Passive mesenterico-saphenous shunt: An alternative to portocaval anastomosis for tailored portal decompression during liver transplantation.

BACKGROUND: Temporary portocaval shunt has a positive impact on short-term outcomes after liver transplantation. An alternative to temporary portocaval shunt is a distal passive decompression through mesenterico-saphenous shunt. The purpose of this study was to compare outcomes of these two types of surgical portosystemic shunt and discuss their respective place during the anhepatic phase. METHODS: Patients transplanted with portal decompression during a 4-year period were included. Patients were compared according to two types of surgical decompression techniques: temporary portocaval shunt (n = 44) and mesenterico-saphenous shunt (n = 77). Spontaneous >5-mm portosystemic shunts were described as absent, nonpersistent, distal, or proximal. Intraoperative portal pressure variations and inhospital course were compared between the two groups, with special attention on the impact of competing spontaneous and surgical shunts. RESULTS: Mesenterico-saphenous shunt and temporary portocaval shunt showed a comparable hemodynamic efficiency, with no significant difference in terms of portal pressure variations. We found no significant difference in terms of reperfusion syndrome (P = .956), transfusion rate (P = .575), renal failure (P = .239) nor early allograft dysfunction (P = .976). There was a significantly higher risk of early allograft dysfunction when competing surgical and spontaneous shunts were used (P = .002) with a lesser hemodynamic efficiency (analysis of variance test; P = .04). CONCLUSION: Portacaval or mesenterico-saphenous shunts offer similar hemodynamic efficiency without impacting the outcomes after liver transplantation. Their respective place and the place of portal decompression should be discussed regarding the presence of portal thrombosis and pre-existing portosystemic shunts. Evaluation of the anatomy and the efficiency of these shunts may guide tailored portal decompression.

Interleukin 6 at reperfusion: A potent predictor of hepatic and extrahepatic early complications after liver transplantation.

BACKGROUND AND AIMS: Ischemia-reperfusion injury impacts early liver graft function. Interleukin 6 (IL-6) as early as at reperfusion has shown to predict in-hospital complications, but its impact on vascular complications and long-term outcomes is not ascertained. METHODS: A retrospective study was conducted on all consecutive patients transplanted during a 6-year period to define significant early systemic inflammatory response (ESIR). The main end-point was 3-year graft survival. Significant ESIR was defined according to IL-6 level at reperfusion on an exploratory set of 121 patients and validated on an independent cohort (n = 153). RESULTS: Significant ESIR was defined as IL-6 at reperfusion >1000 ng/mL in the exploratory cohort. Three-year graft and overall survival were lower in patients with ESIR in the determination set (P = 0.001 and 0.045, respectively). This was confirmed in the validation set (P = 0.045 and 0.027). In patients with high cytolysis, IL-6 identified patients at risk for arterial thrombosis. The main determinants for IL-6 level were intragraft lactate level, cold ischemia time, and anhepatic phase duration (P = 0.005). IL-6 level independently predicted graft survival (P = 0.0003). CONCLUSIONS: IL-6 at reperfusion is a valid biomarker to predict long-term survival. Furthermore, it helps the interpretation of cytolysis in the prediction of early vascular complications.

Pathologic response to non-surgical locoregional therapies as potential selection criteria for liver transplantation for hepatocellular carcinoma.

BACKGROUND: Preoperative locoregional treatments (PLT) are performed to avoid progression before liver transplantation for hepatocellular carcinoma (HCC). The objective of this study was to analyze the prognostic factors affecting the outcome in patients who received PLT. MATERIAL AND METHODS: A retrospective analysis of patients who underwent liver transplantation (LT) was performed. All patients who underwent PLT with confirmed pathological diagnosis of HCC were included. The rate of tumor necrosis (TN) was assessed by microscopic histological examination. RESULTS: From January 1997 to December 2010, PLT was performed in 154 patients ROC analysis individuated a TN cut-off value at 40%. Ninety-one patients (59.1%) of the patients presented TN>40%. At multivariate analysis, TN<40% (HR=1.76; p=0.04) and vascular invasion (VI) (HR=2.16; p<0.01) were associated with lower Overall Survival (OS). At multivariate analysis, TN<40% (HR=1.59; p=0.001) and VI (HR=2.51; p=0.001) were significant associated with lower Disease Free Survival (DFS). One, 3 and 5 years OS was 87.9%, 82.0% and 69.1% for patients with TN>40% and 82.5%, 64.2% and 53.2% for those with TN<40% (p=0.02). Tumour size <5 cm (p=0.02); age <55 years (p=0.02); absence of VI (p=0.02) and multiple procedures (p=0.04) were predictive factors for TN>40%. CONCLUSIONS: Response to preoperative locoregional treatment can be used as potential selection criteria for LT.

Biliary strictures after liver transplantation: is percutaneous treatment indicated?

BACKGROUND: Biliary complications are common after orthotopic liver transplantation. Our study's aim is to evaluate the efficacy of percutaneous treatment of biliary strictures after orthotopic liver transplantation (OLT). MATERIAL/METHODS: Sixty-five patients with biliary anastomotic strictures received percutaneous transhepatic balloon cholangioplasty (PTBC). Three dilatations were performed with a 2- to 4-week period between the procedures. Primary and secondary patency were evaluated, with a follow-up between 6 months and 6 years. RESULTS: PTBC successfully treated strictures in 52.3% (34/65) of cases. The normalization of clinical and biological features was noted at 2.3 months on average. Neither intercurrent episodes of sepsis nor a worsening of liver function were noted during the treatment; a significant complication was recorded in 8 patients. No patient needed surgery for the treatment of complications after PTBC. Factors related to a successful PTBC included older age at transplantation and single-site stricture. There were 7 recurrent strictures after PTBC, all successfully treated by nonsurgical procedures. The number of dilatations performed affected both the likelihood of success and the long-term risk of stricture recurrence. Of the 31 PTBC failures, 19 underwent subsequent surgical revision, 8 were treated endoscopically, and 4 were re-transplanted. Multifocal stenoses, central hepatic duct involvement, and intrahepatic localization resulted associated with treatment failure. CONCLUSIONS: PTBC should be considered as a first choice option for treatment of biliary strictures after liver transplantation as well as endoscopic treatment. For solitary extrahepatic strictures that fail PTBC and ERCP, surgical revision provides good results.

Successful liver transplantation for Rendu-Weber-Osler disease, a single centre experience.

UNLABELLED: BACKROUNDS/PURPOSE: Hereditary hemorrhagic telangiectasia or Rendu-Weber-Osler is an autosomal dominant inherited disorder characterized by arteriovenous malformations and telangiectasia that may affect the nose, skin, lungs, brain and gastrointestinal tract. Liver involvement of the disease has been described to be responsible of biliary tract necrosis, high cardiac output and portal hypertension, due to intra-hepatic vascular shunts. We aimed to present four cases of successful orthotopic liver transplantations in this indication performing our modified Piggy-back technique. PATIENTS AND METHODS: Between 2002 and 2008, four patients have been diagnosed for Rendu-Weber-Osler disease and underwent liver transplantation. Three of them suffered from high cardiac output with heart failure, two presented HBV infection and one patient suffered from renal failure requiring a liver-kidney transplantation. We performed our modified Piggy-back technique for liver implantation, which consists to clamp selectively the hepatic veins during the hepatectomy, without venous bypass, the retro-hepatic vena cava is preserved. RESULTS: No hemodynamic concerns disturbed the surgery and no massive transfusions were needed. The liver replacement corrected the cardiac insufficiency due to high cardiac output for the three patients. At present, the four patients are getting well. CONCLUSIONS: Despite new advances in immunotherapy for the medical treatment of Rendu-Weber-Osler disease, liver transplantation remains the curative option for hepatic based-hereditary hemorrhagic telangiectasia.

Corticosteroid avoidance in adult kidney transplant recipients under rabbit anti-T-lymphocyte globulin, mycophenolate mofetil and delayed cyclosporine microemulsion introduction.

We conducted the first prospective, randomized, open-label multicenter study in low-immunologic risk adult recipients of primary cadaver kidney transplants receiving rabbit anti-T-lymphocyte globulin, mycophenolate mofetil, cyclosporine microemulsion introduced on day 5, with and without corticosteroids. Patients were randomly assigned according to age and cold ischemia time to receive corticosteroids for at least 6 months or no corticosteroids at all. The main efficacy evaluation criterion was acute rejection (including all treated episodes and those biopsy-confirmed) during the first year following transplantation. For this purpose, this report includes the actual results of the whole 12-month follow-up of all randomized patients. For efficacy analysis, 98 patients were evaluated in the Steroid avoidance group and 99 in the Steroid maintenance group. Taken as a whole, 81% of the patients (n = 159) never received anti-rejection treatment. From the 38 patients who received anti-rejection treatment, 25 (25.5%) were in the Steroid avoidance group and 13 (13.1%) in the Steroid maintenance group (P < 0.031), experiencing respectively 17 (17.3%) and 7 (7.1%) biopsy-proven first episodes of acute rejection (P < 0.031). Borderline changes (6 vs. 3) were not considered as biopsy-proven acute rejections. Onset of first rejection was significantly shorter in the Steroid avoidance group (P < 0.027). First-line anti-rejection treatment response, need for any rescue therapy, as well as histologic severity of rejection episodes did not statistically differ between the groups. One-year post-transplantation analysis showed no differences in delayed graft function, serum creatinine, creatinine clearance, 24-h proteinuria, as well as serious adverse events between the groups. De novo diabetes (P < 0.07) or dyslipidemia (P < 0.01) as well as newly diagnosed malignancies (P < 0.059) were however more frequently observed in the Steroid maintenance group. At the end of the first post-transplant year, 99% of patients in the Steroid avoidance group and 97% of patients in the Steroid maintenance group were respectively alive (P = 0.34), with respectively 95% and 93.2% of functioning kidney grafts (P = 0.62). Our results showed that total avoidance of corticosteroids from the day of transplantation was associated with a significantly increased number of clinically diagnosed and treated, and biopsy-proven acute rejections during the first year of transplantation. Nevertheless, overall outcome, 1-year patient and graft survival as well as renal function were similar, and the patients in the Steroid avoidance group exhibited a lower incidence of de novo dyslipidemia, diabetes mellitus and malignancies often associated with steroid treatment.

The venous thrombosis of the pancreatic graft.

BACKGROUND AND AIMS: Venous thrombosis of the pancreatic graft is the main nonimmunological cause of the loss of transplants. It has a frequency between 0.8 to 20% according to literature. In this study our team tried to identify the risk factors related to the donor, the recipient including the surgical techniques involved. METHODS: The study was conducted in the Department of Transplant Surgery, University Hospital Strasbourg-Hautepierre. 37 patients, with type I diabetes who had been submitted to 7 transplantations of segmentary pancreas and 30 of total pancreas and kidney during 09.07.1992 and 14.08.2006 were included in the study. The surgery comprised the retroperitoneal placement of the pancreas and kidney and the anastomosis with the urinary bladder. RESULTS: In the immediate evolution we observed 4 thromboses (10.5%). All 4 thromboses were in the group of kidney and total pancreas transplantations. Two of these 4 patients were retransplanted and presented recurrence of thrombosis at 17 days and 1 year. CONCLUSIONS: To prevent thrombosis, it is necessary to perform surgery which avoids unnecessary handling and which ensures broad, tension free vascular anastomoses. The method of early monitoring by pulsed Doppler related to the biological data and the clinical state are suggestive to diagnose thrombosis. The venous thrombosis of the graft implies pancreatic explantation. Retransplantation in patients who have undergone thrombosis of the graft is possible only in well selected patients.

Early evolution of hepatitis C virus (HCV) quasispecies after liver transplant for HCV-related disease.

BACKGROUND: End-stage liver disease as a result of chronic hepatitis C virus (HCV) infection is the main indication for liver transplant (LT), but allografts are systematically infected with HCV soon after transplant. Viral quasispecies are poorly described during the early posttransplant period. METHODS: For 17 patients who received an LT for HCV disease, plasma viral quasispecies evolution was determined by sequence analysis of hypervariable region 1 of the E2 envelope gene before transplant (BT), after 7 days (D7), and after 1 month (M1). T helper (Th)1/Th2 cytokine levels were determined concomitantly. RESULTS: HCV quasispecies showed a significant decrease in amino acid diversity at D7 and M1, compared with BT (P<.05). A correlation was observed between low plasma tumor necrosis factor-alpha levels at D7 and decreased quasispecies amino acid complexity at the same date. Nucleic acid diversity was lower for genotype 1 than for genotype 3 infection (P<.05). The complexity and diversity of amino acids were lower in patients with hepatocellular carcinoma (HCC) BT than in those without HCC (P<.05). Conserved amino acid residues within quasispecies were shared by the whole cohort before and after LT. CONCLUSION: Viral structural and/or host immunological features could favor the emergence of fitter HCV strains after LT.

Long-term survival in post-transplant lymphoproliferative disorders with a dose-adjusted ACVBP regimen.

Post-transplant lymphoproliferative disorders (PTLD) are severe complications after solid organ transplantation with no consensus on best treatment practice. Chemotherapy is a therapeutic option with a high response and a significant relapse rate leading to a low long-term tolerance rate. Currently, most centres use anthracycline-based drug combinations, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). We assessed the efficacy and safety of a dose-adjusted ACVBP (doxorubicin reduced to 50 mg/m(2), cyclophosphamide adjusted to renal function, vindesine, bleomycin, prednisone) regimen in patients failing to respond to a reduction in immunosuppressive therapy. Favourable responses were observed in 24 (73%) of the 33 treated patients. Fourteen (42%) patients died, mostly from PTLD progression. Actuarial survival was 60% at 5 years and 55% at 10 years. Survival prognostic factors were: number of involved sites (P = 0.007), clinical stage III/IV (P = 0.004), bulky tumour (P < 0.0001), B symptoms (P = 0.03), decreased serum albumin (P = 0.03) and poor performance status (P = 0.06). Both the international and the PTLD prognostic index were predictive for survival (P = 0.001 and P = 0.002, respectively). Overall 128 cycles were given. Grade 3 or 4 neutropenia was recorded after 26 (20%) chemotherapy cycles in 19 (58%) patients. Forty-one (32%) infections were recorded in 26 (79%) patients. This study demonstrated that an individual dose-adjustment of ACVBP regimen was manageable in PTLD patients and favourably impacted on long-term survival.

Cardiac diastolic dysfunction in renal-transplant recipients is associated with increased circulating Adrenomedullin.

BACKGROUND: Renal transplantation is an excellent therapeutic alternative for end-stage renal diseases. Nevertheless, the cardiac function is often impaired in renal-transplant patients (RTR) and importantly determines their prognosis. Adrenomedullin (ADM), a peptide involved in cardiovascular homeostasis, is believed to protect both cardiac and renal functions - by increasing local blood flows, attenuating the progression of vascular damage and remodelling and by reducing glomerular injury - and might be involved in renal-transplantation physiopathology. This work was performed to investigate whether an increase in circulating ADM might be related to RTR cardiac function. METHODS: Twenty-nine subjects, 19 RTR and 10 healthy subjects, participated in the study. After 15 min rest in supine position, heart rate and systemic blood pressure were measured together with cyclosporine through levels, creatinine and ADM. Systolic and diastolic cardiac functions were assessed, using Doppler echocardiography. RESULTS: Subjects were similar concerning age, weight, heart rate and blood pressure. Creatinine and ADM (53.8 +/- 6.9 vs. 27.2 +/- 4.1 pmol/L, p = 0.02) were significantly increased in RTR (73 +/- 10 months after transplantation). Cardiac systolic function was normal, but a reduced mitral E:A ratio was observed in RTR (0.90 +/- 0.06 vs. 1.38 +/- 0.10, p < 0.001), reflecting their impaired left ventricular relaxation. Such a ratio was negatively correlated with ADM (r = -0.55, p = 0.002). CONCLUSIONS: RTR present with an increased ADM is likely related to cardiac diastolic dysfunction. In view of its protective effect on the cardiovascular system, these data support further studies to better define the role and the therapeutic potential of ADM after renal transplantation.

Early decrease in circulating dendritic cells number after liver transplantation could favor hepatitis C virus recurrence.

Cirrhosis and hepatocarcinoma related to hepatitis C virus (HCV) lead to more than 30% of liver transplantations. Host- and virus-related mechanisms, involved in the recurrence of HCV infection of the liver graft, are not yet well known. A weak CD4+ T-cell response was shown to be involved in the outcome of re-infection but whether dendritic cell numbers are modified in patients transplanted for HCV-related disease has never been evaluated. Eight transplanted patients for HCV-related disease and eight non-HCV-infected transplanted controls were included. Blood plasmacytoid dendritic cells and myeloid dendritic cells were quantified before transplantation, at day 7 and 1 month after transplantation. Plasma interferon (IFN)-alpha and interleukin (IL)-12 were concomitantly measured. The results showed a significant decrease in the relative (P < 0.0001) and absolute (P = 0.0002) values of blood plasmacytoid dendritic cells at day 7 after transplantation when compared to the values obtained before transplantation, increasing again 1 month later, in both HCV-infected patients and controls. The same tendency was observed for myeloid dendritic cell relative values (P = 0.0004) and plasma IL-12 (P < 0.05). IFN-alpha appeared to be less often detectable for HCV-infected patients. These results obtained on dendritic cell numbers could explain partially the early and systematic recurrence of HCV infection on the liver graft and contribute to better adapted therapeutic strategies.

Circulating adrenomedullin is increased in relation with increased creatinine and atrial natriuretic peptide in liver-transplant recipients.

OBJECTIVES: Circulating adrenomedullin (ADM), a potent vasorelaxing and natriuretic peptide involved in cardiovascular homeostasis, is increased after cardiac and renal transplantation. ADM is also implicated in hemodynamic abnormalities during liver cirrhosis, but whether ADM is increased late after liver transplantation is unknown. PATIENTS: A total of 18 subjects--10 liver-transplant patients (Ltx) and 8 healthy subjects--were enrolled in the study. DESIGN AND MEASUREMENTS: After a 15-min rest period in supine position, heart rate and systemic blood pressure were determined in all subjects. Then, venous blood samples were obtained in order to simultaneously determine the cyclosporine through levels, the biological (cyclosporine, renal and hepatic functions) and hormonal (ADM and atrial natriuretic peptide (ANP)) characteristics of the Ltx. RESULTS: ADM (27.2+/-4.1 vs. 53.8+/-6.9 pmol/l, P=0.02), and ANP (5.9+/-0.9 vs. 12.8+/-1.4 pmol/l, P=0.001) were significantly increased in late, stable Ltx (35.4+/-9.6 months after transplantation). Furthermore, increased ADM correlated positively with elevated creatinine (r=0.76, P=0.01) and ANP (r=0.64, P=0.04) after liver transplantation. CONCLUSIONS: Liver-transplant patients exhibit a sustained increase in circulating ADM. Such an increase likely results from renal impairment associated with volume regulation abnormalities, suggesting a potential role for ADM in volume regulation after liver transplantation.