advanced (LAPA) or borderline resectable (BRPA) pancreatic adenocarcinoma. We report here a cohort of patients treated with this regimen from the AGEO group. METHODS: This is a retrospective multicentre study. We included all consecutive patients with non-pre-treated LAPA or BRPA treated with FOLFIRINOX. RESULTS: We included 330 patients (57.9% male, 65.4% <65 years, 96.4% PS <2). Disease was classified as BRPA in 31.1% or LAPA in 68.9%. Objective response rate with FOLFIRINOX was 29.5% and stable disease 51%. Subsequent CRT was performed in 46.4% of patients and 23.9% had curative intent surgery. Resection rates were 42.1% for BRPA and 15.5% for LAPA. Main G3/4 toxicities were fatigue (15%), neutropenia (12%) and neuropathy (G2/3 35%). After a median follow-up of 26.7 months, median OS (mOS) and PFS were 21.4 and 12.4 months, respectively. For patients treated by FOLFIRINOX alone, or FOLFIRINOX followed by CRT, or FOLFIRINOX + /- CRT + surgery, mOS was 16.8 months, 21.8 months and not reached, respectively (p < 0.0001). CONCLUSIONS: FOLFIRINOX for LAPA and BRPA seems to be effective with a manageable toxicity profile. These promising results in "real-life" patients now have to be confirmed in a Phase 3 randomised trial.

Correction to: Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).

Following publication of the original article [1], the authors reported an error in the "Samples size calculation and statistical considerations" section.

Impact of Surgical Treatment for Recurrence After 2-Stage Hepatectomy for Colorectal Liver Metastases, on Patient Outcome.

OBJECTIVE: To evaluate the impact of repeat surgery for recurrence on the long-term survival after 2-stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM). BACKGROUND: Although TSH is now deemed effective for selected patients with extensive bilobar CRLM, disease recurrence after TSH is very frequent because of the extensive tumor load. METHODS: Among a total cohort of 1235 patients who underwent hepatectomy for CRLM between 1992 and 2012, 139 with extensive bilobar CRLM were scheduled for TSH. Of these, 93 patients had completion of TSH and were enrolled in this study. RESULTS: The 5-year overall survival (OS) rate after TSH was 41.3%. Twenty-two patients (23.7%) had a concomitant extrahepatic disease (EHD), and curative resection of concomitant EHD was achieved in 13 patients. Among the 81 patients who achieved complete tumor removal for primary, CRLM, and concomitant EHD, 62 (76.5%) had recurrence. Repeat surgery was performed in 38 patients; 35 for recurrence after curative surgery and 3 for liver recurrence with unresected concomitant EHD or primary tumor. Of these 38 patients, 31 were salvaged. The patients who underwent repeat surgery had a significantly longer OS than those who did not (45.8% vs 26.3%; P = 0.0041). A multivariate analysis revealed that repeat surgery was an independent prognostic factor of the OS after TSH (hazard ratio 0.31, P = 0.0012). CONCLUSIONS: Repeat surgery for recurrence after TSH may be crucial for the long-term survival in patients with extensive bilobar CRLM. Intensive oncosurgical surveillance is essential to avoid missing the chance for repeat surgery after TSH.

Left-liver Adult-to-Adult Living Donor Liver Transplantation: Can It Be Improved? A Retrospective Multicenter European Study.

OBJECTIVE: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT). SUMMARY BACKGROUND DATA: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe. METHODS: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT. RESULTS: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ±â€Š3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) <0.6% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual GBWR >0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044). CONCLUSIONS: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

Long-term survival and cure model following liver resection for breast cancer metastases.

INTRODUCTION: Long-term survival is still rarely achieved with current systemic treatment in patients with breast cancer liver metastases (BCLM). Extended survival after hepatectomy was examined in a select group of BCLM patients. PATIENTS AND METHODS: Hepatectomy for BCLM was performed in 139 consecutive patients between 1985 and 2012. Patients who survived < 5 years were compared to those who survived ≥ 5 years from first diagnosis of hepatic metastases. Predictive factors for survival were analyzed. Statistically cured, defined as those patients who their hazard rate returned to that of the general population, was analyzed. RESULTS: Of the 139, 43 patients survived ≥ 5 years. Significant differences between patient groups (< 5 vs. ≥ 5 years) were mean time interval between primary tumor and hepatic metastases diagnosis (50 vs. 43 months), mean number of resected tumors (3 vs. 2), positive estrogen receptors (54% vs. 79%), microscopic lymphatic invasion (65% vs. 34%), vascular invasion (63% vs. 37%), hormonal therapy after resection (34% vs. 74%), number of recurrence (40% vs. 65%) and repeat hepatectomy (1% vs. 42%), respectively. The probability of statistical cure was 14% (95% CI 1.4-26.7%) in these patients. CONCLUSIONS: Hepatectomy combined with systemic treatment can provide a chance of long-term survival and even cure in selected patients with BCLM. Microscopic vascular/lymphatic invasion appears to be a novel predictor for long-term survival after hepatectomy for BCLM and should be part of the review when discussing multidisciplinary treatment strategies.

Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).

BACKGROUND: At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC. METHODS: PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence. DISCUSSION: The "ideal" cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02959879 . Trial registration date: November 9, 2016.

Impact of laparoscopy in patients aged over 70 years requiring distal pancreatectomy: a French multicentric comparative study.

BACKGROUND: Few data are available concerning short-term results of minimally invasive surgery in patients > 70 years old requiring distal pancreatectomy. The aim of this study was to compare short-term results after laparoscopic (LDP) versus open distal pancreatectomy (ODP) in this subgroup of patients. METHODS: All patients > 70 years who underwent distal pancreatectomy in 3 expert centers between 1995 and 2017 were included and data were retrospectively analyzed. Demographic, intraoperative data and postoperative outcomes in LDP and ODP groups were compared. RESULTS: A distal pancreatectomy was performed in 109 elderly patients; LDP group included 53 patients while ODP group included 56. There were 55 (50.5%) males and 54 (49.5%) women with a median age of 75 years (range 70-87). Fifty (45.9%) patients were 70-74, 40 (36.7%) patients were 75-79, and 19 (17.4%) patients were over 80 years. Nine (8.2%) patients required conversion to open surgery. The median operative time was not different between LDP and ODP (204 vs. 220 min, p = 0.62). The intraoperative blood loss was significantly lower in the LDP group (238 ± 312 vs. 425 ± 582 ml, p = 0.009) with no difference regarding the intraoperative transfusion rate. 90-day mortality (0 vs. 5%, p = 0.42), overall complication (45.4 vs. 51.8%, p = 0.53), major complication (18.2 vs. 12.5%, p = 0.43), grade B/C pancreatic fistula (6.8 vs. 7.1%, p = 0.71), were comparable in the 2 groups. Only postoperative confusion rate was significantly lower in the LDP group (4.5 vs. 25%, p = 0.01). Median length of stay was significantly lower in the LDP group (14 ± 10 vs. 16 ± 11 days, p = 0.04). R0 resection was performed in 94% of LDP patients and 89% in ODP patients without significant difference (p = 0.73). CONCLUSIONS: The laparoscopic approach seems to reduce blood loss, postoperative confusion, and length of stay in elderly patients requiring distal pancreatectomy.

Margin Status is Still an Important Prognostic Factor in Hepatectomies for Colorectal Liver Metastases: A Propensity Score Matching Analysis.

OBJECTIVE: The width of resection margin is still a matter of debate in case of colorectal liver metastasis resection. The aim of this study was to determine the risk factors for R1 resection. Once risk factors had been identified, patients were matched according to Fong's prognostic criteria, in order to evaluate whether R1 resection still remained a negative prognostic factor impacting overall and disease-free survival. METHODS: A total of 1784 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were compared before and after a 1:1 propensity score analysis in order to compare R0 versus R1 resections according to Fong criteria. RESULTS: Primary tumor nodes found positive after colorectal resection (RR = 1.20, p = 0.02), operative time (> 240 min) (RR = 1.26, p = 0.05), synchronous liver metastasis (RR = 1.27, p = 0.02), pedicle clamping (> 40 min) (RR = 1.52, p = 0.001), lesion size larger than 50 mm (RR = 1.54, p = 0.001), rehepatectomy (RR = 1.68, p = 0.001), more than 3 lesions (RR = 1.69, p = 0.0001), and bilateral lesions (RR = 1.74, p = 0.0001) were identified as risk factors in multivariate analysis. After a 1:1 PSM according to Fong criteria, R1 resection still remained a negative prognostic factor impacting overall and disease-free survival, with 1-, 3-, 5-year OS at 94, 81, and 70% in R0 and 92, 75, and 58% in R1, respectively, (p = 0.008), and disease-free survival (DFS) with 1-, 3-, 5-year survival at 64, 41, and 28% in R0 versus 51, 28, and 18% in R1 (p = 0.0002), respectively. CONCLUSION: Even after using PSM as an oncological prognostic criterion, R1 resection still impacts overall and disease-free survival negatively.

Prediction of the Total Liver Weight using anthropological clinical parameters: does complexity result in better accuracy?

BACKGROUND: The performance of linear models predicting Total Liver Weight (TLW) remains moderate. The use of more complex models such as Artificial Neural Network (ANN) and Generalized Additive Model (GAM) or including the variable "steatosis" may improve TLW prediction. This study aimed to assess the value of ANN and GAM and the influence of steatosis for predicting TLW. METHODS: Basic clinical and morphological variables of 1560 cadaveric donors for liver transplantation were randomly split into a training (2/3) and validation set (1/3). Linear models, ANN and GAM were built by using the training cohort and evaluated with the validation cohort. RESULTS: The TLW is subject to major variations among donors with similar morphological parameters. The performance of ANN and GAM were moderate and similar to that of linear models (concordance coefficient from 0.36 to 0.44). In 28-30% of cases, TLW cannot be predicted with a margin of error ≤20%. The addition of the variable "steatosis" to each model did not improve their performance. CONCLUSION: TLW prediction based on anthropological parameters carry a significant risk of error despite the use of more complex models. Others determinants of TLW need to be identified and imaging-based volumetric measurements should be preferred when feasible.

Salvage Versus Primary Liver Transplantation for Early Hepatocellular Carcinoma: Do Both Strategies Yield Similar Outcomes?

BACKGROUND DATA: In compensated cirrhotics with early hepatocellular carcinoma (HCC-cirr), upfront liver resection (LR) and salvage liver transplantation (SLT) in case of recurrence may have outcomes comparable to primary LT (PLT). OBJECTIVE: An intention-to-treat (ITT) analysis comparing PLT and SLT strategies. METHODS: Of 130 HCC-cirr patients who underwent upfront LR (group LR), 90 (69%) recurred, 31 could undergo SLT (group SLT). During the same period, 366 patients were listed for LT (group LLT); 26 dropped-out (7.1%), 340 finally underwent PLT (group PLT). We compared survival between groups LR and LLT, LR and PLT, and PLT and SLT. RESULTS: Feasibility of SLT strategy was 34% (31/90). In an ITT analysis, group LLT had better 5-yr/10-yr overall survival (OS) compared with group LR (68%/58% vs. 58%/35%; P = 0.008). Similarly, 5-yr/10-yr OS and disease-free survival (DFS) were better in group PLT versus group LR (OS 73%/63% vs. 58%/35%, P = 0.0007; DFS 69%/61% vs. 27%/21%, P < 0.0001). Upfront resection and microvascular tumor invasion were poor prognostic factors for both OS and DFS, presence of satellite tumor nodules additionally predicted worse DFS. Group SLT had similar postoperative and long-term outcomes compared with group PLT (starting from time of LT) (OS 54%/54% vs. 73%/63%, P = 0.35; DFS 48%/48% vs. 69%/61%, P = 0.18, respectively). CONCLUSIONS: In initially transplantable HCC-cirr patients, ITT survival was better in group PLT compared with group LR. SLT was feasible in only a third of patients who recurred after LR. Post SLT, short and long-term outcomes were comparable with PLT. Better patient selection for the "resection first" approach and early detection of recurrence may improve outcomes of the SLT strategy.

Intention-to-treat analysis of percutaneous endovascular treatment of hepatic artery stenosis after orthotopic liver transplantation.

Hepatic artery stenosis (HAS) is a rare complication of orthotopic liver transplantation (LT). HAS could evolve into complete thrombosis and lead to graft loss, incurring significant morbidity and mortality. Even though endovascular management by percutaneous transluminal angioplasty ± stenting (PTA) is the primary treatment of HAS, its longterm impact on hepatic artery (HA) patency and graft survival remains unclear. This study aimed to evaluate longterm outcomes of PTA and to define the risk factors of treatment failure. From 2006 to 2012, 30 patients with critical HAS (>50% stenosis of HA) and treated by PTA were identified from 870 adult patients undergoing LT. Seventeen patients were diagnosed by post-LT screening, and 13 patients were symptomatic due to HAS. PTA was completed successfully in 27 (90%) patients with angioplasty plus stenting in 23 and angioplasty alone in 4. The immediate technical success rate was 90%. A major complication that was observed was arterial dissection (1 patient) which eventually necessitated retransplantation. Restenosis was observed in 10 (33%) patients. One-year, 3-year, and 5-year HA patency rates were 68%, 62.8%, and 62.8%, respectively. Overall patient survival was 93.3% at 3 years and 85.3% at 5 years. The 3-year and 5-year liver graft survival rates were 84.7% and 64.5%, respectively. No significant difference was observed in patient and graft survivals between asymptomatic and symptomatic patients after PTA. Similarly, no difference was observed between angioplasty alone and angioplasty plus stenting. In conclusion, endovascular therapy ensures a good 5-year graft survival (64.5%) and patient survival (85.3%) in patients with critical HAS by maintaining HA patency with a low risk of serious morbidity (3.3%). Liver Transplantation 22 923-933 2016 AASLD.

Impact of clinically evident portal hypertension on the course of hepatocellular carcinoma in patients listed for liver transplantation.

UNLABELLED: Liver transplantation (LT) is the best curative treatment for early hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the current shortage of organs causes prolonged waiting times and poorer intention-to-treat (ITT) survival (i.e., after listing) owing to tumor progression and dropout. Portal hypertension (PH) is a recognized risk factor of HCC development in patients with cirrhosis and its recurrence after resection. The aim of this study was to evaluate the potential impact of PHT on the results of LT on an ITT basis. Patients with cirrhosis listed for LT for HCC were included and their outcomes after listing were compared according to the presence or absence of PH defined as presence of esophageal varices or ascites or low platelet count and splenomegaly. Among 243 consecutively listed patients, 70% were affected by PH, which was associated with a significantly higher risk of tumor progression (38% vs. 22%; P = 0.017) and a higher risk of dropout (22% vs. 8%; P = 0.01). Transarterial chemoembolization (TACE) was similarly applied to the two groups (60% vs. 67%; P = 0.325). An absence of TACE was the only other independent risk factor of dropout owing to tumor progression. Under an ITT analysis, PH reduced overall survival (OS), but there was no difference in OS and time to recurrence post-LT. The only pathological feature that could potentially explain this observation was the lower complete response to TACE in the PHT group (12% vs. 36%; P = 0.001). CONCLUSION: PH should be regarded as a major risk factor of dropout owing to tumor progression and should be taken into consideration when managing patients with HCC who are waiting for LT.

Outcomes of Rehepatectomy for Colorectal Liver Metastases: A Contemporary Multi-Institutional Analysis from the French Surgical Association Database.

BACKGROUND: Recurrence remains frequent after curative-intent hepatectomy for colorectal liver metastases (CRLM). We sought to define short- and long-term outcomes, and identify prehepatectomy factors associated with survival, following rehepatectomy (RH) for recurrence. METHODS: We conducted a multi-institutional cohort study of hepatectomy for CRLM over 2006-2013. Second-stage resections were excluded. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) assessed using Kaplan-Meier methods. Secondary outcomes included 30-day overall morbidity and mortality, and survival from recurrence. Outcomes of RH and initial hepatectomy (IH) were compared. RESULTS: Of 2771 hepatectomies included in the study, 447 were RH. Median operative time, 30-day morbidity, mortality, and median length of stay did not differ for RH and IH. Five-year OS did not statistically differ, i.e. 56.5 % from RH and 67.6 % from IH [adjusted hazard ratio (HR) 0.9, 95 % confidence interval (CI) 0.5-1.7], and 5-year RFS was inferior after RH (18.5 vs. 28.8 %; adjusted HR 1.3, 95 % CI 1.0-1.7). In patients who eventually recurred, 5-year survival from the time of recurrence did not differ whether it was after RH (46.5 %) or after IH (60.3 %) (adjusted HR 1.1, 95  % CI 0.8-1.8). Rectal primary tumor (HR 1.4, 95 % CI 1.0-2.1) and metastasis ≥3 cm (HR 1.3, 95 % CI 1.1-2.7) were independently associated with RFS, but not OS, after RH. CONCLUSION: Short-term outcomes of RH did not differ from IH. While recurrence was more frequent after RH than IH, it did not impact OS. Survival from the time of recurrence did not differ whether recurrence occurred after RH or after IH. CRLM recurrence can be treated with curative intent with excellent long-term outcomes.

Repeat liver retransplantation: rationale and outcomes.

BACKGROUND: Liver retransplantation remains the only option for recurrent graft failure. The aim of our study is to identify predictive factors involved in patients and graft survival for patients undergoing repeat retransplantation (RRT). METHODOLOGY: From January 1985 to December 2012, 2940 liver transplantations were performed in 2477 patients at Paul Brousse Hospital, Villejuif, France. All patients who underwent third, fourth, and fifth transplantation were included in the study and retrospectively analyzed. RESULTS: In the univariate analysis, the factors that were associated with 90-d patient post-operative survival were pre-operative vasopressors support, pre-operative extra hepatic sepsis, primary non-function (PNF) as indication of RRT, recipient's model of end stage liver disease (MELD), urgent RRT, creatinine value at RRT, and prothrombin ratio. The multivariate logistic regression confirmed the role of systemic septic status (OR = 12.8, p = 0.01) and vasopressor drug support (OR = 4.7, p = 0.05) as predictors of post-operative mortality. In the univariate analysis, the factors that were associated with patient 10 yr long-term survival (were vasopressor support, systemic septic patient, PNF as indication of RRT, RRT occurred between 1985 and 1999, recipient's MELD, creatinine value at RRT, and prothrombin ratio. The multivariate logistic regression confirmed the role of systemic septic patient (OR = 6.4, p = 0.03) and the RRT between 1985 and 1999 (OR = 3.6, p = 0.05) as predictors of long-term mortality. CONCLUSION: RRT represent a valid alternative in selected patients. Selection should be oriented on patients needing third transplant without extra hepatic sepsis and vasoactive drug support at moment of RRT. If necessary, fourth and fifth RRT could be performed with a decision made on case-by-case basis, despite a high post-operative mortality.

Laparoscopic left pancreatectomy: early results after 115 consecutive patients.

INTRODUCTION: Despite its proven feasibility and good results, the use of laparoscopy in left-sided pancreatic lesions is considered a challenging procedure, and therefore, its utilization is still low. In this paper, we aim to describe the early outcomes obtained after laparoscopic left pancreatectomies performed over 15 years. PATIENTS AND METHODS: From 1997 until 2014, 115 consecutive patients underwent laparoscopic left pancreatectomy at CHU Bordeaux and Centre Hépato-Biliaire, which were prospectively recorded in a database. An analysis of this database was performed in order to evaluate preoperative, intraoperative and immediate postoperative outcomes. RESULTS: Laparoscopic left pancreatectomy with spleen conservation was performed in 64 patients (55.7 %). The median operative time was 220 min, and median blood loss was 200 ml. Conversion to open surgery was made in 15 (13 %) patients. Median postoperative hospital stay was 11 days, and overall postoperative complications occurred in 59 patients (51.3 %). Of these, 25.4 % were Clavien-Dindo grade III and above. The rate of clinical PF was 11.3 %. Three of the 64 patients with splenic preservation (4.7 %) developed a splenic infarction, and one of them needed splenectomy. CONCLUSIONS: Results obtained after a long series of laparoscopic left pancreatectomy confirm its favorable outcomes and its association with a low postoperative morbidity rate.

Does pathological response after transarterial chemoembolization for hepatocellular carcinoma in cirrhotic patients with cirrhosis predict outcome after liver resection or transplantation?

BACKGROUND & AIMS: To investigate the prognostic significance of pathologic response (PR) after transarterial chemoembolization (TACE) in cirrhotic patients resected or transplanted for hepatocellular carcinoma (HCC), and to identify predictors of complete pathologic response (CPR). METHODS: Between 1990 and 2010, 373 consecutive cirrhotic patients with HCC were treated by TACE followed by either liver resection (LR:184 patients) or liver transplantation (LT:189 patients). The PR was evaluated as the mean percentage of non-viable tumor area within each tumor. CPR was defined as the absence of any viable tumor area in all the present nodules. RESULTS: A total of 59 (32%) and 37 (20%) patients had CPR after LR and LT, respectively. Five-year overall survival (OS) was higher in patients with CPR compared to those without, after LR (58% vs. 34%; p=0.0006) and tends to be higher after LT (84% vs. 65%; p=0.09). The 5-year recurrence-free survival (RFS) rates were significantly higher in both groups (24% vs. 13% after LR; p=0.008 and 94% vs. 73% after LT, p=0.007). A cut-off value of >90% necrosis emerged as an impacting factor on patient survival after LR or LT. On multivariate analysis stratified on the type of procedure (LR or LT), PR >90% remained an independent factor of better OS and RFS. Independent factors associated with CPR were: a maximal tumor size <30 mm (RR 2.17 [1.27-3.74]), a single tumor (RR 6.08 [3.29-12.07]), and an preoperative AFP<100 ng/ml (see results section) (RR 3.99 [1.63-11.98]). The probability to achieve a CPR ranged from 2% in the absence of any factors to 48% in the presence of all factors. CONCLUSION: In cirrhotic patients with HCC, a complete or nearly complete PR improves long-term survival after LR and LT independently of other pathological factors. This underlines the importance of neoadjuvant treatment to obtain a significant decrease of active tumor load.

Failure to Achieve a 2-Stage Hepatectomy for Colorectal Liver Metastases: How to Prevent It?

OBJECTIVES: The aim of the study was to identify predictive factors of failure of 2-stage hepatectomy (TSH) for the selection of patients with extensive bilobar colorectal liver metastases (CRLM), who are candidates for TSH. BACKGROUND: The main weakness of TSH is the risk of failure to complete both the sequential procedures. METHODS: Between 2000 and 2012, from a total cohort of 845 patients resected for CRLM, 125 patients (14.8%) with extensive CRLM were planned for TSH. All factors related to the failure of TSH were analyzed, and a predictive model was built utilizing the independent predictive factors of failure. RESULTS: Forty-four patients (35.2%) could not proceed to the second stage, and their overall survival (OS) was significantly worse than that of those who completed the TSH (5-year OS: 0% vs 44.2%; P < 0.0001). Multivariate analysis revealed that carcinoembryonic antigen >30 ng/mL [relative risk (RR) 2.73, P = 0.03], tumor size >40 mm (RR 2.89, P = 0.04), chemotherapy cycles >12 (RR 3.46, P = 0.01), and tumor progression during first-line chemotherapy (RR 6.56, P = 0.01) were independent predictive factors of failure. For patients not presenting any factors, the probability of failure was 10.5%, with a 5-year OS rate of 41.9%. The addition of each subsequent factor increased the risk to 43.5%, 72.7%, 88.5%, and 95.5%, and decreased the 5-year OS to 38.8%, 29.2%, 0%, and 0%, respectively, for 1, 2, 3, and 4 factors. CONCLUSIONS: TSH should not be recommended in patients with more than 2 risk factors. Avoidance of these factors significantly reduces the risk of failure and is crucial for long-term survival.

Early and Long-term Oncological Outcomes After Laparoscopic Resection for Colorectal Liver Metastases: A Propensity Score-based Analysis.

OBJECTIVE: To compare early and long-term outcomes in patients undergoing resection for colorectal liver metastases (CLM) by either a laparoscopic (LA) or an open (OA) approach. BACKGROUND: The LA is still a matter of debate regarding the surgical management of CLM. METHODS: Data of all patients from 32 French surgical centers who underwent liver resection for CLM from January 2006 to December 2013 were collected. Aiming to obtain 2 well-balanced cohorts for available variables influencing early outcome and survival, the LA group was matched 1:1 with the OA group by using a propensity score (PS)-based method. RESULTS: The unmatched initial cohort consisted of 2620 patients (LA: 176, OA: 2444). In the matched cohort for operative risk factors (LA: 153, OA: 153), the LA group had shorter hospitalization stays [11.1 (±9) days vs 13.9 (±10) days; P = 0.01] and was associated with lower rates of grade III to V complications [odds ratio (OR): 0.27, 95% confidence interval (CI) 0.14-0.51; P = 0.0002] and inhospital transfusions (OR: 0.33 95% CI 0.18-0.59; P < 0.0001). On a prognostic factors well-balanced population (LA: 73, OA: 73), the LA group and the OA group experienced similar overall (OS) and disease-free (DFS) survival rates [OS rates of 88% and 78% vs 84% and 75% at 3 and 5 years, respectively (P = 0.72) and DFS rates of 40% and 32% vs 52% and 36% at 3 and 5 years, respectively (P = 0.60)]. CONCLUSIONS: In the patients who are suitable for LA, laparoscopy yields better operative outcomes without impairing long-term survival.