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.

Fatal outcome after reactivation of inherited chromosomally integrated HHV-6A (iciHHV-6A) transmitted through liver transplantation.

HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft. Transmission was followed by reactivation, with high viral loads in several compartments. The infection was uncontrollable, leading to severe disease and death, despite antiviral treatments and the absence of resistance mutations. This case highlights the fact that physicians should be aware of the possible horizontal transmission of iciHHV-6 and its consequences in case of reactivation in immunocompromised patients.

Efficacy and Safety of Everolimus and Mycophenolic Acid With Early Tacrolimus Withdrawal After Liver Transplantation: A Multicenter Randomized Trial.

SIMCER was a 6-mo, multicenter, open-label trial. Selected de novo liver transplant recipients were randomized (week 4) to everolimus with low-exposure tacrolimus discontinued by month 4 (n = 93) or to tacrolimus-based therapy (n = 95), both with basiliximab induction and enteric-coated mycophenolate sodium with or without steroids. The primary end point, change in estimated GFR (eGFR; MDRD formula) from randomization to week 24 after transplant, was superior with everolimus (mean eGFR change +1.1 vs. -13.3 mL/min per 1.73 m2 for everolimus vs. tacrolimus, respectively; difference 14.3 [95% confidence interval 7.3-21.3]; p < 0.001). Mean eGFR at week 24 was 95.8 versus 76.0 mL/min per 1.73 m2 for everolimus versus tacrolimus (p < 0.001). Treatment failure (treated biopsy-proven acute rejection [BPAR; rejection activity index score >3], graft loss, or death) from randomization to week 24 was similar (everolimus 10.0%, tacrolimus 4.3%; p = 0.134). BPAR was more frequent between randomization and month 6 with everolimus (10.0% vs. 2.2%; p = 0.026); the rate of treated BPAR was 8.9% versus 2.2% (p = 0.055). Sixteen everolimus-treated patients (17.8%) and three tacrolimus-treated patients (3.2%) discontinued the study drug because of adverse events. In conclusion, early introduction of everolimus at an adequate exposure level with gradual calcineurin inhibitor (CNI) withdrawal after liver transplantation, supported by induction therapy and mycophenolic acid, is associated with a significant renal benefit versus CNI-based immunosuppression but more frequent BPAR.

Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial.

Efficacy and safety of protein kinase C inhibitor sotrastaurin (STN) with tacrolimus (TAC) was assessed in a 24-month, multicenter, phase II study in de novo liver transplant recipients. A total of 204 patients were randomized (1:1:1:1) to STN 200 mg b.i.d. + standard-exposure TAC (n = 50) or reduced-exposure TAC (n = 52), STN 300 mg b.i.d. + reduced-exposure TAC (n = 50), or mycophenolate mofetil (MMF) 1 g b.i.d. + standard-exposure TAC (control, n = 52); all with steroids. Owing to premature study termination, treatment comparisons were only conducted for Month 6. At Month 6, composite efficacy failure rates (treated biopsy-proven acute rejection episodes of Banff grade ≥1, graft loss, or death) were 25.0%, 16.5%, 20.9% and 15.9% for STN 200 mg + standard TAC, STN 200 mg + reduced TAC, STN 300 mg + reduced TAC and control groups, respectively. Median estimated glomerular filtration rates were 84.0, 83.3, 81.1 and 75.3 mL/min/1.73 m(2), respectively. Gastrointestinal events (constipation, diarrhea, and nausea), infection, and tachycardia were more frequent in STN groups. More patients in STN groups experienced serious adverse events compared with the control group (62.3-70.8% vs. 51.9%). STN-based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups.

Recurrence of hepatocellular carcinoma in noncirrhotic liver after hepatectomy.

BACKGROUND: Hepatocellular carcinoma in noncirrhotic liver (HCCNC) is rare. This tumor has a particular epidemiology and presentation, and it requires specific treatment, compared with HCC in cirrhotic liver. The aims of this study were to determine the survival and recurrence rates, prognostic factors, and optimum treatment of HCCNC and to propose a follow-up protocol for patients who have undergone surgery for HCCNC. METHODS: This study included 131 patients who underwent surgical treatment for HCCNC from January 1992 to December 2010. Survival and recurrence rates were evaluated, and the prognostic factors and characteristics of recurrence were analyzed. Pathologic characteristics of the tumors and the nontumoral liver were examined. RESULTS: The mean survival time was 67.9 months. The 5- and 10-year overall survival rates were 72.9 and 36.7 %, respectively. In all, 54 patients (41.2 %) developed recurrence at a median interval of 30.96 months. Of these recurrences, 31.5 % occurred during the first year, and 24.1 % occurred more than 5 years after surgery. Macro- or microvascular invasion and tumor size >5 cm were significantly associated with a poor survival rate. The predictive factors for recurrence were multiple tumors, tumor diameter >5 cm, and satellite nodules. Patients who underwent surgical treatment for recurrence had a significantly longer survival time than those who did not (p < 0.0292). CONCLUSIONS: Recurrence is the most common cause of death after hepatectomy for HCC, and patients should undergo careful, long-term follow-up. Early detection and treatment of recurrence with curative intent should improve the prognosis of these patients.

Skin reference point for the zygomatic branch of the facial nerve innervating the orbicularis oculi muscle (anatomical study).

PURPOSE: Direct access to the zygomatic branch of the facial nerve in the parotid is less invasive and more selective than first dissecting the nerve trunk and then finding the branches. The aim of this study was to confirm the point of reference on the skin which would give direct access to the zygomatic branch for the orbicularis oculi muscle. The skin reference point studied was on the intertragic notch/external canthus line, 2.5 cm in front of the intertragic notch. METHODS: Ten fresh cadavers, and thus 20 sides of faces were dissected. The zygomatic branch of the facial nerve innervating the orbicularis oculi muscle was accessed directly. The dissection was extended to temporofacial and cervicofacial branches and then to the trunk of the facial nerve by a retrograde path in the parotid. RESULTS: Twenty dissections of the parotid area confirmed the validity of the anatomical reference point of the zygomatic branch for the orbicularis oculi muscle considered. CONCLUSIONS: The simplicity and reliability of this landmark is important in clinical practice and has numerous potential applications in surgery for rehabilitation of facial paralysis associated with VII healthy and VII affected neurorraphies, in facial paresis for superneurotizations and in traumatology.

Long term outcome of multidisciplinary management of urethro-rectal fistula after urologic surgery.

Urethro-rectal fistula (URF) is a rare but serious condition whose treatment is poorly codified. This study aims to evaluate the short and long-term results of multidisciplinary management. MATERIAL AND METHODS: We retrospectively collected the records of patients with URF operated on at the University Hospital of Tours between January 1, 2000 and January 1, 2020. Short-term and long-term results according to management are reported. RESULTS: The study included 20 patients. As an initial gesture, 11 patients underwent bladder catheterization and colostomy, seven underwent bladder catheterization alone, one underwent graciloplasty, and one, a York Mason procedure. The success rate of initial conservative management was only 5% (1/20). As a secondary or tertiary intervention, ten patients underwent a York Mason procedure and nine underwent graciloplasty. At the end of the study period, with a median follow-up of 50 months, 19 had been effectively treated for URF, 16 were able to have colostomy closure with restoration of digestive continuity while four had a permanent stoma. One patient had anal incontinence, 14% had major stress urinary incontinence. CONCLUSION: Multidisciplinary care remains a cornerstone of the treatment of URF because iterative surgeries may be required, with an overall success rate of up to 95% at the end of follow-up.

Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study.

We conducted a multicenter randomized study in liver transplantation to compare standard-dose tacrolimus to reduced-dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post-transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety-five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37-0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49-0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29-0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced-dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full-dose tacrolimus in adult liver transplantation.

Anatomic basis of ulnar index metacarpal reverse flow vascularized bone graft for index distal bone loss.

Well-known advantages of vascularized bone grafts led us to determine the anatomical basis of a metacarpal vascularized bone graft to find a solution for distal index bone loss. Seventeen adult human hands from fresh cadavers were dissected and analyzed. For each hand, we studied the second dorsal metacarpal artery, the ulnar dorsal proper digital artery of index, and the ulnar palmar proper digital artery of the index. Location, diameters, origins, and anastomoses were observed, and at the end, the vascularised bone graft was raised. The second dorsal metacarpal artery was present in all hands, always arising from the dorsal carpal arch with a 1-mm mean diameter. The ulnar dorsal proper digital artery of index was isolated on all dissections, with a subcutaneous location on the ulno-dorsal side of the proximal phalanx. The mean diameter of ulnar dorsal proper digital artery at the level of index proximal phalanx was 0.4 mm. We found anastomotic branches between the ulnar dorsal and palmar proper digital artery of index at the level of the proximal phalanx which permitted us to elevate a vascularised bone graft. We succeeded in removing the graft in all specimens. Its pivot point was always more distal than the middle of the proximal phalanx. The arc of rotation allowed the graft to reach the distal phalanx in 80% of the cases. This anatomical study has demonstrated the theoretical possibility of a reversed pedicled bone graft taken from the ulnar neck of the second metacarpal. This graft brings the following benefits: (a) the use of a minor vascular axis, (b) a surgical technique with a dorsal approach allowing the elevation and the use of the graft at the same time. It can be used on the index for failures of DIP joint arthrodesis, huge chondroma, or traumatology.

Management of biliary acute pancreatitis.

Acute pancreatitis is a frequent pathology with 11,000 to 13,000 new cases per year in France. A biliary origin (30 to 70% of the cases) should be suspected when alanine amino-transferases are elevated during the first 48 hours, and it is confirmed by the presence of gallstones at trans abdominal ultrasound. Abdominal computed-tomography scan is performed around the fifth day, and is repeated according to clinical and biological evolution. Management of acute biliary pancreatitis varies according to its severity, which should be assessed according to systemic inflammatory response syndrome and organ failures. For mild acute pancreatitis, cholecystectomy should be performed during in-hospital stay, before oral feeding. For moderately severe and severe acute pancreatitis, treatment is based on resuscitation, early enteral continuous feeding, and management of complications. Interval cholecystectomy is performed at a later stage. Endoscopic retrograde cholangiopancreatography with sphincterotomy should be performed in emergency when angiocholitis is associated, and in delayed emergency before oral feeding for persistent common bile duct stone. A common bile duct stone should be searched for during cholecystectomy and can be treated during the same surgical procedure if local conditions are adequate. Cholelithiasis is the most frequent cause of acute pancreatitis during pregnancy, and its diagnosis and the treatment have some particularities.

Long-term outcome and management of right colonic diverticulitis in western countries: Multicentric Retrospective Study.

AIM OF THE STUDY: Right colonic Diverticulitis (RD) is rare in Europe; few studies have focused on it and its management is not standardised. The aim of this study was to analyse the clinical presentation (complicated, uncomplicated), acute phase management and long-term outcome of RD in western countries. PATIENTS AND METHODS: From 2003 to 2017, 93 consecutive patients who presented with RD were retrospectively included at 11 French Hospital Centres. RESULTS: The study population consisted of two groups: Uncomplicated Right Diverticulitis (URD) group (63.5%, (n=59)) and Complicated Right Diverticulitis (CRD) group (36.5%, [n=34]). 84.7% (n=50/59) of URD were treated conservatively. 41.2% (n=14/34) of patients with CRD had emergency surgery (mostly laparotomy) for Hinchey III peritonitis, clinical intolerance or hemodynamic instability. Altogether 5.2% (n=2/34) patients with CRD had surgery after a cooling off period (initially abscess). The overall rate of severe postoperative complications was low (8%). Recurrence rate was low and comparable in both groups: 6.8% (n=4/59) for URD and 8.8% (n=3/34) for CRD, all recurrences occurred in the same locations with an uncomplicated form, 42.9% (n=3/7) of them had elective laparoscopic surgery and the rest were conservatively treated. Median follow up was 33.2 months. CONCLUSION: Conservative treatment can be proposed safely and efficiently for URD and for selected patients with CRD. Surgery should be reserved for unstable patients or patients with severe forms of complicated diverticulitis in emergency.

[Stereotactic body radiation therapy for hepatocellular carcinoma: Results from a retrospective multicentre study]. / Radiothérapie en conditions stéréotaxiques du carcinome hépatocellulaire : résultats d'une étude rétrospective multicentrique.

PURPOSE: The purpose of this paper was to describe local control, overall survival, progression-free survival and toxicity of CyberKnife®-based stereotactic body radiation therapy of hepatocellular carcinoma. MATERIAL AND METHODS: Records of all the patients treated for hepatocellular carcinoma at the Eugene-Marquis cancer centre, Rennes and the Bretonneau hospital, Tours (France), between November 2010 and December 2016, were reviewed. Radiation therapy was performed as a salvage treatment, while awaiting liver transplantation or if no other treatment was possible. RESULTS: One hundred and thirty-six patients were consecutively included in the study. The median follow-up was 13months. Median total dose prescribed, fractionation and overall treatment time were respectively 45Gy, three fractions and 5 days. Overall survival, progression-free survival and local control rates at 1year and 2years were 79.8 % and 63.5 %, 61.3 % and 39.4 %; 94.5 % and 91 %. Two grade 3 acute toxicity events and two grade 4 late toxicity events corresponding to a duodenal ulcer have been reported. Seven patients underwent classic radiation-induced hepatitis and 13 patients showed non-classical radiation-induced hepatitis. Barcelona Clinic Liver Cancer stage, World Health Organisation grade and planning target volume were correlated with overall survival in univariate Cox analysis. CONCLUSION: Stereotactic body radiation therapy is effective and well-tolerated for inoperable hepatocellular carcinoma or as a bridge to liver transplantation. Toxicity is mainly related to cirrhotic background and requires a selection of patients and strict dose constraints.

Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report.

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver > or =120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven. Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10(-7)). LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.

Hepatitis E virus infection mimicking acute graft rejection in a liver transplant recipient.

INTRODUCTION: In liver transplant (LT) patients, hepatitis E virus (HEV) can lead to acute liver failure, chronic hepatitis and graft cirrhosis. Few data on graft rejection associated with HEV are available and are subject to discussion. CASE REPORT: Here we report the case of a 58-year-old male patient who underwent LT in July 2015 for cirrhosis due to NASH and chronic alcohol intake complicated by hepatocellular carcinoma. LT was performed with a deceased donor isogroup and a mismatch CMV (donor+ and recipient-). HEV serology was negative before LT. In February 2016, we noted abnormal liver function, with increased transaminases and cholestasis parameters, without functional complaints. The patient was immunosuppressed by tacrolimus (4mg) and everolimus (2mg). Abdominal ultrasound was normal and liver biopsy showed signs of acute rejection (Banff score 6/9). We dispensed 500mg of methylprednisolone before obtaining positive serological results for HEV genotype 3 infection. Ribavirin (1,200mg per day) for 3 months was started, leading to rapid improvement in liver tests. Viral load became negative one month later. To date, the patient is under LP 5mg tacrolimus with normal liver tests. CONCLUSION: We describe a case of HEV genotype 3 infection mimicking acute cellular rejection, with a favorable outcome due to ribavirin treatment. As intensive immunosuppressive therapy administered for graft rejection may promote viral replication and worsen liver damage, potential HEV infection must be considered in cases of pathological signs of acute cellular rejection, in order to avoid chronic graft hepatitis, cirrhosis and liver decompensation.

Barriers and Advances in Kidney Preservation.

Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.

[Ecchymosis as the presenting manifestation of Wilson disease: A case report]. / Ecchymoses diffuses révélant une maladie de Wilson : à propos d'un cas.

INTRODUCTION: The presence of a psychiatric disorder during the course of an organic disease is a common cause of delayed diagnosis. CASE REPORT: We report a 16-year-old girl who was admitted with thrombocytopenia and had a two-year history of neuropsychiatric disorder which was attributed to a difficult family situation. Neurological examination showed a frontal lobe disorder and extrapyramidal manifestations. The thrombocytopenia was attributed to liver cirrhosis. These neurological and hepatic injuries were consistent with a metabolic disease, most likely Wilson disease. This was supported by the presence of a corneal Kayser-Fleischer ring and a decreased ceruloplasmin concentration. An urgent liver transplantation was required due to worsening neurological symptoms. CONCLUSION: Wilson disease is a rare genetic disease caused by copper toxicity. It is characterized by combined hepatic and neurologic damage to varying degrees and can develop at any age. Urgent treatment is required, but the diagnosis may be delayed by prevailing psychiatric symptoms.

[Results of resection for ductal adenocarcinoma of the pancreatic head]. / Résultats carcinologiques de l'exérèse chirurgicale du cancer glandulaire céphalique du pancréas.

INTRODUCTION: Pancreaticoduodenectomy (PD) is the only curative treatment for adenocarcinoma of the pancreatic head but is associated with a significant early morbidity and a poor long term survival. Therefore, its value is still debated. The aim of this study was to evaluate early and distant results of PD for pancreatic adenocarcinoma, and to identify prognostic factors. SUMMARY: Seventy-nine patients who underwent PD with curative intent for adenocarcinoma of the pancreatic head from 1982 to 2002 were studied retrospectively. The following data were evaluated: operative mortality, long-term survival, prognostic factors (through univariate and multivariate analysis), and characteristics of 5-year survivors. RESULTS: Mortality rate was 1.3%. Survival at 1, 3 and 5 years was 46%, 26% and 11%. The median survival was 12 months. The prognostic factors were the T stage (T.N.M. classification) and radicality of resection. After multivariate analysis, radicality of resection was the only independent prognostic factor. Five patients survived for more than 5 years. They did not differ of the other patients but none had positive margin or venous invasion. CONCLUSIONS: These results (low mortality, significant distant survival including some long term survivors) suggest that PD for pancreatic adenocarcinoma must be indicated in most low-risk patients. PD remains the only curative treatment allowing prolonged survival.

[Sensitization of tilt-table testing for syncope of unknown etiology: which drug to use?]. / Quel agent pharmacologique utiliser pour la sensibilisation du test d'inclinaison dans l'evaluation des syncopes d'origine indéterminée?

OBJECTIVE: The sensitivity of tilt-table testing in the diagnosis of vasovagal syncope is between 30% and 50% only. The most common method currently used to improve the sensitivity of the test is the administration of isoproterenol i.v. However, this method is difficult to perform and time consuming. The objective of our study was to compare sublingual trinitrin administration to i.v. isoproterenol during tilt-table testing. METHODS: We analyzed the results of 257 consecutive patients referred for tilt testing. Patients who had a negative test received either a ten minutes infusion of i.v. isoproterenol at the dose of 4 mcg/kg/min, or 0.4 mg of trinitrin given sublingually. RESULTS: Two hundred (and) fifty-seven patients underwent tilt-table testing. In the first group (isoproterenol group), 42 patients (39%) had a spontaneous positive tilt test, compared to 45 patients (31%) in the trinitrin group (P = NS). After sensitization, 24 additional patients (22%) had a positive test in the isoproterenol group vs 55 patients (37%) in the trinitrin group (P = NS). The total number of positive tests was 66 (61%) in the isoproterenol group compared to 100 (68%) in the trinitrin group (P = NS). CONCLUSION: Sublingual trinitrin is at least as good as IV isoproterenol during tilt-table testing. Because trinitrin is simpler to use and because its administration is much faster than isoproterenol, it should be recommended as the drug of choice to improve the sensitivity of tilt-table testing.

[Beneficial effect of sildenafil following surgery for mitral stenosis complicated by pre-capillary pulmonary hypertension: report of two cases]. / Effet bénéfique du sildénafil en postopératoire dans le rétrécissement mitral compliqué d'hypertension artérielle pulmonaire précapillaire: a propos de deux cas.

Pulmonary hypertension is a serious disorder, difficult to treat especially in the severe forms. The treatment consists mainly of calcium channel blockers, anti-coagulation, intravenous epoprostenol, inhaled nitric oxide and recent agents as bosentan and sildenafil. Sildenafil, a phosphodiesterase 5 specific inhibitor, has been largely evaluated in primary pulmonary hypertension, and in some cases of secondary pulmonary hypertension including parenchymal and thromboembolic diseases; it has not yet been evaluated in severe pulmonary hypertension with elevated pre-capillary resistance in operated mitral stenosis. We report the cases of two patients operated from mitral valve replacement for severe mitral stenosis with elevated pre-capillary resistance, where oral sildenafil, introduced empirically immediately after the surgical procedure at the dose of 50 mg/d, permitted a significant decrease in pulmonary pressures and resistances, allowing a rapid withdrawal of nitric oxide and reducing therefore hospitalization time in the intensive care unit. We think that this simple treatment, with or without association to nitric oxide, should be generalized to persistent pulmonary hypertension following cardiac surgery.