Influence of Body Mass Index on Venous Thrombotic Complications of Liver Transplants.

OBJECTIVE: To analyze venous thrombotic complications in transplanted patients as a function of their body mass index (BMI). MATERIALS AND METHODS: This single-center, observational retrospective study of individuals undergoing liver transplantation between January 2008 and December 2014 analyzed the frequency of pretransplant portal thrombosis, post-transplant venous complications (early and late portal thrombosis), deep vein thrombosis, pulmonary thromboembolism and the survival outcomes as a function of World Health Organization BMI class. RESULTS: Liver transplantation was performed in 208 patients during the study period. No statistically significant differences in study variables were found as a function of BMI in bivariate analyses (P < .05), and Kaplan-Meier survival analysis results were also nonsignificant. CONCLUSION: No differences in the rate of venous thrombotic complications or survival were found as a function of the BMI class of these liver transplant recipients. These findings are in line with previous reports that complication rates are not higher in obese patients and support the proposal that obesity should not be considered a contraindication for liver transplantation based on the risk of venous complications.

Role of Transarterial Chemoembolization to Downstage Hepatocellular Carcinoma Within the Milan Criteria.

The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplantation centers. We present our results using transarterial chemoembolization (TACE) as a neo-adjuvant treatment in our center between 2002 and 2013 to determine its effectiveness in downstaging (DS) HCC within the Milan criteria (MC). Clinical variables were recorded of both donors and recipients, such as diagnosis and treatment, variables related to its etiology, the use of TACE as a neo-adjuvant treatment, immunosuppressive therapy, toxicity, recurrence of disease, exitus, and others. Sixty-four patients were analyzed. Median age was 57 (range, 51-64) years. In this study, 84% (54) were male and 16% (10) were women. Etiology of HCC was viral in 47% (30), alcoholic in 25% (16), and other in 28% (18). TACE was conducted in 45 patients (70%). Every patient included in our study presented a T2 stage (of tumor-nodes-metastasis [TNM]) before surgery, thus within the MC. However, DS protocol was performed in 5 patients (7.8%). We performed a bivariate analysis, having assessed that the use of TACE decreases T2 stage into T1-T0 stage (P < .05). We have also calculated the recurrence-free survival, which reaches up to 80% to 125 months. Furthermore, even though the statistical differences are not consistent due to the simple size presented, we conclude that TACE is a safe and effective therapy to control HCC progression during the waiting list time.

Influence of Waiting List in Recurrence Disease of Hepatocellular Carcinoma.

BACKGROUND: We describe the results of our liver transplantation (LT) patients for hepatocellular carcinoma (HCC) in 2004 to 2012 to determine the differences on the basis of time on the waiting list to establish the risk of recurrence of liver disease. METHODS: Clinical variables were recorded for both donors and recipients as well as variables of diagnosis, the use of transarterial chemoembolization during the waiting list time (WLT), complications, re-transplantation, and exitus. Fifty-eight patients were analyzed. Mean age was 57 ± 8 years (men, 83%; 48 patients). Viral etiology of HCC was 50% (n = 29); alcoholic, 26% (n = 15); and others, 24% (n = 14). RESULTS: Exitus was established in 24 patients (41%); only 5 patients (7%) were attributable to HCC. In the cohort of patients with less than 6 months of WLT, we registered both higher rates of downstaging protocols (10.7% vs 7.5%) and tumor size (3 cm vs 2 cm) compared with the other group. Bivariate studies were conducted according to the WLT (WLT <6 months, WLT ≥6 months), finding differences in recurrence of liver disease (P < .05). This fact was confirmed after a binary logistic regression. CONCLUSIONS: Our results in a subgroup of less than 6 months of WLT included patients with increased tumor size or presentation of multiple nodes, with a worse prognosis and therefore to be prioritized in the treatment of LT. Therefore, in our population there is a significant risk of tumor recurrence in patients with less WLT for LT, but it cannot be overestimated to all type of patients with HCC.

Complications Associated With Liver Transplantation in Recipients With Body Mass Index >35 kg/m(2): Would It Be a Poor Prognosis Predictive Factor?

BACKGROUND: Obesity is a global epidemic that continues to increase in a great number of countries, and it has become a major public health problem in Spain. Unfortunately, the impact of obesity on survival in liver transplantation (LT) recipients is underestimated and controversial. The aim of this study was to determine if obesity is a risk factor for morbidity and mortality after LT. METHODS: In a retrospective cohort study of the records of 180 consecutive patients who had undergone to LT from 2007 to 2013, 11 obese patients with body mass index (BMI) >35 kg/m(2) were identified. Their data have been compared with recipients with BMI 20-25 kg/m(2). RESULTS: There were no differences in demographic data, Child-Pugh score, Model for End-Stage Liver Disease score, or cause of liver failure. BMI >35 kg/m(2) recipients had a significantly higher rate of portal vein thrombosis before LT, compared with the BMI 20-25 kg/m(2) group (36.5% vs 13.9%; P = .041). There were also no differences in development of post-reperfusion syndrome. The groups were also comparable concerning morbidity rate after LT, stay in the intensive care unit, and global hospital stay. However, the mortality rate was significantly higher in the obese group compared with the nonobese group (72.7% vs 38.9%; P = .032). CONCLUSIONS: The results of the study clearly demonstrate higher mortality rates in obese patients undergoing LT; thus, it is fair to consider obesity as a poor prognosis predictive factor concerning mortality rate.

Immunosuppression Strategies in the Treatment of Hepatocellular Carcinoma in Virgen de las Nieves University Hospital.

BACKGROUND: We describe an observational, retrospective study that included patients who underwent a liver transplantation (LT) for hepatocellular carcinoma (HCC) in our center between 2004 and 2012. METHODS: Clinical variables were recorded for donors and recipients as diagnosis and treatment, immunosuppressive therapy, toxicity, graft dysfunction, recurrence, and exitus. Fifty-eight patients were analyzed. The mean age was 57 ± 8 years. The viral etiology of HCC was 50% (n = 29), alcoholic 26% (n = 15), and others, 24% (n = 14). Regarding initial immunosuppressive strategy (IS), 51 patients (87.9%) were treated with standard regimen with corticosteroids (CS) and tacrolimus (TA), compared with 7 patients with impaired renal function (12.1%) who underwent a delayed therapy with calcineurin inhibitors (CNI) + mycophenolate mophetil (MMF) + CS. Concomitant use of anti-CD25 monoclonal antibodies was less than 10%. Regarding maintenance, 43 patients (74.1%) were treated with MMF + CNI versus 15 treated only with TA (25.9%). RESULTS: Recurrence of HCC was approximately 12%: 7 patients (2 hepatic only, 5 also extra-hepatic). Exitus was established in 19 patients (32.75%); only 3 patients (5.17%) were attributable to HCC. Bivariate studies were conducted according to the initial IS (standard regimen versus delayed therapy) and maintenance therapy (MMF + TA versus TA alone), with no differences in any of them in recurrence, treatment toxicity, graft rejection, and dysfunction. CONCLUSIONS: In our experience with the IS, we found no differences in the development of recurrent disease, treatment toxicity, development of graft dysfunction, or rejection. We believe that individualized immunosuppressive therapy in these patients is safe and effective.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Experience of the transplant unit from Virgen de las Nieves Hospital in using liver grafts from asystolic donors.

Given the shortage of donors, it has become increasingly necessary to use alternative sources to meet the growing demand for organs, and evolution in the use of asystolic donors is proving to be an important resource in helping to meet those needs. The goal of this study is to describe the initial results of our experience with Type II asystolic donation. An observational retrospective study was conducted to analyze the variables of four cases in this type of donation. After the analysis we conclude that, despite the limited number of cases in our series, the results are compatible with larger series and permit us to continue to value this method as a resource for broadening the donor pool.

Liver transplantation using low-weight recipients from a graft split program.

We present our experience with a split liver (SL) program shared with the children's liver transplantation (LT) program from 2 different hospitals in the use of partial grafts from cadaver donors in brain death. We describe an observational, retrospective study, which included patients who underwent a SL transplantation in our center between January 2006 and December 2012. Clinical variables were recorded of both donors and recipients and their data were analyzed using SPSS 19.0 software. Of a total of 204 LT, 4 (2%) patients were treated with a SL. The causes of LT were alcoholic cirrhosis in 2 cases, cryptogenic cirrhosis, and primary biliary cirrhosis (PBC). In all cases there was a temporary portocaval shunt. The confluence of the hepatic veins of the recipient was anastomosed to the donor vena cava and arterial anastomosis was performed. The reconstruction was hepato-choledochal in all cases. There were no cases of postreperfusion syndrome or vascular thrombosis and no retransplantation was necessary. Currently, 3 of the 4 cases are still alive. Death in the other patient was due to mesenteric ischemia. Our center has participated in the development of a protocol that considers the indication of this technique provided expert groups are involved in its development, regardless of hospital level. This will expand the pool of donors and partially solve the current problems with available grafting.

Perioperative values of glutathione peroxidase activity and malondialdehyde levels in enolic cirrhotic recipients of a liver transplant.

Reactive oxygen species play a central role in ischemia-reperfusion injury after organ transplantation. They are degraded by endogenous radical scavengers such as antioxidant enzymes. The purpose of this study was to evaluate the temporal variation in glutathione peroxidase (GPX) activity and malondialdehyde (MDA) levels among alcoholic cirrhotic recipients of liver transplantations. The study included 30 recipients: 26 males and 4 females in the provided blood samples before and after transplantation. The results showed significant enhancement of MDA levels at 1 and 6 hours after transplantation: 4.458 ± 2.273 µmol/L and 4.4628 ± 2.405 µmol/L respectively (P < .001). In contrast, GPX activity showed a maximum at 3 days there after 3.541 ± 2,315 nmol/mg protein. In conclusion, although MDA levels show an enormous increase at 1 hour after transplantation suggesting lipid peroxidation, they were compensated by GPX activity thereafter, indicating control of the oxidative stress generated by liver transplantation.

Short- and long-term overall results of liver retransplantation: "Doce de Octubre" hospital experience.

INTRODUCTION: The liver retransplantation rate in Spain is about 6%. The main causes are primary nonfunction, vascular complications, chronic rejection, and recurrent liver disease. The results of this procedure are worse than those of first transplantations. PATIENTS AND METHODS: This retrospective study evaluated our experience with 54 retransplantations performed between January 1992 and December 2006, which were 5.6% of the 960 orthotopic liver transplantations (OLT) during this period. RESULTS: In this study, 34.7% of the retransplantations were performed between 4 and 30 days after the first transplantation; another 34.7% were within 1 year. Also, 48.9% of the retransplantations were performed in urgent situations. The main causes for retransplantation during the first month were primary hepatic failure (n = 14) and vascular complications (n = 4). After the first month the main causes were chronic rejection (n = 9), recurrence of hepatic disease (n = 3), and biliary complications (n = 4). Postoperative mortality was 23.9% and morbidity was 76.3%. However, 21.2% of the patients needed a third transplant. The overall rate of patient survival was 60.4% (n = 32) and of graft survival was 56.6% (n = 30). The 5-year actuarial graft survival rate was 65.4% with a mean survival time of 89.84 +/- 8.72 months; the 5-year patient survival rate was 64% with a mean survival time of 114.7 +/- 12.53 months. Worse survival was observed in chronic rejection and in retransplantations performed between 31 and 360 days. CONCLUSIONS: Liver retransplantation presents greater surgical complexity than the first transplantation, but is a good option for patients with failure of the first graft with a 5-year patient and graft survival rate greater than 65%.

First Spanish series of intestinal transplantation in adult recipients.

BACKGROUND: short-bowel transplantation has experienced a substantial growth worldwide following improved results from the late 1990's on, and its coverage by Medicare. According to the International Registry (1985-2005), a total of 1,292 intestinal transplants for 1,210 patients in 65 hospitals across 20 countries have been carried out thus far. OBJECTIVE: to know short-term (6 months) results regarding patient and graft survival from the first Spanish series of intestinal transplants in adult recipients. MATERIAL AND METHODS: we present our experience in the assessment of 20 potential candidates to short-bowel transplantation between June 2004 and October 2005. Of these, 10 patients were rejected and 4 were transplanted, which makes up the sample of our study. RESULTS: to this date 5 transplants have been carried out in 4 patients (2 retransplants, 2 desmoid tumors, 1 short bowel syndrome after excision as a result of mesenteric ischemia). Upon study completion and after a mean follow-up of 180 days (range 90-190 days) all recipients are alive, and all grafts but one (75%) are fully operational, with complete digestive autonomy. All patients received induction with alemtuzumab except one, who received thymoglobulin; in all induction was initiated with no steroids. CONCLUSIONS: intestinal transplantation represents a therapeutic option that is applicable in our setting and valid for recipients with an indication who have no other feasible alternative to keep their intestinal failure under control.

Primera serie nacional de trasplante de intestino en receptores adultos / First Spanish series of intestinal transplantation in adult recipients

Introducción: el trasplante de intestino, con la mejoría en los resultadosdesde finales de los años 90 y desde su cobertura por el Medicare,ha experimentado un crecimiento sustancial a nivel internacional.En la actualidad, según el Registro Internacional (1985-2005),se han realizado un total de 1.292 trasplantes de intestino en 1.210pacientes en 65 hospitales distribuidos por 20 países.Objetivo: conocer los resultados a corto plazo (6 meses) entérminos de supervivencia del paciente y del injerto de la primeraserie nacional de trasplante de intestino en receptores adultos.Material y métodos: presentamos nuestra experiencia en laevaluación de 20 potenciales candidatos a trasplante intestinal entrejunio de 2004 y octubre de 2005. De ellos, fueron desestimadosun total 10 pacientes y fueron trasplantados 4, lo que constituyela muestra de nuestro estudio.Resultados: hasta la fecha se han realizado 5 trasplantes en 4pacientes (2 retrasplantes, 2 tumores desmoides, y 1 síndrome deintestino corto tras exéresis por isquemia mesentérica). Al final delestudio y tras un seguimiento medio de 180 días (rango, 90-190días), todos los receptores están vivos, y todos los injertos, a excepciónde uno (75%), están funcionando plenamente, con autonomíadigestiva completa. Todos los pacientes recibieron induccióncon alemtuzumab excepto uno que recibió timoglobulina y entodos se inició la inducción sin esteroides.Conclusiones: el trasplante intestinal constituye una opciónterapéutica aplicable en nuestro medio y válida en receptores enquienes está indicado y que no tienen otra alternativa válida paracontrolar su insuficiencia intestinal

Background: short-bowel transplantation has experienced asubstantial growth worldwide following improved results from thelate 1990s on, and its coverage by Medicare. According to the InternationalRegistry (1985-2005), a total of 1,292 intestinal trasplantsfor 1,210 patients in 65 hospitals across 20 countries have been carriedout thus far.Objective: to know short-term (6 months) results regardingpatient and graft survival from the first Spanish series of intestinaltransplants in adult recipients.Material and methods: we present our experience in the assessmentof 20 potential candidates to short-bowel transplantationbetween June 2004 and October 2005. Of these, 10 patientswere rejected and 4 were transplanted, which makes up thesample of our study.Results: to this date 5 transplants have been carried out in4 patients (2 retransplants, 2 desmoid tumors, 1 short bowelsyndrome after excision as a result of mesenteric ischemia).Upon study completion and after a mean follow-up of 180days (range 90-190 days) all recipients are alive, and all graftsbut one (75%) are fully operational, with complete digestiveautonomy. All patients received induction with alemtuzumabexcept one, who received thymoglobulin; in all induction wasinitiated with no steroids.Conclusions: intestinal transplantation represents a therapeuticoption that is applicable in our setting and valid for recipientswith an indication who have no other feasible alternative tokeep their intestinal failure under control

Results in split liver transplantation.

INTRODUCTION: The shortage in cadaveric grafts has prompted the development of alternative surgical techniques to expand the donor pool. OBJECTIVE: To evaluate the feasibility of split liver transplantation using an observational, retrospective, and longitudinal study. MATERIALS AND METHODS: Between April 1986 and October 2002 we performed 875 liver transplants. From April 1991 to date, we performed 18 split liver transplantations in patients of mean age 42.27+/-25.65 years; five children and 13 adults; and 83.3% women. Urgent transplants accounted for 38.9%. Mean patient weight was 52.29+/-20.87 kg. Ex situ splitting was performed in 33%. The mean cold ischemia time was 460+/-265.69 minutes with a mean warm time of 64.33+/-11.78 minutes. Mean consumption of packed blood was 5.59+/-4.87 units; of frozen fresh plasma, 11.56+/-7.42 units; and of platelets 4.89+/-4.99 units. RESULTS: After a mean follow-up of 10.83+/-12.51 months, 55.56% of the recipients are alive. Actuarial patient and graft survival rates at 1 year are 55.6% and 44.12%, respectively. Actuarial patient and graft survival rates at 1 year, excluding operative mortality were 77% and 68%, respectively. Actuarial patient and graft survival rates at 1 year, comparing urgent and elective transplantations are: 14.29 and 14%, respectively, for urgent cases and 90.91 and 90% for elective ones. Operative mortality was 16.6% while mortality during follow-up was 26.6%. The late complications included arterial thrombosis (n=2): of whom the first needed liver retransplantation 4 months after split liver transplantation; chronic rejection (n=2), recurrence of hepatitis (n=1). CONCLUSIONS: Split liver transplantation is a useful way to expand the graft pool and shows better results in elective liver transplantation.

Advantages of the piggy back technique on intraoperative transfusion, fluid compsumption, and vasoactive drugs requirements in liver transplantation: a comparative study.

INTRODUCTION: The piggyback technique was first described in adult liver transplantation in 1989, although it has been used in conjunction with venous bypass, with cross-clamping the vena cava, or both. In this study, the inferior vena cava was not occluded at any time during the liver transplant. OBJECTIVE: We compared the use of intraoperative blood products, fluid requirements, and vasoactive drugs among patients managed with bypass, without bypass, and with the piggyback technique. MATERIAL AND METHODS: Between May 1986 and October 2002, 875 liver transplants included 50 patients divided into three groups (cases considered to be the preliminary series on each group): group A/piggyback (17 patients:34%), group B/ bypass (16 patients: 32%), and group C/no bypass (17 patients:34%). There were no differences in mean age, gender, UNOS or Child-Pugh score, and indications for liver transplantation. RESULTS: Mean follow up was 134.63+/-32.19 months. At the end of the study, 91.3% of the patients are alive with no operative mortality. There were no differences in postoperative complications, postreperfusion syndrome rate, and postoperative renal failure. However, the number of packed red blood cell units consumed intraoperatively (12+/-7.43 vs 18.03+/-11.46 vs 17.59 +/- 23.8; P =.043), the need for intraoperative crystaloids (3.1 L+/-1.6 vs 6.8+/-4.8 vs 9.1 L+/-3.6; P=.001) and the requirement for vasoactive drugs (18% vs 38% vs 24%; P=.043) was notably lower in group A vs group B vs group C. Operative time was longer in group A (121.54+/-37.77 vs 78.73+/-11.89 vs 87.07+/-14.33 minutes). CONCLUSIONS: The piggyback technique requires a longer operative time but offers the advantages of reducing the red blood cell requirements and preventing severe hemodynamic instability by virtue of reducing the need for vasoactive drugs and for a larger volume of intraoperative fluids.