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The results of this study were presented during the 13th Congress of the E-AHPBA on June 3th 2019, in Amsterdam.; International audience; BACKGROUND: Major bile duct injuries (BDI) following cholecystectomy require complex reconstructive surgery. The aim was to collect the liver transplantations (LT) performed in France for major BDI following cholecystectomy, to analyze the risk factors and to report the results. METHODS: National multicenter observational retrospective study. All the patients who underwent a LT in France between 1994 and 2017, for BDI following cholecystectomy, were included. RESULTS: 30 patients were included. 25 BDI occurred in non hepato-biliary expert centers, 20 were initially treated in these centers. Median time between injury and LT was 3 years in case of an associated vascular injury (11 injuries), versus 11.7 years without vascular injury (p = 0.006). Post-transplant morbidity rate was 86.7%, mortality 23.5% at 5 years. CONCLUSION: Iatrogenic BDI remains a real concern with severe cases, associated with vascular damages or leading to cirrhosis, with no solution but LT. It is associated with high morbidity and not optimal results. This enlights the necessity of early referral of all major BDI in expert centers to prevent dramatic outcome. Decision to perform transplantation should be taken before dismal infectious situations or biliary cirrhosis and access to graft should be facilitated by Organ Sharing Organizations.

Introduction: Splenic parenchymal endometriosis has never been described to date. We report here the case of real parenchymal endometriosis of the spleen. Case description: In this case, a 54-year-old female patient presented a histologically proven metastatic recurrence of breast cancer in the internal breast chain. The CT-scan also detected a large cystic structure developed from the spleen, but non-suspected to be metastasis. The patient was treated with chemotherapy (paclitaxel) and a combination of targeted therapies (everolimus and trastuzumab). While a complete radiological and biological response was noted at 2 months, the splenic cyst gradually decreased over the years. When targeted therapies were stopped, a reincrease of the splenic lesion and de novo significant hypermetabolism of the splenic parenchyma on 18F-FDG PET scan were observed. A splenectomy was finally performed and revealed splenic parenchymal endometriosis. Conclusion: This case once again highlights the complexity of endometriosis disease, from a pathophysiological point of view, but also the difficulties of radiological characterisation, and diagnostic management.

Summary Aim To study morbi-mortality, survival after hepatectomy in elderly patients, and influence on their short-term autonomy. Patients and methods This is a retrospective study conducted between 2002 and 2017 comparing patients less than 65 years old (controls) to those more than 65 years old (cases) from a prospective database, with retrospective collection of geriatric data. Cases were divided into three sub-groups (65–70 years, 70–80 years and > 80 years). Results Four hundred and eighty-two patients were included. There was no age difference in number of major hepatectomies (P = 0.5506), length of stay (P = 0.3215), mortality at 90 days (P = 0.3915), and surgical complications (P = 0.1467). There were more Grade 1 Clavien medical complications among the patients aged over 65 years (P = 0.1737). There was no difference in overall survival (P = 0.460) or disease-free survival (P = 0.108) according to age after adjustment for type of disease and hepatectomy. One-third of patients had geriatric complications. The “home discharge” rate decreased significantly with age from 92% to 68% (P = 0.0001). Early loss of autonomy after hospitalization increased with age, 16% between 65 and 70 years, 23% between 70 and 80 years and 36% after 80 years (P = 0.10). We identified four independent predictors of loss of autonomy: age > 70 years, cholangiocarcinoma, length of stay > 10 days, and metachronous colorectal cancer. Conclusions Elderly patients had the same management as young patients, with no difference in surgery or survival, but with an increase in early loss of autonomy.

Summary Aim of the study Fourteen to seventeen percent of patients suffering from colorectal cancer have synchronous liver metastases (sCRLM) at the time of diagnosis. There are currently three possible strategies for curative management of sCRLM: “classic”, “combined”, and “liver-first”. The aim of our research was to analyze the effects of the three surgical management strategies for sCRLM on postoperative morbidity and mortality and overall and recurrence-free survival. Patients and Methods Patients treated for sCRLM between October 2000 and May 2015 were included. We defined three groups: (1) “classic”: surgery of primary tumor and then surgery of sCRLM; (2) “combined”: combined surgery of primary tumor and sCRLM: and (3) “liver-first”: surgery of sCRLM and then surgery of primary tumor. Results During this period, 170 patients who underwent 209 hepatectomies were included (“classic”: 149, “combined”: 34, “liver-first”: 26). The rate of severe complications was higher in the “combined” group compared to the “classic” group (35% vs. 12%, P = 0.03), and the “liver-first” group (35% vs. 19%, P = 0.25), while there were significantly fewer liver resections. Overall survival at 5 years in our cohort was 46%, without significant differences between the groups, and a median survival of 54 months. Recurrence-free survival of the patients in our cohort was 24% at 5 years, with a median survival time without recurrence of 14 months, without significant differences between the groups. Conclusion All three strategies were feasible and there were no differences regarding overall and recurrence-free survivals between the three approaches. The “combined” strategy group had significantly more severe complications and did not provide better oncological results, despite less aggressive liver disease and more limited liver resections.

Biliary fistula is one of the most common complications after hepatectomy. This study evaluated the effect of transcystic biliary drainage during hepatectomy on the occurrence of postoperative biliary fistula.This multicentre RCT was carried out from 2009 to 2016 in nine centres. Patients were randomized to transcystic biliary drainage or no transcystic drainage (control). Patients underwent hepatectomy (more than 2 segments) of non-cirrhotic livers. The primary endpoint was the occurrence of biliary fistula after surgery. Secondary endpoints were morbidity, postoperative mortality, duration of hospital stay, reoperation, readmission to hospital, and complications caused by catheters. Intention-to-treat and per-protocol analyses were performed.A total of 310 patients were randomized. In intention-to-treat analysis, there were 158 patients in the transcystic group and 149 in the control group. Seven patients were removed from the per-protocol analysis owing to protocol deviations. The biliary fistula rate was 5·9 per cent in intention-to-treat and 6·0 per cent in per-protocol analyses. The rate was similar in the transcystic and control groups (5·7 versus 6·0 per cent; P = 1·000). There were no differences in terms of morbidity (49·4 versus 46·3 per cent; P = 0·731), mortality (2·5 versus 4·7 per cent; P = 0·367) and reoperations (4·4 versus 10·1 per cent; P = 1·000). Median duration of hospital stay was longer in the transcystic group (11 versus 10 days; P = 0·042). The biliary fistula risk was associated with the width and length of the hepatic cut surface.This randomized trial did not demonstrate superiority of transcystic drainage during hepatectomy in preventing biliary fistula. The use of transcystic drainage during hepatectomy to prevent postoperative biliary fistula is not recommended. Registration number: NCT01469442 ( http://www.clinicaltrials.gov).La fístula biliar es una de las complicaciones más comunes después de la hepatectomía. Este estudio evalúa el efecto del drenaje biliar transcístico durante la hepatectomía en la aparición de una fístula biliar postoperatoria. MÉTODOS: Este ensayo prospectivo aleatorizado y multicéntrico (Clinical Trial NCT01469442) con dos grupos de estudio (grupo transcístico versus grupo control) se llevó a cabo de 2009 a 2016 en 9 centros. Los pacientes fueron sometidos a una hepatectomía (≥ 2 segmentos) en hígados no cirróticos. El resultado principal fue la aparición de una fístula biliar después de la cirugía. Los resultados secundarios fueron la morbilidad, la mortalidad postoperatoria, la duración de la estancia hospitalaria, la reintervención, la necesidad de reingreso y las complicaciones causadas por los catéteres. Se realizaron análisis por intención de tratamiento y por protocolo.Un total de 310 pacientes fueron randomizados. Por intención de tratamiento, 158 pacientes fueron aleatorizados al grupo transcístico y 149 al grupo control. Siete pacientes fueron excluidos del análisis por protocolo por desviaciones del protocolo. La tasa de fístula biliar fue del 5,9% en el análisis por intención de tratamiento y del 6,0% en el análisis por protocolo. Esta tasa fue similar para el grupo transcístico y para el grupo control: 5,7% versus 6,0% (P = 1). No hubo diferencias en términos de morbilidad (49,4% versus 46,9%, P = 0,731), mortalidad (2,5% versus 4,7%, P = 0,367) y reintervenciones (4,4% versus 10,1%, P = 1). La mediana de la duración de la estancia hospitalaria fue mayor para el grupo transcístico (11 versus 10 días, P = 0,042). El riesgo de fístula biliar se correlacionó con el grosor y la longitud de la transección hepática. CONCLUSIÓN: Este ensayo aleatorizado no demuestra la superioridad del drenaje transcístico durante la hepatectomía para prevenir la fístula biliar. No se recomienda el uso de drenaje transcístico durante la hepatectomía para prevenir la fístula biliar postoperatoria.

The localization of endometriotic disease in the hepatic pedicle has never been reported to date. We report the first case of a 67-year-old postmenopausal patient having presented an endometriotic lesion in the hepatic pedicle. A surgical biopsy was needed to confirm the diagnosis after a first radiologic biopsy that concluded the presence of a mucinous cystic tumor with low-grade dysplasia. Medical treatment with aromatase inhibitors was carried out because of the inextirpable nature of the lesion. The diagnosis and therapeutic management of this rarely occurring lesion of atypical localization in a postmenopausal patient is presented here. A review of the literature on this localization could have led to a damaging surgical treatment due to the different diagnoses suggested. Management of endometriosis relies on a multidisciplinary approach that each practitioner must know how to broach with patients of all ages.

Background To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in terms of mortality, severity and complications. Methods Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis. Results Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 [15–25] vs. 21 [15–24] respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 [7–36] vs. 6[3–12] days, p p = 0.001), and experienced more complications (reoperation and reintubation) than those with CA-IAI. Conclusion CA-IAI group had higher 28-day mortality rate than HA-IAI group. Mortality was similar at 90 days but those with HA-IAI had a prolonged ICU and hospital stay. In addition, they developed more complications.

BACKGROUND Pancreaticoduodenectomy (PD)-induced morbidity, consisting mainly of the pancreatic fistula and its hemorrhagic and infectious consequences, is well described in the literature, in terms of its definition, risk factors, preventive measures, and standardized management of complications. However, some life-threatening complications remain atypical and undescribed. CASE SUMMARY We report here the case of a 69-year-old patient with Budd-Chiari syndrome that occurred after arterial embolization of postpancreatectomy hemorrhage. Diagnosis was established with biological findings (i.e., acute liver failure) and radiological findings (i.e., compressive hematoma of the retrohepatic vena cava). Emergency surgical revision was performed to evacuate the hematoma. The postoperative course was uneventful, with rapid recovery of liver function. To our knowledge, post-PD Budd-Chiari syndrome has never been described in the literature. CONCLUSION Acute liver failure in early post-PD should prompt investigation to rule out Budd-Chiari syndrome.

Abdominal interventions are usually contraindicated in patients with cirrhosis and portal hypertension because of increased morbidity and mortality. Decreasing portal pressure with transjugular intrahepatic portosystemic shunt (TIPS) may improve patient outcomes. We report our experience with patients treated by neoadjuvant TIPS to identify those who would most benefit from this two-step procedure.All patients treated by dedicated neoadjuvant TIPS between 2005 and March 2013 in two tertiary referral hospitals were included. The primary endpoint was the rate of failure, defined by the inability to proceed to the planned intervention after TIPS placement or persistent liver decompensation 3 months after intervention. The secondary endpoints were the rate of complications, parameters associated with failure, and 1-year survival.Twenty-eight consecutive patients were included, with a mean age of 61.2±6.6 years, mean Child-Pugh score of 6.6±1.5, and mean model for end-stage liver disease score of 10.4±3.3. Procedures were digestive (43%) or liver (25%) resections, abdominal wall surgery (21%), or interventional gastrointestinal endoscopies (11%). The scheduled procedure was performed in 24 (86%) patients within a median of 25 days after TIPS. Procedure failures occurred in six (21%) patients: four did not undergo surgery and two experienced persistent liver decompensation. Seven (25%) patients had postoperative complications, mainly local. Viral origin of cirrhosis, history of encephalopathy, and hepatic surgery were found to be associated with failure. One-year survival in the whole cohort was 70%.In selected patients, extrahepatic surgery or interventional endoscopies can be safely performed after portal hypertension has been controlled by TIPS.

During the last twenty years, a huge progress has been achieved in the treatment of liver cancer and recent strategies include interventional radiology, chemotherapy regimens and surgery. Meanwhile, Stereotactic Body Radiation Therapy (SRBT) has developed in the treatment of all organs with millimetre accuracy, very few side effects and a high control rate. So, SRBT has become a therapeutic weapon in his own right in liver tumour treatment. Many publications have reported encouraging results in colorectal liver metastasis, hepatocellular carcinoma on cirrhosis and peripheric cholangiocarcinoma. It is important that radiation therapists involve systematic multidisciplinary "liver tumour" meetings to discuss therapeutic indications and initiate treatments quickly.

International audience; Background & aims: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.Methods: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times.Results: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P = .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P = .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P = .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001).Conclusion: In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).

ObjectiveHepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells.DesignWe developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions.ResultsPrimary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm3, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient.ConclusionHEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.

BACKGROUND AND OBJECTIVES To analyze overall survival (OS) rates for the three curative treatments of hepatocellular carcinoma (HCC) on an intention-to-treat (ITT) basis. METHODS Cohort study based on data from a multidisciplinary team meeting (MDT) dedicated to HCC. From 2006 to 2013, we included every patient with newly diagnosed HCC, for whom curative treatment (liver transplantation (LT), radiofrequency ablation (RFA), surgical resection (SR)) was decided upon. RESULTS We included 387 consecutive patients. LT was decided in 136 cases, RFA in 131 cases, SR in 120 cases. Sixty-six percent of patients received the planned treatment. Five-year OS on an ITT basis were: 35% for the LT-group, 32% for the RFA-group, 34% for the SR-group (P = 0.77). In multivariate analyses, the main negative prognostic factors were not following the MDT decision (HR: 0.39, CI95% [0.27-0.54], P

Summary Background To evaluate the performance of CT-scans performed one week after pancreato-duodenectomy (PD) to detect severe postoperative complications requiring an invasive treatment. Patients and methods This monocentric retrospective study was conducted on data collected between 2005 and 2013. Patients undergoing PD underwent CT-scan with IV contrast at the end of the first postoperative week. The results of the CT-scans were analyzed to evaluate the usefulness of this procedure. The main assessment criterion was the occurrence of type-III complication (or greater) according to the Dindo-Clavien classification. Results In total, 138 patients were included. The mortality rate was 2.2%. The postoperative complication rate was 57.2%. The pancreatic fistula rate was 19.6%; 46 patients (33.3%) presented with a severe complication. A total of 138 CT-scans were analyzed: 44 (31.8%) were abnormal, 94 (68.2%) were normal. Among patients with abnormal CT-scans, 17 (39%) presented with a severe complication requiring an invasive treatment. Among the 94 patients with normal CT-scans, 14 patients (15%) presented a severe postoperative complication. Evaluation of the performance of the CT-scans at the end of the first postoperative week found a sensitivity of 55%, a specificity of 75%, a positive predictive value of 39%, and a negative predictive value of 85%. Conclusion Systematic CT-scans performed at the end of the first postoperative week do not effectively detect severe complications after PD and do not help to prevent them.

International audience; BACKGROUND:Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation.METHODS:A retrospective cross-sectional study, from 27 European high-volume HPB units.RESULTS:573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients.DISCUSSION:Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.

Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.

International audience; The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

The aim of our study was to perform a 10-year imaging and clinical prospective follow-up of patients with nonoperated branch duct (BD) intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.Forty-nine patients with BD-IPMN who displayed a low probability for malignancy were followed up including a clinical component and a series of imaging techniques such as computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography.After a mean follow-up period of 77 months, 77.5% of patients remained free of symptoms. An increase in the size and number of BD cysts without mural nodules and with no significant increase of main duct size occurred in 18 patients at an average interval of 47 months. Five patients were operated on owing to recurrent pancreatitis and/or an increase in the size of either cysts or the main duct (mean time delay after diagnosis: 20 months). Pathologically, they were diagnosed as benign adenoma (n = 1) or borderline (n = 4).Our long-term clinical and imaging follow-up indicated that none of the patients with BD-IPMNs developed malignancy. Therefore, BD-IPMNs with no signs of malignancy should be managed conservatively. We propose that following a 2-year patient follow-up, biannual imaging follow-ups could be sufficient.

Background. Sorafenib is a molecular-targeted therapy used in palliative treatment of advanced hepatocellular carcinoma in Child A patients.Aims. To address the question of sorafenib as neoadjuvant treatment.Methods. We describe the cases of 2 patients who had surgery after sorafenib.Results. The patients had a large hepatocellular carcinoma in the right liver with venous neoplastic thrombi (1 in the right portal branch, 1 in the right hepatic vein). After 9 months of sorafenib, reassessment showed that tumours had decreased in size with a necrotic component. A right hepatectomy with thrombectomy was performed, and histopathology showed 35% to 60% necrosis. One patient had a recurrence after 6 months and had another liver resection; they are both recurrence-free since then.Conclusion. Sorafenib can downstage hepatocellular carcinoma and thus could represent a bridge to surgery. It may be possible to select patients in good general condition with partial regression of the tumour with sorafenib for a treatment in a curative intent.

Posttransplant patient outcome and quality of life are affected by different factors, such as post-graft context, psychological state, and polymedication. Many surveys have been carried out to study immunosuppressant ADRs, and have mainly used a questionnaire completed by patients, but few have asked patients about their drug exposure. The aim of this study is to describe drug exposure and adverse drug events (ADEs) reported by liver-transplant patients (LTP).This observational, retrospective study assessed questionnaires from LTPs concerning demographic data, drug exposure, and ADEs.118 LTPs exposed to 5.9 (+/- 2.8) drugs with immunosuppressive regimens, consisting mainly of tacrolimus (79.3%), cyclosporine (18.1%), or sirolimus (2.6%), were also exposed to antihypertensive drugs (43.2%), protonpump inhibitors (30.5%), statins (28.8%), drugs acting on bile composition (26.3%), and diuretics (19.5%). 1,389 ADEs were reported: 30.1% neurological, 13.4% cutaneous, 12.4% hematological, 11.1% digestive, 10.1% osteomuscular, 6.6% cardiovascular, and 16.3% others. Significantly more ADEs were reported by patients exposed to cyclosporine than those receiving tacrolimus (p0.05). Patients with a transplant for18 months had more tremors and those with a transplant for79 months reported more hirsutism, gingival hypertrophia, and arterial hypertension.This study shows the value of patient-reporting via structured interviews for both drug exposure and ADEs, and the importance of this approach to complement total data collection.

In cirrhotic patients, alveolar nitric oxide (NO) concentration is increased. This may be secondary to increased output of NO produced by the alveoli (V'(A,NO)) and/or to decreased lung transfer factor of NO. In advanced liver cirrhosis, NO produced by the alveoli may play a role in abnormalities of pulmonary haemodynamics and gas exchanges. In cirrhotic patients, we aimed to measure V'(A,NO) and to compare V'(A,NO) with pulmonary haemodynamics and gas exchange parameters. Measurements were performed in 22 healthy controls and in 29 cirrhotic patients, of whom eight had hepatopulmonary syndrome. Exhaled NO concentrations were measured at multiple expiratory flow rates to derive alveolar NO concentration. V'(A,NO) was the product of alveolar NO concentration by single breath lung transfer factor for NO. V'(A,NO) was increased in patients (median (range) 260 (177-341) nL x min(-1)) compared with controls (79 (60-90), p0.0001). Alveolar-arterial oxygen tension difference failed to correlate with V'(A,NO). However, cardiac index correlated positively and systemic vascular resistance correlated negatively with V'(A,NO) (r = 0.56, p = 0.001 and r = -0.52, p = 0.004, respectively). In cirrhotic patients, NO was produced in excess by the alveolar compartment of the lungs. Alveolar NO production was associated with hyperdynamic circulatory syndrome but not with arterial oxygenation impairment.

Aim To assess the consequences of graft steatosis on postoperative liver function as compared with normal liver grafts. Patients and methods From January 2005 to December 2007, liver transplant patients were prospectively included, excluding those who experienced arterial or biliary complications or presented acute rejection. All patients had a surgical biopsy after reperfusion. Patients were compared according to the rate of macrovacuolar steatosis: namely above or below 20%. Results Fifty-three patients were included: 10 in the steatosis group and 43 in the control group. No significant difference was observed in terms of morbidity, mortality, and primary non- or poor function. Nevertheless, biological changes after the procedure were significantly different during the first postoperative week. Prothrombin time, serum bilirubin, and transaminases were significantly increased among the steatosis group compared with the control group (P Conclusion This case-controlled study including a small number of patients, described postoperative biological changes among liver transplantations with steatosis in the graft.

The incidence of acute rejection is significantly higher in hepatitis C virus (HCV) liver-transplant patients than in patients who have received a graft for other liver diseases, i.e., mainly alcoholic cirrhosis. The aim of this study was to assess T-cell function, i.e., intralymphocyte cytokine expression (IL-2 and TNF-α), T-cell activation [i.e., transferrin receptor (CD71) and interleukin (IL)-2 α-chain (CD25) expression], and T-cell proliferation using a flow-cytometry whole-blood assay in patients waiting for a liver transplantation (n = 49). Our data suggest that, in mitogen-stimulated T-cells, (i) intra-lymphocyte cytokine expression is significantly higher in patients with liver disease than in healthy volunteers (n = 25); (ii) the expression of T-cell activation markers is decreased in patients with liver cirrhosis compared to healthy volunteers, and (iii) the expression of T-cell activation markers and T-cell proliferation are increased in patients with HCV infection (n = 15) compared to those without HCV infection (n = 34), particularly compared to patients with alcoholic liver disease (n = 19). Circulating CD19-positive cells count was also significantly higher in HCV-positive patients. In conclusion, in vitro, mitogen-stimulated T-cell seem to induce a higher immune response in the blood from patients waiting for a liver transplant for HCV-related liver disease than those without HCV infection, and particularly those with alcoholic liver disease.

International audience; In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non–paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance ≥ 60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level \textless 200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level \textgreater 20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level \textless 200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non–paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance. Liver Transpl 21:512-523, 2015. © 2015 AASLD.

We sought to determine the prevalence and predictive factors for posttransplant anemia within the first year after orthotopic liver transplant (OLT) among 97 consecutive patients. Anemia was defined at months 6 and 12 according to the WHO criteria, that is, a hemoglobin (Hb) level of12 g/dL for women and13 g/dL for men. Immunosuppression relied on tacrolimus and steroids, with or without mycophenolate mofetil. Anemia was present in 64.5%, 50%, and 52.8% of patients pre-OLT versus 6 and 12. Thirty-three percent (month 6) and 30.3% (month 12) of anemic patients received recombinant erythropoietin therapy. A multivariate analysis revealed that the independent predictive factors for anemia at month 6 were mean corpuscular volume (85 fL) at day 7, daily steroid dosage (0.3 mg/kg), serum creatinine (130 mumol/L), and Hb level (11 g/dL) at month 1. Independent predictive factors for anemia at month 12 were daily steroid dosage at month 1 (0.3 mg/kg), hematocrit at month 1 (33%), red blood cell count at month 6 (3.75 T/L), daily dosage at month 1 of cyclosporine or tacrolimus, and etiology of end-stage liver disease other than alcohol abuse. We concluded that anemia was highly prevalent within the first year of post-OLT. This observation deserves further investigation and appropriate treatment.

The aim of our study was to determine the prevalence and predictive factors for post-transplant anemia (PTA) at 6 (M6) and 12 (M12) months after orthotopic liver-transplant (OLT) in a cohort of 97 consecutive patients.Anemia was defined at M6 and M12 according to the World Health Organization criteria, i.e., a hemoglobin level of12 g/dL for women and13 g/dL for men. Immunosuppression relied on tacrolimus and steroids with or without mycophenolate mofetil.Anemia was present in 64.5%, 50%, and 52.8% of patients before OLT and at M6 and M12, respectively. Of the anemic patients, 33% (M6) and 30.3% (M12) received recombinant erythropoietin therapy. In multivariate analysis, the independent predictive factors for anemia at M6 were mean corpuscular volume (85 fl) at day 7, daily steroid dosage (0.3 mg/kg), serum creatinine (130 micromol/L), and hemoglobin level (11 g/dL) 1 month after OLT (M1). Independent predictive factors for anemia at M12 were daily steroid dosage at M1 (0.3 mg/kg), hematocrit at M1 (33%), red blood cell count at M6 (3.75 T/L), daily dosage at M1 of cyclosporine and tacrolimus, and OLT for causes other than alcohol abuse.Anemia is highly prevalent within the first year post-OLT. This deserves further investigation and appropriate treatment.

Impact of intraoperative blood salvage autotransfusion (IBSA) on neoplastic recurrence. during liver transplantations for hepatocellular carcinoma (LT-HCC). Between January 1989 and February 2003, 16 patients received a LT-HCC without IBSA. This group was compared with 31 patients who received the same surgical procedure during the same period, but with IBSA. Data were prospectively collected. All patients had at least a 1-year postoperative follow up. Pairing was made according to the size of the largest nodule. The percentage of recurrence observed in the two groups was similar: 6.4% in the IBSA group vs. 6.3% in the group without IBSA. The median amount of transfused salvage blood was 1558 ml. The differences observed between the two groups concerned the Child score which was A in 58% patients of the IBSA group vs. 80% in the other group; the percentage of severe portal hypertension was 55% in the IBSA group vs. 31%; the median number of packed red blood cell units transfused intraoperatively was 7 in the IBSA group vs. 0, and the median number of frozen fresh plasma units transfused intraoperatively was 11 in the IBSA group vs. 4.5. It appears that IBSA, essentially used during the most haemorrhagic transplantations, could be used in the case of HCC because it does not modify the risk of neoplastic recurrence.

We evaluated the peri- and postoperative effects of the lack of a temporary portocaval anastomosis (TPCA) during orthotopic liver transplantation (OLT) in 84 patients with cirrhosis.From December 1996 to December 2002, 156 liver transplant recipients included (54%; 60 men and 24 women) of mean age 52 +/- 9 years with portal hypertension. In whom peri- and postoperative data were analyzed.The median fall in mean arterial pressure upon vascular clamping and unclampings was 20 mm Hg (range 15 to 75), while the median duration of portal vein clamping was 77 minutes. The median amount of blood autotransfusion was 1100 mL (range 0 to 5400). The median number of red blood cell and fresh-frozen plasma units transfused were 5 and 6.5, respectively. The median intraoperative urinary output was 72 mL/h (range 11 to 221). Three patients (3.5%) presented a perioperative complication, but no perioperative death was observed. Six patients experienced an early postoperative complication (10 days): five hemodynamic complications and one transient renal failure, which did not require hemodialysis. One patient (1%) died at 12 hours after OLT from acute pulmonary edema.This study shows that systematic TPCA during OLT with preservation of the native retrohepatic vena cava in cirrhotic patients does not appear to be justified. In contrast, peri- and postoperative hemodynamic parameters as well as blood component requirements were comparable to those of the literature reporting OLT with straightforward TPCA.

Background: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti-CD25 monoclonal antibodies. Methods: From January 2000 to January 2003, 31 patients underwent OLT for HCV-related ESLD, and survived more than 1 month post-transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins®; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 ± 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end-points were at 6 months post-transplantation. Results: Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post-transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated. Conclusion: RATG induction therapy is as efficient and as safe as induction with anti-CD25 monoclonal antibodies.

Background: Several methods have been suggested to treat the hepatic raw surface after resection. Among these, omentoplasty (OP) has been employed occasionally but there are no clinical studies that clearly demonstrate its usefulness. Methods: Of 172 randomized patients undergoing hepatic resection between January 1991 and December 1994, 5 were withdrawn for protocol violation, leaving 167 who were randomly allotted to undergo OP (n = 87) on the hepatic raw surface or not (NO; n = 80). This procedure was performed for malignant tumor in 125 cases, benign tumor in 33, and for other causes in 15. Six patients had more than two types of lesions, and 32 patients had associated cirrhosis. Sixty-five major and 102 minor hepatic resections were performed. The main outcome measures studied were the number of patients with deep abdominal complications (DAC; deep bleeding or hematoma, deep infection, with or without pus discharge through drains, bile leakage), as well as repeat operations and postoperative death. Patients were divided into two strata according to the site of the lesion with respect to the diaphragm: (1) in contact (posterosuperior segments II, VII and VIII) or (2) not in contact (anterior segments III, IV, V, and VI). Results: Both groups were comparable as regards patient demographics, intraoperative procedures, intraoperative search for bile leaks and intraoperative transfusion requirements. Fewer patients had DAC in OP (n = 11) than in NO (n = 15) (difference not significant). Ten patients (6%) required repeat operations: 4 in OP without immediate mortality and 6 in NO, 3 followed by death. One further patient in OP required repeat operation after discharge and died. Four patients died in OP and 7 in NO, 1 and 4 of DAC, respectively (not significant). Deep abdominal complications were significantly associated with major hepatic resection (P

We report a case of secondary syphilis hepatitis in a liver-transplant patient. This homosexual male patient presented, 15 years after orthotopic liver transplantation, with non-squamous papulomacular rash, mild cytolysis, and anicteric cholestasis. Laboratory tests showed syphilis seroconversion with a venereal diseases research laboratory (VDRL) titer of 1/256, a Treponema pallidum hemaglutination assay (TPHA) of 1/5120, and a positive IgM fluorescent Treponemal antibody absorbance (FTA-abs). A liver biopsy performed 13 months after the diagnosis showed low-grade hepatitis with a Metavir score of A1F1; it also showed non-specific portal moderate inflammation consisting primarily of neutrophils, with no evidence of cholestasis. He was given benzathine-penicillin at 2,400,000 IU with a transient increase in prednisolone doses. Cytolysis rapidly, and cholestasis progressively disappeared. IgM FTA-abs became negative, whereas VDRL and TPHA titers decreased slightly over time.

Background/Aims: Currently, surgical treatment of hepatocellular carcinoma in patients with cirrhosis is not clearly defined. The objective of this study was, in patients with cirrhosis with hepatocellular carcinoma, to compare liver resection to transplantation assessed by patient survival and to determine whether the tumor recurrence might be influenced by prognostic factors. Methods: We have gathered all the available data from six French Medical Universities, for 215 patients with cirrhosis with hepatocellular carcinoma surgically treated either by liver resection (102) or by transplantation (113). Results: The overall 5-year survival rate was similar in the transplantation group and in the resection group (32% vs. 31%, p 0.7). However, the 5-year survival rate without recurrence was higher in the transplantation group than in the resection group (60% vs. 14%, p p p p Conclusions: These results and this prognostic index are encouraging for liver transplantation as treatment of hepatocellular carcinoma in selected patients with cirrhosis.

OBJECTIVE:: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND:: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS:: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS:: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS:: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (10 ng/ml) and increased-level group (10 ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10-150, 150-500, and ≥ 500 ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4 %, respectively, for those with normal AFP; 57 and 10 %, respectively, for those with AFP 10-150 ng/ml; 46 and 24 %, respectively, for those with AFP 150-500 ng/ml; and 28 and 62 %, respectively, for those with AFP ≥ 500 ng/ml.This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.

Background Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed. Aims We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers. Methods Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing. Results Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome. Conclusion This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.

The aim of this study was to estimate the survival rates and define risk factors for tumor recurrence after resection surgery for single hepatocellular carcinomas (HCCs)≤5 cm (on preoperative imaging) that developed on compensated cirrhosis.A retrospective review studied patients treated by surgical resection. Overall survival (OS), disease-free survival (DFS), recurrence rates, and risk factors were studied for all patients.A total of 49 patients were treated by resection. The 5-year OS and DFS rates were 52 and 41%, respectively, after 2000. Three independent risk factors were found for OS and DFS: macroscopic vascular invasion, satellite nodules, R1 resection. In the absence of these three factors, the 5-year OS was 59%. Recurrence rates were 63%. Delayed recurrence was significantly related to the 5-year OS. One factor was correlated with early recurrence: the presence of satellite nodules; and one factor was correlated with late recurrence: hepatitis C virus infection.R0 resection for HCC on compensated cirrhosis may offer good long-term survival in the absence of satellites nodules and macrovascular invasion. Thus, a "first approach" resection is proposed with the possibility of "salvage transplantation." In other cases, resection may be a bridge to transplantation ("transplantation de principe").

A prospective study was undertaken to evaluate selective visceral angiography (SVA) in the management of patients with pancreatic and periampullary cancer. Over a 30-month period 52 patients with potentially resectable pancreatic or periampullary cancer underwent SVA; 4 patients had obvious angiographic evidence of widely disseminated disease and were not subjected to laparotomy while 2 further patients were eventually considered too frail for resection. The remaining 46 patients (median age 58 years, range 37-73 years, males 26, females 20) had no evidence of disseminated disease on ultrasonography and/or CT scanning and had both SVA and surgery and form the basis of this study. Vascular anomalies were detected in 16/46 (35%) patients. Hepatic metastases were wrongly diagnosed by angiography in 7 out of 9 patients (77%). SVA correctly predicted resectability or irresectability in 28/46 patients (overall predictive value 61%). Of the 27 patients who proved to have irresectable disease at operation, 11 were correctly identified by SVA (sensitivity 41%). Of the 13 patients reported to have irresectable disease, 2 underwent resection (false-positive rate 15%). Of the 33 patients reported to have resectable disease, 16 were irresectable (false-negative rate 48%). Overall there was a poor relationship between resectability and the angiographic features. On the basis of these data, SVA cannot be considered a sufficiently accurate means of assessing resectability. Its use for this purpose in patients with pancreatic and periampullary cancer is not justified.

Background. The records of 98 consecutive patients (58 males and 40 females; median age, 27 years; age range, 2–64 years) who presented with a primary germ cell tumor (GCT) of the mediastinum between January 1950 and December 1990 were reviewed. There were 45 mature teratomas, 8 immature teratomas, 16 pure seminomas, and 24 malignant nonseminomatous GCT (MNSGCT). Results. All patients with mature teratomas were cured by radical resection alone, except one patient who died intraoperatively. Among the eight patients with immature teratomas, five were treated before the advent of cisplatin treatment (two children younger than 15 years were cured by surgery alone and three adults died within 7 months after operation). Three patients underwent surgery followed by cisplatin-based chemotherapy (two are still alive and one died of an associated rhabdomyosarcoma). Thirteen of 16 patients with seminomas (81%) were cured by surgery either alone (5 patients) or with adjuvant radiation therapy (8 patients). Among the 24 MNSGCT, 10 were treated before 1980 without cisplatin and all but 1 died of disease progression. Fourteen patients were treated by initial high-dose cisplatin combination chemotherapy and 8 (57%) achieved complete remission (2 died of systemic mastocytosis development). Conclusions. Results indicate the benignity of mature teratomas of the mediastinum, the age-dependent clinical course of immature teratomas, and the excellent prognosis of seminomas. The improved survival advantage resulting from cisplatin-based chemotherapy in MNSGCT is impaired by the propensity to nongerminal solid tumor development and hematologic malignancies.

Therapeutic drug monitoring of mycophenolate mofetil (MMF) was found to be beneficial in preventing acute rejection after kidney transplantation. The aim of this pilot prospective study was to evaluate the efficacy of MMF dose adjustment in de novo liver transplant patients receiving MMF at fixed versus concentration-controlled doses [ie, adapted to mycophenolic acid (MPA) AUC0-12h] and tacrolimus during the first 12 months posttransplant. Twenty-nine patients received steroids only up to day 10, induction therapy by lymphoglobulins followed by tacrolimus and MMF. In all patients, MPA AUC0-12h were measured on posttransplant days 7 and 14 and at months 1, 2, 3, 6, and 12. From March 2006 to March 2007, 15 patients received MMF at a fixed dose of 1 g twice a day for 12 months. From April 2007 to December 2007, MMF was given to 14 patients at a dose of 1 g twice a day until day 7 and was then adapted to reach an MPA AUC0-12h target of 30-60 mg x h/L. The proportion of MPA AUC0-12h values within the target range was similar in both groups. The proportion of patients with MPA AUC0-12h below 30 mg x h/L tended to be higher in the fixed dose group within the first month posttransplant. However, MMF dose did not differ significantly between the 2 groups at any period except month 1. MPA AUC0-12h tended to be higher in the concentration-controlled group at day 14 and month 2 and was significantly so at month 1. Tacrolimus trough concentrations tended to be lower in the concentration-controlled group at all study periods and was significantly so at month 3. At 12 months posttransplant, patient and graft survivals, acute rejection rate, and adverse events were similar in both groups. We concluded that adapting the dose of MMF resulted in a significant increase in MPA AUC0-12h at month 1. There was a trend toward a lower proportion of patients with MPA AUC0-12h below 30 mg x h/L in the concentration-controlled group. No difference in outcome was found between both groups.

Background To help increase the number of transplants available for hepatocellular carcinoma in cirrhotic livers, this single-centre retrospective study compared the safety and feasibility of new, more liberal, selection criteria—no more than five tumours, with the largest tumour no greater than 5 cm (5/5 criteria)—with classical criteria. Methods Data from operations performed in 1990–2005 were extracted from preoperative radiological findings and postoperative specimen analyses, and four groups were constructed: Paul Brousse, Milan, University of California, San Francisco (UCSF) and 5/5 criteria. A fifth group comprised patients whose tumour load exceeded the 5/5 criteria. Survival and recurrence rates were compared. Results For the 110 patients in the study, survival rates (overall and disease-free) were 72·8 and 66·8 per cent at 5 and 10 years respectively, with a 5·5 per cent recurrence rate. The 5-year survival rate was 65, 77, 68 and 77 per cent for Paul Brousse, Milan, UCSF and 5/5 preoperative radiological criteria, with recurrence rates of 4, 4, 3 and 3 per cent, respectively. On multivariable analysis, the only factor that influenced survival was tumour load in excess of the 5/5 criteria. Conclusion Use of the more liberal 5/5 criteria for selecting patients for liver transplantation results in similar disease-free and overall survival rates to classical criteria.

International audience; AIMS: The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN). METHODS: During a 17-year period, 99 successive IPMN patients (52 men, 47 women; mean age, 64 years) were included and divided into two groups for further comparison: one group had branch duct IPMN, whereas the other had mixed IPMN. RESULTS: Patients from the mixed IPMN group (n = 52) displayed a greater rate of symptoms (83% vs 55%, P = 0.004), pancreatic resection (67% vs 38%, P = 0.007), malignancy (35% vs 13%, P = 0.017) and death (15% vs 4%, P = 0.09) than those from the branch duct IPMN group. A 38-month follow up of non-operated, symptom-free patients confirmed that more than 85% of branch duct IPMN patients were asymptomatic without evidence of malignancy. Borderline lesions and carcinoma are found in up to 50% of symptomatic resected branch duct IPMN cases. CONCLUSION: Patients with the mixed form of IPMN as well as with symptomatic branch duct IPMN should require pancreatic resection because of symptoms and the risk for malignancy. In silent branch duct IPMN without radiological signs of malignancy, a non-operative watch-and-wait strategy can be discussed.

Management of Budd-Chiari syndrome, from simple medical treatment to liver transplantation, depends on the acute and chronic evolution of the disease and on the degree of hepatic insufficiency. Herein we have reported the case of a man who underwent transplantation after evolution of a Budd-Chiari syndrome with membranous obstruction of the vena cava and developed 2 lesions of hepatocellular carcinoma. Surgery was difficult due to previous procedures requiring reconstruction of the supra-hepatic vena cava. This case emphasized the timing of liver transplantation versus other treatments to decrease the operative risk.

We evaluated the relevance of human cytomegalovirus (HCMV) monitoring with quantitative real-time polymerase chain reaction in 42 consecutive HCMV positive liver transplant patients, and we analyzed the factors that determined the treatment of the first episode of HCMV DNAemia. No patients received anti-HCMV prophylaxis. HCMV infection monitoring was assessed every 2 weeks until day 90 and thereafter at every 3 to 4 weeks until day 180. HCMV infection was detected among 27 patients (64%, ie, 92/380 samples). Of these, 12 had their first HCMV DNAemia treated with IV gancyclovir (group I), whereas the other 15 patients were not treated (group II). Immunosuppressive treatment was not modified in cases of HCMV DNAemia. The median time between transplantation to the first CMV DNAemia was 37 days in group I and 52 days in group II (NS). Median HCMV viral load, whatever the treatment group and whatever the time of DNAemia, was 3 log copies/mL (0.48 to 5.80). Median HCMV viral load of the first positive DNAemia was 3.45 log copies/mL (1.69 to 5.80) in group I and 2.70 log copies/mL (1.15 to 3.94) in group II (P = .01). Even though liver enzymes were increased in almost all patients presenting with HCMV infection, comparison of liver-enzyme levels and hematological parameters between the two groups at first HCMV viremia showed that alkaline phosphatase levels were significantly higher (P = .0011) and hemoglobin levels were significantly lower in group I patients (P = .0443). The only factor that predicted treatment for the first episode of HCMV DNAemia was an alkaline phosphatase level >150 UI/mL at the time of the first HCMV reactivation [odds ratio 20 (1.96 to 203.3); P = .01].

Chronic renal failure (CRF) is increasingly prevalent in solid-organ-transplant patients. This is in part related to the long-term use of calcineurin inhibitor (CNI) agents. However, in orthotopic liver-transplant (OLT) patients, the effects of superimposed hepatitis C virus (HCV)-related renal lesions could also be a factor. The aim of this cohort study (February 2000 to September, 2003) was to identify the predictive factors at one year post-transplantation for CRF in OLT patients associated with induction therapies. CRF was defined as having a creatinine clearance (CC) lower than 60 mL/min. Of the 97 transplants performed during that period, 72 were still functioning after one year. Of these, 33 patients (45.8%) had CRF. In univariate analysis, the predicting factors for CRF were recipient sex (female), initial liver disease (HCV-related cirrhosis), pre-transplant CC (80 mL/mn), and post-transplant serum creatinine130 micromol/L at day 3 and months (M) 1, 3, and 6. In multivariate analysis, the independent predictive factors for CRF included female sex [OR: 11.5 (2.3-58.3); p = 0.003], HCV infection [OR: 5.01 (1.1-22.7); p = 0.03], pre-OLT CC80 mL/mn [OR: 5.4 (1.2-23.7); p = 0.025], and serum creatinine at M6 greater than 130 micromol/L [OR: 19.6 (3.7-102.5); p = 0.0004]. Among all of the predictive factors for post-OLT CRF, only one is modifiable: post-transplant serum creatinine, which could be, to some extent, related to the long-term use of CNIs.

Background Studies of risk factors after pancreatoduodenectomy are few: some concern restricted populations and others are based on administrative data. Methods Multicenter clinical data were collected for 300 patients undergoing pancreatoduodenectomy to determine (by univariate and multivariate analysis) preoperative and intraoperative risk factors for mortality and intra-abdominal complications (IACs), including pancreatic fistula. Fourteen factors including the center and volume effect were analyzed. Results In univariate analysis, mortality was increased with age 70 years or more, extended resection(s), and volume and center effects. IACs occurred more often with main pancreatic duct diameter of 3 mm or less, normal parenchyma texture, extended resection(s), and the center effect. Pancreatic fistula was more frequent with main pancreatic duct diameter of 3 mm or less, normal parenchyma texture, and the center effect. In multivariate analysis, independent risk factor(s) for mortality were age greater than 70 years (odds ratio [OR], 3; 95% confidence interval [CI], 1.3-8) and extended resection (OR, 5; 95% CI, 1.2-22), risk factors for IACs were extended resection (OR, 5; 95% CI, 1.2-22) and main pancreatic duct diameter of 3 mm or less (OR, 2; 95% CI, 1.1-3), and the risk factor for pancreatic fistula was main pancreatic duct diameter of 3 mm or less (OR, 2.5; 95% CI, 1.2-4.6). Conclusions Age more than 70 years, extended resections, and main pancreatic duct diameter less than 3 mm are independent risk factors that should be considered in indications for and techniques of pancreatoduodenectomy.

Background The purpose of this study was to analyze the short-term outcome and to determine risk factors after distal pancreatectomy (DP). Methods This prospective single-center study included 61 patients undergoing DP with splenic preservation in 6 (10%). The diagnoses included pancreatic adenocarcinoma (n = 9), neuroendocrine neoplasms (n = 17), benign neoplasm (n = 26), pseudocyst (n = 4), chronic pancreatitis (n = 2), and other diagnoses (n = 3). Twelve clinical factors were studied. The chi-square test was used for univariate analysis. Results The median duration of the postoperative hospital stay was 10 days (range, 5-155 days). Two patients (3%) died postoperatively; 12 patients (20%) had one or more intra-abdominal complications with reoperation necessary in 3 patients (5%): 6 pancreatic fistula (10%), 11 intra-abdominal collections (18%), 1 postoperative hemorrhage (2%). Univariate analysis showed that a body mass index >25 kg/m 2 was the only risk factor for intra-abdominal complication ( P = .003). Conclusions DP is associated with an intra-abdominal morbidity rate of 20%, which is increased for patients with a body mass index >25 kg/m 2 .

Background Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). However, in recent years, the long-term results of OLT in this setting are worsening, possibly due to the powerful immunosuppressants in use. The aim of our study was to assess the safety and efficacy of induction therapy using rabbit antithymocyte globulin antibodies (RATG). Methods Over an 18-month period from January 2000 to June 2001, 16 patients underwent OLT for HCV-related ESLD and survived more than 1 month posttransplantation. They received induction therapy based on RATG (Thymoglobulins, Sangstat, France) at 1 mg/kg per day for 3 consecutive days, and it was then adjusted to maintain a CD2 count below 50/mm3. Overall, RATG was given for a median of 5 days for a total dose of 406 ± 45 mg. Steroids were started pretransplant and tacrolimus on day 1. The primary end-points were patient and graft survivals at 6 months posttransplantation, incidence of rejection, infectious complications (bacterial, viral, and fungal) and recurrence of HCV infection based on biochemical, virological, and histologic criteria. Results The survival rates were 100% for patients and 93.7% for grafts. The acute rejection rate was 37.5%. The median time to acute rejection was 15.5 days. There was only one serum sickness case. Cytomegalovirus infections occurred in 25% of patients. The rate of de novo diabetes that required insulin therapy was at 50%. The rate of HCV recurrence was 56.25%. In addition, HCV RNA serum concentrations increased significantly posttransplantation (>1 log). In conclusion, RATG induction therapy is safe and efficient in HCV-positive liver recipients.