Antoni Rafecas

A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization.

Transcatheter arterial chemoembolization (TACE) has been used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its prognostic usefulness has not previously been clarified.

Tranexamic Acid Reduces Red Cell Transfusion Better than ε-aminocaproic Acid or Placebo in Liver Transplantation

We evaluated the efficacy of the prophylactic administration of &egr;-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg · kg−1 · h−1; &egr;-aminocaproic acid, 16 mg · kg−1 · h−1, and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the &egr;-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not &egr;-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT. Implications In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not &egr;-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion.

The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: A comparative study †

The efficacy of tranexamic acid (TA) and aprotinin (AP) in reducing blood product requirements in orthotopic liver transplantation (OLT) was compared in a prospective, randomized and double‐blind study. One hundred and twenty seven consecutive patients undergoing OLT were enrolled; TA was administered to 64 OLT patients at a dose of 10mg /kg/h and aprotinin was administered to 63 OLT patients at a loading dose of 2x106 KIU followed by an infusion of 500,000 KIU/h. The portocaval shunt could not be performed in 14 OLT patients in the TA group and in 13 OLT patients in the AP group. However, all OLT patients that received either drug were included in the analysis. Perioperative management was standardized. Hemogram, coagulation tests, and blood product requirements were recorded during OLT and during the first 24 hours. No differences in diagnosis, Child score, preoperative coagulation tests, and intraoperative data were found between groups. No significant differences were observed in hemogram and intraoperative coagulation tests with the exception of activated partial thromboplastin time (aPTT). Similarly, there were no intergroup differences in transfusion requirements. Thromboembolic events, reoperations and mortality were similar in both groups. In conclusion, administration of regular doses of TA and AP during OLT did not result in large differences between the two groups. (Liver Transpl 2004;10:279–284.)

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.

Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft.

We performed a prospective, randomized study of adult patients undergoing orthotopic liver transplantation, comparing hemodynamic and tissular oxygenation during reperfusion of the graft. In 30 patients, revascularization was started through the hepatic artery (i.e., initial arterial revascularization) and 10 minutes later the portal vein was unclamped; in 30 others, revascularization was started through the portal vein (i.e., initial portal revascularization) and 10 minutes later the hepatic artery was unclamped. The primary endpoints of the study were mean systemic arterial pressure and the gastric‐end‐tidal carbon dioxide partial pressure (PCO2) difference. The secondary endpoints were other hemodynamic and metabolic data. The pattern of the hemodynamic parameters and tissue oxygenation values during the dissection and anhepatic stages were similar in both groups At the first unclamping, initial portal revascularization produced higher values of mean pulmonary pressure (25 ± 7 mm of Hg vs. 17 ± 4 mm of Hg; P < 0.05) and wedge and central venous pressures. At the second unclamping, initial portal revascularization produced higher values of cardiac output and mean arterial pressure (87 ± 15 mm of Hg vs. 79 ± 15 mm of Hg; P < 0.05) and pulmonary blood pressure. Postreperfusion syndrome was present in 13 patients (42.5%) in the arterial group and in 11 patients (36%) in the portal group. During revascularization, the values of gastric and arterial pH decreased in both groups and recovered at the end of the procedure, but were more accentuated in the initial arterial revascularization group. In conclusion, we found that initial arterial revascularization of the graft increases pulmonary pressure less markedly, so it may be indicated for those patients with poor pulmonary and cardiac reserve. Nevertheless, for the remaining patients, initial portal revascularization offers more favorable hemodynamic and metabolic behavior, less inotropic drug use, and earlier normalization of lactate and pH values. Liver Transpl, 2006.

Prophylactic use of Tranexamic Acid and Incidence of Arterial Thrombosis in Liver Transplantation

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Prophylaxis versus preemptive therapy for cytomegalovirus disease in high‐risk liver transplant recipients

Cytomegalovirus (CMV) infection is an opportunistic infection frequently found after solid organ transplantation, and it contributes significantly to mortality and morbidity. CMV‐seronegative recipients of grafts from CMV‐seropositive donors have the highest risk of CMV disease. The most appropriate strategy for preventing CMV disease in this population is a matter of active debate. In this study, we compared prophylaxis and preemptive therapy for the prevention of CMV disease in donor‐seropositive/recipient‐seronegative (D+/R−) liver recipients. To this end, we selected a retrospective cohort of liver recipients (1992‐2009) for analysis. D+/R− patients were identified from the liver transplant program database. Eighty of 878 consecutive liver recipients (9%) were D+/R−. Six of these patients died within 30 days of transplantation and were excluded. Thirty‐five of the remaining D+/R− patients (47%) received prophylaxis, and 39 patients (53%) followed a preemptive strategy based on CMV antigenemia surveillance. Fifty‐four (73%) were men, the median age was 49 years (range = 15‐68 years), and the mean follow‐up was 68 months (range = 8‐214 months). The baseline characteristics and the initial immunosuppressive regimens were similar for the 2 groups. Ganciclovir or valganciclovir was the antiviral drug used initially in both strategy groups. CMV disease occurred more frequently among D+/R− liver recipients receiving preemptive therapy (33.3% versus 8.6% for the prophylaxis group, P = 0.01), whereas late‐onset CMV disease was found only in patients receiving prophylaxis (5.7% versus 0% for the preemptive therapy group, P = 0.22). No significant differences in acute allograft rejection, other opportunistic infections, or case fatality rates were observed. According to our data, prophylaxis was more effective than preemptive therapy in preventing CMV disease in high‐risk liver transplant recipients. Liver Transpl, 2012.