Search

Background: Right hepatectomy (RH) is the most common type of major hepatectomy and can be achieved without portal triad clamping (PTC) in non-cirrhotic liver. The present study reviews our standardized policy of performing RH without systematic PTC., Methods: One hundred and eighty-one consecutive RH were performed in non-cirrhotic patients, with division of the right afferent and efferent blood vessels prior to transection, without systematically using PTC. Prospectively collected data were analysed, focusing on the following endpoints: need for salvage PTC, ischaemic time, blood loss and post-operative outcome., Results: Extra-hepatic division of the right hepatic vessels was feasible in all patients, but was ineffective in 48 patients (26.5%) who required salvage PTC during transection. In those patients, the median ischaemic time was 20 min. The median blood loss was 500 ml (50-3000). Six patients (3.3%) experienced post-operative liver failure. Overall morbidity, severe morbidity and mortality were 42%, 12.1% and 1.6%, respectively, with peri-operative transfusion rate (16.6%) being the only factor associated with morbidity., Discussion: By performing RH with extra-hepatic vascular division prior to transection, PTC can be safely avoided in the majority of patients., (© 2012 International Hepato-Pancreato-Biliary Association.)

Obesity has become a major public health concern. More and more patients with substantial obesity require surgery including complex hepatobiliary interventions. The morphology of these patients can make surgery difficult, especially in terms of exposure. We report the case of an obese patient who required a left hemihepatectomy for colorectal liver metastasis. It was very difficult to obtain adequate exposure; this problem was solved by transcutaneous introduction of the handle of a broad costal margin retractor. We describe this maneuver, which allowed us to carry out the intervention under excellent conditions., (Copyright © 2012. Published by Elsevier Masson SAS.)

Background: Preoperative measurement of hepatic venous pressure gradient (HVPG) is not performed routinely before hepatectomy in patients with cirrhosis, although it has been suggested to be useful. This study investigated whether preoperative HVPG values and indirect criteria of portal hypertension (PHT) predict the postoperative course in these patients., Methods: Between January 2007 and December 2009, consecutive patients with resectable hepatocellular carcinoma (HCC) in a cirrhotic liver were included in this prospective study. PHT was assessed by transjugular HVPG measurement and by classical indirect criteria (oesophageal varices, splenomegaly and thrombocytopenia). The main endpoints were postoperative liver dysfunction and 90-day mortality., Results: Forty patients were enrolled. A raised HVPG was associated with postoperative liver dysfunction (median 11 and 7 mmHg in those with and without dysfunction respectively; P = 0·017) and 90-day mortality (12 and 8 mmHg in those who died and survivors respectively; P = 0·026). Oesophageal varices, splenomegaly and thrombocytopenia were not associated with any of the endpoints. In multivariable analysis, body mass index, remnant liver volume ratio and preoperative HVPG were the only independent predictors of postoperative liver dysfunction., Conclusion: An increased HVPG was associated with postoperative liver dysfunction and mortality after liver resection in patients with HCC and liver cirrhosis, whereas indirect criteria of PHT were not. This study suggests that preoperative HVPG measurement should be measured routinely in these patients., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Transplant glomerulitis (TG) can lead to the diagnosis of acute humoral rejection when associated with C4d. Recent data have shown that, in patients with donor-specific antibodies, TG is a sign of humoral rejection, even in the absence of C4d. However, the clinical significance of isolated TG, i.e. TG without C4d deposition or morphological evidence of rejection, has not been specifically studied in protocol biopsies of recipients without donor-specific antibodies. We compared 20 isolated TG-patients with 44 selected recipients without TG or any rejection-associated change. The two groups had similar baseline characteristics. After a 3 year follow-up, renal function, acute rejection rate, and development of HLA antibodies were not significantly different between the two groups. Isolated TG had no deleterious consequences on the 3 year graft outcome. Eleven patients of the glomerulitis-group had another allograft biopsy during follow-up: glomerular lesions returned to normal in six patients whereas the persistence of glomerulitis or features consistent with chronic transplant glomerulopathy were noticed in the remaining five patients. Four of these five patients had pretransplant non-donor specific HLA antibodies. In conclusion, although isolated TG had no impact on allograft function at 3 year, histological outcome could be related to patient sensitization., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

Background: A 6-month abstinence from alcohol is usually required before patients with severe alcoholic hepatitis are considered for liver transplantation. Patients whose hepatitis is not responding to medical therapy have a 6-month survival rate of approximately 30%. Since most alcoholic hepatitis deaths occur within 2 months, early liver transplantation is attractive but controversial., Methods: We selected patients from seven centers for early liver transplantation. The patients had no prior episodes of alcoholic hepatitis and had scores of 0.45 or higher according to the Lille model (which calculates scores ranging from 0 to 1, with a score ≥ 0.45 indicating nonresponse to medical therapy and an increased risk of death in the absence of transplantation) or rapid worsening of liver function despite medical therapy. Selected patients also had supportive family members, no severe coexisting conditions, and a commitment to alcohol abstinence. Survival was compared between patients who underwent early liver transplantation and matched patients who did not., Results: In all, 26 patients with severe alcoholic hepatitis at high risk of death (median Lille score, 0.88) were selected and placed on the list for a liver transplant within a median of 13 days after nonresponse to medical therapy. Fewer than 2% of patients admitted for an episode of severe alcoholic hepatitis were selected. The centers used 2.9% of available grafts for this indication. The cumulative 6-month survival rate (±SE) was higher among patients who received early transplantation than among those who did not (77 ± 8% vs. 23 ± 8%, P<0.001). This benefit of early transplantation was maintained through 2 years of follow-up (hazard ratio, 6.08; P = 0.004). Three patients resumed drinking alcohol: one at 720 days, one at 740 days, and one at 1140 days after transplantation., Conclusions: Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy. (Funded by Société Nationale Française de Gastroentérologie.).

Background: Sorafenib increases median survival and time to radiological progression in patients with advanced hepatocellular carcinoma, but its benefit for Child-Pugh B patients remains uncertain., Aim: To evaluate the safety and efficacy of sorafenib in real-life clinical practice conditions and to assess the influence of Child-Pugh class B on safety and efficacy., Methods: All patients treated with sorafenib for advanced hepatocellular carcinoma in our institution were included prospectively. Adverse events, overall survival and time to progression were recorded. A case control study was performed to compare outcome of patients with comparable stages of hepatocellular carcinoma, but a different Child-Pugh class., Results: From March 2007 to May 2009, 120 patients were included. Overall survival was 11.1 months, Child-Pugh A patients (n=100) had significantly higher median survival than Child-Pugh B patients (n=20) (13 vs. 4.5 months, P=0.0008). In multivariate analysis, Child-Pugh class B, α-fetoprotein level and total size of lesions were independent predictive factors of death. Patients with radiological progression in the first 3 months had shorter median survival (5.4 vs. 17.4 months). In a case control study, time to symptomatic progression (2.5 vs. 3.6 months), frequency of adverse events and discontinuation of sorafenib were not correlated with Child-Pugh class., Conclusions: Patients with advanced hepatocellular carcinoma treated with sorafenib had a median survival of 11 months. Sorafenib therapy must be considered with caution in Child-Pugh B patients due to their poor survival. Radiological assessment of tumour progression at an early stage may be advantageous when tailoring sorafenib therapy., (© 2011 Blackwell Publishing Ltd.)

Background: Studies that compare laparoscopic to open liver resection for hepatocellular carcinoma (HCC) in cirrhotic patients are rare and may have suffered from low patient numbers. This work was designed to determine the impact of laparoscopic resection on postoperative and long-term outcomes in a large series of cirrhotic patients with hepatocellular carcinoma (HCC) compared with open resection., Methods: From 2002 to 2009, 36 patients with chronic liver disease with complicating HCC were selected for laparoscopic resection (laparoscopic group, LG). The outcomes were compared with those of 53 patients who underwent open hepatectomy (open group, OG) during the same period in a matched-pair analysis. The two groups were similar in terms of tumor number and size and number of resected segments., Results: Morbidity and mortality rates were similar in the two groups (respectively 25 and 0% in LG vs. 35.8 and 7.5% in OG; p = 0.3). Severe complications were more frequent in OG (13.2%) than in LG (2.8%; p = 0.09). Despite similar portal hypertension levels, complications related to ascites (namely evisceration or variceal bleeding) were fatal in 4 of 12 affected patients in OG but 0 of 5 cases in LG (p = 0.2). The mean hospitalization durations were 6.5 ± 2.7 days and 9.5 ± 4.8 days in LG and OG, respectively (p = 0.003). The surgical margins were similar in the two groups. Although there was a trend toward better 5-year overall survival in LG (70 vs. 46% in OG; p = 0.073), 5-year disease-free survival was similar (35.5 vs. 33.6%)., Conclusions: Laparoscopic resection of HCC in patients with chronic liver disease has similar results to open resection in terms of postoperative outcomes, surgical margins, and long-term survival.

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.

Unlabelled: Osteoporosis is common in liver transplant recipients as a result of both iatrogenic factors and preexisting hepatic osteodystrophy., Objectives: To assess the prevalences of osteoporosis and fractures and to identify risk factors for these two abnormalities in patients awaiting liver transplantation for end-stage liver disease., Methods: Between January 2006 and December 2007, patients on a liver transplant waiting list underwent a routine evaluation comprising the identification of risk factors for osteoporosis, radiographs of the spine, bone mineral density measurements (BMD), and laboratory tests (phosphate and calcium levels, hormone assays, liver function tests, and bone turnover markers)., Results: We studied 99 patients (70 males and 20 females; mean age, 55 ± 8 years) including 75% with alcohol-induced cirrhosis with or without hepatocarcinoma. Among them, 36% had radiographic vertebral fractures, 38% had osteoporosis, 35% had osteopenia, and 88% had vitamin D insufficiency or deficiency (25(OH)vitamin D3<20 ng/mL). Lower BMD values were associated with vertebral fractures; the odds ratios and 95% confidence intervals for each BMD decrease of 1 SD were as follows: spine, 1.45 (95%CI, 1.1-1.9); total hip, 2.1 (95%CI, 1.3-3.2); and femoral neck, 2 (95%CI, 1.3-3.1) (P<0.05). Levels of bone resorption markers correlated negatively with BMD at the spine and hip. The Model for End-Stage Liver Disease score correlated negatively with hip BMD., Conclusion: Our findings suggest high prevalences of low BMD values and vertebral fractures among patients awaiting liver transplantation. Bone status should be evaluated routinely in candidates to liver transplantation., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

At present, no method is available for accurately monitoring the degree of immunosuppression induced by antirejection therapies. The aim of this study was to determine whether CD28 and CD38 expression by peripheral blood mononuclear cells could be useful in predicting the development of de novo malignancies after liver transplantation. Flow cytometry analysis was used to measure the expression of CD28 and CD38 by peripheral blood lymphocytes in 134 stable, long-term survivors of liver transplantation. Patients who developed a de novo malignancy after undergoing a medical checkup were entered into a cancer group. Twenty-two patients (16.4%) developed at least 1 de novo malignancy over a mean interval of 22 ± 14 months (1.2-49.4 months) after the checkup. The mean frequency of CD28(+)CD8(+) cells was significantly lower in the cancer group versus the noncancer group (39% ± 22 versus 51% ± 21, P = 0.008), but CD38 expression was similar in the 2 groups. Multivariate analysis indicated that an age greater than 50 years (odds ratio = 5.81) and a low frequency of CD28(+)CD8(+) cells at the time of the checkup (odds ratio =3.16) were the only significant predictors of the development of de novo malignancies (P = 0.027). The actuarial proportion of patients with de novo malignancies was significantly lower when the frequency of CD28(+)CD8(+) cells was greater than or equal to 40% instead of less than 40% (P = 0.01). Flow cytometry measurements of CD28 expression by peripheral blood lymphocytes may facilitate the identification of patients at a high risk of developing de novo malignancies. Further prospective studies are necessary to determine whether such measurements could have a place in routine clinical practice to enable the intensity of immunosuppression to be minimized in patients who have an increased risk of developing cancer., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Objectives: This study seeks to identify factors for hepatectomy in the management of post-cholecystectomy bile duct injury (BDI) and outcome via a systematic review of the literature., Methods: Relevant literature was found by searching the PubMed database and the bibliographies of extracted articles. To avoid bias selection, factors for hepatectomy were analysed in series reporting both patients undergoing hepatectomy and patients undergoing biliary repair without hepatectomy (bimodal treatment). Relevant variables were the presence or absence of additional hepatic artery and/or portal vein injury, the level of BDI, and a previous biliary repair., Results: Among 460 potentially relevant publications, only 31 met the eligibility criteria. A total of 99 hepatectomies were reported among 1756 (5.6%) patients referred for post-cholecystectomy BDI. In eight series reporting bimodal treatment, including 232 patients, logistic regression multivariate analysis showed that hepatic arterial and Strasberg E4 and E5 injuries were independent factors associated with hepatectomy. Patients with combined arterial and Strasberg E4 or E5 injury were 43.3 times more likely to undergo hepatectomy (95% confidence interval 8.0-234.2) than patients without complex injury. Despite high postoperative morbidity, mortality rates were comparable with those of hepaticojejunostomy, except in urgent hepatectomies (within 2 weeks; four of nine patients died). Longterm outcome was satisfactory in 12 of 18 patients in the largest series., Conclusions: Hepatectomies were performed mainly in patients showing complex concurrent Strasberg E4 or E5 and hepatic arterial injury and provided satisfactory longterm outcomes despite high postoperative morbidity.

Liver metastases from endocrine tumors can reduce 5-year survival from 90% to 40% and, in cases of functional gastrointestinal endocrine tumors, lead to a carcinoid syndrome. Complete resection of cancerous disease should be considered in all cases. Indeed, after hepatectomy, prolonged survival (41-86% at five years) can be achieved, with low rates of surgery-related mortality (0-6.7%). Extended liver resection is required in most cases. Percutaneous portal embolization increases the volumetric feasibility of resection, and sequential hepatectomy techniques enable a two-stage resection of both bilobar metastases and the primary tumor. For carcinoid syndrome that does not respond to medical therapy, incomplete resection of liver metastases, by reducing tumor volume, may be indicated to reduce symptoms and halt the progression of carcinoid heart disease. In cases of non-resectable liver metastases in selected patients, liver transplantation can lead to 5-year survival rates as high as 77%., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Primary sarcomas of the liver are rare tumors and their diagnosis is difficult to assess, particularly on percutaneous liver biopsy. Epithelioid hemangioendothelioma (EHE) is an infrequent indication for liver transplantation, and angiosarcoma (AS) is a widely recognized contraindication because of its poor prognosis. We report the case of a young woman who underwent liver transplantation (LT) for an infiltrative hepatic tumor with several features suggestive of EHE, although the analysis of the native liver revealed AS. Everolimus was used as the main immunosuppressive drug. More than two years after LT, her physical condition remained stable despite a local recurrence at 10 months. In this setting, the ranking of new immunosuppressive agents belonging to the family of the proliferation signal inhibitors will need to be precise, but their intrinsic properties suggest a potential use in treatments after LT for atypical malignancies.

It is now accepted that patients with a liver transplantation regain the ability to lead a normal life within months of surgery, but at the price of lifetime immunosuppressive treatment and specific regular surveillance. A balanced and diversified diet, together with regular physical activity is necessary to prevent, limit, or delay the development of the cardiovascular complications that determine the prognosis for long-term survival. Attenuated live vaccines are contraindicated in patients treated with immunosuppressants to avoid the risk of reversion of the attenuation of the virus or bacteria. Travel abroad is possible to places with good sanitary conditions, if the patient increases his or her vigilance for any contagious infection. The global incidence of cancer is higher than in the general population, justifying specific and regular testing and clinical monitoring. A planned pregnancy is possible in patients stabilized after liver transplantation, and prognosis is most often good for mother and child. Early multidisciplinary management is essential because of the elevated risks of fetal growth restriction and preterm delivery. The global perception of quality of life increases after liver transplantation, but remains lower than in healthy subjects.

While the natural history and appropriate diagnostic and management practices are relatively well defined for hepatocellular carcinoma (HCC), data are scarce concerning the characteristic features and treatment modalities for recurrent HCC after liver transplantation. The time of recurrence appears to impact survival more significantly than localization, but to date, guidelines for therapeutic management of recurrent HCC have not been established. Data in the literature shows that late and unifocal recurrence has a better prognosis when treated by surgery or radiofrequency. In the event of early recurrence, surgery cannot be recommended due to the lack of evidence and the high risk of advanced disease. Systemic therapy can be discussed in a situation of multifocal recurrence. Proliferative signal inhibitors exhibit both immunosuppressive and antiproliferative properties and liver transplantation teams tend to introduce such treatment despite the lack of extensive data.

Organ shortage remains a major problem in liver transplantation for which the number of patients on the waiting list is superior to the number of liver grafts harvested each year. In 2007, 1061 liver transplantations have covered 78.7% of the needs for 1348 new candidates. Improvement of the results (5 year-survival 74.9% and 63% at 10 years) do not influence the number of major indications (hepatocellular carcinoma, hepatitis C virus, alcohol), despite a slight decrease in the rate of activity of 1 to 2% per year. Introduction of the national score for each patient to be registered on the waiting list, the use of split grafts or grafts from marginal criteria donors may enlarge the donor pool. Liver grafts from cardiac deceased donors or from living donors are less frequent and are controversial from a technical and psychological point of view. The most efficient solution in order to overcome organ shortage is the increase in the pool of brain dead donors by accompanying people acceptance of organ donation and the use of parts of human body after death. Such education of the population could be made by the valorisation of organ donation, through public campaigns suggesting reflexion rather than coercition.

Withdrawal of calcineurin inhibitors (CNI) followed by mycophenolate mofetil (MMF) monotherapy after liver transplantation (LT) remains controversial due to the increased risk of acute rejection and graft loss. The aim of the present study, performed in a large cohort of liver-transplanted patients with severe CNI-induced side effects, was to assess renal function recovery, and safety in terms of liver function, of complete CNI withdrawal and replacement by MMF monotherapy. Fifty-two patients treated with MMF monotherapy for CNI-induced toxicity were analyzed. Mean estimated glomerular filtration rate (eGFR) increased significantly during the period of MMF monotherapy, from 37 +/- 10 to 44.7 +/- 15 mL/min/1.73 m(2) at 6 months (p = 0.001) corresponding to a benefit of +17.4% in renal function. eGFR stabilized or improved in 86.5%, 81% and 79% of cases, and chronic renal dysfunction worsened in 13.5%, 19% and 21% of cases, at 6, 12 and 24 months after CNI withdrawal, respectively. Only two patients experienced acute rejection. MMF monotherapy may be efficient at reversing/stabilizing CRD, and appears relatively safe in terms of liver graft function in long-term liver-transplanted patients. However, clinicians must bear in mind the potential risk of rejection and graft loss, and should be very cautious in the management of such 'difficult-to-treat patients'.

Human herpesvirus-6 (HHV-6) has been identified as the causal agent of exanthema subitum in early childhood (also called sixth disease or roseola), a mononucleosis-like disease in adults, and as an opportunistic pathogen in transplant recipients. In the latter setting, most infections are caused by reactivation of the latent virus in the recipient and generally have a paucisymptomatic course. Only limited data on HHV-6 infection are available for liver transplant recipients. Herein we have reported a case of fatal hemophagocytic syndrome related to HHV-6 reactivation 2 weeks after liver transplantation (LT). This case suggests that this virus may be a serious and potentially life-threatening pathogen following LT.

We report two cases of iatrogenic occlusion of the superior mesenteric artery (SMA) and celiac axis (CA) during left nephrectomy. A patient with a urothelial carcinoma (open surgery) and one with coralliform calculi (laparoscopy) experienced injury to both the SMA and/or CA due to bulky perihilar adenopathy and kidney adherence to surrounding tissue. The cancer patient survived after fast repair. Repair was delayed in the second patient who subsequently died. It is essential to identify each arterial branch carefully on the preoperative CT-scan to identify any duplicate renal arteries and avoid mistaking the SMA and/or CA for the renal artery.

Background: Oxygen consumption at peak exercise (peak VO2) is the most accurate index of aerobic capacity (AC), which reflects the physical condition of an individual and is currently considered the gold standard for cardiorespiratory fitness. Evaluation of peak VO2 to identify high-risk candidates for liver transplantation (LT) may represent an interesting approach. The aims of this study were (a) to describe AC and identify factors independently associated with peak VO2; (b) to analyze the prognostic value of peak VO2 in patients referred for preliminary evaluation of LT; and (c) to provide preliminary data on the influence of peak VO2 on length of hospitalization and the need for oxygen support after LT., Results: Peak VO2 was determined in patients referred for preliminary evaluation for LT. One hundred thirty-five candidates were included. More than half had severe alterations in peak VO2. Age, gender, model-for-end-stage liver disease (MELD) score, tobacco use, and hemoglobin were independently associated with peak VO2. Candidates with severe alterations in peak VO2 had a lower 1-year survival than others. Model-for-end-stage liver disease score and peak VO2 were independently associated with survival. In patients with a MELD above 17, those with severe alterations of peak VO2 AC had lower 1-year survival than the others. Among patients who underwent LT, those with severe impairment of peak VO2 showed a trend toward a higher mean length of hospitalization after LT and had significantly longer need for oxygen support., Conclusions: Peak VO2 is severely impaired in candidates for LT and affects survival and post-LT course. Perioperative respiratory rehabilitation programs validated in lung and heart transplantation must be tested.

Background/aim: The aim of this study was to determine whether the expression of CD25, CD28 and CD38 (which reflects the degree of T-cell activation) by peripheral blood mononuclear cells constitutes a useful means of measuring the immune status of liver transplant recipients., Methods: Fifty-two patients enrolled in a prospective randomized study comparing cyclosporine and tacrolimus as the principal immunosuppressive drugs were monitored prospectively. The expression of CD25, CD28 and CD38 was analyzed on CD3-, CD4- and CD8-positive cells from whole blood using flow cytometry. The prognostic value of baseline and day 14 measurements regarding acute rejection was examined using Kaplan-Meier estimates for univariate analyses and the Cox model for multivariate analyses., Results: The mean frequencies of CD28 and CD38-expressing T cells were significantly higher in patients with acute rejection (p = 0.01 and p = 0.001, respectively), whereas the frequency CD25-expressing T cells did not differ significantly. Under univariate analysis, baseline CD25 levels, the type of calcineurin inhibitor, as well as the CD28 and CD38 frequencies obtained at day 14 were associated with the subsequent development of acute rejection. Under multivariate analysis, only CD28 and CD38 frequencies obtained at day 14 were independently associated with acute rejection., Conclusions: The evaluation of CD28 and CD38 expression in peripheral blood lymphocytes is a simple marker that could be used routinely in clinical practice to assess the level of immunosuppression.

Objective: The use of ultrasonography is widespread for both the diagnosis and treatment of liver tumors. However, the measurement of liver volume by ultrasonography is not commonly done. We report an original method of liver volumetry using ultrasonography and an investigation into the usefulness of ultrasonography in this context., Methods: The data for 50 patients undergoing various types of major hepatectomy were collected. We preoperatively measured liver volume using ultrasonography, dividing the liver into three main compartments according to precise anatomical landmarks, and then made comparisons with the volume of the actual specimen after hepatectomy, for all of the study participants., Results: Total volume correlation between the two groups was good (r = 0.916, P < 0.001). However, the correlation was weaker in cases of right hepatectomy compared with other types of hepatectomy., Conclusion: This study demonstrates the possibility of doing liver volumetry using an ultrasound device. Further investigation to establish the reliability of this easily available and noninvasive approach is needed.

Background: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up., Material and Methods: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT., Results: HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6-98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion., Conclusions: The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.

Unlabelled: Early identification of patients with severe (discriminant function > or = 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies. Three hundred twenty patients with AH prospectively treated by corticosteroids were included in the development cohort and 118 in its validation. Baseline data and a change in bilirubin at day 7 were tested. The model was generated by logistic regression. The model combining six reproducible variables (age, renal insufficiency, albumin, prothrombin time, bilirubin, and evolution of bilirubin at day 7) was highly predictive of death at 6 months (P < 0.000001). The area under the receiver operating characteristic (AUROC) curve of the Lille model was 0.89 +/- 0.02, higher than the Child-Pugh (0.62 +/- 0.04, P < 0.00001) or Maddrey scores (0.66 +/- 0.04, P < 0.00001). In the validation cohort, its AUROC was 0.85 +/- 0.04, still higher than the other models, including MELD (0.72 +/- 0.05, P = 0.01) and Glasgow scores (0.67 +/- 0.05, P = 0.0008). Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival as compared with others: 25% +/- 3.8% versus 85% +/- 2.5%, P < 0.0001. This cutoff was able to identify approximately 75% of the observed deaths., Conclusion: In the largest cohort to date of patients with severe AH, we demonstrate that the term "nonresponder" can now be extended to patients with a Lille score above 0.45, which corresponds to 40% of cases. Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies.

Supraselective transarterial chemoembolization (STACE) more efficiently targets chemotherapy delivered via the feeding arterial branches of the tumor than does conventional transarterial chemoembolization (TACE). However, the hypothesis of its greater efficacy compared with the latter is subject to controversy. The aim of the present study was to compare STACE to conventional TACE in a controlled study of candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients were matched for factors associated with HCC recurrence and survival. Sixty patients were included: 30 who were treated with STACE and 30 treated with conventional TACE. The 2 groups were similar in terms of matched criteria. In the overall population (uni- and multinodular HCC), there was no marked difference between the 2 groups in 5-year disease-free survival: 76.8% vs. 74.8%. In sensitivity analysis of patients considered to be the best candidates for TACE (uninodular HCC < or =5 cm), there was a trend toward significance between STACE and TACE in 5-year disease-free survival: 87% vs. 64% (P = 0.09). The only factor associated with complete tumor necrosis was STACE in the overall population (30.8% vs. 6.9%, P = 0.02), with a similar trend in the subgroup of patients with a single nodule (33.3% vs. 6.7%, P = 0.06), whereas the mean number of procedures was similar in the 2 groups (mean, 1.3 procedures; range 1-5 procedures; P = NS). STACE is more efficient at inducing complete tumor necrosis in the liver. This study observed trends toward improvement in the disease-free survival of patients with uninodular HCC < or =5 cm. Future studies focusing on such patients are warranted.

Dermatological complications following transplantation are very common and the majority of immunosuppressed transplant recipients develop some to many warts due to human papillomavirus (HPV) infection. In the setting of immunosuppression, therapeutic management may be disappointing because of the extent of the lesions in patients unable to develop a sufficient immune response directed against HPV. We report here a case of a young liver transplant recipient who developed diffuse recalcitrant HPV-induced warts leading to an impairment of her quality of life. Taking into account the antiproliferative and cytostatic properties of the target-of-rapamycin (TOR) inhibitors, a new class of immunosuppressive drug, we significantly modified the immunosuppressive regimen. Conversion to sirolimus was followed by a rapid improvement of cutaneous state suggesting that this strategy may be useful for recalcitrant cutaneous viral warts in transplant recipient.

Objective: To investigate the population pharmacokinetics of tacrolimus in an adult liver transplant cohort using routine drug monitoring data and to identify patient characteristics that influence pharmacokinetic parameters., Methods: Tacrolimus pharmacokinetics was studied in 37 adult patients using a population approach performed with NONMEM., Results: A one-compartment open model with linear absorption and elimination adequately described the data. The apparent clearance (CL) was approximately zero in the immediate post-operative days (PODs) and then rapidly increased as a function of POD to reach a plateau. This was modelled as a sigmoid relationship with the characteristic parameters CL(max) (plateau), TCL(50) (time to obtain 50% of the plateau) and gamma (coefficient of sigmoidicity). This clearance model was thought to describe the hepatic function regeneration after transplantation. Typical population estimates (percentage inter-individual variability) of CL(max), TCL50, and gamma and apparent distribution volumes (V) were 36 l/h (43%), 6.3 days (33%), and 4.9 l and 1870 l (49%), respectively. The CL(max) was negatively related to plasma albumin, and TCL50 was positively related to aspartate amino transferase (ASAT). Bayesian estimations performed at different POD times indicated that acceptable precisions in individual pharmacokinetic predictions could be obtained after the 15th POD., Conclusion: Tacrolimus clearance modelling showed that there was a large variation in individual CL estimates up to the 15th day post-surgery. After this period, the mean error resulting from the Bayesian estimation was strongly decreased and this estimation method could be applicable and should limit tacrolimus monitoring.

Background: The aim of this study was to evaluate calcineurin activity and interleukin-2 (IL-2) expression by peripheral blood cells as a means of assessing the immune status of liver transplant recipients., Methods: Twenty-one patients were studied in a randomized study comparing cyclosporine and tacrolimus as the main immunosuppressive drug. Calcineurin activity was determined after separation of phosphorylated and dephosphorylated products of a calcineurin specific peptide substrate by high performance liquid chromatography(HPLC). Intracellular IL-2 expression was measured by flow cytometry. In 34 additional patients, intracellular IL-2 expression was prospectively measured., Results: Calcineurin activity fell after transplantation. Values were marginally higher in patients with acute rejection (P=0.059). The percentage of IL-2-producing T cells fell after transplantation. This percentage did not differ between patients with and without rejection. In contrast, the proportion of IL-2-producing CD8+ T cells was higher in patients with acute rejection than in patients free of acute rejection (P=0.003). Moreover, pretransplantation IL-2 expression by CD8+ T cells was higher in patients who subsequently developed acute rejection, suggesting that IL-2 production may be constitutively higher in those patients. The results obtained in the 34 additional patients confirmed these results., Conclusions: These data suggest that quantification of intracellular IL-2 in CD8+ T cells may be a useful index of immune status in liver transplant recipients. Preoperative IL-2 levels might serve to individually tailor the immunosuppressive regimen.

Background: New therapies are needed to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Various gemcitabine-oxaliplatin combinations have been tested recently in patients with ovarian and pancreatic carcinoma, yielding interesting results with little toxicity. Therefore, the authors evaluated the activity and toxicity of two such combinations in patients with HCC., Methods: Twenty-one patients were enrolled prospectively in the study. Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100 mg/m2 on Day 2 (GEMOX-1), and 10 patients received gemcitabine 1500 mg/m2 on Day 1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX-2). Treatment was repeated every 2 weeks until disease progression developed or until unacceptable adverse effects occurred., Results: All patients were assessable for response and toxicity. Four patients (19%) achieved objective responses (95% confidence interval, 13-26%), including 3 patients in the GEMOX-1 group and 1 patient in the GEMOX-2 group. Ten patients (48%) had stable disease, and 7 patients (33%) experienced disease progression. The median progression-free survival was 5 months, and the median overall survival was 12 months. Fifty-four percent of patients in the GEMOX-1 group and 50% of patients in the GEMOX-2 group had received previous systemic chemotherapy or cisplatin-based chemoembolization. Grade 3-4 hematologic toxicity, according to National Cancer Institute Common Toxicity Criteria, consisted of thrombocytopenia (GEMOX-1 vs. GEMOX-2, 18% vs. 40%) and neutropenia (0% vs. 30%). No Grade 3-4 nonhematologic toxicity was observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients and 7 patients receiving GEMOX-1 and in 7 patients and 1 patient receiving GEMOX-2., Conclusions: Gemcitabine-oxaliplatin combination therapy is feasible in patients with advanced HCC. The GEMOX-1 regimen was tolerated better than the GEMOX-2 regimen. Currently, the GEMOX-1 regimen is being evaluated in a Phase II study in previously untreated patients with HCC., (Copyright 2003 American Cancer Society.)

Background: The multidrug resistance pump, P-glycoprotein 170 (P-gp), the MDR1 gene expression product, is expressed in peripheral blood mononuclear cells (PBMC). Cyclosporine (CsA) and tacrolimus are inhibitors and substrates of the pump, and can induce its expression. The aim of the present study was to assess MDR1 gene expression in PBMC after liver transplantation., Methods: P-gp expression was examined in PBMC from 23 adult patients by flow cytometry analysis using UIC2, a monoclonal anti-Pgp antibody, on days 7, 14, 21, 28, 90, and 180, and whenever a rejection episode was suspected. MDR1 mRNA was estimated by reverse transcription-polymerase chain reaction., Results: P-gp expression, assessed as the ratio of the mean fluorescence, increased from 1.59 before transplantation to 2.05 after transplantation, and did not vary significantly thereafter. There was no significant difference in P-gp expression between CsA and tacrolimus-based treatments. MDR1 mRNA levels did not vary significantly under CsA or tacrolimus therapy until day 28. P-gp expression was marginally higher in patients before acute rejection (P=0.054), and was lower in patients with severe infection (P=0.003) than in those with uneventful evolution. Alcoholic patients exhibited higher levels of P-gp expression than other patients., Conclusion: P-gp expression increases after liver transplantation. Its variations do not allow the ability to predict acute rejection, but could help in making the diagnosis of overimmunosuppression.

Background: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases., Methods: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation., Results: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery., Conclusions: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.

The aim of this prospective study was to determine whether plain abdominal radiographs (PAX) are helpful in the management of adult patients presenting with acute pain of the right lower quadrant (RLQ). A questionnaire was filled in for each patient admitted to our hospital for acute abdominal pain of the RLQ, before and after PAX were obtained. The initial questionnaire indicated the suspected diagnosis and a provisional therapeutic option. A total of 104 consecutive patients were included in this study, 76 of whom underwent surgery. The negative laparotomy rate was 22%. PAX changed the suspected diagnosis and management for six patients (6%), leading in one case to negative laparotomy. Of the remaining five patients, three were operated (two for acute appendicitis and one for small bowel obstruction), and two were treated conservatively for ureteral calculi. This prospective study seems to demonstrate that the indiscriminate use of PAX is not helpful for most patients with acute pain of the RLQ. However, it may be performed in selected patients with clinically suspected small bowel obstruction or urinary symptoms.

Background: The aim of this study was to compare retrospectively the longterm functional results of straight or J-pouch coloanal anastomosis and low colorectal anastomosis in patients operated for rectal carcinoma., Study Design: Of the 260 patients who underwent rectal resection for carcinoma in our department during a 12-year period, 105 were included in this study. Of these, 37 had straight coloanal, 15 J-pouch coloanal, and 53 low colorectal anastomoses., Results: At 1 year of followup, continence was significantly better after low colorectal than straight coloanal anastomosis (perfect continence: 81% versus 51%; p < 0.01). No significant difference was observed for continence after J-pouch coloanal and low colorectal anastomosis. Stool frequency during a 24-hour period was significantly higher after straight coloanal anastomosis than after either J-pouch coloanal (p < 0.05) or low colorectal anastomosis (p < 0.01). Night stools were significantly more frequent after straight than J-pouch coloanal anastomosis (p < 0.05). Three years after surgery, continence had improved in the three groups, as 70% of the straight coloanal group, 91% of the J-pouch coloanal group, and 94% of the colorectal anastomosis group had perfect continence (p < 0.02 versus straight coloanal anastomosis). No significant difference for continence was observed between the J-pouch coloanal and low colorectal anastomosis groups. Neither were significant differences observed among the three groups for urgency, gas/stool discrimination, stool frequency (including night stools), or the need for medication., Conclusions: The functional results of both J-pouch coloanal and low stapled colorectal anastomosis seem better than those of straight coloanal anastomosis. Both J-pouch and low-stapled procedures can safely be proposed for patients with rectal carcinoma requiring total mesorectal rectal excision; however, because low stapled colorectal anastomosis seems to us easier and faster to perform, we consider it the best option for rectal reconstruction after proctectomy for carcinoma, provided it is possible based on the level of the tumor.