Improving the waiting list by using 75-year-old donors for recipients with hepatocellular carcinoma.

The best treatment for hepatocellular carcinoma (HCC) associated with liver cirrhosis is liver transplantation and the best results are obtained when the tumors fulfill the Milan criteria. However, although the number of transplants is increasing, the organ deficit is growing, which lengthens time on the waiting list, increasing the risk of tumor progression of and exclusion from the list. The use of elderly donors is a valid option for patients on the transplant waiting list with HCC, reducing time on the waiting list. We report our experience with patients transplanted for HCC associated with hepatic cirrhosis using livers from donors >75 years of age. Our preliminary results supported the use of elderly suboptimal donors making it possible to give priority to these patients. All patients in the series achieved good graft function after a follow-up of 2 years with a 100% disease-free survival rate. More extensive long-term studies are needed to confirm these findings.

Liver transplantation in Wilson's disease: are its indications established?

UNLABELLED: The indications of progressive neurological deterioration despite no hepatic insufficiency, for liver transplant (OLT) in patients with Wilson's disease (WD) who do not improve with medical treatment is widely debated. The aim of this paper was to present our OLT experience in WD. PATIENTS AND METHODS: Fourteen patients were given a transplant after the diagnosis of WD for the following indications: in four patients, a steady neurological deterioration that failed to respond to chelation treatment (all with Child grade A liver function); in nine patients, Child grade C hepatic insufficiency, in whom medical treatment had failed (one of these patients also presented with severe neurological alterations); and in one patient, acute hepatic failure secondary to E. Coli infection of the ascitic fluid. RESULTS: Two patients died, one due to severe pancreatitis in the immediate postoperative period and the other, who was transplanted for neurological involvement, experienced an acute rejection episode treated with methylprednisolone in the first postoperative month and, in the 4th month, another episode of acute rejection, failed to respond to corticoids and required OKT-3 administration. She subsequently developed bilateral bronchopneumonia due to cytomegalovirus that led to her death. During the immediate postoperative period all of the cupremia, cupriuria, and ceruloplasmin levels returned to normal. The liver function in the 12 patients currently alive was totally normal after a follow-up of 8 years (range, 1-15 years) with actuarial 5-year survival of 85.7%. CONCLUSIONS: These cases demonstrated that OLT may mobilize copper sufficiently from the central nervous system to correct severe neurological deficits, a result that medical therapy alone cannot achieve. We suggest that OLT be considered for patients with WD who have crippling neurological and psychological diseases, even if liver function is stable.

Role of liver transplantation in the management of unresectable neuroendocrine liver metastases.

UNLABELLED: The use of OLT in the management of liver metastases of any origin is highly controversial, as most patients receiving a transplant for this indication display poor results owing to early tumor spread secondary to the effects of immunosuppression. However, as they have a better biological behavior, neuroendocrine (NE) tumors may be a good indication for OLT. Our aim was to present our experience in the management of unresectable liver metastases of tumors of NE origin. PATIENTS AND METHODS: Between January 1996 and April 2006, 10 patients underwent OLT for unresectable liver metastases of a neuroendocrine origin, accounting for 1.2% of all transplants performed to date in our unit (n = 626). The most common location of the primary tumor was the pancreas in six cases: three in the pancreatic tail--one carcinoid tumor, one gastrinoma, and one nonfunctioning NE [NF-NE] tumor; and three cases in the pancreatic head--three NF-NE tumors. In the remaining four cases, including three carcinoid tumours and one NF-NE tumors, two were located in the small bowel (at the ileum and ileocecal valve) and two in the lung. The liver metastases were synchronous with the primary tumor in seven cases and metachronous in three cases. RESULTS: The morbidity rate was 75% and the mortality rate, 10% (n = 1). The tumor recurrence rate was 33% with 1- and 3-year survival rates of 86% and 57%, respectively.

Hemodynamic changes during reperfusion of the graft in an animal model of liver xenotransplantation.

UNLABELLED: Our goal was to determine the hemodynamic changes that are witnessed during the initial minutes of reperfusion of the graft in liver xenotransplantation from pig to baboon. METHOD: We studied a group of 12 baboons undergoing transplantation of a pig liver via the classic technique with arterial anastomosis to the aorta. The anesthesia technique was similar to that used in humans. Hemodynamic monitoring, due to the size of the recipient, consisted of heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP) recorded at the beginning and end of each of the three phases: preanhepatic (A1, A2), anhepatic (B1, B2), and neohepatic (C1 and C2). We aimed to maintain the following values by means of crystalloids, colloids, and blood derivates: HR >50 beats/minute; MAP >60 mm Hg; and CVP >10 mm Hg. RESULTS: Both HR and CVP remained unchanged throughout the procedure. MAP droped briefly after vascular clamping (B1) but not on reperfusion (C1). CONCLUSION: In cirrhotic patients there is an autonomic dysfunction, demonstrated as cardiovascular instability at times like the clamping of major vessels and reperfusion of the graft. On the other hand, the intact baboon has an intact nervous system. After vascular clamping, the sharp decrease in venous return lead to an adequate vasopressor response. Likewise, the extreme vasodilatation involved with reperfusion managed to maintain MAP above 70 mm Hg.

Risk factors of acute renal failure after liver transplantation.

The objective of this study was to determine the risk factors of postoperative acute renal failure (ARF) in orthotopic liver transplantation (OLT). We reviewed 184 consecutive OLT. Postoperative ARF was defined as a persistent rise of 50% increase or more of the S-creatinine (S-Cr). The patients were classified as early postoperative ARF (E-ARF) (first week) and late postoperative ARF (L-ARF) (second to fourth week). Preoperative variables were age, sex, comorbidity, indication for OLT, Child-Pugh stage, united network for organ sharing status, analysis of the blood and urine, and donor's data. Intraoperative variables were systolic arterial pressure, mean arterial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance index. Surgical technique, number of blood products transfused, need for adrenergic agonist drugs, and intraoperative complications were also important. Postoperative variables were duration of stay in the intensive care unit, time on mechanic ventilation, liver graft dysfunction, need for adrenergic agonist drugs, units of blood products infused, episodes of acute rejection, re-operations, and bacterial infections. Firstly we carried out a univariate statistical analysis, and secondly a logistic regression analysis. The risk factors for E-ARF were: pretransplant ARF (odds ratio (OR)=10.2, P=0.025), S-albumin (OR=0.3, P=0.001), duration of treatment with dopamine (OR=1.6, P=0.001), and grade II-IV dysfunction of the liver graft (OR=5.6, P=0.002). The risk factors for L-ARF were: re-operation (OR=3.1, P=0.013) and bacterial infection (OR=2.9, P=0.017). The development of E-ARF is influenced by preoperative factors such as ARF and hypoalbuminemia, as well as postoperative factors such as liver dysfunction and prolonged treatment with dopamine. The predicting factors of L-ARF differ from E-ARF and correspond to postoperative causes such as bacterial infection and surgical re-operation.

Portopulmonary hypertension and liver transplantation: hemodynamic consequences at reperfusion.

BACKGROUND: The absence of portopulmonary hypertension (PH) upon preoperative evaluation for liver transplantation (OLT) does not exclude the occasional occurrence of an acquired PH while awaiting a graft. We sought to estimate hemodynamic changes and right ventriculoarterial coupling during reperfusion. METHODS: We studied 11 cirrhotic patients diagnosed with mild PH, according to the current classification: mean pulmonary artery pressure (MPAP)-25 to 34 mm Hg. These patients underwent OLT, using the piggyback technique (group PH). None of them had exhibited criteria for PH on preoperative echocardiography. This cohort was compared with 20 consecutive cirrhotic patients with normal MPAP at OLT. We performed a complete hemodynamic profile using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) before and 5 minutes after reperfusion. The variables were MPAP and right ventricular (RV) end-diastolic volume index (RVEDVI). Using standard formulas we calculated RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio. Systolic ventricular function was expressed as RVSWI versus RVEDVI. RESULTS: During the anhepatic phase, MPAP, Ees, Ea, and RVSWI were higher in the PH group; but RVEDVI was lower. After reperfusion the pressure (MPAP), contractility (RVSWI) and preload (RVEDVI) increased in both groups. However, afterload (Ea) decreased in the non-PH group; accordingly, Es/Ea increased only in these patients. DISCUSSION: At reperfusion, the expansion in preload and cardiac output, without a similar afterload decrease, is responsible for the steady increase in pressure. Our results have shown that in the PH patient group, systolic ventricular function improves during reperfusion by a Frank-Starling mechanism; however, ventricular-arterial uncoupling is maintained (Ees/Ea < 1) because ventricular contractility is not appropriately balanced by simultaneous declines in afterload.

Effects of rapid paracentesis on right ventricular-arterial coupling in liver transplantation.

BACKGROUND: In cirrhotic patients intra-abdominal pressure (IAP) changes markedly modify splanchnic and systemic hemodynamics. Previous studies have evaluated the effects of increased IAP on steady-state cardiac performance, showing that right ventricular (RV) function becomes more depressed than that of the left ventricular. We sought to evaluate the effects of paracentesis on RV function and ventricular-arterial coupling among cirrhotics undergoing liver transplantation (OLT). METHODS: Twelve cirrhotic patients undergoing OLT underwent hemodynamic profiles before and 5 minutes after paracentesis, employing a right ventricular ejection fraction catheter in the pulmonary artery. We studied heart rate, systolic pulmonary artery pressure, central venous pressure (CVP), stroke volume index (SVI), RV end-diastolic volume index (RVEDI), and RV ejection fraction. In addition RV stroke work index (RVSWI), RV end-diastolic compliance (RVEDC), RV end-systolic elastance (Ees), pulmonary artery effective elastance (Ea), and RV coupling efficiency (Ees/Ea ratio) were calculated employing standard formulas. RESULTS: After removal of mean ascites volume of 5.6 +/- 2.2 L (range 4.0 to 8.04 L), SVI, RVEDI, RVSWI, and RVEDC were significantly increased and conversely CVP, Ees, and Ea were decreased with an ea/ea ratio unchanged. CONCLUSIONS: Before paracentesis Ees/Ea is preserved by increased of RV contractility; after paracentesis the coupling was maintained.

Effects of dobutamine on right ventricular function and pulmonary circulation in pulmonary hypertension during liver transplantation.

INTRODUCTION: In the setting of orthotopic liver transplantation (OLT), pulmonary hypertension (PH) affects right ventricular (RV) function. When RV failure occurs, reducing RV afterload, optimizing RV preload, and preserving coronary perfusion through maintenance of systemic blood pressure are the primary goals of intraoperative treatment. PATIENTS AND METHODS: To verify the effect of dobutamine on RV function and RV-arterial coupling, we compared a group of 9 cirrhotic patients with mild PH treated with OLT to a group of 20 patients with normal mean pulmonary artery pressure (MPAP). All patients received dobutamine (5-10 microg/kg/min) to maintain a cardiac index (CI) >3 L/min/m(2), during the anhepatic phase. Hemodynamic profile, using a pulmonary artery catheter, was performed before and during dobutamine infusion, studying MPAP, CI, and RV end-diastolic volume index (RVEDVI). RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio were also calculated. RESULTS: RV contractility (Ees and RVSWI) and afterload (Ea) were significantly higher among the PH group. In both groups, all the studied variables improved with dobutamine: RV contractility increased, afterload decreased, and thus Ees/Ea coupling markedly increased. CONCLUSION: Cirrhotic patients with mild PH who were undergoing OLT still have a reserve of RV contractile performance and pulmonary vasodilation.

Differential response of the systemic and pulmonary circulation related to disease severity of cirrhosis.

BACKGROUND: In cirrhotic patients, the degree of hepatic insufficiency has been related to a physiological landmark: arterial vasodilatation. We sought to assess how the severity of disease, which was stratified according to the Child-Pugh criteria, influences the pulmonary and systemic circulation among patients undergoing liver transplantation. METHODS: We studied 86 cirrhotic patients in three groups: grade A (n = 10), grade B (n = 54), and grade C (n = 22). The outurnes were classified based upon a complete hemodynamic profile obtained using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) after induction of anesthesia. The variables were mean arterial and pulmonary artery pressures and cardiac index (CI). Using standard formulae, afterload was calculated as elastance of systemic (Es) and pulmonary (Ep) arterial beds, expressed by the ratio of end-systolic pressure to stroke volume. The relation between pulmonary and systemic circulation was also evaluated by the ratio (Ep/Es). RESULTS: Es was significantly lower in each class than in previous one. Also, Ep was smaller in class B than in class C patients. In addition, CI was significantly higher with disease severity. CONCLUSION: We observed that the hyperdynamic circulation in cirrhosis is directly related to severity of disease. Nevertheless Ep/Es was progressively higher among each group; these data suggest that the hyperdynamic circulation is mainly due to circulatory alterations in the splanchnic area. We conclude that pulmonary vasodilatation is directly related to the severity of cirrhosis, although its evolution is independent of other vascular areas.

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.

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

INTRODUCTION: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. METHODS: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. RESULTS: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01). CONCLUSION: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.