Laura Lladó

Spanish Experience in Liver Transplantation for Hilar and Peripheral Cholangiocarcinoma

Objective:To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival. Summary Background Data:Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs. Methods:We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival. Results:The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III–IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma. Conclusions:OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.

The impact of donor age on liver transplantation: influence of donor age on early liver function and on subsequent patient and graft survival.

BACKGROUND The urgent need to increase the organ donor pool has led to the expansion of criteria for donor selection. The aim of this study was to analyze the influence of donor age on early graft function, subsequent graft loss, and mortality after liver transplantation (LT). METHODS Data on LT were evaluated retrospectively in a population-based cohort of 400 LTs in 348 patients. Of these, 21 (5%) were from donors >70 years old. Pretransplantation donor and recipient characteristics and the evolution of recipients were analyzed. The influence of donor age as a risk factor was assessed using univariate and multivariate analyses. RESULTS Actuarial graft survival was 89% at 1 month after LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis demonstrated that only donor age (>70 years old) was associated with a higher risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6 months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier curves) also demonstrated worse evolution in recipients of livers from old donors (log-rank test, P<0.001). CONCLUSIONS Advanced donor age is associated with lower graft and recipient survival.

Complete Versus Selective Portal Triad Clamping for Minor Liver Resections: A Prospective Randomized Trial

Objective:To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections. Summary Background Data:Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia. Patients and Methods:Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded. Results:No differences were observed in the amount of hemorrhage (671 ± 533 mL versus 735 ± 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 ± 4.6 versus 4.5 ± 2.7 μkat/L, P = 0.01) and AST (10.2 ± 8.7 versus 4.9 ± 2.1μkat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity. Conclusions:Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.

Application of fibrin glue sealant after hepatectomy does not seem justified: results of a randomized study in 300 patients.

Objective:To evaluate the efficacy, amount of hemorrhage, biliary leakage, complications, and postoperative evolution after fibrin glue sealant application in patients undergoing liver resection. Summary Background Data:Fibrin sealants have become popular as a means of improving perioperative hemostasis and reducing biliary leakage after liver surgery. However, trials regarding its use in liver surgery remain limited and of poor methodologic quality. Patients and Methods:A total of 300 patients undergoing hepatic resection were randomly assigned to fibrin glue application or control groups. Characteristics and debit of drainage and postoperative complications were evaluated. The amount of blood loss, measurements of hematologic parameters liver test, and postoperative evolution (particularly involving biliary fistula and morbidity) was also recorded. Results:Postoperatively, no differences were observed in the amount of transfusion (0.15 ± 0.66 vs. 0.17 ± 0.63 PRCU; P = 0.7234) or in the patients that required transfusion (18% vs. 12%; P = 0.2), respectively, for the fibrin glue or control group. There were no differences in overall drainage volumes (1180 ± 2528 vs. 960 ± 1253 mL) or in days of postoperative drainage (7.9 ± 5 vs. 7.1 ± 4.7). Incidence of biliary fistula was similar in the fibrin glue and control groups, (10% vs. 11%). There were no differences regarding postoperative morbidity between groups (23% vs. 23%; P = 1). Conclusions:Application of fibrin sealant in the raw surface of the liver does not seem justified. Blood loss, transfusion, incidence of biliary fistula, and outcome are comparable to patients without fibrin glue. Therefore, discontinuation of routine use of fibrin sealant would result in significant cost saving.

Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality

Abstract:  Background:  Splanchnic thrombosis is a surgical challenge in liver transplantation (LT). The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution.

Hilar Dissection versus the “Glissonean” Approach and Stapling of the Pedicle for Major Hepatectomies: A Prospective, Randomized Trial

Objective A randomized study was conducted of hilar dissection and the “glissonean” approach and stapling of the pedicle for major hepatectomies to contrast their feasibility, safety, amount of hemorrhage, postoperative complications, operative times, and costs. Summary Background Data The “glissonean” approach is reported as requiring a shorter portal triad closure time; furthermore, the procedure seems to expedite the transection of the liver. Patients and Methods Between 1998 and 2001, 80 patients were enrolled in this study. The major liver resections included 15 extended right, 7 extended left, 42 right, and 16 left hepatectomies. The patients were randomly assigned to the hilar dissection group (G1; n = 40) or to the “glissonean” approach and stapling of the portal triad group (G2; n = 40). Results The groups were equally matched for age, sex, diagnosis, mean resected specimen weight, number of tumoral lesions, type of liver resection performed, and percentage of patients with margin invasion (G1: 4; 10% vs G2: 5; 12.5%). The duration of the 2 procedures was similar (G1: 247 ± 54 min vs G2: 236 ± 43 min; P = 0.4). However, the duration of the hilar dissection was shorter for G2 (50 ± 17 min) versus G1 (70 ± 26 min; P <0.001). By contrast, the duration of pedicular clamping was shorter for G1 (43 ± 15 min) versus G2 (51 ± 15 min; P = 0.015). No differences were observed in the amount of hemorrhage (G1: 887 ± 510 mL vs G2: 937 ± 636 mL; P = 0.7), and only 6 patients in G1 and 10 in G2 were transfused (P = 0.26). Morbidity rates were similar for both groups (G1: 23% vs G2: 33%; P = 0.3). Surgical injury of the contralateral biliary duct was not observed. However, 3 patients in G1 and 4 patients in G2 presented a biliary fistula that resolved spontaneously. Postoperative hospital stay was similar (G1: 8 [range, 6-24] vs G2: 9 [range, 5-31] days; P = 0.6). The postoperative levels of alanine transaminase (ALT) during the 2 first postoperative days were lower for G1 than G2. Cost of the surgical material was 1235.80 US for G1 and 1301.10 US for G2. Conclusions The 2 techniques are equally effective procedures for treating hilar structures. Although en bloc stapling transection is faster, hilar dissection was associated with a shorter pedicular clamping time, less cytolysis, and the materials required were less expensive.

Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation

Recent reports of the transmission of systemic transthyretin (TTR) amyloidosis after domino liver transplantation (DLT) using grafts from patients with familial amyloid polyneuropathy (FAP) have raised concerns about the procedure. The aim of this study was to evaluate the transmission incidence of systemic TTR amyloidosis after DLT with a complete clinical, neurological, and pathological assessment. At our institution, DLT has been performed 31 times with livers from patients with FAP. Seventeen of the 19 patients still alive in 2008 agreed to enter the study. This cross‐sectional study of this cohort of patients included clinical assessments, rectal biopsy, and electroneuromyography (as well as sural nerve biopsy when it was indicated). The mean follow‐up at the time of the study was 62.6 ± 2.9 months. Clinically, 3 patients complained of weak dysesthesia. When a focused study was performed, 8 patients reported some kind of neurological and/or gastrointestinal disturbance. Six of the rectal biopsy samples showed amyloid deposits (TTR‐positive). Electromyography (EMG) showed signs of mild sensorimotor neuropathy in 3 cases and moderate to severe sensorimotor neuropathy in 1 case. Only 2 of the 4 patients with EMG signs of polyneuropathy showed amyloid deposits in their rectal biopsy samples. Sural nerve biopsy revealed amyloid deposits (TTR‐positive) in all 4 patients with EMG signs of polyneuropathy. Two patients with normal EMG findings had TTR‐positive amyloid deposits in their sural nerve biopsy samples. In conclusion, de novo systemic amyloidosis after DLT may be more frequent and appear earlier than was initially thought. In our opinion, however, the graft shortage still justifies DLT in selected patients, despite the risk of de novo systemic amyloidosis. Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded. Liver Transpl 16:1386–1392, 2010.

Impact of immunosuppression without steroids on rejection and hepatitis C virus evolution after liver transplantation: Results of a prospective randomized study

The purpose of this study was to evaluate the influence of a steroid‐free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV‐infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV‐recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short‐term evolution of HCV recurrence. Liver Transpl 14:1752–1760, 2008.

Risk Factors and Outcomes of Bacteremia Caused by Drug-Resistant ESKAPE Pathogens in Solid-Organ Transplant Recipients

Background Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant (SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients. Methods All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed. Results Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant Staphylococcus aureus [5], extended-spectrum &bgr;-lactamase–producing Klebsiella pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem- and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal &bgr;-lactam and extended-spectrum &bgr;-lactamase–producing Enterobacter species [5]). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001). Conclusions Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use.

Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma on the Waiting List for Orthotopic Liver Transplantation

OBJECTIVE The objective of this study was to perform a retrospective analysis of patients with hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE) before undergoing liver transplantation at our institution. SUBJECTS AND METHODS From January 2000 to August 2005, 56 patients with HCC underwent TACE before orthotopic liver transplantation (OLT). Radiologic findings before and after TACE were assessed and correlated with histologic findings after OLT. The area of induced necrosis was pathologically evaluated in each HCC nodule. RESULTS One hundred thirty-one HCC nodules were detected at histologic study. One hundred seventeen HCC nodules (91.4%) were hyperenhancing in the arterial phase on the preoperative imaging studies. The percentage of tumor necrosis was greater than 90% in 48 nodules (38%), between 50% and 90% in 19 nodules (15%), and less than 50% in 61 nodules (48%); tumor necrosis data were not recorded for the remaining three nodules. The size of the preoperatively detected lesions ranged from 0.2 to 9 cm (mean, 2.58 cm). The mean percentage of tumor necrosis was 67.8% in this group, but it rose to 79.2% in the hypervascular lesions. The size of the nodules that were not detected preoperatively ranged from 0.1 to 1.9 cm (mean, 0.68 cm), and the mean percentage of tumor necrosis was only 1.57%. CONCLUSION TACE is a safe treatment in well-selected patients. Its antitumoral effect is high in hypervascular lesions (mean necrosis, 79.2%). It provides good local control in preoperatively diagnosed HCC (mean necrosis, 67.8%), but its impact is limited in lesions not detected preoperatively (mean necrosis, 1.57%).