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Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection., Background: Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL., Methods: Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n=593) were compared with those treated by primary surgery (n=1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics., Results: Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P=0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P=0.110) and 33.4% versus 32.1% (P=0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P=0.291), whereas chylothorax (2.5% vs 1.2%; P=0.020), cardiovascular complications (8.6% vs 0.1%; P=0.037), and thromboembolic events (8.6% vs 6.0%; P=0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P=0.228), with more chylothorax (2.5% vs 0.7%; P=0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P=0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT., Conclusions: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).

Liver tumors bleed rarely; management has changed radically during the last 20years, advancing from emergency surgery with poor results to multidisciplinary management. The first steps are the diagnosis and control of bleeding. Abdominopelvic CT scan should be performed as soon as patient hemodynamics allow. When active bleeding is visualized, arterial embolization, targeted as selectively as possible, is preferable to surgery, which should be reserved for severe hemodynamic instability or failure of interventional radiology. When surgery is unavoidable, abbreviated laparotomy (damage control) with perihepatic packing is recommended. The second step is determination of the etiology and treatment of the underlying tumor. Adenoma and hepatocellular carcinoma (HCC) are the two most frequently encountered tumors in this context. Liver MRI after control of the bleeding episode generally leads to the diagnosis although sometimes the analysis can be difficult because of the hematoma. Prompt resection is indicated for HCC, atypical adenoma or lesions at risk for degeneration to hepatocellular carcinoma. For adenoma with no suspicion of malignancy, it is best to wait for the hematoma to resorb completely before undertaking appropriate therapy., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: The objective of this study was to gain detailed insight concerning liver transplanted patients' representations about transplantation, graft rejection and immunosuppressive drugs to adapt the educational follow-up., Patients and Methods: Semi-structured interviews were conducted with 8 patients. Each interview was recorded and fully transcribed. The verbatim was first coded according to the themes of the Common Sense Model and an inductive approach for the remaining text., Results: Transplantation is perceived both as a recovery and a new chronic condition. Participants feel powerless in the face of the risk of graft rejection. This risk is perceived as out of control as it is not associated with specific symptoms and external causes. The individual knowledge gained about transplantation relies on real-life experience shared between patients. Many participants feel anxiety. It responds to stress caused by immunosuppressant medication intake, routine check-ups, potential side effects and chronicity of immunodepression. Messages stressing the importance of the tacrolimus in the medication therapy are strengthened by a pre-discharge pharmaceutical consultation., Discussion and Conclusions: This study suggests that healthcare providers should systematically seek to determine illness representations to optimize the educational follow-up. The patient education program for liver transplanted patients should include three types of intervention: individualized education, behavioral intervention and psychological support. It should provide a support for stress management and acceptance of the new chronic condition. The involvement of a clinical pharmacist is relevant., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the capacity of diffusion-weighted imaging (DWI) to determine the histological grade of small-sized hepatocellular carcinomas (HCCs) in liver cirrhosis in comparison with T2 weighted imaging., Methods: 51 cirrhotic patients with 63 histologically proven HCCs ≤2 cm underwent abdominal MRI, including DWI (b-values 50, 400 and 800 s mm(-2)) and T2 weighted sequences. HCCs were classified into well-differentiated HCCs (n = 37) and moderately differentiated HCCs (n = 26). Relative contrast ratios (RCRs) between the lesions and the surrounding liver were performed and compared between the two groups for T2 weighted images, each b-value and apparent diffusion coefficients (ADCs). A receiver operating characteristic (ROC) analysis was performed to compare RCRs in T2 and diffusion-weighted images., Results: We found significant differences in RCRs between well-differentiated vs moderately differentiated HCCs for b = 50, 400 and 800 s mm(-2) and T2 weighted images (1.35 ± 0.36 vs 1.86 ± 0.62; 1.35 ± 0.38 vs 1.82 ± 0.60; 1.27 ± 0.30 vs 1.74 ± 0.53; 1.14 ± 0.18 vs 1.43 ± 0.28, respectively; p < 0.001), whereas no significant differences were observed in ADC and ADC RCR (1.05 ± 0.19 vs 0.99 ± 0.15 and 1.1 ± 0.22 vs 1.09 ± 0.23; p = 0.16 and p = 0.82, respectively). No significant difference was found in the areas under the ROC curve for RCRs of T2 weighted images and every DWI b-value (p = 0.18)., Conclusion: The RCR measurement performed in DWI 50, 400 and 800 b-values and T2 demonstrated a significant difference between well-differentiated and moderately differentiated small-sized HCCs. Furthermore, no difference was shown by using either ADC or ADC RCR., Advances in Knowledge: DWI with RCR measurement may be a valuable tool for non-invasively predicting the histological grade of small HCCs.

Background: The aim of this study was to compare postoperative outcome and long-term results after management of liver hydatid cysts (LHC) by subadventitial cystectomy (SC) and resection of the protruding dome (RPD) in two tertiary liver surgery centers., Methods: Medical records of 52 patients who underwent SC in one center, and 27 patients who underwent RPD in another center between 1991 and 2011 were reviewed. Patients underwent long-term follow-up, including serology tests and morphological examinations., Results: Postoperative mortality was nil. The rate of severe morbidity was 7.7 and 22% (p = 0.082), while the rate of serological clearing-up was 20 and 13.3% after SC and RPD, respectively (p = 1.000). After a mean follow-up of 41 months (1-197), four patients developed a long-term cavity-related complication (LTCRC) after RPD (including one recurrence) and none after SC (p = 0.012). All LTCRCs occurred in patients with hydatid cysts located at the liver dome; three required an invasive procedure by either puncture aspiration injection re-aspiration (N = 1) or repeat surgery (N = 2)., Conclusions: RPD exposes to specific LTCRC, especially when hydatid cysts are located at the liver dome, while SC allows ad integrum restoration of the operated liver. Therefore, SC should be considered as the standard surgical treatment for LHC in experienced hepato-pancreato-biliary centers.

Unlabelled: The prevention of tumor recurrence after curative treatment of hepatocellular carcinoma (HCC) is unresolved. Postoperative intraarterial injection of (131)I-labeled lipiodol has been proposed as adjuvant treatment. The aim of this prospective randomized trial was to evaluate if a single dose of postoperative adjuvant intraarterial (131)I-lipiodol (vs. unlabeled lipiodol) could reduce the rate of intrahepatic recurrence at 2 y., Methods: Patients who underwent curative treatment for HCC and recovered within 6 wk were randomly assigned to receive a single 2,200-MBq (131)I-lipiodol dose or a single unlabeled lipiodol dose on a 1:1 basis. Recurrence-free and overall survival rates were analyzed., Results: Between June 2005 and February 2009, we included 58 patients (median age of 63 y [range, 23-85 y]): 29 received intraarterial (131)I-lipiodol and 29 received lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with intrahepatic recurrence was 28% in the (131)I-lipiodol group and 56% in the lipiodol group (P = 0.0449). The Kaplan-Meier analysis confirmed this result, with a 2-y recurrence-free survival in the (131)I-lipiodol and lipiodol groups of 73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in the (131)I-lipiodol and lipiodol groups were 40% and 0%, respectively (P = 0.0184). The overall and specific survivals were not significantly different between groups (P = 0.9378 and P = 0.1339, respectively). (131)I-lipiodol had no severe toxic effects., Conclusion: After curative treatment of patients with HCC, one 2,200-MBq dose of intraarterial (131)I-lipiodol significantly decreased the rate of intrahepatic recurrence but failed to improve overall or specific survival., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objective: To assess clinical presentation and long-term results of surgical management of congenital intrahepatic bile duct dilatation (IHBDD) (Caroli disease and syndrome) in a multicenter setting., Background: Congenital IHBDD predisposes to biliary stasis, resulting in intrahepatic lithiasis, septic complications, and cholangiocarcinoma. Although liver resection (LR) is considered to be the treatment of choice for unilobar disease extent into the liver, the management of bilobar disease and/or associated congenital hepatic fibrosis remains challenging., Methods: From 1978 to 2011, a total of 155 patients (median age: 55.7 years) were enrolled from 26 centers. Bilobar disease, Caroli syndrome, liver atrophy, and intrahepatic stones were encountered in 31.0%, 19.4%, 27.7%, and 48.4% of patients, respectively. A complete resection of congenital intrahepatic bile ducts was achieved in 90.5% of the 148 patients who underwent surgery., Results: Postoperative mortality was nil after anatomical LR (n = 111) and 10.7% after liver transplantation (LT) (n = 28). Grade 3 or higher postoperative morbidity occurred in 15.3% of patients after LR and 39.3% after LT. After a median follow-up of 35 months, the 5-year overall survival rate was 88.5% (88.7% after LT), and the Mayo Clinic score was considered as excellent or good in 86.0% of patients. The 1-year survival rate was 33.3% for the 8 patients (5.2%) who presented with coexistent cholangiocarcinoma., Conclusions: LR for unilobar and LT for diffuse bilobar congenital IHBDD complicated with cholangitis and/or portal hypertension achieved excellent long-term patient outcomes and survival. Because of the bad prognosis of cholangiocarcinoma and the sizeable morbidity-mortality after LT, timely indication for surgical treatment is of major importance.

Background/aims: The Up7 criteria for HCC have recently emerged to identify potential candidates for OLT. The aim of this study was to assess the validity of the Up7 criteria according to the pathological analysis of the explanted livers., Methodology: For recurrence risk calculation 669 HCC transplanted patients were classified according to both the pathological Milan and Up7 criteria. In order to identify potential predictors of recurrence, selected biological tumor markers and morphological features were then tested by Cox regression., Results: The 5-year HCC recurrence rate for the Milan out/Up7 in subgroup (n=87), was significantly higher than patients meeting Milan criteria (n=299), 15.8% vs. 9.4% (p=0.0290). For patients within the Up7 criteria (n=383), only pre-OLT AFP level >1000ng/mL and microvascular invasion were significant predictors for recurrence, and for those beyond the Up7 criteria (n=286), pre-OLT AFP level >1000ng/mL, poor differentiation grade and microvascular invasion remained significant., Conclusions: Compared to the current Milan staging system, HCC patients within the pathological Up7 criteria were associated with a higher, but acceptable risk of recurrence after OLT, and along with tumor burden, other parameters can potentially be used for further refinement of HCC staging, such as AFP levels and microvascular invasion.

Although the feasibility of oral tacrolimus administration in the presence of jejunostomy has already been reported, few studies monitoring tacrolimus trough blood levels have been analyzed in detail, either during or after a jejunostomy closure. We report on our experience with a 34-year-old patient who underwent liver transplantations, with a proximal jejunostomy constructed a few days prior to the second transplantation. He was administered tacrolimus by a predominantly oral route, and less frequently received it by jejunostomy. The aim of this paper is to discuss this administration strategy and whether a different method could have been more suitable. This case report highlights that during the jejunostomy period, the tacrolimus doses that were required to maintain trough concentrations within the therapeutic range were four times higher than those administered after the closure of the jejunostomy. We observed an increase in the Dose-Normalized Trough Concentration (DNTC) values when tacrolimus was administered for 4 consecutive days by jejunostomy as compared to oral administration, indicating that the relative bioavailability of tacrolimus increased. Moreover, when returning to oral administration, the subsequent DNTC value was halved, highlighting a reduction in the tacrolimus bioavailability. Thus, in such a case, administration by jejunostomy could be more appropriate., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Clinical pharmacists can help prevent medication errors. However, data are scarce on their role in preventing medication prescription errors in the post-operative period, a high-risk period, as at least two prescribers can intervene, the surgeon and the anesthetist. We aimed to describe and quantify clinical pharmacist' intervention (PIs) during validation of drug prescriptions on a computerized physician order entry system in a post-surgical and post-transplantation ward. We illustrate these interventions, focusing on one clearly identified recurrent problem., Methods: In a prospective study lasting 4 years, we recorded drug-related problems (DRPs) detected by pharmacists and whether the physician accepted the PI when prescription modification was suggested., Results: Among 7005 orders, 1975 DRPs were detected. The frequency of PIs remained constant throughout the study period, with 921 PIs (47%) accepted, 383 (19%) refused and 671 (34%) not assessable. The most frequent DRP concerned improper administration mode (26%), drug interactions (21%) and overdosage (20%). These resulted in a change in the method of administration (25%), dose adjustment (24%) and drug discontinuation (23%) with 307 drugs being concerned by at least one PI. Paracetamol was involved in 26% of overdosage PIs. Erythromycin as prokinetic agent, presented a recurrent risk of potentially severe drug-drug interactions especially with other QT interval-prolonging drugs. Following an educational seminar targeting this problem, the rate of acceptation of PI concerning this DRP increased., Conclusion: Pharmacists detected many prescription errors that may have clinical implications and could be the basis for educational measures., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: The purpose of this study was to determine whether or not adding diffusion-weighted magnetic resonance imaging (DWI) to conventional magnetic resonance (MR) imaging sequences improves the characterization of small hepatocellular carcinoma (HCC) (≤2 cm) in the setting of cirrhotic liver compared to conventional sequences alone., Materials and Methods: A total of 62 cirrhotic liver patients with 82 nodules smaller than 2 cm in diameter were enrolled, and all lesions were pathologically confirmed. For the first reading session, which included precontrast T1- and T2-weighted images and T1 dynamic contrast-enhanced images, preindicated lesions by a study coordinator were characterized by two radiologists. They determined the confidence levels in consensus for the presence of small HCC into four grades. In another session, respiratory-triggered diffusion-weighted MR images (b factor=50, 400 and 800 s/mm(2)) were added to the previously reviewed images, and the same two radiologists again determined the confidence levels. The diagnostic performance of the combined DWI-conventional sequences set and the conventional sequences alone set was evaluated using receiver operating characteristic curves. Sensitivity and specificity values for characterizing small HCCs were also calculated., Results: The area under the receiver operating characteristic curve for the second interpretation session (0.86) was significantly higher (P=.038) than that of the first session (0.76). The sensitivity was significantly increased from 75.7% to 87.8% by adding DWI to the conventional sequences (P=.015). No significant differences were observed for specificity values., Conclusion: Adding DWI to conventional imaging modalities improves the diagnosis of small HCCs in the cirrhotic liver in terms of diagnostic performance and sensitivity by increasing reader confidence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The purpose of this prospective, nine-center, non-randomized study was to assess the efficacy and safety of Celsior preservation fluid in liver transplantation using unselected donors. As data comparing allograft outcomes following liver transplantation using Celsior and University of Wisconsin (UW) preservation fluids are limited, we also compared our cohort with matched controls selected from the European Liver Transplant Registry (ELTR) who received total liver grafts preserved with UW solution during the same period. One hundred and forty patients who received livers preserved with Celsior were included. The primary endpoint, graft loss at one-yr post-transplantation, was observed in 24 patients (17.1%) which was not significantly different from the 20.0% pre-defined threshold rate (95% confidence interval [CI] 10.9, 23.4; p=0.398). Predictive factors for graft loss on univariate analysis were moderate-to-severe steatosis on the donor graft (5/22 patients with graft loss vs. 8/107 patients without, p=0.046) and duration of warm ischemia (1.4±1.1 h in patients with graft loss vs. 0.9±0.5 h in patients without, p=0.034). Hepatic artery thrombosis and stenosis occurred in seven (5.0%) and six (4.3%) patients, respectively. The comparison of our patients to 420 ELTR controls showed that one-yr graft survival rates (Celsior: 82.9%, 95% CI 75.8, 88.2; UW: 78.6%, 95% CI 74.4, 82.2) and Kaplan-Meier one-yr graft survival distributions (p=0.285) were similar. Within the cold ischemia time achieved in our study, liver preservation with Celsior appeared efficient and safe. Comparison with ELTR patients suggested that liver allograft survival was similar using Celsior or UW solution for preservation of unselected donor grafts., (© 2011 John Wiley & Sons A/S.)

Malignant transformation of hepatic adenoma (HA) is now a well-documented phenomenon. Recent pathological and immunophenotypic studies have identified several subtypes with different prognoses. In many cases the HA subtype can be determined by modern radiological methods, including contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI). Based on a series of 26 cases of HA studied with CEUS, MR1 histopathology and immunochemistry, we propose tailored therapeutic options. Watchful waiting is appropriate in some cases, while others require biopsy or resection. Management is more conservative than in previous years.

Objective: To determine the safety and the self-reported efficacy of botulinum toxin injections for adult spasticity in current clinical practice., Design: A prospective observational study., Subjects: A total of 406 adult patients with focal spasticity received of 1136 series botulinum toxin injections at Bordeaux University Hospital from January 2007 to December 2009., Methods: Adverse events following botulinum toxin injections were reported. Their severity and the therapeutic efficacy of botulinum toxin injections were estimated with a four-point self-reporting scale (0 to 3). Latency and duration of adverse events and subjective improvement were also noted., Results: The data of 640 series of injections were analyzed. Forty-six (7.2%) adverse events were reported, of which 36 (78%) were local. There were 18 (39%) cases of local muscular weakness with an average duration of 30.0 (SD 38.2) days, and an average severity score of 1.0 (SD 0.97). Among systemic adverse events, there were 8 (17%) cases of excessive fatigue without global muscular weakness and 2 (4%) cases of transitory generalized muscular weakness. The average subjective improvement score was 1.89 (SD 0.97) and was higher for upper, than for lower, limbs (P=0.007)., Conclusion: Self-reported adverse events following botulinum toxin injections in spasticity are rare, often benign and of short duration in current clinical practice. Botulinum toxin is considered effective by patients in treating spasticity of the upper and lower limbs.

Abdominal approach is commonly used for resection of liver tumors. However, in rare cases, transthoracic approach may be a valuable option for management of lesions located in the hepatic dome or involving the cavo-hepatic junction for very selected patients. This approach can be an open procedure (thoracotomomy), a video-assisted minimally invasive technique (thoracoscopy), or a strictly percutaneously treatment (CT-guided radiofrequency ablation). This approach seems useful for high-risk patients, with previous major abdominal surgery, or awaiting for liver transplantation (bridge concept) with cranially located single lesions. A limited liver resection (tumorectomy or segmentectomy) can be performed, but this approach is also suitable for percutaneous ablation therapy (radiofrequency or cryotherapy), with an acceptable morbidity., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Purpose. To review the contrast-enhanced ultrasonographic (CEUS) and magnetic resonance (MR) imaging findings in 25 patients with 26 hepatocellular adenomas (HCAs) and to compare imaging features with histopathologic results from resected specimen considering the new immunophenotypical classification. Material and Methods. Two abdominal radiologists reviewed retrospectively CEUS cineloops and MR images in 26 HCA. All pathological specimens were reviewed and classified into four subgroups (steatotic or HNF 1α mutated, inflammatory, atypical or β-catenin mutated, and unspecified). Inflammatory infiltrates were scored, steatosis, and telangiectasia semiquantitatively evaluated. Results. CEUS and MRI features are well correlated: among the 16 inflammatory HCA, 7/16 presented typical imaging features: hypersignal T2, strong arterial enhancement with a centripetal filling, persistent on delayed phase. 6 HCA were classified as steatotic with typical imaging features: a drop out signal, slight arterial enhancement, vanishing on late phase. Four HCA were classified as atypical with an HCC developed in one. Five lesions displayed important steatosis (>50%) without belonging to the HNF1α group. Conclusion. In half cases, inflammatory HCA have specific imaging features well correlated with the amount of telangiectasia and inflammatory infiltrates. An HCA with important amount of steatosis noticed on chemical shift images does not always belong to the HNF1α group.

Arterial allograft represents a material of choice for primary arterial revascularization in liver transplantation (LT) when interposition of a vascular conduit is required. In case of non-availability of such graft, the use of cryopreserved vessels should be an interesting option. Three patients were grafted using a cryopreserved iliac artery allograft (CIAA) previously harvested and stored at -140°C in a tissue bank. An auxiliary partial LT was performed in one patient for acute liver failure. During follow-up, an efficient regeneration of the native hemi-liver was observed while atrophy of the auxiliary graft occurred, leading to functional portal vein and hepatic artery thrombosis at six and nine months, respectively. Two other patients presented with celiac trunk compression because of arcuate ligament without available arterial allograft in the donor. Late arterial thrombosis occurred at six months in one patient without impairment of graft function. The last patient was alive and symptom free 29 months after LT with a patent cryopreserved arterial conduit. Our preliminary results suggest that CIAA might represent an efficient solution as vessel interposition for primary arterial hepatic revascularization in LT setting when no other suitable graft is available. However, long-term patency of CIAA remains questionable., (© 2011 John Wiley & Sons A/S.)

Objective: Define the optimal surgical margin in patients undergoing surgery for intrahepatic cholangiocarcinoma (IHCC)., Background Data: Surgery is the most effective treatment for IHCC. However, the influence of R1 resection on outcome is controversial and that of margin width has not been evaluated., Methods: We studied 212 patients undergoing curative resection of mass-forming-type IHCC. The respective influences on survival of resection status (R0 vs R1), surgical margin width, pTNM stage, and the latter's components were evaluated., Results: Incidence of R1 resection was 24%. Overall, R1 resection was not an independent predictor of survival [odds ratio (OR) 1.2 (0.7-2.1)] in contrast to the pTNM stage [OR 2.10 (1.2-3.5)]. In the 78 pN+ patients, survival was similar after R0 and R1 resections (median: 18 vs 13 months, respectively, P = 0.1). In the 134 pN0 patients, R1 resection was an independent predictor of poor survival [OR 9.6 (4.5-20.4)], as was the presence of satellite nodules [OR 1.9 (1.1-3.2)]. In the 116 pN0 patients with R0 resections, median survival was correlated with margin width (≤1 mm: 15 months; 2-4 mm: 36 months; 5-9 mm: 57 month; ≥10 mm: 64 month, P < 0.001) and a margin >5 mm was an independent predictor of survival [OR 2.22 (1.59-3.09)]., Conclusion: Patients undergoing surgery for IHCC are at high risk of R1 resections. In pN0 patients, R1 resection is the strongest independent predictor of poor outcome and a margin of at least 5 mm should be created. The survival benefits of resection in pN+ patients and R1 resection in general are very low.

Botulinum toxin (BTA) is a safe and effective therapeutic tool for many neurological conditions but few studies have investigated its real cost in neurological practice. We evaluated the daily cost of botulinum toxin type A (BTA) treatment through a cost effectiveness analysis alongside a prospective study of BTA injections at a French University Hospital over a 2-year follow-up period. The data of 3,108 BTA injections performed in 870 adult patients presenting with dystonia, facial hemispasm, or spasticity were entered in the database. Patients were questioned at each visit about the subjective effectiveness of the previous injection. The daily cost of BTA treatment was calculated as the ratio of each session's cost (including all additional costs) to the duration of subjective efficacy. The subjective rating of efficacy duration was 17.3 ± 7.7 weeks for facial hemispasm, 15.4 ± 7.7 for blepharospasm, 14.3 ± 6.7 for cervical dystonia, 14.5 ± 7.8 and 14.1 ± 7.4 weeks for upper and lower limb spasticity, respectively. The daily cost of BTA injections was 0.57 ± 0.20 for facial hemispasm, 0.95 ± 0.30 for blepharospasm, 2.85 ± 0.86 for cervical dystonia, 3.38 ± 1.49 and 3.62 ± 1.81 for upper and lower limb spasticity, respectively. When associated costs were considered, the daily cost of BTA injections was clearly increased (45-93%) in limb spasticity or rigidity but remained only modestly increased (15-37%) in other indications. These results obtained in a large cohort of patients show that BTA treatment has a low daily cost for a long-lasting effect, with a daily cost/benefit ratio that greatly depends on the indications.

Aim: To generate a new score with improved accuracy compared with Milan criteria to select patients., Patients: The training cohort comprised 373 patients transplanted for hepatocellular carcinoma (HCC) between 1988 and 1998 (cohort 1). An algorithm was derived from the analysis of patient data by the proportional hazard Cox regression model. The area under the receiver operating characteristic (AUROC) was used to determine a cut-off value. The validation cohort comprised 140 patients transplanted between 1999 and 2001 (cohort 2)., Results: Multivariate analysis identified three predictors of 5-year tumour-free survival: tumour differentiation (P=0.02), diameter (P<0.0001) and number of nodules (P=0.04). A cut-off value of 4 was derived from the AUROC of the final score. Five-year tumour-free survival was 60.2 ± 3.1% in patients with as score <4 and 36.4 ± 4.7% in individuals with a score ≥4, P<0.0001. In the validation cohort, 5-year tumour-free survival was 82.8 ± 3.6% (score <4) and 50.0 ± 10.7% (score ≥4), P=0.0003. In patients with a score <4, there was no significant difference in 5-year tumour-free survival between Milan+ and Milan- patients, either in cohort 1 or 2. Five-year tumour-free survival of Milan- patients was significantly better in individuals with a score <4 compared with those with a score ≥4, both in cohort 1 (61.5 ± 9.1 vs 31.4 ± 4.6%, P=0.009) and in cohort 2 (P=0.02)., Conclusion: A novel score taking into account tumour differentiation shows higher accuracy than Milan criteria in predicting 5-year tumour-free survival following liver transplantation for HCC. Prospective studies should validate these findings., (© 2011 John Wiley & Sons A/S.)

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., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Radiofrequency ablation, partial or total hepatectomy represent curative treatment options for patients suffering from hepatocellular carcinoma in 2010. In this review article, the role (indication, limits, results) of hepatic resection and liver transplantation are discussed., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection., Methods: This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months., Results: The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time., Conclusions: Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.

Background and Objectives: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular neoplasm of the liver. Its therapeutic management remains difficult to define in curative intent. The aim of this study was to report long-term results of surgically managed patients., Methods: From 1990 to 2006, nine patients (25-64 years) were retrospectively enrolled in this study. Intrahepatic disease extent was monolobar and bilobar in two and seven patients, respectively. As primary treatment, liver resection (LR) and liver transplantation (LT) were performed in three (two monolobar and one bilobar extent) and six patients, respectively., Results: Postoperative mortality was nil. During a median follow-up of 117 months, four patients developed intrahepatic and/or extrahepatic recurrence. One resected patient (with bilobar extent) presented with intrahepatic recurrence was secondary treated by LT. At the time of the follow-up, seven out of the nine patients treated (two after LR, and five after LT) were alive and disease-free., Conclusions: Surgical treatment offers good long-term results in patients suffering from HEHE when LR is tailored to the intrahepatic disease extent: LT has to be considered in patients with bilobar intrahepatic disease whereas LR should be strictly limited to patients presenting with localized and monolobar intrahepatic disease., ((c) 2008 Wiley-Liss, Inc.)

1. Hepatitis B virus replication is associated with a severe outcome in patients with decompensated cirrhosis. 2. Viral suppression induced by antivirals results in a clinical improvement that allows liver transplantation to be delayed or avoided. 3. Early treatment intervention is mandatory in patients with decompensated cirrhosis because of the delay in the restoration of liver functions. 4. Lamivudine is no longer the drug of choice because the initial enthusiasm has been tempered by the high rate of resistance development. 5. Early add-on therapy with adefovir allows us to rescue lamivudine resistance, but its use may be limited by nephrotoxicity. 6. Studies are ongoing with the newer generation of antivirals (telbivudine, tenofovir, entecavir, and emtricitabine) in monotherapy or in combination to determine the best strategy for achieving rapid and prolonged suppression of viral replication. These improved strategies should enhance treatment success enough to obtain clinical stabilization, to delay or prevent the need for transplantation, and to reduce the risk of hepatitis B virus recurrence on the graft.AASLD.

Purpose: To characterize and compare hepatocellular carcinoma and liver metastases of colorectal metastatic cancer (CMC) by means of quantitative liver perfusion MRI., Materials and Methods: Liver perfusion was assessed in 26 HCC and CMC patients (50 nodules) by means of contrast-enhanced MRI. Six perfusion parameters-hepatic perfusion index (HPI), mean transit time (MTT), distribution volume (DV), total blood flow (F(T)), arterial blood flow (F(A)), and portal blood flow (F(P))-were calculated in tumor nodules and the adjacent hepatic parenchyma., Results: The values of F(T), F(A), F(P), and DV were significantly higher in the HCC than in the CMC group, whereas MTT was significantly higher in the CMC group. There was no significant difference in HPI. Arterial blood flow was higher than portal blood flow in the CMC group, while portal blood flow was slightly higher than arterial blood flow in the HCC group., Conclusion: The present work describes the use of dynamic MRI to quantitatively assess liver perfusion, which in the future may help studying liver cancers on the basis of their microvascular characteristics., ((c) 2008 Wiley-Liss, Inc.)

In case of clinical suspicion of symptomatic bile duct stones, percutaneous ultrasonography and liver function tests should be performed as a primary evaluation. In the absence of predictive factors of common bile duct stones, laparoscopic cholecystectomy represents the treatment of choice for symptomatic gallstones. In case of clinical, radiological or biochemical suspicion of common bile duct stones, endoultrasonography or magnetic resonance cholangiography are efficient to confirm choledocolithiasis. In this instance, surgical approach permits simultaneous treatment of both choledocolithiasis and cholecystolithiasis while endoscopic sphincterotomy has to be followed by secondary cholecystectomy in a 2-stage procedure. Laparoscopic common bile duct exploration should be preferred to endoscopic clearance of the common bile duct but requires specific equipment and surgical experience.

Objective: To report clinical presentation, perioperative outcome, and long-term results of surgical management of congenital intrahepatic bile duct (IHBD) dilatations (including Caroli disease) in a multi-institutional setting., Summary Background Data: Congenital IHBD dilatations are a rare congenital disorder predisposing to intrahepatic stones, cholangitis, and cholangiocarcinoma. The management remains difficult and controversial for bilobar forms of the disease or when concurrent congenital hepatic fibrosis is associated., Methods: From 1976 to 2004, 33 patients (range 11 to 79 years) were retrospectively enrolled. Disease extent into the liver was unilobar in 26 patients and bilobar in 7 patients (21%). Cholangiocarcinoma, congenital hepatic fibrosis, and intrahepatic stones were present in 2, 10, and 20 patients, respectively. Transplantations or liver resections were performed in 5 and 27 patients, respectively, whereas 1 asymptomatic patient was managed conservatively., Results: Postoperative mortality was nil. Postoperative complications occurred in 16 of 32 operated patients (50%) and additional procedures for residual stones were required in 5 patients. During a median follow-up of 80 months (1 patient being lost for follow-up) no patient developed metachronous carcinoma. Six patients (30%) developed recurrent intrahepatic stones but satisfactory late outcome was achieved in 27 patients (87%)., Conclusions: Partial or total liver resection achieves satisfactory late outcome in congenital IHBD dilatations, when the affection is treated at an early stage and when the extent of liver resection is tailored to intrahepatic disease extent and takes into consideration the presence and severity of underlying chronic liver and renal diseases.

Background: Complete cyst excision of the extrahepatic disease component with biliary reconstruction on proximal healthy bile ducts is considered to be the treatment of choice in patients with congenital bile duct cysts (BDC). Proximal cystic disease that extends to the roof of the main biliary convergence (MBC) might challenge this standard of surgical care., Methods: A retrospective multicenter study was conducted in 4 European surgical centers concerning their experience with adult patients suffering from type I and IV BDC according to the Todani classification. Clinical presentation, operative management, and postoperative outcome were compared between patients with or without proximal extrahepatic cystic disease that involved at least the roof of the MBC (defined as being BDC with MBC involvement subgroup)., Results: From an overall series of 49 adult patients suffering from type I or IV BDC according to the Todani classification, 7 patients had BDC with MBC involvement (14%). Patient age, clinical presentation, duration of symptoms, associated major coexistent hepatobiliary and pancreatic diseases, and synchronous cancer were not significantly different in these patients compared with a control group of 42 adult patients with BDC without MBC involvement. Incomplete proximal cyst excision rate was 86% in the cases of BDC with MBC involvement. Early and late postoperative results were similar in BDC with MBC involvement and in the control group of adult patients, but the incidence of subsequent cancer was significantly higher in the BDC with MBC involvement group (29% vs 0%; P < .02)., Conclusion: BDC that involves the roof of the MBC is a real surgical challenge to obtain complete proximal cystic disease excision. As suggested in this small study, primary incomplete excision of this particular form of BDC might expose the patient to the risk of subsequent cancer, a feature that must be confirmed in larger series.

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.

Serous cystadenomas (SCAs) of the pancreas are benign cystic tumors. Although still controversial, asymptomatic SCAs, in contrast to their mucinous counterparts, can be treated conservatively. This attitude is mostly defendable for lesions of the pancreas head or multiple lesions distributed throughout the entire pancreas, as their surgical resection is still associated with significant morbidity. Thus, correct diagnosis is essential, and this relies on radiological and biological characteristics. Asymptomatic multiple SCAs are rare. Most cases described in the literature are either symptomatic, degenerated, or both. We present a case of huge (>10 cm), multiple asymptomatic SCAs, not associated with von Hippel-Lindau disease, involving the entire pancreas. The patient has been followed up for 3 years and remains asymptomatic. Tumor markers were within normal ranges. On abdominal computed tomography (CT) and magnetic resonance imaging (MRI), the lesions showed pathognomonic characteristics of SCAs, and their uncommon dimensions and number remained stable over time. 18-Fluorodeoxyglucose positron emission tomography (PET) scan performed at 3-year follow-up did not show hypermetabolic lesions.

Aim: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT)., Methods: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence., Results: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), alpha fetoprotein level (< 200, 200 to 2000, or > 2000; P < 0.0001), gamma-GT activity (N, N to 2N or > 2N; P = 0.02), the number of nodules (1, 2-3 or > or = 4; P = 0.02), maximal diameter of the largest nodule (< 3 cm, 3 to 5 cm or > 5 cm; P < 0.0001), the sum of the diameter of the nodules (< 3 cm, 3 to 5 cm, 5 to 10 cm or > 10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06)., Conclusion: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation.

Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma (HCC) is currently based on the Milan criteria. The University of California, San Francisco (UCSF) recently proposed an expansion of the selection criteria according to tumors characteristics on the explanted liver. This study: 1) assessed the validity of these criteria in an independent large series and 2) tested for the usefulness of these criteria when applied to pre-OLT tumor evaluation. Between 1985 and 1998, 479 patients were listed for liver transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics, patients were retrospectively classified according to both the Milan and UCSF criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%, and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically lower in UCSF+ Milan- patients compared to Milan+ but this difference was not significant (P = 0.10). Based on pathological features of the explanted liver, 5-yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+ patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n = 238), respectively (P < 0.001). However, the 5-yr survival did not differ between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results show that when applied to pre-OLT evaluation, the UCSF criteria are associated with a 5-yr survival below 50%. Their applicability is therefore limited, despite similar survival rates compared to the Milan criteria, when the explanted liver is taken into account.

The aim of this study was to identify and to classify anatomical hepatic artery (HA) variations concerning 932 HA dissections in liver transplantation (LT). Normal HA distribution was found in 68.1%. Variations of HA were detected in 31.9% and were divided into three groups describing 48 common hepatic artery (CHA) anomalies, 236 left or right hepatic artery (RHA) anomalies and 13 rare variations including one case of RHA stemmed from the inferior mesenteric artery and one case of normal CHA passed behind the portal vein. The authors propose a modified classification for HA anomalies which are based on the origin of the hepatic arterial supply (either by the CHA as the only source of the arterial vascularization or by additional or replaced right and left arteries) in order to improve management of liver disease thus as in LT.

Gastrojejunocolic fistulae, ultimate complication of anastomotic peptic ulceration, are presently uncommon. We report two recent cases of postoperative gastrojejunocolic fistulas (after duodenal ulcer surgery and total duodenopancreatectomy), which were complicated at time of diagnosis (acute peritonitis and liver cirrhosis) and required a two-stage treatment.

Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis and graft loss after liver transplantation. Treatment for post-transplant recurrence results in sustained virological response (SVR) in up to 30% of cases. The aim of this study was to evaluate the impact of SVR on patients and graft survival. Thirty-four patients with an SVR to IFN-ribavirin were included. Forty-six nonresponders to the combination formed the control group. Follow-up data were recorded every 6 months and included HCV RNA, and the occurrence of clinical problems (cirrhosis, decompensation, hepatocellular carcinoma, death). A graft biopsy was performed every year. The mean follow-up duration was 52 months in responders and 57 months in nonresponders. Two patients died in each group of patients. Two patients with SVR developed late virological relapse. Fibrosis decreased in 38% of patients with SVR, remained stable in 44% and worsened in 18%. In contrast, fibrosis increased in the majority of nonresponder patients (74%, p<0.001). At the end of follow-up, no patient without cirrhosis at inclusion developed cirrhosis of the graft versus 9 among nonresponder patients (p=0.009). No difference in patient survival was observed in the two groups. In conclusion, this study shows that HCV eradication has a positive impact on graft survival.

The actual impact of transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were evaluated for LT. Among these 479 patients, this case-control study included 100 patients who received transarterial chemoembolization before LT (TACE group) and 100 control patients who did not receive chemoembolization (no-TACE group). Patients and controls were matched for the pre-LT tumor characteristics, the period of transplantation, the time spent on the waiting list, and pre- and posttransplantation treatments. Kaplan-Meier estimates were calculated 5 years after LT and were compared with the log-rank test. The mean waiting time before LT was 4.2 +/- 3.2 months in the TACE group and 4.3 +/- 4.4 months in the no-TACE group. The median number of TACE procedures was 1 (range: 1-12). Demographic data, median alpha-fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively), and pre- and post-LT morphologic characteristics of the tumors did not differ in the TACE and no-TACE groups. Overall 5-year survival was 59.4% with TACE and 59.3% without TACE (ns). Survival rates did not differ significantly between the two groups with respect to the time on the waiting list, the tumor diameter, or the type of TACE (selective or nonselective). In the TACE group, 30 patients had tumor necrosis > or =80% on the liver explant with a 5-year survival rate of 63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion, with a mean waiting period of 4.2 months and 1 TACE procedure, pre-LT TACE does not influence post-LT overall survival and disease-free survival.

Aim of the Study: To report a series of 17 patients operated for a complication oesophagocoloplasty, with evaluation of therapeutic modalities, and both early and distant results., Materials and Method: From 1985 to 2003, 17 patients with a mean age of 50 years (range: 23-76) were reoperated after coloplasty pediculated on left superior colic vessels. Initial diseases were caustic ingestion (N=7), cancer (N=6), oesophageal perforation (N=2), gastric lymphoma (N=1) and oesotracheal fistula (N=1). Coloplasty has been performed as a first-intent procedure in 13 cases and as a second-intent procedure after failure of a previous operation in 4 cases. Nine patients were initially operated in another center and were subsequently referred in our unit. Complications needing reoperation were graft necrosis in 8 cases (47%) and stricture in 9 cases (53%). All patients with necrosis were reoperated within the 10 first postoperative days., Results: Necroses were treated by complete (N=5) or partial (N=3) resection of the coloplasty. Strictures were treated by resection-reanastomosis (N=3), right ileocoloplasty (N=2), colic stricturoplasty (N=2), a free antebrachial flap (N=1) and a tubulized latissimus dorsi myocutaneous pedicled flap (N=1). The 30-day mortality rate was 12% (N=2) and the overall morbidity rate was 66%. All deaths occurred after reoperation for necrosis. Eleven patients (65%) kept or recovered digestive continuity (including the 9 with stenosis) and 8 (73%) eat normally. Four patients with transplant necrosis died before reestablishment. Four patients operated for necrosis died before restoration of digestive continuity and 2 patients are still awaiting restoration., Conclusion: Use of colon as an oesophageal substitute is risky. Reoperations for stenosis allows satisfactory oral feeding, while reoperation for necrosis is associated with both high early mortality and a low rate of restoration or digestive continuity. This later requires a range of complex surgical procedures.

Background: HCV reinfection after liver transplantation is universal and has an accelerated course with a high risk of progression to cirrhosis. It is now established that combination therapy with interferon (IFN) alpha and ribavirin may achieve a sustained virological response in 20% of transplanted patients. However, the optimal therapy for nonresponders remains an unresolved issue. We conducted a pilot study to determine the efficacy and safety of triple antiviral therapy in IFN-ribavirin nonresponders with recurrent chronic hepatitis C., Methods: Twenty-four nonresponders to the IFN-ribavirin combination were enrolled in this pilot study. Patients were treated with IFN-alpha (3 million units three times a week subcutaneously with ribavirin [800-1,000 mg daily]) and amantadine 200 mg daily for 48 weeks. The primary end point was the loss of HCV RNA 6 months after the end of treatment., Results: Median age was 50 years; 72% were men and 82% had genotype 1. The median interval between the end of combination therapy and enrollment was 11 months. Twenty-four patients started therapy, but five (21%) withdrew due to side effects, including two with anemia. On an intent-to-treat basis, 18 patients (75%) had a biochemical response and 9 (37%) had a virologic response at the end of triple antiviral therapy. Eight of these nine patients (33%) had a sustained virological response. The mean METAVIR score improved from A 2.2 F2.1 before treatment to A 1.2 F1.9 in sustained virological responders. In virological nonresponders, inflammatory activity did not change, but fibrosis worsened. Several patients required treatment with erythropoietin for anemia. Triple therapy was well tolerated and neither increased the frequency nor severity of side effects., Conclusion: Our results show that triple antiviral therapy for 48 weeks induced a sustained virological response in 33% of IFN-ribavirin nonresponders with recurrent hepatitis C.

Background/aims: Worldwide experience with laparoscopic pancreatic resection remains limited. The aim of the study was to assess the feasibility, safety and outcome of laparoscopic pancreatic resection., Methodology: 15 consecutive patients suffering from benign cystic pancreatic (n=6), neuroendocrine tumors (n=8) or pancreatic metastasis from renal carcinoma (n=1) undergoing laparoscopic pancreatic resection were retrospectively collected from 5 academic hospitals., Results: Laparoscopic procedure was completed in 10 patients, including 7 distal pancreatectomies (with 5 spleen preservation), 2 tumor enucleations and 1 partial cystic resection. Conversion was due to inappropriate operative finding for laparoscopic approach in 2 patients and for uncontrollable bleeding in 3 patients. Postoperative pancreatic-related complications included pancreatic fistula in 20% and peripancreatic collection in 13% of the patients., Conclusions: Laparoscopic pancreatic resection is feasible for distal pancreatic tumors. However, successful management of the pancreatic stump remains the challenge of this procedure, in order to achieve a clear benefit in the patient outcome.

This open, randomized (1 : 1), multicenter, 3-month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole-blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups: 26.5% in the Tac / steroids group and 25.4% in the Tac / Dac group (P = .727). However, the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8%; P = .027). Kaplan-Meier estimates of graft survival (92.2 vs. 90.5%) and patient survival (94.5 vs. 93.7%) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7%, respectively; P < .001) and cytomegalovirus infection (11.5 vs. 5.1%, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16% in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid-resistant acute rejection.

Some clinical studies in liver transplantation have recently reported safety advantages and similar acute rejection rates with early steroid withdrawal. The aim of this study was to evaluate the efficacy and safety of an immunosuppressive regimen with steroid withdrawal at day 14. A multicenter, 1-year, comparative, double blind, placebo-controlled study was performed. Patients undergoing a first cadaveric liver transplantation were recruited and all received basiliximab + cyclosporine + intravenous methylprednisolone. Patients without severe postoperative complications were randomized at day 7 to receive a maintenance regimen with Neoral (cyclosporine) + prednisolone (group 1) or without steroids (Neoral + placebo; group 2), after a 7-day blinded oral steroid tapering period. A total of 174 patients were randomized at day 7 (group 1: n = 90; group 2: n = 84). The incidence of biopsy-confirmed and treated acute rejection at 6 months was 38.1% in group 2 vs. 24.4% in group 1 (P = .03) with a trend for a higher incidence of Grade II / III acute rejection (28.6% vs. 18.9%; P = .12). Changes from baseline were similar with regard to metabolic parameters (glycemia, total cholesterol, and triglycerides). A trend toward a better glucose tolerance was observed, as fewer patients received an antidiabetic treatment in the placebo group (2 vs. 10). In conclusion, this first double-blind, placebo-controlled study of steroid withdrawal at day 14 showed a higher incidence of acute rejection, only balanced by a trend of a lower need of antidiabetic treatment.

Over the past 20 years there have been many advances in the management of rectal cancer. The medico-surgical school in Lyon, France, has a long tradition in managing this malignancy. The progression of ideas and practices requires a better knowledge of the patterns of tumor spread and local recurrence. Technical advances have greatly helped to facilitate sphincter preservation. Advances in radiotherapy have led to its routine use in the preoperative period. This approach has now emerged as the best therapeutic sequence. Our experience concerns 46 patients with low rectal carcinoma treated with this strategy. There were no post-operative deaths and no leakage. One patient (2%) had a pelvic abscess. Median follow-up was 50 months (1-151). At five years, the local recurrence rate was 8.5% and the actuarial survival rate was 72%, with a local control rate of 91%. Functional outcome, evaluated with a scoring system, was good in 60% of cases at one year and 78% at 5 years. Quality of life, evaluated with the American Society of Colon and Rectal Surgeons scale (A.S.C.R.S.), was 107 +/- 21 (range 33-140). The absence of defunctioning stoma (initial or late), good sexual and urinary well-being, and psychologic assessment are essential factors, requiring rigorous evaluation before the operation and specialized management after the operation. The proposed strategy based on this safe procedure and "French-type" neoadjuvant radiotherapy, permits sphincter preservation in patients with T2 and T3 tumors located near the dentate line, with good late oncological outcome. It is often amenable to the laparoscopic approach.

The analysis of the literature demonstrated that pharmacy counselling influenced patient outcome after transplantation. This was the reason we established pharmacy consultation in 1999. The aim of this study was to determine patient knowledge before and after pharmacy counselling. Twenty-nine patients were questioned about the identification, role and dosage of prescribed drugs. The mean duration of pharmacy counselling was 54 minutes. Before pharmacy consultation, the knowledge score was 53.7%. Afterwards, the mean score value reached 75% and seven patients had a score of 100%. The anti-rejection therapy was understood by 93% of patients. However, the associated drugs were poorly known: less than 15% of patients initially knew about the purpose of the antimicrobial agent, compared with 50-60% after counselling. During counselling, two women were identified as regularly using St John's Wort and were informed that this herbal medicine can endanger the success of organ transplantation. Five patients or family members called the pharmacist to obtain additional information. Among these, two medication errors, both with corticosteroid drugs, were reported by family members of patients of foreign origin who had difficulty in understanding and speaking French. Pharmacy counselling improved patient knowledge about therapy after transplantation.

Background and Aims: Hepatitis C virus (HCV) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis. The use of antiviral therapy in this situation remains controversial. This study aimed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation., Methods: Transplant recipients with recurrent chronic hepatitis C were randomized to receive either no treatment or therapy with interferon alfa-2b (3 MU 3 times a week) plus 1000-1200 mg/day ribavirin for 1 year. Patients were followed up for 6 months after the end of treatment. The primary end point was loss of HCV RNA 6 months after the end of treatment., Results: Fifty-two patients were randomized (treatment, 28; placebo, 24). Sixteen patients were withdrawn from the study; 12 (43%) were from the treated group (mainly for anemia [7 patients]) and 4 (17%) from the control group. In the treated group, serum HCV RNA was undetectable in 9 patients (32%) at the end of treatment and 6 (21.4%) at the end of the follow-up period, whereas no patient in the control group lost HCV RNA at any point (P = 0.036 at the end of follow-up). However, there was no significant histologic improvement., Conclusions: The combination of interferon alfa-2b plus ribavirin induced a sustained virologic response in 21% of transplant recipients with recurrent hepatitis C. However, 43% discontinued therapy due to adverse events (primarily severe anemia). Strategies to enable treatment with lower doses of ribavirin need to be explored.