Félix Cambra Molero

Using old liver grafts for liver transplantation: where are the limits?

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

Trasplante hepático como tratamiento de la polineuropatía amiloidótica familiar en pacientes mayores de 60 años

BACKGROUND AND OBJECTIVE Familial amyloid polyneuropathy (FAP) is the most prevalent type of hereditary systemic amyloidosis. It is an autosomal dominant disease characterized by the deposition of an abnormal variant transthyretin. It has a worldwide distribution, with localized endemic areas in Portugal, Sweden and Japan. In Spain there is an endemic focus, located in Mallorca. Liver transplantation is the only curative option for patients with FAP. The aim of this study was to describe the clinical and demographic characteristics of patients transplanted with a diagnosis of PAF. MATERIAL AND METHOD Six patients with PAF underwent liver transplantation between April 1986 and December 2012. RESULTS The mean age was 57.7+16 years, patients of Spanish origin were older than 60 years. All patients had progressive symptoms as mixed polyneuropathy. In 2 patients, combined heart-liver transplants sequentially were performed. Patient survival and graft was 80% at one, 3 and 5 years. CONCLUSIONS The only effective treatment for etiologic PAF is liver transplantation. Early detection is the key to the treatment and control, avoiding the irreversible organ damage.

Liver Transplantation from Donor after Cardiac Death (DCD) Maastricht type IIA, our Experience after 10 years

Introduction Ten years after the beginning of the donation after cardic death (DCD) programme in the University Hospital 12 de Octubre, we study the evolution of the results of said programme over time. Objectives To compare the results of liver transplantation (LT) using grafts obtained from donors after cardiac death (DCD type Maastricht IIA) performed during the first period (A) of the programme (January 2006 to December 2010) versus those performed during a later period defined from January 2011 to December 2016 (B). Materials and Methods Retrospective analysis of the DCD liver transplantation series in the University Hospital 12 de Octubre. Results 75 LT from DCD type IIA have been reviewed, 44 performed during period A and 31 during period B. Mean recipient ages were 59+8 y 58+6 (NS) respectively, with a similar number of male patients (79,5% vs. 71% NS). There were no statistically significant differences found regarding other recipient characteristics such as MELD score, hepatocellular carcinoma or HCV infection. Mean donor age was 38+9 years in group A and 46+7 in group B (p 0.000). When reviewing ischemia times (IT), cold IT was shorter in group B (A 7:00 vs. B 6:05; p 0.046) as was warm IT (A 1:08 vs. B 0:58, p 0.025). However NECMO time was significantly shorter during the first period (3:16 vs. 3:37 min, p 0.027). Recipient survival during period A at 1, 3 and 5 years was 77.3%, 61.4% and 59.1% while during period B it was 87.1%, 83.7% and 83.7% (p 0.039). Graft survival after period A was significantly lower as well (63.6%, 50% and 47.7% vs. 83.9%, 80.5% and 80.5% in group B; p 0.008). The incidence of ischemic cholangiopathy was higher in group A (43.2% vs. 13.3%; p 0.006), as well as the retransplantation rate (A 18.2% vs. B 3.2%; p 0.05). There were non-statistically significant differences found regarding the incidence of primary graft non-function (A 11.4% vs. 3.3% in group B; p 0.214). Conclusions The study shows a significant improvement in the results of DCD liver transplantation through time, possibly related to graft ischemia time optimization.

Influence of Graft Steatosis on the Outcome of Liver Transplantation

Introduction Steatotic liver grafts represent the most common type of extended criteria of liver grafts organ that have been introduced in the last decade due to the disparity between liver transplant candidates and the number of available organs. The aim of this study was to determine the effect of donor graft steatosis on the outcomes of liver transplantation (LT). Material and Methods We performed a retrospective study during the period between 2006-2016. Excluding HIV positive recipients, split grafts, simultaneos liver-kidney transplantation, donors eldier than 70 years, we analyzed 172 patients. The sample divided into 3 groups: normal histology (steatosis<10%), mild steatosis (10-30%), and moderate steatosis (30-60%). Factors such as mortality, overall survival, graft surgical complications, graft rejection were analyzed following the degrees of steatosis. Results Among the existing pathology reports of the 172 cases we found 94 (54%) with normal pathology (steatosis less than 10%), 74 (43%) with mild steatosis (10-30%) and 4 (3%) patients with moderate steatosis (30-60%). If we compare the MELD score before transplantation or the transfusional requierements using the McCluskey index, no differences were seen among the three groups. Mean ICU stay were also similar: 6.7 days in the non steatosis group, 7.6 days in mild steatosis and 3,5 in moderate steatosis (p=0.6). No difference was observed between the three groups for the incidence of complications such as acute graft rejection (p=0,1), ischemic cholangiopathy (p=0,1), hepatic artery thrombosis or chronic rejection (p=0,2). Regarding the early allograft disfunction (EAD) and primary non function (PNF), no differences were observed: 8 EAD (8,5%) in no steatosis group and 6 (8,1%) in the mild steatosis. No difference was found on the actuarial survival (AS) at 1,3 and 5 years, being for each group: steatosis<10%, the AS was 87%, 82% and respectively 81%. In mild steatosis group the AS was 85%, 83% and respectively 82% (p=0,5). If we take a look to the early mortality, during the hospitalization stay, 3 (3%) died in the non steatosis group and 6 (8%) in the mild steatosis. Conclusion Though we need a larger sample size, we did not find differences in terms of overall survival or complications after LT using grafts with middle to moderate steatosis (<60%).

Long Term Outcome of Patients with Portal Thrombosis Previous to Liver Transplantation

Introduction Portal vein thrombosis is a late consequence of advanced cirrhosis. Its development has been associated with worse long term patient and graft survival, as well as a higher risk of vascular complications after liver transplantation. Material and Methods We reviewed all patients over 18 years old who underwent liver transplantation (LT) at University Hospital “12 de Octubre” between January 2002 and January 2017. Pediatric recipients and cases of retransplantation were excluded. Patients were divided according to the presence of preoperative portal thrombosis (PT, 126 patients) or no PT (N-PT, 724 patients). Results Mean recipient age was 55.5±9 in PT vs 53.7±11 in N-PT (p 0.085), with a similar number of male patients in both groups (76.2% en PT vs 72.8% in N-PT; p 0.431). There was a 59,2% rate of HCV infection in the PT group (52.4% in N-PT; p 0.157), and 22.2% of patients in the same group had a diagnosis of hepatocellular carcinoma (vs 29,9% in N-PT group; p 0.080). Mean preoperative MELD score was 14.7 en TP vs 15.6 in N-PT (p 0.067). There were no significant differences found regarding preoperative BMI, haemoglobin, MELD-Na score and Child-Pugh score.16.7 % of patients in the PT group received a subobtimal graft for LT, vs 21.7% in the N-PT group (p 0.204). In relation to blood products transfusion, an average of 12.3 units of RBC was administered in the the PT group and 9.2 in the N-PT (p 0.084), with an average of 14.6 and 12.8 FFP units respectively (p 0.093) and no differences found when reviewing platelets and fibrinogen. Mean ICU stay was 9.2 days in PT vs 6.7 in N-PT (p 0.075), while mean ward stay was 17.7 days in PT vs 19.4 in N-PT (p 0.429). Portal thrombosis recurrence rate was 4% in patients with a previous diagnosis of PT, significantly higher than in those without said previous history (1.1% in N-PT; p 0.015). However, the rate of arterial thrombosis was 4.8% in the PT group vs 3.8% in the N-PT group with no statistical significance (p 0.890). Retransplantation rate was 4% in PT and 6.2% in N-PT (p 0.326). Actuarial survival at 1, 3 and 5 years was 86.5%, 79.1% and 76.2% respectively in the PT group, vs 84.5%, 78.3% y 74.3% in the N-PT group (p=0.489). Conclusion Pretransplant portal thrombosis is a diagnosis that has not been associated with a decreased survival after LT in our series; but seems to determine an increase in transfusion requirements and a higher risk of postoperative vascular complications.

Liver Transplantation as Curative Treatment in Severe Pulmonary Hypertension due to Hepatic Vascular Malformations in Rendu-Osler-Weber Disease

Introduction Hereditary haemorragic telangiectasia (HHT) is an autosomal dominant disease characterised by development of arterio-venous malformations (AVM) more common in mucosa, brain, lung, liver and gastrointestinal tract. Pulmonary hypertension (PH) is defined as mean pulmonary arterial pressure (mPAP) > 25 mmHg. Liver transplatation is still controversial in this patients. MaterialsMethods Woman, 38 years old, with personal history of eclampsia, HELLP síndrome and HHT type 2 (Rendu-Osler-Weber) with exon 9 in the ALK1 gen mutation that presents as systemic manifestations self-limited epistaxis and liver AVM with mainly arterio-systemic intrahepatic shunt which lead to high output cardiac arrest and moderate to severe PH with a NYHA II functional class. Lung and brain AVM were not observed in radiologic tests and bubble test was positive due to extracardiac shunt (>6 heart-beats). Results Due to the high risk related to liver transplantation (LT) in this patient, transarterial embolization of liver vascular malformations was performed first, with a 24% reducción in cardiac output (table 1) and development of several complications as intranodal reentry tachycardia and ischemic hepatitis. Because of partial improvement treatment with bevacizumab was iniciated, despite this, the patient suffered recurrent episodes of cardiac arrest and liver function deterioration (MELD 25). In July 2016, orthotopic LT was performed with a cold ischemia time of 355 min and a warm ischemia time of 40 min, during which he bled profusely requiring massive blood transfusion. After LT, a 53.2% reduction in the cardiac output was observed in a right catheterism, because extracardiac shunt was eliminated. Furthermore, a pulmonary vascular resistance (PVR) reduction, wich means an absence of vascular branch remodelation, and a normalization in mPAP was shown; which demonstrate the resolution of HP after LT (table 2). Table. No title available. Table. No title available. Conclusion - LT might be a curative treatment in patients with haemorrhagic vascular diseases if severe HP and cardiac arrest are due to liver AVM - Liver AVM embolization in moderate-severe HP with elevated cardiac output has mild results - Diagnosis of Lung AVM causing HP, by angio-TC or angiography, is essential because might contraindicated isolated LT.

Use of Norepinephrine in Pancreas Donors and its Influence on Patient and Graft Survival

Introduction Brain death originates a vasomotor center dysfunction, a decrease in catecholamine release and finally vasodilatation secondary to the decrease of the peripheral vascular resistence. To this we should add the relative dehydration resulting from a mixture of previous water restriction and polyuria secondary to vasopresin deficiency that will originate hypovolemia and hypotension in a potential donor. Because the most important factor in the viability and graft function is adequate donor perfusion, it has been postulated that donor catecholamines administration might have a beneficial effect on kidney function, while its effect on other organs is unknown. The aim of this study was to determine if norepinephrine in the donor is associated with recipient and pancreatic graft survival. Methods We performed a retrospective and comparative study, between the patients transplantated with a pancreatic graft proceeding from a donor where norepinephrine was used (Group A) and patients transplantated with a graft where norepinephrine was not used (Group B). Results 165 patients that underwent simultaneous pancreatic-kidney transplantation were included. The mean recipient age was 38.9 years, while the donor age was 28.6 years. 58.4% of the donors and 66.5% of the recipients were men. Grafts from group A presented an adequate function in 69% of the cases (p=0.03). The patient actuarial survival at 1.3 and 5 years in group A was: 94.9%, 93.3% and 92.5% respectively and in group B: 96.6%, 89.5% and 89.5% (p=0.6). The graft actuarial survival in group A was 82.8%, 78.9%, 72.9%, as compared to 75,9%, 68,4% and 63,8% respectively in group B (p=0.05). Conclusion Pancreatic grafts proceeding from donors who received norepinephrine present a significantly increased graft survival compared to grafts proceeding from donors without norepinephrine. No differences were seen in the patient survival between both groups.

Risk Factors and Consequences of Ischemic Cholangiopathy in Liver Transplantation from DCD Maastricht IIA

Introduction Although donors after cardiac death (DCD) Maastricht type IIA have been established as an acceptable source of grafts in the current setting of organ shortage, biliary complications, especially ischemic cholangiopathy (IC), remain a considerable difficulty in the management of these patients, with a significant impact in long term results and quality of life. Objectives To study the incidence and impact of ischemic cholangiopathy among DCD IIA liver transplant recipients, and identify risk factors related to this complication. Materials and Methods Retrospective analysis of the DCD Maastricht type IIA liver transplantation series in University Hospital 12 de Octubre, registered from January 2006 to December 2016. Results 75 LT from DCD type IIA were performed during the study period, with 23 cases of IC diagnosed (30.7%). Comparing patients who suffered this complication (IC) with those who did not (no-IC), there were no significant differences found in recipient age (no-IC 58.4+7.7, IC 59.5+7.7 years), MELD score (no-IC 13.9+4.8 vs IC 15.6+4.8), donor age, HCV infection or hepatocellular carcinoma prevalence. Mean MELD-Na was 19+7 in those patients who developed IC, and 15.9+5.8 in those who did not, although the difference was not significant. Ischemia times and ECMO flow rates were similar in both groups. Retransplantation rate was higher in the no-IC group (11.5% vs. 13%, NS). No differences were achieved comparing liver function tests. Median time from transplantation to development of ischemic cholangiopathy was 5.8 months (range 1.2-70.3). Multivariate analysis shows an increased risk of IC in those grafts with AST levels over four times the upper limit of the normal range in the last blood sample obtained during NECMO (OR, 5.93; 95% CI, 1.001-35.208; p 0.05). No other statistically relevant risk factors were identified in this analysis. Differences found when comparing actuarial survival at 1, 3 and 5 years in recipients who did not develop IC (76.5%, 70.3% and 70.3%) with those who did (91.3%, 69.6% and 65.2%) were not statistically significant (p 0.915). Similar results were obtained when studying graft survival (no IC 70.6%, 64.3%, 64.3% vs. IC 78.3%, 60.9%, 56.5%; p 0.958). Conclusions AST levels 4 times above the usual laboratory range have been identified as a significant risk factor in the developement of ischemic cholangiopathy, suggesting that grafts with this characteristic should be discarded to minimize said complication.

Liver-kidney simultaneous transplantation in adult patients with primary hyperoxaluria. Experience at Hospital Universitario 12 de Octubre

Primary hyperoxaluria (PH) is a metabolic liver disease with an autosomal recessive inheritance that results in oxalate overproduction that cannot be metabolized by the liver. Urinary excretion of oxalate results in lithiasis and nephrocalcinosis leading to a progressive loss of renal function that often requires renal replacement therapy despite medical treatment. Type 1 PH is the most common form and is due to a deficiency in the alanine-glycolate aminotransferase enzyme found in hepatic peroxisomes. Therefore, a liver-kidney simultaneous transplant (LKST) is the definitive treatment for end-stage renal disease (ESRD) patients. However, some studies suggest that the morbidity and mortality rates are greater when this procedure is performed instead of only a kidney transplant (IKT). Herein, we report five patients with PH and a mean glomerular filtration rate of 20.2 ± 1.3 ml/min/1.73 m2 who received a LKST between 1999 and 2015 at the Hospital Universitario 12 de Octubre. Recurrence and liver or kidney graft loss was not observed during the postoperative period and only one case of late acute rejection without graft loss was diagnosed. The recipient survival rate was 100% with a median follow up of 84 months. As LKST is a curative and safe procedure with a low mortality and high survival rate, it must be considered as the treatment of choice in adults with HP and ESRD.

Tumores mucinosos del apéndice: incidencia, diagnóstico y tratamiento quirúrgico

INTRODUCTION Mucinous tumors of the appendix are a rare pathology, with a prevalence below 0.5%. Clinical presentation usually occurs during the sixth decade of life, and mucinous tumors can clinically mimic acute appendicitis. The aim of this study is to describe the clinical and demographic variables, therapeutic procedure and diagnosis of these tumors. We analyze the association between mucinous tumors and pseudomyxoma peritonei (PP), as well as the association with colorectal and ovarian tumors. METHODS A retrospective study was performed including patients who underwent an appendectomy between December 2003 and December 2014. RESULTS Seventy-two mucinous tumors of the appendix were identified among 7.717 patients reviewed, resulting in a prevalence of 0.9%. Mean age at presentation was 64 years, 62% patients were female and 38% males. An incidental diagnosis was made in 43% of patients. Mucinous tumors of low malignant potential were significantly related to the presence of pseudomyxoma peritonei, identified in 16 (22%) of the cases. We also observed an increased risk of ovarian mucinous tumors in patients with a diagnosis of appendiceal mucinous neoplasm. In our sample, 22 (30.5%) patients showed a synchronous or metachronous colorectal cancer. CONCLUSIONS Appendiceal mucinous tumors are frequently an incidental finding. The diagnosis of mucinous tumors of low malignant potential is a factor associated with the development of pseudomyxoma peritonei. Histologic tumor grade and the presence of peritoneal dissemination will determine surgical treatment that can vary, from appendectomy to cytoreductive surgery.