French legislation on retrospective clinical research: What to know and what to do.

The French legislation on human subject research known as the Jardé law of 5th March 2012 has been applicable since November 2016. It concerns all research involving human subjects (RIPH, in French) and is defined according to 3 categories: high-risk interventional RIPH, low-risk interventional RIPH and non-interventional RIPH. This recent development in the supervision of research on human subjects had several objectives: to redefine the various categories of research, to strengthen data protection and to effectively address the ethical guidelines of international journals. The levels of constraint differ between categories of research according to level of risk, the common objective being to ensure patient protection. Retrospective studies based on information drawn from medical records or other databases, which are widely used in the surgical field, are not covered by the Jardé law. However, they require approval by local ethics committees and compliance with European legislation on personal data protection. Simplified procedures have been set up by the research and innovation departments in our university hospitals. In this update, we shall synthesize the legal prerequisites applying to retrospective studies on data from medical files.

Laparoscopic versus open resection of intrahepatic cholangiocarcinoma: nationwide analysis.

BACKGROUND: The relevance of laparoscopic resection of intrahepatic cholangiocarcinoma (ICC) remains debated. The aim of this study was to compare laparoscopic (LLR) and open (OLR) liver resection for ICC, with specific focus on textbook outcome and lymph node dissection (LND). METHODS: Patients undergoing LLR or OLR for ICC were included from two French, nationwide hepatopancreatobiliary surveys undertaken between 2000 and 2017. Patients with negative margins, and without transfusion, severe complications, prolonged hospital stay, readmission or death were considered to have a textbook outcome. Patients who achieved both a textbook outcome and LND were deemed to have an adjusted textbook outcome. OLR and LLR were compared after propensity score matching. RESULTS: In total, 548 patients with ICC (127 LLR, 421 OLR) were included. Textbook-outcome and LND completion rates were 22.1 and 48.2 per cent respectively. LLR was independently associated with a decreased rate of LND (odds ratio 0.37, 95 per cent c.i. 0.20 to 0.69). After matching, 109 patients remained in each group. LLR was associated with a decreased rate of transfusion (7.3 versus 21.1 per cent; P = 0.001) and shorter hospital stay (median 7 versus 14 days; P = 0.001), but lower rate of LND (33.9 versus 73.4 per cent; P = 0.001). Patients who underwent LLR had lower rate of adjusted TO completion than patients who had OLR (6.5 versus 17.4 per cent; P = 0.012). CONCLUSION: The laparoscopic approach did not substantially improve quality of care of patients with resectable ICC.

Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation.

OBJECTIVE: The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). PATIENTS AND METHODS: This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. RESULTS: Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P<0.001), but this effect disappeared in multivariate analysis when the center performing the transplantation was accounted for. CONCLUSION: The type of preservation solution used (CS, IGL-1, SCOT 15 or UW) did not have any influence on patient or graft survival after LT.

Enhanced recovery after liver surgery.

INTRODUCTION: In a majority of cases, enhanced recovery after surgery program (ERP) leads to a reduced rate of postoperative complications and shortened hospital stays following digestive surgery. The program's preoperative, perioperative and postoperative measures are implemented by the members of a motivated multidisciplinary team. Having shown its merits in digestive surgery, ERP would be particularly useful in liver surgery due to the elevated rates of morbidity and mortality this type of operation continues to entail. The objective of this review was to evaluate the efficacy of ERP in liver surgery. METHOD: This is a systematic narrative review of the literature on the efficacy of ERP in liver surgery by laparotomy or laparoscopy. RESULTS: Notwithstanding a number of studies (n=30: 5 randomized trials, 14 cohort studies and 11 meta-analyses) less sizable than with regard to digestive surgery in general and colorectal surgery in particular, analysis of the literature confirms that in liver surgery, ERP is associated with an overall decrease in complications by 30 to 60%, but without improvement in the rates of hospital readmission and postoperative mortality. All of the studies report a reduction in average length of stay (ALOS) by 2.3 days and in functional recovery, a more objective indicator than ALOS, by 2.5 days. As of now, the economic impact of the ERP programs in liver surgery is neither positive nor negative, the above-mentioned savings being counterbalanced by heightened costs for material and equipment. Laparoscopic surgery is independently associated with better outcomes in terms of complications, functional recovery and ALOS; that is why it is important to incorporate this surgical approach in ERP as often as possible. Given a lack of robust evidence, Prehabilitation, which is a preoperative optimization process leading to improved functional reserve, has yet to be assigned a place in ERP programs pertaining to liver surgery. Possible roadblocks to application of an ERP program can be overcome through coordination by a team leader, a motivated multidisciplinary team, training courses and dedicated teaching sessions. CONCLUSION: ERP is a care improvement process that has a major play to play in organization of liver surgery, and its large-scale application is to be recommended.

Sleeve Gastrectomy: You Might Lose your Liver!

Sleeve gastrectomy (SG) is currently the most popular bariatric procedure. Portomesenteric venous thrombosis (PVT) is a feared and increasingly reported complication. Herein, we describe the history of a patient who developed a post-operative PVT after SG, aggravated with refractory ascites, and finally required orthotopic liver transplantation (LT). Acquired thrombophilia-anti-cardiolipin syndrome was present. As SG expands worldwide, this first case of LT for PVT following SG may warrant a systematic screening for prothrombotic condition and information on the possible consequences of PVT prior to bariatric surgery.

Temporal trends, clinical patterns and outcomes of NAFLD-related HCC in patients undergoing liver resection over a 20-year period.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) worldwide. NAFLD-HCC often occurs in noncirrhotic liver raising important surveillance issues. AIM: To determine the temporal trends for prevalence, clinical characteristics and outcomes of NAFLD-HCC in patients undergoing liver resection. METHODS: Consecutive patients with histologically confirmed HCC who underwent liver resection over a 20-year period (1995-2014). NAFLD was diagnosed based on past or present exposure to obesity or diabetes without other causes of chronic liver disease. RESULTS: A total of 323 HCC patients were included, 12% with NAFLD. From 1995-1999 to 2010-2014, the prevalence of NAFLD-HCC increased from 2.6% to 19.5%, respectively, P = .003, and followed the temporal trends in the prevalence of metabolic risk factors (28% vs 52%, P = .017), while hepatitis C-HCC decreased (from 43.6% to 19.5%, P = .003). NAFLD-HCC occurred more frequently in the absence of bridging fibrosis/cirrhosis (63% of cases, P < .001 compared to other aetiologies). Within the NAFLD group, tumour characteristics were similar between F0-F2 and F3-F4 patients, except for a higher proportion of single nodules (95% vs 54%, P < .01). A total of 53% patients had tumour recurrence and 40% died. NAFLD-HCC had similar time to recurrence and survival as HCCs of other aetiologies. Satellite nodules, tumour size, microvascular invasion and male sex but not the aetiology were independently associated with recurrence. CONCLUSION: Non-alcoholic fatty liver disease increased substantially over the past 20 years among resectable HCCs. It is now the leading cause of HCC occuring without/or with only minimal fibrosis. NAFLD patients are older, with larger tumours while survival and recurrence rates are as severe as in other aetiologies.

Risk factors and consequences of conversion in laparoscopic major liver resection.

BACKGROUND: Although recent reports have suggested potential benefits of the laparoscopic approach in patients requiring major hepatectomy, it remains unclear whether conversion to open surgery could offset these advantages. This study aimed to determine the risk factors for and postoperative consequences of conversion in patients undergoing laparoscopic major hepatectomy (LMH). METHODS: Data for all patients undergoing LMH between 2000 and 2013 at two tertiary referral centres were reviewed retrospectively. Risk factors for conversion were determined using multivariable analysis. After propensity score matching, the outcomes of patients who underwent conversion were compared with those of matched patients undergoing laparoscopic hepatectomy who did not have conversion, operated on at the same centres, and also with matched patients operated on at another tertiary centre during the same period by an open laparotomy approach. RESULTS: Conversion was needed in 30 (13·5 per cent) of the 223 patients undergoing LMH. The most frequent reasons for conversion were bleeding and failure to progress, in 14 (47 per cent) and nine (30 per cent) patients respectively. On multivariable analysis, risk factors for conversion were patient age above 75 years (hazard ratio (HR) 7·72, 95 per cent c.i. 1·67 to 35·70; P = 0·009), diabetes (HR 4·51, 1·16 to 17·57; P = 0·030), body mass index (BMI) above 28 kg/m(2) (HR 6·41, 1·56 to 26·37; P = 0·010), tumour diameter greater than 10 cm (HR 8·91, 1·57 to 50·79; P = 0·014) and biliary reconstruction (HR 13·99, 1·82 to 238·13; P = 0·048). After propensity score matching, the complication rate in patients who had conversion was higher than in patients who did not (75 versus 47·3 per cent respectively; P = 0·038), but was not significantly different from the rate in patients treated by planned laparotomy (79 versus 67·9 per cent respectively; P = 0·438). CONCLUSION: Conversion during LMH should be anticipated in patients with raised BMI, large lesions and biliary reconstruction. Conversion does not lead to increased morbidity compared with planned laparotomy.

An update on laparoscopic liver resection: The French Hepato-Bilio-Pancreatic Surgery Association statement.

Laparoscopic liver resection has been recognized as a safe and efficient approach since the Louisville Conference in 2008, but its use still remains confined to experienced teams in specialized centers, and may lack some standardization. The 2013 Session of French Association for Hepatobiliary and Pancreatic Surgery (ACHBT) specifically focused on laparoscopic liver surgery and the particular aspects and issues arising since the 2008 conference. Our objective is to provide an update and summarize the current French position on laparoscopic liver surgery. An overview of the current practice of laparoscopic liver resections in France since 2008 is presented. The issues surrounding standardization for left lateral sectionectomy and right hepatectomy, hybrid and hand-assisted techniques are raised and discussed. Finally, future technologies and technical perspectives are outlined.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): impact of the inter-stages course on morbi-mortality and implications for management.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was recently developed to induce rapid hypertrophy and reduce post-hepatectomy liver failure in patients with insufficient remnant liver volume (RLV). However, mortality rates >12% have been reported. This study aimed to analyze the perioperative course of ALPPS and to identify factors associated with morbi-mortality. METHODS: Between April 2011 and September 2013, 62 patients operated in 9 Franco-Belgian hepatobiliary centres underwent ALPPS for colorectal metastases (N = 50) or primary tumors, following chemotherapy (N = 50) and/or portal vein embolization (PVE; N = 9). RESULTS: Most patients had right (N = 31) or right extended hepatectomy (N = 25) (median RLV/body weight ratio of 0.54% [0.21-0.77%]). RLV increased by 48.6% [-15.3 to 192%] 7.8 ± 4.5 days after stage1, but the hypertrophy decelerated beyond 7 days. Stage2 was cancelled in 3 patients (4.8%) for insufficient hypertrophy, portal vein thrombosis or death and delayed to ≥9 days in 32 (54.2%). Overall, 25 patients (40.3%) had major complication(s) and 8 (12.9%) died. Fourteen patients (22.6%) had post-stage1 complication of whom 5 (35.7%) died after stage2. Factors associated with major morbi-mortality were obesity, post-stage1 biliary fistula or ascites, and infected and/or bilious peritoneal fluid at stage2. The latter was the only predictor of Clavien ≥3 by multivariate analysis (OR: 4.9; 95% CI: 1.227-19.97; p = 0.025). PVE did not impact the morbi-mortality rates but prevented major cytolysis that was associated with poor outcome. CONCLUSIONS: The inter-stages course was crucial in determining ALPPS outcome. The factors of high morbi-mortality rates associated with ALPPS are linked to the technique complexity.

Pure laparoscopic right hepatectomy in a living donor.

After reporting the first laparoscopic hepatectomy in a living donor for pediatric liver transplantation, we now report a case of pure laparoscopic right hepatectomy for adult transplantation. A 50-year-old female volunteered for living donation to her sister who suffered from primary biliary cirrhosis. The volume of the planned hepatic graft (segments 5-8) was 620 cm(3) , representing 56% of her entire liver. Five ports were used in the donor to perform the operative procedure. The right hepatic artery and portal vein were isolated. Parenchymal division was performed using an ultrasonic dissector, bipolar coagulation and clips for hemostasis. Cholangiography was performed and the right bile duct was cut at the level of a marker thread. The right liver graft was placed in a bag and removed through a 10-cm suprapubic incision. The veins of segments 5 and 8 were recanalized and the graft was transplanted in the recipient. The postoperative course was uneventful for both the donor and recipient. This case offers evidence that the right liver can be procured via a total laparoscopic approach. This technique may allow for an early rehabilitation for the living donor.

Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre.

BACKGROUND: Vascular inflow occlusion is effective in avoiding excessive blood loss during hepatic parenchymal transection but may cause ischaemic damage to the remnant liver. Intermittent portal triad clamping (IPTC) is superior to continuous hepatic pedicle clamping as it avoids severe ischaemia-reperfusion (IR) injury in the liver remnant. Ischaemic preconditioning (IPC) before continuous Pringle manoeuvre may protect against IR during major liver resection. METHODS: This RCT assessed the impact of IPC in major liver resection with intermittent vascular inflow occlusion. Patients undergoing major liver resection with intermittent vascular inflow occlusion were randomized, during surgery, to receive IPC (10 min inflow occlusion followed by 10 min reperfusion) or no IPC (control group). Data analysis was on an intention-to-treat basis. The primary endpoint was serum alanine aminotransferase (ALT) level on the day after surgery. RESULTS: Eighty four patients were enrolled and randomized to IPC (n = 41) and no IPC (n = 43). The groups were comparable in terms of demographic data, preoperative American Society of Anesthesiologists grade and extent of liver resection. Intraoperative morbidity and postoperative outcomes were also similar. ALT levels on the day after operation were not decreased by IPC (mean(s.d.) 537·6(358·5) versus 525·0(400·6) units/ml in IPC and control group respectively; P = 0·881). Liver biochemistry tests in the week after operation showed the same pattern in both groups. CONCLUSION: IPC did not reduce liver damage in patients undergoing major liver resection with IPTC. REGISTRATION NUMBER: NCT00908245 (http://www.clinicaltrials.gov).

Cyclosporine inhibits profibrotic effects of interleukin-4 and transforming growth factor ß on human intrahepatic fibroblasts cultured in vitro.

BACKGROUND: Hepatic fibrosis, an outcome of chronic liver diseases, is characterized by an accumulation of collagen, which is produced by activated human intrahepatic fibroblasts (HIF). Transforming growth factor (TGF) ß is an important inducer of fibrogenesis, in collaboration with other cytokines, such as interleukin (IL) 4. IL-4 is overexpressed in severe recurrent hepatitis C after liver transplantation, exerting profibrotic effects. In contrast, cyclosporine (CsA) had been shown to decrease fibroblast activation and collagen production. We therefore investigated the effects of CsA on TGF-ß and IL-4 profibrotic activities on HIF in vitro. METHODS: Isolated HIF were cultured without or with human TGF-ß, human IL-4, CsA, or combined TGF- ß+CsA or IL-4+CsA. We performed real-time polymerase chain reaction for collagen types I, III, and IV and alpha-SMA, a marker of fibroblast activation we also measured total collagen in supernates. TGF-ß and IL-4 increased the expressions of alpha smooth muscle action (SMA) collagen I, III, and IV mRNAs (P < .05 vs untreated cells) as well as the overall collagen level in the supernates (P < .01). CsA decreased the expression of mRNAs encoding alpha-SMA and collagens (P < .01). Expressions of alpha-SMA and collagens I, III, and IV mRNAs were significantly lower under combined treatments (TGF-ß vs TGF-ß+CsA [P < .01] and IL-4 vs IL-4+CsA [P < .01]). Collagen level was decreased by combined treatments (TGF-ß vs TGF-ß+CsA [P < .05] and IL-4 vs IL-4+CsA [P = .05]). CONCLUSION: CsA inhibited the profibrotic effects of TGF-ß and IL-4 by decreasing the activation and production of collagen by HIF. CsA may decrease fibroblast activation and collagen accumulation, exerting beneficial effects on fibrosis progression, particularly among patients with recurrent hepatitis C.

Increased expression of regulatory Tr1 cells in recurrent hepatitis C after liver transplantation.

Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: 'Treg' and CD49b+CD18+ cells: 'T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management.

APRI and FIB-4 Scores Are Useful After Liver Transplantation Independently of Etiology.

Noninvasive liver fibrosis scores are evaluated in hepatitis C virus-infected patients but are less known in liver transplant recipients. Fibrosis is a frequent, multifactorial event in these patients. This preliminary retrospective study reviewed the diagnostic performance of 3 simple scores for liver fibrosis in transplant patients: namely, APRI (aspartate aminotransferase to platelet ratio index), FORNS (platelets, gamma-glutamyltransferase, patient age, and cholesterol), and FIB-4 (patient age, aspartate aminotransferase, alanine aminotransferase, and platelets). Ninety-four biopsies were collected from 50 liver transplant recipients at a mean period after orthotopic liver transplantation (OLT) of 30.7 months (range, 12-108 months). The indications for OLT were hepatitis C in 23% of cases, hepatitis B in 14%, alcoholic disease in 33%, cholestatic disease in 19%, and others in 11%. According to the Metavir classification, 72% of biopsies revealed no significant histological fibrosis (F0-1 = group 1) and 28% showed significant fibrosis (F2-4 = group 2). A correlation was observed between the histological stage of fibrosis and albumin, gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and hyaluronic acid levels. APRI and FIB-4 correlated significantly with the histological stage of fibrosis both globally and in the subgroup of nonhepatitis C liver recipients. When APRI and FIB-4 tests were applied to predict fibrosis (area under the receiver operating characteristic curve), the results were 0.87 and 0.78, respectively. Values were not significant with the FORNS test. In conclusion, APRI and FIB-4 enabled accurate prediction of significant fibrosis after OLT. In the nonhepatitis C subgroup, we found similar predictive performances. These simple scores may be applied in clinical practice in the context of follow-up after OLT independent of hepatitis C status.

Significance of serum tumor markers carcinoembryonic antigen, CA 19-9, CA 125, and CA 15-3 in pre-orthotopic liver transplantation evaluation.

Tumor markers are elevated in a variety of nonneoplastic clinical situations, including liver diseases. Their sensitivity and specificity are lower for tumor screening in these cases. In this study, we investigated the frequency and significance of elevated tumor markers in the pre-orthotopic liver transplantation (OLT) evaluation among patients with end-stage liver disease who did not develop tumors after a long follow-up post-OLT. We performed a retrospective analysis of clinical and biological parameters of 100 OLT candidates comparing data for CA 125, CA 19-9, CA 15-3, and carcinoembryonic antigen (CEA) levels. CA 125, CA 19-9, CA 15-3, and CEA levels were elevated in 59%, 53%, 29%, and 28% of cases, respectively. CA 125, CA 15-3, and CEA were associated with disease severity (Child-Pugh classification). CA 125 was also elevated among patients with ascites, esophageal varices, or alcohol-related cirrhosis. Elevated CA 19-9 levels were associated with increased CA 15-3 and CEA levels. CA 15-3 levels were also increased among patients with elevated alkaline phosphatase, while elevated CEA was related to ascites, bilirubin, and prothrombin time (PT) levels, as well as alcohol-related cirrhosis. There was no association between hepatocellular carcinoma and tumor markers. In conclusion, CA 125, CA 19-9, CA 15-3, and CEA were frequently elevated among end-stage liver disease patients. These elevations were not associated with tumor diseases in this population.

Portal venous gas following chemotherapy for colorectal cancer liver metastasis.

The standard of care for patients with colorectal liver metastases is a combination of chemotherapy and surgery. New chemotherapy regimens with biologic agents (cetuximab, bevacizumab) have been shown to increase tumor response rates. Although this might be beneficial and this is an expected endpoint, it should be noted that patients with synchronous colorectal and liver metastases are at risk of septic complications. We recently encountered a case of hepatic portal venous gas after two cycles of chemotherapy in a patient with right colon cancer liver metastases. Complete necrosis of the liver metastasis subsequently turned into a liver abscess, which fistulized in the right portal vein. Infection of the necrotized metastasis was thought to be promoted by the colic tumor. Although this is a dramatic situation, it does not contraindicate a curative surgical resection.

Median arcuate ligament in orthotopic liver transplantation: relevance to arterial reconstruction.

Median arcuate ligament (MAL) syndrome results from luminal narrowing of the celiac artery by the insertion of the diaphragmatic muscle fibers or by fibrous bands of the celiac nervous plexus. In 10% to 50% of cases it is responsible for significant angiographic celiac trunk compression. In orthotopic liver transplantation (OLT), the presence of celiac compression by MAL is considered to be a risk factor for hepatic arterial thrombosis (HAT); it may lead to graft loss. Various surgical procedures have been proposed to overcome the impact of MAL in OLT, but their impact is still ill defined. The aim of our study was to compare standard hepatic artery reconstruction and graft reconstruction (aortohepatic bypass) in terms of HAT among patients with MAL undergoing OLT. We retrospectively reviewed 168 adult recipients of OLT performed from January 1991 to December 1998. Ten cases (5.6%) of celiac compression by MAL were identified after celiomesenteric arteriography. There was no significant difference in terms of HAT incidence when aortohepatic bypass was performed compared to a standard anastomosis; moreover, this was greater in the graft reconstruction group (25% vs 17%; P = .67). In our opinion, the presence of an arcuate ligament should not contraindicate a routine hepatic artery reconstruction.