François Faitot

Liver transplantation in critically ill patients: Preoperative predictive factors of post-transplant mortality to avoid futility

The allocation of liver transplants to patients with acute liver failure (ALF) and acute‐on‐chronic liver failure (ACLF) with multi‐organ failure who are admitted in ICU remains controversial due to their high post‐transplant mortality rate and the absence of identified mortality risk factors.

Impact of real-time metabolomics in liver transplantation: Graft evaluation and donor-recipient matching

BACKGROUND & AIMS There is an emerging need to assess the metabolic state of liver allografts especially in the novel setting of machine perfusion preservation and donor in cardiac death (DCD) grafts. High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS-NMR) could be a useful tool in this setting as it can extemporaneously provide untargeted metabolic profiling. The purpose of this study was to evaluate the potential value of HR-MAS-NMR metabolomic analysis of back-table biopsies for the prediction of early allograft dysfunction (EAD) and donor-recipient matching. METHOD The metabolic profiles of back-table biopsies obtained by HR-MAS-NMR, were compared according to the presence of EAD using partial least squares discriminant analysis. Network analysis was used to identify metabolites which changed significantly. The profiles were compared to native livers to identify metabolites for donor-recipient matching. RESULTS The metabolic profiles were significantly different in grafts that caused EAD compared to those that did not. The constructed model can be used to predict the graft outcome with excellent accuracy. The metabolites showing the most significant differences were lactate level >8.3 mmol/g and phosphocholine content >0.646 mmol/g, which were significantly associated with graft dysfunction with an excellent accuracy (AUROClactates = 0.906; AUROCphosphocholine = 0.816). Native livers from patients with sarcopenia had low lactate and glycerophosphocholine content. In patients with sarcopenia, the risk of EAD was significantly higher when transplanting a graft with a high-risk graft metabolic score. CONCLUSION This study underlines the cost of metabolic adaptation, identifying lactate and choline-derived metabolites as predictors of poor graft function in both native livers and liver grafts. HR-MAS-NMR seems a valid technique to evaluate graft quality and the consequences of cold ischemia on the graft. It could be used to assess the efficiency of graft resuscitation on machine perfusion in future studies. LAY SUMMARY Real-time metabolomic profiles of human grafts during back-table can accurately predict graft dysfunction. High lactate and phosphocholine content are highly predictive of graft dysfunction whereas low lactate and phosphocholine content characterize patients with sarcopenia. In these patients, the cost of metabolic adaptation may explain the poor outcomes.

Liver transplantation for hereditary hemorrhagic telangiectasia: a systematic review

AIM To evaluate the indications, timing and results of liver transplantation in patients affected by hereditary hemorrhagic telangiectasia (HHT), by undertaking a systematic review of the current literature. METHODS Electronic bibliographical databases were searched on MEDLINE and Pubmed according to the PRISMA criteria. A total of 58 articles were initially found, 11 have been excluded because of single center series later included in the European Liver transplant Registry (ELTR), already reported in this study. Thirty-eight articles have been excluded because they did not report specifically new cases of liver transplantation for hereditary hemorrhagic telangiectasia. Finally 9 articles were included in the analysis. RESULTS A total of 56 patients who underwent liver transplantation for HHT are present in the English literature. One additional patient is presented in this article, for a total of 57 patients worldwide. To date, the most consistent published series is the one of the ELTR, including patients from 15 liver transplantation centers in the period 1985-2003 with a mean follow-up of 69 months. Ten-year patient and graft survival is 82.5% CONCLUSION: Liver transplantation should be considered as a radical but definitive treatment option in patients affected by HHT with liver or cardiac involvement not responsive to medical treatment.

Management of the splenic vein during a pancreaticoduodenectomy with venous resection for malignancy

Nowadays, pancreaticoduodenectomies (PD) with an “en-bloc” resection of the spleno-mesenterico-portal (SMP) venous axis are safely performed at tertiary centers for patients presenting venous invasion. However, for tumors infiltrating the SMP confluence optimal management of the splenic vein (SV) remains a matter of debate. Simple SV ligation has been associated with the development of sinistral portal hypertension, gastrointestinal bleeding and hypersplenism over the long term. To avoid these complications, reconstructive methods such as the direct implantation of the SV into a SMP “neoconfluence”, the inferior mesenteric vein-SV anastomosis and the distal spleno-renal shunt have been reported. This article summarizes the different technical solutions available and the current evidence supporting the optimal management of the SV stump during a “safe” radical PD for pancreatic cancer. Technical issues, advantages as well as drawbacks of the different techniques, are discussed.

Hepatocellular Carcinoma Spreading Through the Round Ligament

A 70-year-old man with a previous past medical history significant for alcoholic cirrhosis was referred to our unit for the treatment of multifocal hepatocellular carcinoma (HCC). An abdominal magnetic resonance imaging (MRI) showed five nodules of HCC ranging from 2 to 5 cm in diameter involving the right and left liver lobes. Biologic data and clinical status classed the patients as Child-Pugh A 6. There was minimal portal hypertension with grade 1 oesophageal varices, no previous history of liver decompensation and serum alphafetoprotein was elevated at 50 μg/l (normal values < 13 μg/ l). After multidisciplinary discussion, the patient was treated by sequential (right-liver first) transarterial chemoembolization (TACE) in order to downstage HCC. Following TACE, alpha-fetoprotein dropped within normal values and MRI showed complete tumoral necrosis. The patient was then followed up radiologically and clinically in outpatient clinic and liver transplantation (LT) work-up was considered after 1 year of clinical remission. Fourteen months after TACE, serum alpha-fetoprotein level increased to 56μg/l and abdominal MRI showed a non hypervascularized recurrent noudule 1, 5 cm in size in the segment 4 inferior close to the segmental portal pedicle and 4, 5 cm exophytic nodule under the left liver lobe (Fig. 1). The abdominal examination found a round, mobile nodule on the epigastrium. Complete work-up did not found any recurrence into the chest and bone. In order to rule out the presence of a peritoneal implant, the patient underwent explorative laparoscopy which found HCC spreading through the round ligament (RL). The RL was excised and pathology confirmed HCC diffusion through the RL (Fig. 2). The patient was delisted from LT and treated by sorafenib®. The round ligament of the liver connects the umbilical portion of the left portal vein to the umbilicus. RL is a fibrous cord which originates from the involution of the umbilical vein which transfers oxygenated blood from the placenta into the growing foetus. Under increased intrahepatic pressures the round ligament reopens allowing a wide communication between the portal and systemic circulation such as seen in cirrhotic patients with portal hypertension. Tumoral spreading through the RL and umbilical metastases represents rare manifestations of digestive cancers. Spreading to the umbilicus can arise from cutaneous lymphatics by retrograde lymphatic flow, by direct peritoneal implantation from the anterior peritoneal surface and by arterial embolization from distant sites. The final localization of tumoral disease at the umbilicus is known as the sister Mary Joseph’s nodule. However because of his vascular structure, the RL can also be the source of tumoral diffusion directly from the liver. HCC has an elevated propensity toward diffusion through portal system into the same liver segment and toward the main portal branches. In the presence of portal hypertension and reopened umbilical vein, HCC invading a segmental branch of the umbilical left portal vein can spread through the RL such as in the present case. Considering the RL as a major branch of the portal system, invasion form HCC should be considered such as macrovascular invasion and precludes the performance of LT. * Pietro Addeo pietroad@hotmail.com

Interleukin 6 at reperfusion: A potent predictor of hepatic and extrahepatic early complications after liver transplantation

Ischemia‐reperfusion injury impacts early liver graft function. Interleukin 6 (IL‐6) as early as at reperfusion has shown to predict in‐hospital complications, but its impact on vascular complications and long‐term outcomes is not ascertained.

Prognostic value of venous invasion in resected T3 pancreatic adenocarcinoma: Depth of invasion matters

Background. Incomplete evaluation of venous invasion has led to conflicting results regarding the prognosis of patients undergoing pancreatectomy with a synchronous venous resection. This study evaluates the prognostic value associated with the presence and the depth of venous invasion in T3 pancreatic adenocarcinoma. Methods. This study evaluated retrospectively 181 consecutive pancreatoduodenectomies performed for T3N0M0 and T3N1M0 pancreatic adenocarcinomas (stages IIA and IIB) from January 2006 to December 2014. Univariate and multivariate Cox analyses were performed to assess survival prognostic factors. Results. Pancreatoduodenectomies with a segmental venous resection was performed on 91 patients, while 90 other patients had a standard pancreatoduodenectomies without venous resection. Pathologic venous invasion was detected in 68 (74%) of the 91 venous resection patients. Depth of venous invasion was into the adventitia (n = 25), media (n = 28), and intima (n = 15). The overall survival rates at 1, 3, 5, and 10 years were 75%, 33%, 21%, and 6%, respectively. There were no differences in survival between patients undergoing standard pancreatoduodenectomies and pancreatoduodenectomies with venous resection (27 vs 22 months; P = .28) or between patients with and without venous invasion (20 vs 27 months; P = .08). In multivariate analysis, depth of venous invasion into the intima (hazard ratio, 2.25; 95% confidence interval, 1.16–4.34; P = .0001) and adjuvant chemotherapy (hazard ratio, 0.16; 95% confidence interval, 0.09–0.43; P ≤ .0001) were identified as independent prognostic factors of overall survival. Conclusion. Depth of venous invasion into the intima indicates poor survival in pancreatic T3 adenocarcinoma. Preoperative identification of this factor could be helpful for better selection of patients for curative operation.

A Steatosic Pancreas in a Non-obese Patient

We recently observed a steatosic pancreas with a minimal parenchymal component during a pancreaticoduodenectomy in an 80-year-old patient (Fig. 1). The patient presented to the emergency room with jaundice and abdominal pain. The computed tomography examination showed the presence of common bile duct dilatation secondary to a 30-mm tumour located in the head of the pancreas. The past medical history showed the patient had received a triple coronary artery bypass and had arterial hypertension and hypercholesterolaemia. The patient’s body mass index was 24.5 kg/m. The pre-operative imaging studies showed a fatty pancreas with a Brarified^ parenchymal component (Fig. 2) and no Wirsung duct dilatation. The parenchymal section inside the pancreatic capsule revealed a steatosic pancreas that had a fatty appearance and consistency. The Wirsung duct and pancreatic parenchyma were surrounded by adipose tissue, which was easily recognized by its different consistency and colour (Fig. 1). There was no postoperative pancreatic fistula observed. The pathological analysis showed a periampullary adenocarcinoma