Historical Background of Pediatric Kidney and Liver Transplantation in Turkey.

The cornerstone events of kidney and liver transplant history in Turkey are summarized herein. In 1975, we performed the first pediatric living-related renal transplant in Turkey. We followed this in 1978 with the first deceased donor kidney transplant, using an organ supplied by Eurotransplant. In 1979 the law on harvesting, storage, grafting, and transplant of organs and tissues was enacted; the first local deceased donor kidney transplant was performed by our team in 1979. In 1988, another ground-breaking event in Turkey, the Middle East, and North Africa was successfully achieved: the first successful deceased-donor liver transplant, and in 1990, the first pediatric living-related segmental liver transplant in Turkey, the region and Europe was performed by our team. One month later, an adult-to-adult living-related liver transplant (left lobe) in the World was successfully performed. On May 16, 1992, we performed the first combined liver-kidney transplant from a living-related donor, which was the first operation of its kind in the World. Between November 1975 and January 2022, we have performed 3288 kidney (380 pediatric) at the Hacettepe University Hospitals and later on at Baskent University; since 1988, 701 (334 pediatric) liver transplants have been performed. In over 40 years of kidney and liver transplants history in Turkey, 46876 kidney (2502 pediatric patients) and 18203 liver (2612 pediatric patients) transplants have been performed nationwide. In 2001, the Ministry of Health established the National Coordination Center as an umbrella organization to promote transplant activities, especially for deceased donor organ procurement. Transplant activities are accelerating daily throughout the country, but deceased donors are still far below the desired rates.

Teniente Coronel Médico Profesor Agregado de Cirugía Edgardo Torterolo Prado (1939 ­ 2003), precursor del trasplante hepático en Uruguay / Lieutenant Colonel Medical Attaché Professor of Surgery Edgardo Torterolo Prado (1939 - 2003), precursor of liver transplantation in Uruguay / Tenente Coronel Médico Adido Professor de Cirurgia Edgardo Torterolo Prado (1939 - 2003), precursor do transplante de fígado no Uruguai

Edgardo Gualberto Torterolo Prado, nació en Montevideo el 20 de diciembre de 1939 y falleció en esa ciudad, en la plenitud de su ejercicio profesional, el 31 de julio de 2003. Fueron sus padres Pío Gualberto Torterolo y María Rosaura Prado. Estaba unido en matrimonio con María Elena Minetti (1966) del cual nació su hijo Pablo Daniel un año después. Su vocación lo dirigió hacia la medicina, ingresando a la Facultad oficial en 1959. Luego de su desempeño como practicante interno del Ministerio de Salud Pública (1964-69) obtuvo el título de médico (1968). Se hizo cirujano y en esa especialidad desarrolló dos carreras paralelas: Facultad de Medicina y Servicio de Sanidad Militar.

Edgardo Gualberto Torterolo Prado was born in Montevideo on December 20, 1939 and died in that city, in the fullness of his professional practice, on July 31, 2003. His parents were Pío Gualberto Torterolo and María Rosaura Prado. He was married to María Elena Minetti (1966) and their son Pablo Daniel was born a year later. His vocation directed him towards medicine, entering the official School of Medicine in 1959. After working as an intern at the Ministry of Public Health (1964-69), he obtained his medical degree (1968). He became a surgeon and in that specialty he developed two parallel careers: Medical School and Military Health Service.

Edgardo Gualberto Torterolo Prado nasceu em Montevidéu em 20 de dezembro de 1939 e morreu em Montevidéu, no auge de sua carreira profissional, em 31 de julho de 2003. Seus pais eram Pío Gualberto Torterolo e María Rosaura Prado. Ele foi casado com María Elena Minetti (1966), com quem seu filho Pablo Daniel nasceu um ano mais tarde. Sua vocação o levou à medicina, e ele entrou na Faculdade oficial em 1959. Após trabalhar como estagiário no Ministério da Saúde Pública (1964-69), ele obteve seu diploma de médico (1968). Ele se tornou cirurgião e nessa especialidade desenvolveu duas carreiras paralelas: Faculdade de Medicina e Serviço de Saúde Militar.

Persistent sex disparity in liver transplantation rates.

BACKGROUND: Studies have demonstrated that there are sex disparities in the rate of liver transplantation. However, little is known statistically about whether this disparity is caused by liver compartment size, Model for End-Stage Liver Disease adjustments, or regional differences. METHODS: We use retrospective data from the United Network for Organ Sharing Standard Treatment Analysis and Research data files for liver transplantation from 1995 through 2012. The final sample consists of 150,149 patients. These data contain information on all individuals who registered for the liver transplant waiting list as well as updated outcome data. Linear probability and logistic regression models were both used. RESULTS: Women were 4.8 percentage points less likely to receive a transplant. Adjustment for race, weight, body mass index, region, education, and other characteristics attenuated the sex difference by roughly 19% (from 4.8 to 3.9 percentage points). The disparity was consistent across the 11 United Network for Organ Sharing allocation regions. Comparing the heaviest women to the lightest men, the disparity flipped. Pairwise comparisons between men and women of various sizes suggest that disparities in favor of men increase with the ratio of male-to-female size. CONCLUSION: Our results document persistent sex disparity in liver transplantation, only 19% of which is explained by size differentials between men and women. Differences in rates of transplantation are increasing in the ratio of male-to-female height and weight, suggesting that some of the disparity is explained by differences in liver compartment size.

Trasplante hepático en Chile: pasado, presente y futuro / Hepatic transplantation in Chile: past, present and future

Resumen La donación de órganos en Chile es insuficiente, con una tasa histórica de alrededor de seis donantes por millón de habitantes. Las reformas legales, mejoras organizacionales y campañas comunicacionales han permitido hacer del año 2019 el más exitoso en cuanto a donación de órganos y trasplantes. El trasplante hepático en Chile fue realizado por primera vez en el año 1969 en el Hospital Naval de Valparaíso, falleciendo el receptor precozmente. El primer trasplante exitoso fue realizado en el año 1985 en el Hospital Militar de Santiago. Desde esa fecha hasta la actualidad se han realizado 1.812 trasplantes de hígado, el 43,6% en hospitales universitarios, el 35,1% en clínicas privadas y un 21,5% en hospitales estatales. El 23,1% en la Pontificia Universidad Católica (PUC), el 20,6% en el Hospital Clínico de la Universidad de Chile (HCUCH), el 15,9% en el Hospital Luis Calvo Mackenna (HLCM), el 15,9% en Clínica Las Condes (CLC), el 14,3% en Clínica Alemana de Santiago (CA), el 5,6% en el Hospital del Salvador (HdS), 2% en Clínica Dávila (CD), 2% en el Sanatorio Alemán de Concepción (SA) y 0,9% en Clínica Santa María (CSM) De este total, 455 son en pacientes pediátricos, de ellos 63,3% en Hospital Luis Calvo Mackenna el 21,1% en la Clínica Las Condes el 7,7% en la Pontificia Universidad Católica de Chile, el 6,4% en la Clínica Alemana y 1,5% en el Sanatorio Alemán. Desde el 2015, aproximadamente el 80% de los trasplantes pediátricos se realizan en el HLCM. Sobrevidas reportadas en adultos van del 75% a 85% al año y de 75% a 92% al año en pacientes pediátricos dependiendo el período. Hay centros que nunca han reportado sus resultados. Se espera mejorar la educación en pro de una sociedad proclive en la donación, mejorar la organización de detección, mantención y procuramiento, aumentar la utilización de órganos, potenciar la utilización los de donantes cadáveres, con técnica Split o hígado dividido y, mientras no tengamos un sistema de donación que dé cuenta de las necesidades del país, mantener los programas de donante vivo. Finalmente debe motivarse a generaciones jóvenes para que se dediquen a esta importante actividad.

Organ donation in Chile is insufficient, with a historical rate of six donors per million inhabitants. Legal reforms, organizational improvements, and communications campaigns have made 2019 the most successful year in terms of organ donations and transplants. The first liver transplant in Chile was performed in 1969 at the Naval Hospital in Valparaíso. However, the patient passed away shortly after. The first successful transplant was performed in 1985 at the Militar Hospital in Santiago. As of that date to present day, 1.812 liver transplants have been performed: 43.6% of these in university hospitals, 35.1% in private clinics, and 21.5% in state hospitals. Of these, 23.1% were performed at the Pontificia Universidad Católica de Chile (PUC), 20.6% at the Universidad de Chile Clinical Hospital (HCUCH), 15.9% at the Luis Calvo Mackenna Hospital (HLCM), 15.9% at the Las Condes Clinic (CLC), 14.3% at the Alemana Clinic in Santiago (CA), 5.6% at the del Salvador Hospital (HdS), 2% at the Dávila Clinic (CD), 2% at the Alemán Sanatorium in Concepción (SA), and 0.9% at the Santa María Clinic (CSM). Of this total, 455 correspond to pediatric patients. Of these patients, 63.3% were at the Luis Calvo Mackenna Hospital, 21.1% at the Las Condes Clinic, 7.7% at the Pontificia Universidad Católica de Chile, 6.4% at the Alemana Clinic, and 1.5% at the Alemán Sanatorium. Since 2015, approximately 80% of pediatric transplants are performed at the HLCM. Reported one-year survival range from 75% to 85% in adults and 75% to 92% in pediatric patients per year, depending on the period. Some centers have never reported their results. It is expected that education of a society prone to organ donation improves, as well as improving the detection, maintenance, and procurement of potential donors, increasing the utilization of organs, enhancing the utilization of organs from deceased donors with Split technique, and, while we are building towards a donation system that responds to the needs of the nation, upholding live donor programs. Finally, younger generations are to be motivated so that they dedicate themselves to this important activity.

Challenge to ABO blood type barrier in living donor liver transplantation.

ABO incompatible living donor liver transplantation has the potential to expand the donor pool for patients with end stage liver diseases on the expense of challenges to overcome immunological barriers across blood type. There is a profound impact of age on incidence and severity of antibody mediated rejection (AMR). Even children older than 1 year have chances of AMR; children aged 8 years or older have risks of hepatic necrosis similar to adult liver recipients. The mechanism of AMR is based on circulatory disturbances secondary to inflammation and injury of the vascular endothelium caused by an antibody-antigen-complement reaction. The strategy to overcome ABO blood type barrier is based on both pre-transplant desensitization and adequate treatment of this phenomenon. Nowadays, rituximab is the standard means of desensitization but unfortunately an insufficient aid to treat AMR. Because of low incidence (less than 5% in the rituximab era), in practice of AMR only some case reports about the treatment of clinical AMR are available in the literature. Initial experiences revealed that the proteasome inhibitor, bortezomib might be a promising treatment based on its capacity to deplete plasma cell agents. Although ABO blood type barrier has been counteracted in 95% of patients by applying "rituximab-desensitization", many issues, such as prediction of high-risk patients of infection and AMR and secure treatment strategies for evoked AMR, remain to be resolved.

Solid Organ Transplantation Activities Evolution in Brazil: Analysis of 20 Years.

BACKGROUND: From 1968 until 1997, transplantation-related activities were not properly regulated and were informally practiced. During 20 years, many legal and political changes influenced it. OBJECTIVE: To provide a historical overview of the 20 years with a descriptive data analysis of a 20-year data set. METHODOLOGY: We investigated information from Brazilian Transplantation Reports between 1997 and 2017. In this way, we classified all data into 5 Brazilian macro regions: Center-West, Northeast, North, Southeast, and South. In total, we included 27 states (including Capital District) and limited study to the heart, liver, and kidney. RESULTS: We analyzed 2835 data entries and associated population information from the Brazilian Institute of Geography and Statistics. We observed 2 distinct groups, one uniquely formed by the North region, with figures significantly lower than the remaining regions. After 2003, Southeast, South, and Northeast regions indicated a growing movement, whereas Center-West indicated certain stability in 50 and ranging between 50 and 100 cases (yearly basis) after 2011. Recently (2016 and 2017), the South region indicates another crescendo movement suggesting another detachment from the other regions, but it is something not clearly observed and, if true, should be figured in new reports of Brazilian Association of Organ Transplantation. CONCLUSION: This study identified and observed the time-spatial progress of organ transplantation in Brazil. In conclusion, after analysis of this 20-year data consolidation related to organ transplantation in Brazil, we observed a public investment in implementing quality evaluation and safety to provide figures that deliver visibility to the numbers reported in this article.

Pumping new life into old ideas: Preservation and rehabilitation of the liver using ex situ machine perfusion.

Recent advances in machine perfusion technology have reinvigorated the field of liver transplantation with the possibilities of vastly improving the efficiency and safety of the life-saving procedure. With this improved preservation technology, transplant surgeons are now able to use previously untransplantable donor livers without significantly compromising patient outcomes. Early clinical studies demonstrate the ability to extend preservation times and assess a graft's potential viability using normothermic machine perfusion, in addition to restoring the energy supply in donor livers by supporting metabolism through circulation of vital nutrients and blood-based oxygen carriers. Future endeavors for surgeons and scientists should focus on improving criteria to assess viability, optimizing protocols for perfusion research, investigating mechanisms of poor graft viability, and targeting these mechanisms with novel therapies to improve graft function prior to transplantation. Long-term goals include extending preservation times on the scale of days to weeks, enabling long-distance organ sharing, and establishing regional organ perfusion centers to streamline the procurement, perfusion, and transplantation process.

Liver Transplant in Colombia.

Liver transplantation began in Colombia in 1979. It is one of the most active countries in this field in Latin America but has faced problems with the regulation and appropriate management of solid organ transplantations, including transplant tourism, which is a worldwide problem. There is a well-structured donation and transplant network regulated by the government in all the stages of the process. In 2017, the country was ranked fourth for the number of liver transplantations (LTs) performed in Latin America, after Brazil, Argentina, and Uruguay, with a rate of 5.6 LTs per million population. Current regulatory bodies were created to coordinate and provide transparency and equality to transplant recipients. This article describes the evolution, government commissions, assignation criteria, and current status of LT in Colombia.

Liver transplantation for alcoholic hepatitis.

While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.

History of liver transplantation in Poland.

Experimental research on liver transplantation was introduced in Poland by Waldemar Olszewski with his team. It was in 1972. Not until 15 years later, in 1987, did Stanislaw Zielinski in Szczecin and Marian Pardela in Katowice make an attempt of transplanting liver in humans. In 1989, the attempt was made by Jacek Pawlak and Marek Krawczyk in Warsaw. The first successful liver transplantation in Poland was performed by Piotr Kalicinski at the Children's Memorial Health Institute, Warsaw. Also, in early 1990s the attempts were made by Jerzy Polanski in Warsaw and Piotr Szyber in Wroclaw. In the next years, liver transplantations were connected with three centers in Szczecin and were associated with the following persons: Roman Kostryka, Maciej Wójcicki and Samir Zeaira. In Warsaw, 1994, Jacek Pawlak, Bogdan Michalowicz and Krzysztof Zieniewicz performed another successful liver transplantation. The program started to develop rapidly and is still up and running. In 2000, Wojciech Rowinski and Marek Pacholczyk created another liver transplant center in Warsaw, while in 2005 Lech Cierpka and Robert Król did the same in Katowice. In the following years, liver transplantation was initiated by Maciej Slupski in Bydgoszcz (2017) and Zbigniew Sledzinski in Gdansk (2018). In the developing liver transplant centers, an exceptional contribution was made by Pawel Nyckowski, Jacek Pawlak, Krzysztof Zieniewicz, Waldemar Patkowski, Tadeusz Wróblewski, Rafal Paluszkiewicz, Marek Pacholczyk, Andrzej Chmura, Maciej Kosieradzki and Marek Krawczyk - all employees of the Medical University of Warsaw. In Wroclaw, Dariusz Patrzalek and Pawel Chudoba were very active in the field of liver transplantations. In 1996, the Organizing-Coordinating Center for Transplantation POLTRANSPLANT was brought to life. It was directed by Janusz Walaszewski, then by Roman Danielewicz and Artur Kaminski. In 1999, Piotr Kalicinski and Marek Krawczyk started the program for liver fragment harvesting and transplantation from living donors. Until the end of 2016, 4186 liver transplantations including 314 liver transplants from living donors were performed in Poland. Currently, the active centers are three centers from Warsaw, namely Pediatric Surgery and Transplantation Surgery, Children's Memorial Health Institute; Department of General, Transplant and Liver Surgery, Medical University of Warsaw; Department of General and Transplant Surgery, Medical University of Warsaw. Other active centers include Department of General and Transplant Surgery, Provincial Hospital in Szczecin, Department of General, Vascular and Transplant Surgery, Medical University of Silesia, Katowice, Department of Vascular, General and Transplant Surgery in Wroclaw. Liver transplant programs have also been initiated at the Department of Liver and General Surgery, Bydgoszcz, and Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk.

Current Status and Future Challenges of Liver Transplantation Programs in Chile.

Liver transplantation (LT) was performed for the first time in Chile in 1969, but only since the 1990s has it been systematically performed. Our health system is strongly centralized, which is a severe limitation for the patients who need to be evaluated and subsequently listed. Although proper human and technological resources are available and our results are comparable to international outcomes (overall patient survival at 1, 5, and 10 years of 82%, 70%, and 64%, respectively), we are limited because of a severe scarcity of grafts, which translates into an availability of approximately 7 organs per million persons and a wait-list dropout rate of 40% every year. Thus, our main challenge for the next few years is to improve access to LT among the populations from the extreme regions of the country and overall to improve the availability of grafts by increasing the awareness of physicians in intensive care units and emergency departments, to develop living donor LT programs, to educate the population in order to decrease family refusal, and to reinforce the system of potential donor detection. Although hard work is mandatory for these improvements, none of these tasks seem to be unreachable in the midterm.

Liver Transplantation Today: Where We Are Now and Where We Are Going.

Liver transplantation was made a reality through the bravery, innovation, and persistence of Dr. Thomas Starzl. His death in 2017, at the age of 90, makes us pause to consider how far the field has come since its inception by this remarkable pioneer. It also is an opportunity to evaluate the continued novel innovations which contribute to the growth and potential for liver transplantation in the future. The liver transplant community in 2017 continued to be most significantly challenged by an overwhelming disparity between the need for liver transplant and the shortage of donor organs. The many ways in which this critical shortage are being addressed are examined in this article. The continued debate about equitable and efficacious organ allocation, "the liver wars," has dominated much of the recent past, while efforts to optimize current organ availability have also been aggressively pursued. Efforts to optimize the use of marginal and expanded criteria organs have escalated in recent years and have been accompanied by rigorous scientific evaluation. The ongoing opioid epidemic, combined with the approval and availability of highly effective hepatitis C treatment options, has allowed the increased use of HCV positive organs in HCV positive and negative recipients. Machine perfusion, both cold and warm, has moved solidly into the liver transplant world potentiating optimization of marginal donors and also offering potential modulation of liver grafts (ie, gene therapy, stem cell therapy, and defatting). Finally, pharmacological and mechanical interventions in DCD procurement techniques have contributed to improved outcomes in DCD transplants. All of these are explored in this article as a tribute to innovative spirit of Dr. Starzl and his continued impact on liver transplant today.