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Journal of Hepatology 04/2013; · 9.26 Impact Factor
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ABSTRACT: INTRODUCTION: Post-operative pancreatic fistula (POPF) is a common complication after partial pancreatic resection, and is associated with increased rates of sepsis, mortality and costs. The role of fibrin sealants in decreasing the risk of POPF remains debatable. The aim of this study was to evaluate the literature regarding the effectiveness of fibrin sealants in pancreatic surgery. METHODS: A comprehensive database search was conducted. Only randomized controlled trials comparing fibrin sealants with standard care were included. A meta-analysis regarding POPF, intra-abdominal collections, post-operative haemorrhage, pancreatitis and wound infections was performed according to the recommendations of the Cochrane collaboration. RESULTS: Seven studies were included, accounting for 897 patients. Compared with controls, patients receiving fibrin sealants had a pooled odds ratio (OR) of developing a POPF of 0.83 [95% confidence interval (CI): 0.6-1.14], P = 0.245. There was a trend towards a reduction in post-operative haemorrhage (OR = 0.43 (95%CI: 0.18-1.0), P = 0.05) and intra-abdominal collections (OR = 0.52 (95%CI: 0.25-1.06), P = 0.073) in those patients receiving fibrin sealants. No difference was observed in terms of mortality, wound infections, re-interventions or hospital stay. CONCLUSION: On the basis of these results, fibrin sealants cannot be recommended for routine clinical use in the setting of pancreatic resection.
HPB 03/2013; · 1.60 Impact Factor
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ABSTRACT: Natural killer (NK) cells are considered to play a critical role in liver disease. However, the available numbers of intrahepatic lymphocytes (IHL) derived from liver biopsies (LB) for ex vivo analysis of intrahepatic NK cells is very limited; and the isolation method may hamper not only yields and viability, but also phenotype and function of IHL. The aim of the present study was therefore to (1) refine and evaluate the cell yields and viability of a modified isolation protocol from standard size needle LB; and (2) to test the effects of mechanical dissociation and enzymatic tissue digestion, as well as the analysis of very low cell numbers, on the phenotype and function of intrahepatic NK cells. Peripheral blood mononuclear cells (PBMC) and IHL, freshly isolated from the peripheral blood, LB (n = 11) or partial liver resections (n = 5), were used for phenotypic analysis by flow cytometry. NK cell function, i.e., degranulation and cytokine production, was determined by staining of CD107a and intracellular IFN-γ following in vitro stimulation. The mean weight of the LB specimens was 9.1 mg, and a mean number of 7,364 IHL/mg were obtained with a viability of >90%. Exposure of IHL and PBMC to 0.5 mg/ml collagenase IV and 0.02 mg/ml DNase I for 30 min did affect neither the viability, NK cell function, nor the percentages of CD56+, NKp46+, and CD16+ NK cells, whereas the level of CD56 surface expression was reduced. The phenotype of LB-derived NK cells was reliably characterized by acquiring as few as 2,500 IHL per tube for flow cytometry. The functional assay of intrahepatic NK cells was miniaturized by culturing as few as 25,000 IHL in 25 μl (106/ml) using 96-well V-bottom plates with IL-2 and IL-12 overnight, followed by a 4 h stimulation with K562 cells at a NK:K562 ratio of 1:1. In summary, we report reliable phenotypic and functional analyses of small numbers of intrahepatic NK cells isolated from LB specimens providing us with a tool to better address the emerging role of human NK cell immunobiology in liver diseases.
Frontiers in immunology. 01/2013; 4:61.
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JAMA surgery. 01/2013; 148(1):99.
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ABSTRACT: Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post-transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13-1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84-0.96, and HR = 0.86, 95% CI: 0.79-0.93 respectively). Female patients gaining weight over 18.5 kg/m(2) while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28-0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m(2) . Obesity does not constitute an absolute contraindication to liver transplantation.
Transplant International 12/2012; · 2.92 Impact Factor
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ABSTRACT: BACKGROUND:: Liver-first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver-directed chemotherapy, the resection of the CRLM, and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80% of patients can successfully undergo a complete RM, whereas less than 30% of those undergoing classical management (CM) do so. This registry-based study compared the 2 approaches. METHODS:: The study was based on the LiverMetSurvey (January 1, 2000 to December 31, 2010) and included patients with 2 or more metastases. All patients had irinotecan and/or oxaliplatin-based chemotherapy before liver surgery. Patients undergoing simultaneous liver and colorectal surgery were excluded. RESULTS:: A total of 787 patients were included: 729 in the CM group and 58 in the RM group. Patients in the 2 groups had similar numbers of metastases (4.20 vs 4.80 for RM and CM, P = 0.231) and Fong scores of 3 or more (79% vs 87%, P = 0.164). Rectal cancer, neoadjuvant rectal radiotherapy, and the use of combined irinotecan/oxaliplatin chemotherapy were more frequent in the RM group (P < 0.001), whereas colorectal lymph node involvement was more frequent in the CM group (P < 0.001). Overall survival and disease-free survival were similar in the RM and CM groups (48% vs 46% at 5 years, P = 0.965 and 30% vs 26%, P = 0.992). CONCLUSIONS:: Classical and reversed managements of metastatic liver disease in colorectal cancer are associated with similar survival when successfully completed.
Annals of surgery 11/2012; 256(5):772-779. · 7.90 Impact Factor
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ABSTRACT: The aim of the present study was to assess the efficiency of cell-based immune assays in the detection of alloreactivity after islet transplantation and to correlate these results with clinical outcome. Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients (n=14), donors or third party. The immune reactivity was assessed by the release of IFNγ (ELISpot), cell proliferation (FACS analysis for Ki67) and cytokine quantification (Bioplex). Islet function correlated with the number of IFNγ-secreting cells following incubation with donor cells (p=0.007, r=-0.50), but not with third party cells(p=0.61). Similarly, a high number of donor-specific proliferating cells was associated with a low islet function (p=0.006, r=-0.51). Proliferating cells were mainly CD3⁺CD4⁺ lymphocytes and CD3-CD56⁺ natural killer cells (with low levels of CD3⁺CD8⁺ lymphocytes). Patients with low islet function had increased levels of CD4⁺Ki67⁺cells (p≤0.0001), while no difference was observed in CD8⁺Ki67⁺ and CD56⁺Ki67⁺ cells. IFNγ, IL-5 and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFNγ-ELISPOT, proliferation and cytokines were similarly accurate in predicting clinical outcome (AUC=0.77 +/- 0.088, 0.85 +/- 0.084 and 0.88+/- 0.074 respectively). Cellular immune reactivity against donor cells correlates with post-transplant islet function. The tested assays have the potential to be of substantial help in the management of islet graft recipients and deserve prospective validation.
Cell Transplantation 09/2012; · 5.13 Impact Factor
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Surgical Endoscopy 07/2012; · 4.01 Impact Factor
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Christian Toso,
Sonia Cader,
Ariane Mentha-Dugerdil,
Glenda Meeberg,
Pietro Majno,
Isabelle Morard,
Emiliano Giostra,
Thierry Berney,
Philippe Morel,
Gilles Mentha,
Norman M Kneteman
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ABSTRACT: BACKGROUND: Although factors associated with an increased risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been extensively studied, the history of patients with a post-transplant recurrence is poorly known. METHODS: Patients experiencing a post-transplant HCC recurrence from 1996 to 2011 in two transplant programs were included. Demographic, transplant, and post-recurrence variables were assessed. RESULTS: Thirty patients experienced an HCC recurrence-22 men and 8 women with a mean age of 55 ± 6 years. Sixteen (53 %) were outside the Milan criteria at the time of transplantation. Most recurrences (60 %) appeared within the first 18 months after transplantation, ranging between 1.7 and 109 months (median 14.2 months). Mean post-recurrence survival was 33 ± 31 months. On univariate analysis, total tumor volume (TTV; p = 0.047), microvascular invasion (p = 0.011), and time from transplant to recurrence (p = 0.001) predicted post-recurrence survival. On multivariate analysis, both time from transplant to recurrence (p = 0.001) and history of rejection (p = 0.043), but not the location of the recurrence or the type of recurrence treatment, predicted post-recurrence survival. CONCLUSION: This study suggests that patients with early post-transplant HCC recurrence have worse outcomes. Those with a history of graft rejection have better survivals, possibly due to more active anti-cancer immunity.
Journal of hepato-biliary-pancreatic sciences. 06/2012;
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ABSTRACT: Hydatid liver cysts can rupture into neighboring structures in 15-60% of patients, and most often involves the bile duct, the bronchi, and the peritoneal/pleural cavities. Rarely, chest or abdominal wall involvement occurs that are challenging to manage. This case report and literature review describes the management of patients with chest wall and rib invasion.
A 74-year-old woman, of Spanish origin, presented with right upper quadrant abdominal pain and tender localized swelling. On computer tomography (CT) assessment, the rupture of a hydatid cyst into the right anterior chest wall was identified. Partial involvement of the 10th and 11th rib were noted. The diagnosis was confirmed by a serological test. Surgical treatment involved a radical en bloc right hepatic resection together with resection of the involved ribs, diaphragm and subcutaneous tissue. Primary diaphragm and wall closures were performed. The postoperative course was uneventful with three weeks of albendazole treatment. CT follow-up at six months demonstrated the absence of recurrence.
Complete resection is the gold standard treatment of patients with hydatid cysts with the aim to remove all parasitic and pericystic tissues.
The present report illustrates that an aggressive surgical en bloc resection is feasible and should be preferred for the treatment of hydatid cysts with rupture into the chest wall, even when the ribs are involved.
International journal of surgery case reports. 03/2012; 3(7):253-6.
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ABSTRACT: Hepatoblastoma is the most common malignant liver tumour in infants and young children. Its occurrence in the adult population is debated and has been questioned. The aim of this paper is to review the histological and clinical features of adult hepatoblastoma as described in the adult literature, and to compare the findings with those of paediatric hepatoblastoma. The developmental and molecular aspects of hepatoblastoma are reviewed and their potential contribution to diagnosis of adult hepatoblastoma discussed. Case reports of adult hepatoblastoma identified by a PubMed search of the English, French, German, Italian, and Spanish literature through March 2011 were reviewed. Forty-five cases of hepatoblastoma were collected. Age at presentation was variable. Survival was uniformly poor, except for the rare patients who presented with the relatively differentiated, foetal type. The common denominator between adult and paediatric cases is the occurrence of embryonal or immature aspect of the tumours. Whether the adult cases of hepatoblastoma represent blastemal tumours, stem cell tumours, or unusual differentiation patterns in otherwise more frequent adult liver tumours remains to be established. Adult tumours labelled as hepatoblastoma are characterised by malignant appearing mesenchymal components. Surgical management is the cornerstone of therapy in children and also appears to confer an improved prognosis in adults. Whether adult hepatoblastoma exists, remains controversial. Indeed, several features described in adult cases are markedly different from hepatoblastoma as it is understood in children, and other differential diagnoses should also be entertained. Nonetheless, hepatoblastoma should be considered in adults presenting with primary liver tumours in the absence of pre-existing liver disease. Adult and paediatric patients with immature hepatoblastoma appear to have worse outcomes, and adults presenting with presumed hepatoblastoma have an overall poorer prognosis than children with hepatoblastoma. In all patients, surgery should be the treatment of choice, neoadjuvant chemotherapy is advisable.
Journal of Hepatology 02/2012; 56(6):1392-403. · 9.26 Impact Factor
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ABSTRACT: In many countries, the allocation of liver grafts is based on the Model of End-stage Liver Disease (MELD) score and the use of exception points for patients with hepatocellular carcinoma (HCC). With this strategy, HCC patients have easier access to transplantation than non-HCC ones. In addition, this system does not allow for a dynamic assessment, which would be required to picture the current use of local tumor treatment. This study was based on the Scientific Registry of Transplant Recipients and included 5,498 adult candidates of a liver transplantation for HCC and 43,528 for non-HCC diagnoses. A proportional hazard competitive risk model was used. The risk of dropout of HCC patients was independently predicted by MELD score, HCC size, HCC number, and alpha-fetoprotein. When combined in a model with age and diagnosis, these factors allowed for the extrapolation of the risk of dropout. Because this model and MELD did not share compatible scales, a correlation between both models was computed according to the predicted risk of dropout, and drop-out equivalent MELD (deMELD) points were calculated. CONCLUSION: The proposed model, with the allocation of deMELD, has the potential to allow for a dynamic and combined comparison of opportunities to receive a graft for HCC and non-HCC patients on a common waiting list.
Hepatology 01/2012; 56(1):149-56. · 11.66 Impact Factor
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Axel Andres,
Eric Gerstel,
Christophe Combescure,
Sonal Asthana,
Shaheed Merani,
Pietro Majno,
Thierry Berney,
Philippe Morel,
Norman Kneteman,
Gilles Mentha, Christian Toso
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ABSTRACT: Approximately one fourth of patients transplanted for hepatitis C virus (HCV)-induced liver failure progress to cirrhosis within 5 years, potentially requiring retransplantation. Although the relisting decision can be difficult in these patients, a score could help in selection of candidates with the best potential outcomes.
A total of 1422 HCV-positive patients having undergone a retransplantation were included in this registry-based study. A multivariate Cox regression was performed, and an Akaike procedure was applied to design a score predicting survival after retransplantation and to allow an internal validation. Retained variables were donor age (DnAge), serum creatinine (Creat), International Normalized Ratio (INR), and serum albumin (Alb) at the second transplantation, recipient age (RecAge) at the first transplantation, and the interval between both transplantations (Int).
The score was designed as 0.23×DnAge+4.86×log Creat-2.45×log Int+2.69×INR+0.10×RecAge-3.27× Alb+40. The receiver operating characteristic area under curve was 0.643 at 3 years, and survivals were 71%, 56%, and 37% for scores <30, 30 to 40, and >40, respectively (log rank <0.0001).
Overall, the proposed score is specifically designed for HCV-positive patients, accurately predicts survival after a liver retransplantation, and is helpful in the selection of candidates with the best potential outcomes.
Transplantation 01/2012; 93(7):717-22. · 4.00 Impact Factor
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ABSTRACT: Clinical progress in the field of liver transplantation has been largely supported by animal models(1,2). Since the publication of the first orthotopic rat liver transplantation in 1979 by Kamada et al.(3), this model has remained the gold standard despite various proposed alternative techniques(4). Nevertheless, its broader use is limited by its steep learning curve(5). In this video paper, we show a simple and easy-to-establish revision of Kamada's two-cuff technique. The suprahepatic vena cava anastomosis is performed manually with a running suture, and the vena porta and infrahepatic vena cava anastomoses are performed utilizing a quick-linker cuff system(6). Manufacturing the quick-linker kit is shown in a separate video paper.
Journal of Visualized Experiments 01/2012;
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Gunilla T Westermark,
Alberto M Davalli,
Antonio Secchi,
Franco Folli,
Tatsuya Kin, Christian Toso,
A M James Shapiro,
Olle Korsgren,
Gunnar Tufveson,
Arne Andersson,
Per Westermark
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ABSTRACT: The reasons for the long-term complete or partial loss of islet graft function are unknown, but there are obviously other reasons than just pure allogeneic graft rejection. Earlier studies have shown that deposition of islet amyloid polypeptide amyloid in transplanted islets may indicate a mechanism for loss of β cells.
Sections from liver material from four deceased islet-bearing recipients have been scrutinized for the presence of amyloid. Clinical data and certain aspects of the islet graft pathology of these patients have been published previously.
With this extended histological analysis, we demonstrate the occurrence of amyloid deposits in islets transplanted into the liver in three of four patients with type 1 diabetes.
The finding adds evidence to the assumption that aggregation of islet amyloid polypeptide might be an important cause of progressing β-cell dysfunction in clinically transplanted islets.
Transplantation 12/2011; 93(2):219-23. · 4.00 Impact Factor
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ABSTRACT: AEB071 (AEB, sotrastaurin), a specific inhibitor of protein kinase C, reduces T-lymphocyte activation and cytokine release. AEB delays islet allograft rejection in rats and prevents rejection when combined with cyclosporine. Since many immunosuppressive agents have toxic effects on the function of transplanted islets, we investigated whether this was also the case with AEB. Human islets were transplanted into Rag-knockout mice randomly assigned to vehicle control, AEB or sirolimus treatment groups. Non-fasting blood glucose levels, body weight and glucose tolerance was measured in recipients. In a separate experiment, human islets were cultured in the presence of AEB and assayed for glucose dependent insulin secretion and level of β-cell apoptosis. Eighty-six percent of the AEB-treated recipients achieved normoglycemia following transplant (compared with none in sirolimus-treated group, p < 0.05). AEB-treated recipients exhibited similar glucose homeostasis as vehicle-treated controls, which was better than in sirolimus-treated recipients. Human islets cultured with AEB showed similar rates of β-cell apoptosis (p = 0.98 by one-way ANOVA) and glucose stimulated insulin secretion (p = 0.15) as those cultured with vehicle. These results suggest that AEB is not associated with toxic effects on islet engraftment or function. AEB appears to be an appropriate immunosuppressive candidate for clinical trials in islet transplantation.
Islets 11/2011; 3(6):338-43.
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ABSTRACT: Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF), primarily affecting immunocompromised patients. So far, 148 cases have been published, of which 9 underwent liver transplantation (LT). The reported post-transplant survival is poor, with over 60% dying in the first year. Dosing and duration of antiviral therapy after LT are not established. Concerns include both the risk of hepatic recurrence after LT and emergence of viral resistance during prolonged therapy. HSV DNA plasma levels might be helpful to monitor therapeutic response and guide duration of therapy. We present a case of ALF complicating a primary HSV-1 infection in an immunocompetent host, who required emergency LT. We further discuss the value of measuring serial HSV DNA plasma loads to monitor antiviral therapy.
Antiviral therapy 10/2011; 17(2):401-4. · 3.16 Impact Factor
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Sophie Borot,
Nadja Niclauss,
Anne Wojtusciszyn,
Coralie Brault,
Sandrine Demuylder-Mischler,
Yannick Müller,
Laurianne Giovannoni,
Géraldine Parnaud,
Raphael Meier,
Lionel Badet, [......],
Laurence Kessler,
Emmanuel Morelon,
Alfred Penfornis,
Charles Thivolet, Christian Toso,
Philippe Morel,
Domenico Bosco,
Cyrille Colin,
Pierre-Yves Benhamou,
Thierry Berney
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ABSTRACT: Insulin independence after islet transplantation is generally achieved after multiple infusions. However, single infusion would increase the number of recipients. Our aim was to evaluate the results of islet-after-kidney transplantation according to the number of infusions.
Islets were isolated at the Geneva University, shipped, and transplanted into French patients from the Swiss-French GRAGIL network, on the "Edmonton" immunosuppression protocol between 2004 and 2010.
Nineteen patients were transplanted with 33 preparations. Fifteen patients reached 24 months follow-up; eight subjects were single-graft recipients and seven were double-graft recipients. Finally, single-graft recipients received a median of 5312 islet equivalents/kg (5186-6388) vs. 10,564 (10,054-11,375) for double-graft recipients (P=0.0003) with similar islet mass at first infusion. Insulin independence was achieved in five of eight single-graft subjects (62.5%) versus five of seven in double-graft subjects (71.4%), not significant. Median insulin independence duration was 4.7 (3.1-15.2) months after one infusion vs. 19 (9.6-20.8) months after two infusions (not significant). At 24 months posttransplant, comparing single- with double-graft patients, insulin doses were 0.23 (0.11-0.34) U/kg vs. 0.02 (0.0-0.23) U/kg, P=0.11; HbA1c was 6.5% (5.9%-6.8%) vs. 6.2% (5.9%-6.3%), P=0.16; and basal C-peptide was 302 (143-480) pmol/L vs. 599 (393-806) pmol/L, P=0.05. Only 37.5% of single-graft patients had a β-score ≥4 compared with 100% of double-graft patients (P=0.03). Two recipients experienced postinfusion bleeding, and two patients (13%) showed renal dysfunction in the absence of biopsy-proven rejection.
One infusion achieves good glycemic control and sometimes insulin independence. However, double-graft patients remain insulin-free longer, tend to have lower HbA1c, and show better graft function 24 months after transplant.
Transplantation 09/2011; 92(9):1031-8. · 4.00 Impact Factor
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ABSTRACT: Since the Edmonton trials, insulin independence can reproducibly be achieved after islet transplantation. However, a majority of patients resume insulin treatment in the first 5 years after transplantation. Several mechanisms have been proposed but are difficult to pinpoint in one particular patient. Current tools for the metabolic monitoring of islet grafts indicate islet dysfunction when it is too late to take action. Noninvasive imaging of transplanted islets could be used to study β-cell mass and β-cell function just after infusion, during vascularization or autoimmune and alloimmune attacks. This review will focus on the most recent advances in various imaging techniques (bioluminescence imaging, fluorescence optical imaging, MRI, and positron emission tomography). Emphasis will be placed on pertinent approaches for translation to human practice.
Current Diabetes Reports 07/2011; 11(5):375-83. · 2.50 Impact Factor
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ABSTRACT: To develop a score predicting the morbidity of liver resections in a center with low mortality.
The study was based on a prospective database of all liver resections performed at the Geneva University Hospitals between January 1, 1991, and October 30, 2009 (a total of 726 elective liver resections in 689 patients). Perioperative complications and their severity were graded according to the original classification by Clavien et al. Variables independently associated with the occurrence of complications were identified using a linear regression analysis model. A score was computed with all independent variables in an assessment population including two-thirds of the liver resections and was further validated in a population including one-third of the liver resections.
Overall mortality was 0.7% (5 of 726 liver resections). We recorded 375 different complications in 259 hepatic resections (36% of resections had ≥ 1 complication). In the assessment group, resection of 3 or more segments, an American Society of Anesthesiologists score of 3 or higher, and resection for a malignant neoplasm independently predicted the risk of complications. A score integrating these 3 factors significantly predicted the risk of postoperative complications. The score also correlated with the occurrence of major complications.
The score allows for identification of patients most susceptible to complications, in whom efforts against specific postoperative morbidities can be concentrated.
Archives of surgery (Chicago, Ill.: 1960) 07/2011; 146(11):1246-52. · 4.32 Impact Factor
