- Email: [email protected]
Analysis of the First 1000 Liver Transplants in Virgen del Rocío Hospital
Analysis of the First 1000 Liver Transplants in Virgen del Rocío Hospital J. Tinoco-González*, G. Suárez-Artacho, C. Bernal-Bellido, C. Cepeda-Franco, I. Ramallo-Solis, L. Marín-Gómez, J.M. Álamo-Martínez, J. Serrano-Díez-Canedo, J. Padillo-Ruíz, and M.A. Gómez-Bravo University Hospital Virgen del Rocío, Liver Transplant Unit, Seville, Spain
ABSTRACT The goal of this work has been to analyze the first 1000 liver transplantations (LTs) performed in the Virgen del Rocío Hospital of Seville and to evaluate the changes in that time. We included 916 patients who had 1000 LTs. We distinguish 2 stages in the followup: the first stage, between 1990 and 2002, and the second, from 2003 to 2013 (Model for End-stage Liver Disease [MELD] stage). We analyzed recipient features, LT indications, donation criteria, surgical technique, complications, and survival both for patients and grafts. The median age of recipients was 53.50 46.49 years old, with a noticeable increase after 2000. There were 3 times as many men as women. The most frequent indications for LT were hepatocellular disease (48.8%), followed by hepatocarcinoma (17.8%), retransplantation (8.1%), and cholestatic diseases (3.6%). Donors of Andalusian centers accounted for 88.2% of LTs, and 8.3% of LTs presented some arterial or venous complication. Biliary complications occurred in 15.6%. Patient survival at 1, 5, and 10 years was 77%, 63.5%, and 51.3%, respectively. In conclusion, some of the factors that negatively influenced survival of the patient were stage of the LT, hepatitis C virusepositive recipient, emergency cases, hepatocarcinoma, high consumption of blood products, and second transplantations.
L
IVER transplantation (LT) has progressed since 1963, when it was first performed by Starlz [1]. It is currently considered the treatment of choice for most patients with terminal liver diseases [2,3]. Improved surgical and anesthetic techniques and preservation solutions and development of new immunosuppressive agents of the late ’80s and early ’90s, as well better selection of candidates, have increased survival in transplant recipients [4,5]. The aim of this work was to analyze the first 1000 LTs performed in the Virgen del Rocío Hospital of Seville and to evaluate the changes in donor, grafts, and recipients used in the LT, as well as surgical technique, to compare the results obtained in different stages. MATERIALS AND METHODS A retrospective study was performed of the first 1000 LTs performed at the Hospital Virgen del Rocío of Seville between 1991 and 2013. Two stages of study were distinguished: the first stage, between 1991 and 2002 (406 LTs), was before the -Model for End-stage Liver Disease (MELD), and the second stage, beginning in 2003, once MELD was established as a system of ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2973e2976 (2016)
prioritization of patients on the waiting list for LT (MELD era; 594 LTs). The first 1000 LTs were performed in 916 patients; 17 patients simultaneously received 2 organs (15 liver-kidney, 1 liver-pancreas, and 1 liver-heart); 11 patients received a complete graft from a living donor with familial amyloid polyneuropathy (FAP), and 1 patient received a reduced graft from an adult donor. Seventy-eight patients required a second liver transplantation (retransplantation). The most common indications for LT in the study where hepatocellular diseases (alcoholic cirrhosis, cirrhosis post hepatitis B virus and hepatitis C virus) in 48.8%, followed by hepatocellular carcinoma (17.8%), liver retransplantation on its different modalities, acute and elective procedures (8.1%), and cholestatic disease (3.6%). The demographic variables of both donors and recipients, as well as transplant etiology, surgical complications, use of blood products, and the survival rate according groups were analyzed. The analysis was performed with the statistical software SPSS-20 (SPSS Inc., Chicago, Ill), with the c2 test used for the quantitative variables and Student t test used for the qualitative variables.
*Address correspondence to José Tinoco-González, University Hospital Virgen del Rocío, Manuel Siurot Avenue n/n, Seville 41013, Spain. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.09.031
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RESULTS
The average age of LT recipients during the study period was 53.5 years (14 to 69); the median age in the pre-MELD era was 49.2 years and in the MELD era was 53.4 years (P ¼ .040). Since 2000, up to 22.4% of recipients have been over 60 years, and in the pre-MELD period, the number was 12.8% (P ¼ 043; Table 1). The overall prevalence of hepatitis C virus was 27.6%, with no significant differences between the 2 analyzed stages (28.08% pre-MELD and 27.3% in the MELD era, P ¼ .23). Hepatocarcinoma as the indication for LT in the 2 stages was 8.6% vs 24.1%, respectively (P ¼ .23). The prevalence of retransplantation was increased in the second stage (5.9% vs 9.6%, P ¼ .04). Most LTs (95.5%) were performed as an elective procedure, and 4.5% needed urgent surgery because of different situations: acute hepatic failure (2.2%), hepatic trauma (0.2%), and acute liver retransplantation (1.9%), without differences between stages. In the pre-MELD era, more donors were from national centers than Andalusian centers. In the MELD stage, 88.2% of donors came from Andalusian centers: 44.4% from the Seville zone (Seville and Huelva) and 43.8% from other zone of Andalucía (Cordoba, Malaga, and Granada); only 11.6% of grafts were from national centers and 2 grafts were from European centers. The age of donation rose from 27.7 years in 1990 to 62.9 years in 2012 (P ¼ .001). Donors over 75 years were 6.6% of total donors in the MELD stage (66 donors), most of them donating in the last 5 years (50 donors). Most transplants were from brain-dead donors (98.9%), and 11 grafts were from living donors with FAP. The surgical technique used to perform hepatectomy in the recipient was the classical technique of retrohepatic vena cava resection in the first 130 LTs performed and thereafter sporadically in 11 LTs for different reasons (neoplasms near a vena cava, vena cava tears). The piggyback technique (hepatectomy with the retrohepatic vena cava preservation) was performed in 85.9% of LT series, and even in 10 recipients with FAP whose grafts were used for domino transplant. The procedure was performed with portacaval shunt in 9.1% of the LT series. Suprahepatic vein anastomosis was changed from anastomosis of 2 veins (middle-left) in 28.3% of cases at the beginning of the series (first 283 LTs) to Table 1. Characteristics of Donors and Recipients Donors
Male (%) Age (y), % 18e40 40e60 >60 Age (average)
Recipients
Pre-MELD
MELD
P
Pre-MELD
MELD
P
65.3
61.6
.438
75.3
73.8
.812
38.0 35.2 26.8 38.4
18.7 30.4 50.9 54.8
.001
14.3 72.9 1.8 53.4
6.7 69.1 24.2 49.3
.043
.002
Abbreviation: MELD, Model for End-stage Liver Disease.
.040
become a plasty between 3 suprahepatic veins in 57.4% of LTs, and occasionally a cavocaval laterolateral anastomosis was used (in 11 cases), generally for technical difficulties, such as agenesis or atrophy in some of the recipient’s suprahepatic veins. Portal thrombosis (complete or partial) was present in 13% of recipients and required thrombectomy in most cases, except in 11 cases where other techniques of portal revascularization were necessary: anastomosis with choledocian varicose vein in 3 cases, cavoportal transposition in 2 cases, renoportal anastomosis in 1 case, elective liver retransplantation with a 10-mm Goretex (W.L. Gore & Associates, Inc., Newark, DE) prosthetic ringed graft in 1 case, and in 4 cases, interposition of a vascular graft from the donor was necessary and in any case the arterialization of portal vein was necessary. Arterial reconstruction was performed using some bifurcations of the hepatic artery recipient in 98.6% of cases. Arterial reconstruction was used with the splenic artery in 6 cases, interposition of arterial grafts from the donor in 4 cases, and direct anastomosis with the supraceliac aorta in 4 cases. The most commonly used biliary reconstruction technique in this study in both stages was the terminoterminal choledoco-choledocian anastomosis in 92.5% of LT; the biliary tutor T (Kehr) was used in the 55.4% of the series, 89.5% in the pre-MELD era and 29.8% in the MELD era (P ¼ .001). Biliary-enteric shunts were used in 6.5% of LTs in the series. The median consumption of packed red blood cells between the 2 stages changed from 11 U to 0 U, frozen plasma changed from 7 U to 4 U, and platelets changed from 5.5 U to 0 U. The percentage of LTs not requiring blood transfusion doubled in the second stage (6.16% and 14.31%, P ¼ .001). Vascular complications were not present in 917 LTs of the series, and 8.3% of the LTs presented some venous or arterial complication, including presence of arterial thrombosis in 4.1%, portal thrombosis in 1.2%, and 1 vena cava thrombosis, but differences between the 2 analyzed stages were not significant. Biliary complications occurred in 15.6% of LTs of the analyzed series in the form of biliary fistula in 58 cases, biliary stricture in 38 cases, bile leakage in 15 cases, and bile peritonitis in 16 cases; there was a clinically significant decrease in the second stage (P ¼ .31; Table 2). Survival of patients at 1, 5, and 10 years was 77%, 63.5%, and 51.3%, respectively. The improvement in the survival in the second stage of the analysis is statistically significant with a gain in survival in the first month (94.7%, P ¼ .008). The 1-year post-transplant survival in the series was not significantly different in grafts from elderly donors (P ¼ .09). On the other hand, the survival of the patients who needed liver retransplantation was less than the survival in those patients who received a first LT; there was a meaningful drop in the patients who received an elective retransplantation (P ¼ .055) (Fig 1).
FIRST 1000 LIVER TRANSPLANTS IN VIRGEN DEL ROCÍO HOSPITAL Table 2. Major Clinical Events
Acute rejection Chronic rejection Disease recurrence Bacterial infection CMV disease Vascular complication Biliary complication
Global (%)
Pre-MELD (%)
MELD (%)
P
28.2 11.8 19.8 51.9 11.1 11.6
43.5 9.1 24.1 62.8 Not registered 7.6 10.8
19.9* 13.5 16.8 44.3 5.7 13.5 12.6
.001 .087 .451 .871 .071 .230
Abbreviations: CMV, cytomegalovirus; MELD, Model for End-stage Liver Disease. *Only biopsy.
DISCUSSION
Between 1991 and 2012, the first 1000 LTs were performed in Virgen del Rocío Hospital of Seville. The changes that took place in different aspects during those decades have been enough important to separate into two stages, because of the arrival of MELD as a graft assignation system, aging of the population, the improvement of the road safety health, and new immunosuppressive drugs with more personalized profiles. In the first stage (1990 to 2002), advanced donor age was considered a contraindication for donation; in the second stage, the results of grafts considered aged were explored and currently there is no limit in the age to be a liver donor and few situations are contraindicated for donation. We observed a change in the donation age during this 23 years, from 27.7 years in 1990 to 62.9 years old in 2012; age was even higher in women (53 vs 49). According to the Spanish Register of Hepatic Transplantation (RETH), during the last 5 years, the number of donors of advanced age (>75 years old) has grown considerably. Our population of valid donors aged >75 years old also increased in the last stage by 6.6% (66 donors), with
Fig 1. Survival of liver transplant recipients according to the stages.
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most in the last 5 years (50 donors). The results of this group of aged donors have been similar to results of other donors, although we recommend aged donors be used in stable hepatitis C virus (HCV)-positive recipients with a low MELD score to obtain the best survival results [6,7]. The kind of donation was mostly complete grafts from brain-dead donors (98.9%), and 11 were complete grafts coming from living donors with FAP. The most common surgical technique used in the donor was described by Starlz et al in 1984 [8], with liver hilum dissection performed carefully and double aortic and splenic-portal cannulation; in cases of donor hemodynamic instability, to reduce time in surgery and avoid loss of grafts, quick total abdominal evisceration as described by Nakazato et al [9] was used, in which we proceeded to a quick aortic and lower mesenteric vein cannulation without previous liver hilum dissection. Portacaval derivation was used during the anhepatic phase with the purpose of minimizing the adverse effects of the splanchnic collapse for the first time in 2002 in our series. In this way, we reduced the time for retrohepatic cava vein dissection and improved different hemodynamic patterns such as cardiac output [10]. This kind of derivation was used in 9.1% of LT series, and it is reserved for those recipients who do not tolerate portal venous clamping or in the absence of manifest portal hypertension. In cases in which the vena cava was preserved (piggyback), we performed anastomosis in the recipient’s suprahepatic veins and the donor’s suprahepatic vena cava, to improve the venous drainage. There has been an evolution of the technique; initially drainage was carried out from 2 suprahepatic veins (middle-left) in 28.3% of the cases, and then we moved to plasty between the 3 suprahepatic veins in the 57.4% of LTs, and occasionally a cava-cava laterolateral anastomosis was used in 11 cases, generally for technical difficulties, such as agenesis or atrophy in the recipient suprahepatic veins. Portal vein vascular anastomosis was performed in 99% of LTs. It was performed between the donor’s and the recipient’s portal veins by a continuous suture in terminoterminal anastomosis with polypropylene 5-0 sutures with 2 independent faces. Arterial reconstruction was always performed by experienced surgeons in this kind of anastomosis. Most anastomoses were performed taking advantage of the bifurcation of the recipient’s hepatic artery; we tried to develop it in the gastroduodenal artery split or less frequently in the right-left hepatic artery split. Use of other arterial reconstruction modalities were exceptional, including revascularization with the splenic artery in 6 cases, interposition of arterial grafts from the donor in 4 cases, and anastomosis directly to supraceliac aorta in 4 cases. The most commonly used biliary reconstruction technique in this series, in both stages, was the terminoterminal choledoco-choledocian anastomosis in 92.5% of LTs, even though the T-shaped biliary tutor (Kehr) was used in 55.4% of the series; in the second stage, its use was reserved for
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those cases with bile duct that presented important size differences or technical difficulties in the reconstruction. Bilioenteric derivations were used in 6.5% of LTs in the series, and were reserved for primary sclerosing cholangitis patients, retransplantations, or technical difficulties that blocked the primary anastomosis of the bile duct. One of the biggest achievements comes from the decline in the use of hemoderivatives thanks to restrictive therapies, the mainstreaming of a mobile lab in 2010 in the surgical area, implementation of thromboelastometry, fibrinogen use, and improvement in the selection of the patients, which allowed a reduction in median red cells from 11 U to 0 U, frozen plasma from 7 U to 4 U, and platelets from 5.5 U to 0 U. The percentage of LTs that did not need hemoderivative transfusion has been duplicated in the second stage (6.16% vs 14.31%, P ¼ .001). In conclusion, LT activity on the Virgen del Rocío Hospital has evolved, similar to the LT activity of the rest of the country; its activity is consolidated with a majority of hepatocellular hepatopathies as LT indications. There have not been any changes in the prevalence of patients with HCVþ serology in the second stage, and the indications for hepatocarcinoma and the elective retransplants has grown. The donation criteria have evolved over the years, and in the second stage, donation age has tripled. Most of the grafts were complete and from the same autonomous community/region, taking into account that among donors, 11 donors were from FAP patients because there is a concentration of FAP in the Seville-Huelva sector. The most commonly used surgical technique was the classic extraction described by Starlz with some particular modifications in the donor and the vena cava preservation technique in the recipient, using portacaval derivation in selected patients. The vascular reconstruction has remained unchanged during the whole program, decreasing the use of a biliary tutor in the second stage. Acute arterial thrombosis as the most frequent vascular complication, with other vascular complications rarely encountered. Biliary complications happened in 15.6% of the series, and biliary fistula was the most frequent complication.
We identified a larger loss of patients and grafts in the first month after LT in the first stage, and we saw important improvements in the survival during the last stage due to a decrease in the mortality in the first month. Some of the factors that negative influenced graft and patient survival were stage of LT, HCV-positive recipient serology, emergency need, hepatocarcinoma, high consumption of hemoderivatives, and second transplantations. ACKNOWLEDGMENTS We thank Ángel Bernardos Rodríguez, José Manuel Sousa Martínez, Juan Manuel Pascasio Acevedo, Teresa Ferrer Ríos, Elisa Cordero Matía, Álvaro Giráldez, and Manuel Francisco Porras López.
REFERENCES [1] Starlz TE, Marchiaro TL, Von Kaulla K, et al. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963;117: 659e76. [2] Busuttil RW, Shaked A, Millis JM, et al. One thousand liver transplants. The lessons learned. Ann Surg 1994;219:490e9. [3] Bismuth H, Farges O, Castaing D, et al. Evaluation of results of liver transplantation: experience based on a series of 1052 transplantations. Presse Med 1995;24:1106e14. [4] Wiesner RH, Rakela J, Ishitani MB, et al. Recent advances in liver transplantation. Mayo Clin Proc 2003;78:197e210. [5] López-Navidad A, Caballero F. Extended criteria for organ acceptance. Strategies for achieving organ safety and for increasing organ pool. Clin Transplant 2003;17:308e24. [6] Álamo JM, Olivares C, Jiménez G, et al. Donor characteristics that are associated with survival in liver transplant recipients older than 70 years with grafts. Transplant Proc 2013;45:3633e6. [7] Cuende N, Grande L, Sanjuan F, Cuervas Mons V. Liver transplant with elderly donors. Spanish experience with more than 300 livers donors over 70 years of age. Transplantation 2002;73: 1360. [8] Starlz TE, Hakala TR, Shaw Jr BW, et al. A flexible procedure for multiple cadaveric organ procurement. Surg Gynecol Obstet 1984;158:223e30. [9] Nakazato PZ, Concepcion W, Bry W, et al. Total abdominal evisceration: an en bloc technique for abdominal organ harvesting. Surgery 1992;111:37e47. [10] Figueras J, Llado L, Ramos E, et al. Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study. Liver Transpl 2001;7(10):904e11.
ABSTRACT The goal of this work has been to analyze the first 1000 liver transplantations (LTs) performed in the Virgen del Rocío Hospital of Seville and to evaluate the changes in that time. We included 916 patients who had 1000 LTs. We distinguish 2 stages in the followup: the first stage, between 1990 and 2002, and the second, from 2003 to 2013 (Model for End-stage Liver Disease [MELD] stage). We analyzed recipient features, LT indications, donation criteria, surgical technique, complications, and survival both for patients and grafts. The median age of recipients was 53.50 46.49 years old, with a noticeable increase after 2000. There were 3 times as many men as women. The most frequent indications for LT were hepatocellular disease (48.8%), followed by hepatocarcinoma (17.8%), retransplantation (8.1%), and cholestatic diseases (3.6%). Donors of Andalusian centers accounted for 88.2% of LTs, and 8.3% of LTs presented some arterial or venous complication. Biliary complications occurred in 15.6%. Patient survival at 1, 5, and 10 years was 77%, 63.5%, and 51.3%, respectively. In conclusion, some of the factors that negatively influenced survival of the patient were stage of the LT, hepatitis C virusepositive recipient, emergency cases, hepatocarcinoma, high consumption of blood products, and second transplantations.
L
IVER transplantation (LT) has progressed since 1963, when it was first performed by Starlz [1]. It is currently considered the treatment of choice for most patients with terminal liver diseases [2,3]. Improved surgical and anesthetic techniques and preservation solutions and development of new immunosuppressive agents of the late ’80s and early ’90s, as well better selection of candidates, have increased survival in transplant recipients [4,5]. The aim of this work was to analyze the first 1000 LTs performed in the Virgen del Rocío Hospital of Seville and to evaluate the changes in donor, grafts, and recipients used in the LT, as well as surgical technique, to compare the results obtained in different stages. MATERIALS AND METHODS A retrospective study was performed of the first 1000 LTs performed at the Hospital Virgen del Rocío of Seville between 1991 and 2013. Two stages of study were distinguished: the first stage, between 1991 and 2002 (406 LTs), was before the -Model for End-stage Liver Disease (MELD), and the second stage, beginning in 2003, once MELD was established as a system of ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2973e2976 (2016)
prioritization of patients on the waiting list for LT (MELD era; 594 LTs). The first 1000 LTs were performed in 916 patients; 17 patients simultaneously received 2 organs (15 liver-kidney, 1 liver-pancreas, and 1 liver-heart); 11 patients received a complete graft from a living donor with familial amyloid polyneuropathy (FAP), and 1 patient received a reduced graft from an adult donor. Seventy-eight patients required a second liver transplantation (retransplantation). The most common indications for LT in the study where hepatocellular diseases (alcoholic cirrhosis, cirrhosis post hepatitis B virus and hepatitis C virus) in 48.8%, followed by hepatocellular carcinoma (17.8%), liver retransplantation on its different modalities, acute and elective procedures (8.1%), and cholestatic disease (3.6%). The demographic variables of both donors and recipients, as well as transplant etiology, surgical complications, use of blood products, and the survival rate according groups were analyzed. The analysis was performed with the statistical software SPSS-20 (SPSS Inc., Chicago, Ill), with the c2 test used for the quantitative variables and Student t test used for the qualitative variables.
*Address correspondence to José Tinoco-González, University Hospital Virgen del Rocío, Manuel Siurot Avenue n/n, Seville 41013, Spain. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.09.031
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RESULTS
The average age of LT recipients during the study period was 53.5 years (14 to 69); the median age in the pre-MELD era was 49.2 years and in the MELD era was 53.4 years (P ¼ .040). Since 2000, up to 22.4% of recipients have been over 60 years, and in the pre-MELD period, the number was 12.8% (P ¼ 043; Table 1). The overall prevalence of hepatitis C virus was 27.6%, with no significant differences between the 2 analyzed stages (28.08% pre-MELD and 27.3% in the MELD era, P ¼ .23). Hepatocarcinoma as the indication for LT in the 2 stages was 8.6% vs 24.1%, respectively (P ¼ .23). The prevalence of retransplantation was increased in the second stage (5.9% vs 9.6%, P ¼ .04). Most LTs (95.5%) were performed as an elective procedure, and 4.5% needed urgent surgery because of different situations: acute hepatic failure (2.2%), hepatic trauma (0.2%), and acute liver retransplantation (1.9%), without differences between stages. In the pre-MELD era, more donors were from national centers than Andalusian centers. In the MELD stage, 88.2% of donors came from Andalusian centers: 44.4% from the Seville zone (Seville and Huelva) and 43.8% from other zone of Andalucía (Cordoba, Malaga, and Granada); only 11.6% of grafts were from national centers and 2 grafts were from European centers. The age of donation rose from 27.7 years in 1990 to 62.9 years in 2012 (P ¼ .001). Donors over 75 years were 6.6% of total donors in the MELD stage (66 donors), most of them donating in the last 5 years (50 donors). Most transplants were from brain-dead donors (98.9%), and 11 grafts were from living donors with FAP. The surgical technique used to perform hepatectomy in the recipient was the classical technique of retrohepatic vena cava resection in the first 130 LTs performed and thereafter sporadically in 11 LTs for different reasons (neoplasms near a vena cava, vena cava tears). The piggyback technique (hepatectomy with the retrohepatic vena cava preservation) was performed in 85.9% of LT series, and even in 10 recipients with FAP whose grafts were used for domino transplant. The procedure was performed with portacaval shunt in 9.1% of the LT series. Suprahepatic vein anastomosis was changed from anastomosis of 2 veins (middle-left) in 28.3% of cases at the beginning of the series (first 283 LTs) to Table 1. Characteristics of Donors and Recipients Donors
Male (%) Age (y), % 18e40 40e60 >60 Age (average)
Recipients
Pre-MELD
MELD
P
Pre-MELD
MELD
P
65.3
61.6
.438
75.3
73.8
.812
38.0 35.2 26.8 38.4
18.7 30.4 50.9 54.8
.001
14.3 72.9 1.8 53.4
6.7 69.1 24.2 49.3
.043
.002
Abbreviation: MELD, Model for End-stage Liver Disease.
.040
become a plasty between 3 suprahepatic veins in 57.4% of LTs, and occasionally a cavocaval laterolateral anastomosis was used (in 11 cases), generally for technical difficulties, such as agenesis or atrophy in some of the recipient’s suprahepatic veins. Portal thrombosis (complete or partial) was present in 13% of recipients and required thrombectomy in most cases, except in 11 cases where other techniques of portal revascularization were necessary: anastomosis with choledocian varicose vein in 3 cases, cavoportal transposition in 2 cases, renoportal anastomosis in 1 case, elective liver retransplantation with a 10-mm Goretex (W.L. Gore & Associates, Inc., Newark, DE) prosthetic ringed graft in 1 case, and in 4 cases, interposition of a vascular graft from the donor was necessary and in any case the arterialization of portal vein was necessary. Arterial reconstruction was performed using some bifurcations of the hepatic artery recipient in 98.6% of cases. Arterial reconstruction was used with the splenic artery in 6 cases, interposition of arterial grafts from the donor in 4 cases, and direct anastomosis with the supraceliac aorta in 4 cases. The most commonly used biliary reconstruction technique in this study in both stages was the terminoterminal choledoco-choledocian anastomosis in 92.5% of LT; the biliary tutor T (Kehr) was used in the 55.4% of the series, 89.5% in the pre-MELD era and 29.8% in the MELD era (P ¼ .001). Biliary-enteric shunts were used in 6.5% of LTs in the series. The median consumption of packed red blood cells between the 2 stages changed from 11 U to 0 U, frozen plasma changed from 7 U to 4 U, and platelets changed from 5.5 U to 0 U. The percentage of LTs not requiring blood transfusion doubled in the second stage (6.16% and 14.31%, P ¼ .001). Vascular complications were not present in 917 LTs of the series, and 8.3% of the LTs presented some venous or arterial complication, including presence of arterial thrombosis in 4.1%, portal thrombosis in 1.2%, and 1 vena cava thrombosis, but differences between the 2 analyzed stages were not significant. Biliary complications occurred in 15.6% of LTs of the analyzed series in the form of biliary fistula in 58 cases, biliary stricture in 38 cases, bile leakage in 15 cases, and bile peritonitis in 16 cases; there was a clinically significant decrease in the second stage (P ¼ .31; Table 2). Survival of patients at 1, 5, and 10 years was 77%, 63.5%, and 51.3%, respectively. The improvement in the survival in the second stage of the analysis is statistically significant with a gain in survival in the first month (94.7%, P ¼ .008). The 1-year post-transplant survival in the series was not significantly different in grafts from elderly donors (P ¼ .09). On the other hand, the survival of the patients who needed liver retransplantation was less than the survival in those patients who received a first LT; there was a meaningful drop in the patients who received an elective retransplantation (P ¼ .055) (Fig 1).
FIRST 1000 LIVER TRANSPLANTS IN VIRGEN DEL ROCÍO HOSPITAL Table 2. Major Clinical Events
Acute rejection Chronic rejection Disease recurrence Bacterial infection CMV disease Vascular complication Biliary complication
Global (%)
Pre-MELD (%)
MELD (%)
P
28.2 11.8 19.8 51.9 11.1 11.6
43.5 9.1 24.1 62.8 Not registered 7.6 10.8
19.9* 13.5 16.8 44.3 5.7 13.5 12.6
.001 .087 .451 .871 .071 .230
Abbreviations: CMV, cytomegalovirus; MELD, Model for End-stage Liver Disease. *Only biopsy.
DISCUSSION
Between 1991 and 2012, the first 1000 LTs were performed in Virgen del Rocío Hospital of Seville. The changes that took place in different aspects during those decades have been enough important to separate into two stages, because of the arrival of MELD as a graft assignation system, aging of the population, the improvement of the road safety health, and new immunosuppressive drugs with more personalized profiles. In the first stage (1990 to 2002), advanced donor age was considered a contraindication for donation; in the second stage, the results of grafts considered aged were explored and currently there is no limit in the age to be a liver donor and few situations are contraindicated for donation. We observed a change in the donation age during this 23 years, from 27.7 years in 1990 to 62.9 years old in 2012; age was even higher in women (53 vs 49). According to the Spanish Register of Hepatic Transplantation (RETH), during the last 5 years, the number of donors of advanced age (>75 years old) has grown considerably. Our population of valid donors aged >75 years old also increased in the last stage by 6.6% (66 donors), with
Fig 1. Survival of liver transplant recipients according to the stages.
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most in the last 5 years (50 donors). The results of this group of aged donors have been similar to results of other donors, although we recommend aged donors be used in stable hepatitis C virus (HCV)-positive recipients with a low MELD score to obtain the best survival results [6,7]. The kind of donation was mostly complete grafts from brain-dead donors (98.9%), and 11 were complete grafts coming from living donors with FAP. The most common surgical technique used in the donor was described by Starlz et al in 1984 [8], with liver hilum dissection performed carefully and double aortic and splenic-portal cannulation; in cases of donor hemodynamic instability, to reduce time in surgery and avoid loss of grafts, quick total abdominal evisceration as described by Nakazato et al [9] was used, in which we proceeded to a quick aortic and lower mesenteric vein cannulation without previous liver hilum dissection. Portacaval derivation was used during the anhepatic phase with the purpose of minimizing the adverse effects of the splanchnic collapse for the first time in 2002 in our series. In this way, we reduced the time for retrohepatic cava vein dissection and improved different hemodynamic patterns such as cardiac output [10]. This kind of derivation was used in 9.1% of LT series, and it is reserved for those recipients who do not tolerate portal venous clamping or in the absence of manifest portal hypertension. In cases in which the vena cava was preserved (piggyback), we performed anastomosis in the recipient’s suprahepatic veins and the donor’s suprahepatic vena cava, to improve the venous drainage. There has been an evolution of the technique; initially drainage was carried out from 2 suprahepatic veins (middle-left) in 28.3% of the cases, and then we moved to plasty between the 3 suprahepatic veins in the 57.4% of LTs, and occasionally a cava-cava laterolateral anastomosis was used in 11 cases, generally for technical difficulties, such as agenesis or atrophy in the recipient suprahepatic veins. Portal vein vascular anastomosis was performed in 99% of LTs. It was performed between the donor’s and the recipient’s portal veins by a continuous suture in terminoterminal anastomosis with polypropylene 5-0 sutures with 2 independent faces. Arterial reconstruction was always performed by experienced surgeons in this kind of anastomosis. Most anastomoses were performed taking advantage of the bifurcation of the recipient’s hepatic artery; we tried to develop it in the gastroduodenal artery split or less frequently in the right-left hepatic artery split. Use of other arterial reconstruction modalities were exceptional, including revascularization with the splenic artery in 6 cases, interposition of arterial grafts from the donor in 4 cases, and anastomosis directly to supraceliac aorta in 4 cases. The most commonly used biliary reconstruction technique in this series, in both stages, was the terminoterminal choledoco-choledocian anastomosis in 92.5% of LTs, even though the T-shaped biliary tutor (Kehr) was used in 55.4% of the series; in the second stage, its use was reserved for
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those cases with bile duct that presented important size differences or technical difficulties in the reconstruction. Bilioenteric derivations were used in 6.5% of LTs in the series, and were reserved for primary sclerosing cholangitis patients, retransplantations, or technical difficulties that blocked the primary anastomosis of the bile duct. One of the biggest achievements comes from the decline in the use of hemoderivatives thanks to restrictive therapies, the mainstreaming of a mobile lab in 2010 in the surgical area, implementation of thromboelastometry, fibrinogen use, and improvement in the selection of the patients, which allowed a reduction in median red cells from 11 U to 0 U, frozen plasma from 7 U to 4 U, and platelets from 5.5 U to 0 U. The percentage of LTs that did not need hemoderivative transfusion has been duplicated in the second stage (6.16% vs 14.31%, P ¼ .001). In conclusion, LT activity on the Virgen del Rocío Hospital has evolved, similar to the LT activity of the rest of the country; its activity is consolidated with a majority of hepatocellular hepatopathies as LT indications. There have not been any changes in the prevalence of patients with HCVþ serology in the second stage, and the indications for hepatocarcinoma and the elective retransplants has grown. The donation criteria have evolved over the years, and in the second stage, donation age has tripled. Most of the grafts were complete and from the same autonomous community/region, taking into account that among donors, 11 donors were from FAP patients because there is a concentration of FAP in the Seville-Huelva sector. The most commonly used surgical technique was the classic extraction described by Starlz with some particular modifications in the donor and the vena cava preservation technique in the recipient, using portacaval derivation in selected patients. The vascular reconstruction has remained unchanged during the whole program, decreasing the use of a biliary tutor in the second stage. Acute arterial thrombosis as the most frequent vascular complication, with other vascular complications rarely encountered. Biliary complications happened in 15.6% of the series, and biliary fistula was the most frequent complication.
We identified a larger loss of patients and grafts in the first month after LT in the first stage, and we saw important improvements in the survival during the last stage due to a decrease in the mortality in the first month. Some of the factors that negative influenced graft and patient survival were stage of LT, HCV-positive recipient serology, emergency need, hepatocarcinoma, high consumption of hemoderivatives, and second transplantations. ACKNOWLEDGMENTS We thank Ángel Bernardos Rodríguez, José Manuel Sousa Martínez, Juan Manuel Pascasio Acevedo, Teresa Ferrer Ríos, Elisa Cordero Matía, Álvaro Giráldez, and Manuel Francisco Porras López.
REFERENCES [1] Starlz TE, Marchiaro TL, Von Kaulla K, et al. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963;117: 659e76. [2] Busuttil RW, Shaked A, Millis JM, et al. One thousand liver transplants. The lessons learned. Ann Surg 1994;219:490e9. [3] Bismuth H, Farges O, Castaing D, et al. Evaluation of results of liver transplantation: experience based on a series of 1052 transplantations. Presse Med 1995;24:1106e14. [4] Wiesner RH, Rakela J, Ishitani MB, et al. Recent advances in liver transplantation. Mayo Clin Proc 2003;78:197e210. [5] López-Navidad A, Caballero F. Extended criteria for organ acceptance. Strategies for achieving organ safety and for increasing organ pool. Clin Transplant 2003;17:308e24. [6] Álamo JM, Olivares C, Jiménez G, et al. Donor characteristics that are associated with survival in liver transplant recipients older than 70 years with grafts. Transplant Proc 2013;45:3633e6. [7] Cuende N, Grande L, Sanjuan F, Cuervas Mons V. Liver transplant with elderly donors. Spanish experience with more than 300 livers donors over 70 years of age. Transplantation 2002;73: 1360. [8] Starlz TE, Hakala TR, Shaw Jr BW, et al. A flexible procedure for multiple cadaveric organ procurement. Surg Gynecol Obstet 1984;158:223e30. [9] Nakazato PZ, Concepcion W, Bry W, et al. Total abdominal evisceration: an en bloc technique for abdominal organ harvesting. Surgery 1992;111:37e47. [10] Figueras J, Llado L, Ramos E, et al. Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study. Liver Transpl 2001;7(10):904e11.