Value of HR-MAS-NMR metabolomics in hepatobiliary surgery and liver transplantation

La principale limite en chirurgie hépatobiliaire est représentée par l’insuffisance hépatocellulaire (IHC) posthépatectomie (Hx) ou la dysfonction du greffon (EAD) après transplantation (TH). Peu d’études ont évalué le métabolisme du foie dans son ensemble, du fait du manque de technique utilisable en clinique. La métabolomique HR-MAS-RMN pourrait pallier à ce manque. Le but de cette thèse était d’évaluer l’apport de cette technique en chirurgie hépatobiliaire.En TH (n=42), le profil métabolique (PM) prédisait le risque d’EAD et identifiait le lactate et la phosphocholine comme biomarqueurs permettant d’envisager un matching métabolique. Après Hx majeure (n=45), le PM prédisait la survenue d’un décès par IHC. Ce PM différait du profil cirrhotique en décompensation et était compatible avec celui de système cellulaire prolifératif. Une étude préliminaire montrait que le PM prédisait la récidive à 1 an après hépatectomie. Ce travail montre l’intérêt de la métabolomique par HR MAS RMN pour prédire l’issue d’une Hx ou d’une TH dans un temps compatible avec la clinique. Ces données orientent vers la piste de l’intervention métabolique en chirurgie hépatique.One of the main limits in liver surgery is the risk of liver failure (LF) after hepatectomy (Hx) or graft dysfunction (EAD) after liver transplantation (LT). Few studies have evaluated global liver metabolism, probably due to the lack of clinically relevant techniques. HR-MAS-NMR metabolomics may fulfill this lack and the goal of this work was to evaluate its capacity to predict early outcomes after hepatectomy and LT. In LT (n=42), metabolic profile predicted EAD and lactate and phosphocholine were potent biomarkers providing means for metabolic matching. In liver biopsies harvested at the end of major Hx (n=45), metabolic profile predicted PHLF. The profile at risk of LF differed from that of decompensated cirrhosis but correlated to that of proliferative multicellular systems. A preliminary study showed that the metabolic profile predicted the risk of liver metastases recurrence at 1 year. This work underlines the potential value of HR-MAS-NMR metabolomics in the prediction of short-term outcomes in liver surgery. It provides clues to be further investigated for future evaluation of metabolic intervention in the field of liver surgery

Value of HR-MAS-NMR metabolomics in hepatobiliary surgery and liver transplantation

La principale limite en chirurgie hépatobiliaire est représentée par l’insuffisance hépatocellulaire (IHC) posthépatectomie (Hx) ou la dysfonction du greffon (EAD) après transplantation (TH). Peu d’études ont évalué le métabolisme du foie dans son ensemble, du fait du manque de technique utilisable en clinique. La métabolomique HR-MAS-RMN pourrait pallier à ce manque. Le but de cette thèse était d’évaluer l’apport de cette technique en chirurgie hépatobiliaire.En TH (n=42), le profil métabolique (PM) prédisait le risque d’EAD et identifiait le lactate et la phosphocholine comme biomarqueurs permettant d’envisager un matching métabolique. Après Hx majeure (n=45), le PM prédisait la survenue d’un décès par IHC. Ce PM différait du profil cirrhotique en décompensation et était compatible avec celui de système cellulaire prolifératif. Une étude préliminaire montrait que le PM prédisait la récidive à 1 an après hépatectomie. Ce travail montre l’intérêt de la métabolomique par HR MAS RMN pour prédire l’issue d’une Hx ou d’une TH dans un temps compatible avec la clinique. Ces données orientent vers la piste de l’intervention métabolique en chirurgie hépatique.One of the main limits in liver surgery is the risk of liver failure (LF) after hepatectomy (Hx) or graft dysfunction (EAD) after liver transplantation (LT). Few studies have evaluated global liver metabolism, probably due to the lack of clinically relevant techniques. HR-MAS-NMR metabolomics may fulfill this lack and the goal of this work was to evaluate its capacity to predict early outcomes after hepatectomy and LT. In LT (n=42), metabolic profile predicted EAD and lactate and phosphocholine were potent biomarkers providing means for metabolic matching. In liver biopsies harvested at the end of major Hx (n=45), metabolic profile predicted PHLF. The profile at risk of LF differed from that of decompensated cirrhosis but correlated to that of proliferative multicellular systems. A preliminary study showed that the metabolic profile predicted the risk of liver metastases recurrence at 1 year. This work underlines the potential value of HR-MAS-NMR metabolomics in the prediction of short-term outcomes in liver surgery. It provides clues to be further investigated for future evaluation of metabolic intervention in the field of liver surgery

Intérêt de la métabolomique par HR-MAS-RMN en chirurgie hépato-biliaire et transplantation hépatique

One of the main limits in liver surgery is the risk of liver failure (LF) after hepatectomy (Hx) or graft dysfunction (EAD) after liver transplantation (LT). Few studies have evaluated global liver metabolism, probably due to the lack of clinically relevant techniques. HR-MAS-NMR metabolomics may fulfill this lack and the goal of this work was to evaluate its capacity to predict early outcomes after hepatectomy and LT. In LT (n=42), metabolic profile predicted EAD and lactate and phosphocholine were potent biomarkers providing means for metabolic matching. In liver biopsies harvested at the end of major Hx (n=45), metabolic profile predicted PHLF. The profile at risk of LF differed from that of decompensated cirrhosis but correlated to that of proliferative multicellular systems. A preliminary study showed that the metabolic profile predicted the risk of liver metastases recurrence at 1 year. This work underlines the potential value of HR-MAS-NMR metabolomics in the prediction of short-term outcomes in liver surgery. It provides clues to be further investigated for future evaluation of metabolic intervention in the field of liver surgery.La principale limite en chirurgie hépatobiliaire est représentée par l’insuffisance hépatocellulaire (IHC) posthépatectomie (Hx) ou la dysfonction du greffon (EAD) après transplantation (TH). Peu d’études ont évalué le métabolisme du foie dans son ensemble, du fait du manque de technique utilisable en clinique. La métabolomique HR-MAS-RMN pourrait pallier à ce manque. Le but de cette thèse était d’évaluer l’apport de cette technique en chirurgie hépatobiliaire.En TH (n=42), le profil métabolique (PM) prédisait le risque d’EAD et identifiait le lactate et la phosphocholine comme biomarqueurs permettant d’envisager un matching métabolique. Après Hx majeure (n=45), le PM prédisait la survenue d’un décès par IHC. Ce PM différait du profil cirrhotique en décompensation et était compatible avec celui de système cellulaire prolifératif. Une étude préliminaire montrait que le PM prédisait la récidive à 1 an après hépatectomie. Ce travail montre l’intérêt de la métabolomique par HR MAS RMN pour prédire l’issue d’une Hx ou d’une TH dans un temps compatible avec la clinique. Ces données orientent vers la piste de l’intervention métabolique en chirurgie hépatique

Quel est l'impact de l'hypertension portale sur la progression du carcinome hépato-cellulaire chez les patients en attente de transplantation hépatique?

La transplantation hépatique est le meilleur traitement curatif du carcinome hépatocellulaire (CHC) sur cirrhose. Pendant la période d attente de la greffe, il existe un risque de progression tumorale rendant la greffe non bénéfique. L impact de l hypertension portale sur la croissance du CHC n est pas rapporté dans la littérature et fait l objet de cette étude. Chez 245 patients inscrits sur liste sur une période de 10 ans, le taux de progression tumorale chez les patients avec hypertension portale était de 44% versus 21% dans le groupe sans hypertension portale. L hypertension portale était un facteur prédictif indépendant de progression tumorale et de sortie de liste mais sans impact sur la survie chez les patients transplantés. L hypertension portale s avère un facteur pronostique intéressant chez les patients en attente de transplantation dont la prise en compte pourrait améliorer la survie en intention de traiter.Liver transplantation is the best treatment for hepatocellular carcinoma (HCC) in cirrhotic patients. During the waiting time, tumor progression can render liver transplantation unbeneficial. The impact of portal hypertension on HCC growth in patients waiting for a liver graft has never been reported. Among 245 patients listed on a 10 years period, tumor progression was significantly more frequent in patients with portal hypertension than in those without (44% versus 21%). Portal hypertension was an independent risk factor for tumor progression and drop out. However its presence did not impact survival in transplanted patients. Portal hypertension is an interesting prognostic factor in patients waiting for a liver graft. Taking in consideration this factor could help ti increase the survival in intention-to-treat.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Simultaneous Resection of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases: Safety and Oncological Efficacy

Whether the simultaneous resection of pancreatic neuroendocrine tumors (PNET) with synchronous liver metastases (LM) is safe and oncologically efficacious remains to be debated. We retrospectively reviewed clinical data from patients who underwent the simultaneous resection of PNETs with LMs over the last 25 years. Fifty-one consecutive patients with a median age of 54 years (range 27–80 years) underwent pancreaticoduodenectomy (PD) (n = 16), distal pancreatosplenectomy (DSP) (n = 32) or total pancreatectomy (n = 3) with synchronous LM resection. There were no differences in the postoperative outcomes in term of mortality (p = 0.33) and morbidity (p = 0.76) between PD and DSP. The median overall survival (OS) was 64.78 months (95% CI: 49.7–119.8), and the overall survival rates at 1, 3, and 5 years were 97.9%, 86.2% and 61%, respectively. The OS varied according to the tumor grade (G): G1 (OS 128 months, 5-year OS 83%) vs. G2 (OS 60.5 months, 5-year OS 58%) vs. G3 (OS 49.7 months, 5-year OS 0%) (p = 0.03). Multivariate Cox analysis identified G as the only prognostic factor (HR: 5.56; 95% CI: 0.91–9.60; p = 0.01). Simultaneous PNETS with LMs can be performed safely with acceptable morbidity and mortality at tertiary centers. Well-differentiated PNETs had longer survival and might benefit the most from these extended surgeries

Intensive care for patients with gastric cancers: outcome and survival prognostic factors

Background: Admission and management of patients with solid malignancies in intensive care unit (ICU) is a controversial topic. To this day, there is no data published concerning patients with gastric cancers hospitalized in ICU. This single center retrospective study reports the characteristics, outcome and prognostic factors of patients hospitalized in ICU for medical reasons over a period of 10 years. Methods: We performed a single center retrospective study which reports the characteristics, outcome and prognostic factors of patients hospitalized in ICU for medical reasons over a period of 10 years. Results: Thirty-seven patients were included, among whom 24 (64.9%) had metastatic cancer. The most frequent diagnosis on admission was septic shock (48.6%) and 24 patients (64.9%) required intubation. Ten patients (27.0%) were alive 3 months after their admission in ICU. Metastatic cancer and intubation were independently associated with a higher risk of dying within 3 months of admission in multivariate analysis: odds ratio (OR) =13.7; 95% confidence interval (CI), 1.7-108 (P<0.01). Seventeen patients (45.9%) died during their ICU stay. Metastatic cancer: OR =89; 95% CI, 2.7-6,588, therapeutic intensification: OR =1,471; 95% CI, 9.8-811,973 and the logistic organ dysfunction score (LODS) on admission: OR =1.4; 95% CI, 1.1-2.3 were independently associated with mortality within the ICU in multivariate analysis (P<0.01). Conclusions: This is the first study that examines the outcome and prognostic factors of patients with gastric cancers who require life-sustaining therapy in ICU. The identification of 3 months and ICU mortality prognostic factors could contribute to guiding clinicians in the management of these patients and assist health professionals in their discussions with these patients and their families

Major hepatectomy decreased tumor growth in an experimental model of bilobar liver metastasis

International audienceTwo-stage hepatectomy (TSH), is associated with a risk of drop-out due to tumoral progression following portal vein occlusion (PVO). We explored the impact of majorhepatectomy on tumor growth by objective radiological measures comparing to PVO and minor hepatectomy, using a model of bilobar colorectal liver metastasis (CLM)