RESUMO Contexto: A Síndrome Hepatorrenal (SHR) é a forma mais grave de lesão renal aguda em pacientes com cirrose avançada, estando diretamente associada a alta taxa de mortalidade. Normalmente é diagnosticada seguindo critérios definidos pela International Ascites Club (IAC). Atualmente, as terapias farmacológicas mais indicadas no tratamento da SHR são a combinação de vasoconstritores esplâncnicos (terlipressina ou norepinefrina) associados à albumina. Com o aumento progressivo dos gastos em saúde, torna-se relevante realizar uma análise de custo-efetividade do tratamento farmacológico em pacientes com diagnóstico de SHR. Objetivo: Realizar avaliação de custo-efetividade do uso da terlipressina associada à albumina no tratamento da SHR em pacientes com cirrose. Métodos: Avaliação econômica de custo-efetividade, com base em dados secundários de estudos publicados com resultado da eficácia da terapia com terlipressina, em comparação com norepinefrina combinada com albumina ou apenas albumina. A análise de custo-efetividade foi calculada usando a razão de custo-efetividade incremental (RCEI) e uma análise de sensibilidade foi desenvolvida variando os valores das terapias e probabilidades. O real foi a moeda utilizada na análise. Resultados: Após a seleção, elegibilidade e avaliação da qualidade das publicações, os resultados demonstraram que a administração da associação de terlipressina ou norepinefrina com albumina em pacientes diagnosticados com SHR tipo 1 possui eficácia comprovada. Os custos do tratamento com a terapia combinada de terlipressina com albumina foram de USD $1,644.06, administração de somente albumina USD $912.02 e norepinefrina mais albumina USD $2,310.78. Considerando as terapias combinadas com efetividade terapêutica comprovada, isto é, terlipressina e norepinefrina associada a albumina, o custo incremental foi de USD $666.73 e efetividade de 0,570 para o grupo da terlipressina associada a albumina e de 0,200 para o grupo da norepinefrina associada a albumina. A efetividade incremental foi de 0,370 e o valor da RCEI foi de USD $1,801.97. Assim, os fatores de incremento do custo por terapia e razão de custo-efetividade incremental definem que a terapia combinada de terlipressina mais albumina é custo efetiva quando comparada a administração de somente albumina ou norepinefrina no cenário do sistema único de saúde. Conclusão: O estudo demonstrou por meio de uma análise de custo-efetividade que a terlipressina associada à albumina quando administrada concomitantemente a pacientes com diagnóstico de SHR tipo 1 é custo-efetiva quando comparada à albumina sozinha e com norepinefrina associada à albumina administrada em um ambiente controlado.

ABSTRACT Background Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. Objective: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. Methods: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. Results: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. Conclusion: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.

SUMMARY OBJECTIVE: A survey among medical students in a Brazilian public university was performed to investigate the acceptance of organ donation in Brazil, particularly donation after circulatory death (DCD). METHODS: A questionnaire including 26 objectives and Likert scale questions was validated and sent to all medical students of our institution. The answers were analyzed considering the whole set of individuals as well as by dividing the medical students into two groups: less graduated students and more graduated students. RESULTS: From 1050 students, 103 spontaneous answers (9.8%) were retrieved after 3 weeks. A total of 89.3% agreed totally with deceased donor organ donation and 8.7% agreed partially. However, only 50.5% of the students agreed totally and 31.1% agreed partially to living donation. Students revealed that 82.6% know the concept of brain death. On the other hand, 71.8% of them declared not knowing the concept of planned withdrawal of life-sustaining therapy, mainly cardiorespiratory support. A total of 85.4% of students agreed totally with donation after brain death and 11.7% agreed partially. However, when questioned about donation in awaiting circulatory death after a planned withdrawal of life-sustaining therapy, only 18.4% agreed totally and 32% agreed partially. Both groups of less and more graduated students showed similar results. CONCLUSIONS: Our study found a clear lack of information and consequently in acceptance of DCD. Education in the field of end-of-life management may improve not only the acceptance of DCD donation but also the whole understanding of planned withdrawal of life-sustaining therapy.

RESUMO - RACIONAL: O câncer colorretal é a terceira neoplasia mais frequente e metade dos pacientes desenvolvem metástase hepática. O melhor fator prognóstico na metástase hepática de câncer colorretal (MHCCR) é a possibilidade de ressecção com margens livres, porém a maioria permanece irressecável. O racional em realizar transplante hepático (TH) em pacientes portadores de MHCCR está na ampliação do número de pacientes ressecáveis através de uma hepatectomia total. OBJETIVO: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com MHCCR irressecável. MÉTODO: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela Universidade de Oslo. A elaboração foi dividida em 4 etapas. RESULTADO: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. CONCLUSÃO: Foi possível elaborar protocolo de transplante hepático para MHCCR irressecável a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

ABSTRACT - BACKGROUND: Colorectal cancer (CRC) is the third most common neoplasm, and half of the patients with CRC develop liver metastasis. The best prognostic factor for colorectal liver metastasis (CRLM) is the possibility of performing a resection with free margins; however, most of them remain unresectable. The justification for performing liver transplantation (LT) in patients with CRLM regards an increase in the number of resectable patients by performing total hepatectomy. AIM: The aim of this study was to provide a Brazilian protocol for LT in patients with unresectable CRLM. METHOD: The protocol was carried out by two Brazilian institutions, which perform a large volume of resections and LTs, based on the study carried out at the University of Oslo. The elaboration of the protocol was conducted in four stages. RESULT: A protocol proposal for this disease is presented, which needs to be validated for clinical use. CONCLUSION: The development of an LT protocol for unresectable CRLM aims to standardize the treatment and to enable a better evaluation of surgical results.

RESUMO Racional: O colangiocarcinoma hilar representa mais da metade de todos os casos de colangiocarcinoma; tem prognóstico reservado e sobrevida global mediana de 12- 24 meses após o diagnóstico. A proposta de realizar transplante hepático surgiu para ampliar a possibilidade de margens livres através de hepatectomia total nos portadores de tumoresirressecáveis com melhor prognóstico. Objetivo: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com colangiocarcinoma hilar. Método: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela MayoClinic. A elaboração foi dividida em quatro etapas. Resultado: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. Conclusão: Foi possível elaborar protocolo de transplante hepático para colangiocarcinoma a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

ABSTRACT Background: Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy. Aim: To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma. Method: The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages. Result: A protocol proposal for this disease is presented, which needs to be validated for clinical use. Conclusion: The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.

RESUMO CONTEXTO: O período pré-transplante é complexo e inclui grande quantidade de procedimentos. A gravidade da doença hepática predispõe a um alto número de internações e procedimentos de alto custo. Estudos em avaliação econômica são uma importante ferramenta para o manejo dos custos em lista de espera para o transplante hepático. OBJETIVO: O objetivo do presente estudo foi avaliar o custo total do paciente em lista de espera para o transplante hepático e os principais recursos relacionados ao alto custo. MÉTODOS: Foi realizado um estudo de coorte em 482 pacientes registrados em lista de espera para o transplante hepático. Os pacientes foram acompanhados por um período de 24 meses, no qual foram avaliados todos os custos de materiais, medicamentos, consultas, procedimentos internações, exames laboratoriais e de imagem, reposição de hemocomponentes e nutrição recebida. A quantidade total de cada recurso e componente utilizado foi obtida e multiplicada pelo seu valor unitário e, desta maneira, o custo individual de cada paciente foi obtido. RESULTADOS: O total gasto pelos 482 pacientes foi de US$ 6.064.986,51. Os custos ambulatoriais corresponderam a 32,4% do total (US$ 1.965.045,52) e os custos em internação corresponderam a 67,6% do total (US$ 4.099.940,99). Os principais determinantes do custo em ambulatório foram: medicamentos (44,31%) e exames laboratoriais e de imagem (31,68%). Os principais determinantes de custo em internações foram: medicamentos (35,20%), utilização do leito em enfermaria e em UTI (26,38%) e exames laboratoriais (13,72%) Pacientes com valores de MELD entre 25-30 foram os de maiores custos em lista de espera (US$ 16.686,74 ± 16,105.02) e os de menor custo foram os pacientes com MELD abaixo de 17 (US$ 5.703,22 ± 9.318,68). CONCLUSÃO: O custo total em lista de espera para o transplante hepático aumenta de acordo com a gravidade do paciente. Individualmente, internações, reposição de hemocomponentes e o tratamento do paciente com carcinoma hepatocelular são os principais determinantes de custo para os pacientes em lista de espera para o transplante hepático. Quanto maior o tempo de espera, maiores serão os custos em lista, causando maior impacto nos sistemas de saúde.

ABSTRACT BACKGROUND: The pre-transplant period is complex and includes lots of procedures. The severity of liver disease predisposes to a high number of hospitalizations and high costs procedures. Economic evaluation studies are important tools to handle costs on the waiting list for liver transplantation. OBJECTIVE: The objective of the present study was to evaluate the total cost of the patient on the waiting list for liver transplantation and the main resources related to higher costs. METHODS: A cost study in a cohort of 482 patients registered on waiting list for liver transplantation was carried out. In 24 months follow-up, we evaluated all costs of materials, medicines, consultations, procedures, hospital admissions, laboratorial tests and image exams, hemocomponents replacements, and nutrition. The total amount of each resource or component used was aggregated and multiplied by the unitary cost, and thus individual cost for each patient was obtained. RESULTS: The total expenditure of the 482 patients was US$ 6,064,986.51. Outpatient and impatient costs correspond to 32.4% of total cost (US$ 1,965,045.52) and 67.6% (US$ 4,099,940.99) respectively. Main cost drivers in outpatient were: medicines (44.31%), laboratorial tests and image exams (31.68%). Main cost drivers regarding hospitalizations were: medicines (35.20%), bed use in ward and ICU (26.38%) and laboratorial tests (13.72%). Patients with MELD score between 25-30 were the most expensive on the waiting list (US$ 16,686.74 ± 16,105.02) and the less expensive were those with MELD below 17 (US$ 5,703.22 ± 9,318.68). CONCLUSION: Total costs on the waiting list for liver transplantation increased according to the patient’s severity. Individually, hospitalizations, hemocomponents reposition and hepatocellular carcinoma treatment were the main cost drivers to the patient on the waiting list. The longer the waiting time, the higher the total cost on list, causing greater impact on health systems.

OBJECTIVES: Although liver transplantation procedures are common and highly expensive, their cost structure is still poorly understood. This study aimed to develop models of micro-costs among patients undergoing liver transplantation procedures while comparing the role of individual clinical predictors using tree regression models. METHODS: We prospectively collected micro-cost data from patients undergoing liver transplantation in a tertiary academic center. Data collection was conducted using an Intranet registry integrated into the institution’s database for the storing of financial and clinical data for transplantation cases. RESULTS: A total of 278 patients were included and accounted for 300 procedures. When evaluating specific costs for the operating room, intensive care unit and ward, we found that in all of the sectors but the ward, human resources were responsible for the highest costs. High cost supplies were important drivers for the operating room, whereas drugs were among the top four drivers for all sectors. When evaluating the predictors of total cost, a MELD score greater than 30 was the most important predictor of high cost, followed by a Donor Risk Index greater than 1.8. CONCLUSION: By focusing on the highest cost drivers and predictors, hospitals can initiate programs to reduce cost while maintaining high quality care standards.

Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

CONTEXTO E OBJETIVO:Dados sobre os custos do seguimento ambulatorial pós-transplante de fígado são escassos no Brasil. O objetivo do presente estudo foi estimar os custos diretos médicos do seguimento ambulatorial pós-transplante de fígado a partir da primeira visita ambulatorial pós-transplante até cinco anos após o transplante.TIPO DE ESTUDO E LOCAL:Estudo de descrição de custos realizado em um hospital universitário em São Paulo, Brasil.MÉTODOS:Dados de custos estavam disponíveis para 20 adultos que foram submetidos a transplante de fígado devido a insuficiência hepática aguda (IHA) de 2005 a 2009. Os dados foram retrospectivamente obtidos em prontuários médicos e no sistema de informação contábil hospitalar de dezembro de 2010 a janeiro de 2011.RESULTADOS:A média de custo por paciente/ano foi de R$ 13.569 (US$ 5.824). O primeiro ano de acompanhamento foi o mais caro, R$ 32.546 (US$ 13,968), e medicação foi o principal impulsionador dos custos totais, respondendo por 85% dos custos totais no período de cinco anos e 71,9% dos custos totais do primeiro ano. No segundo ano pós-transplante, os custos médios totais foram cerca da metade do montante de custos do primeiro ano (R$ 15.165 ou US$ 6,509). Medicação foi o maior contribuinte para os custos seguido da internação, no período de cinco anos. No quarto ano, os custos dos testes diagnósticos superam os custos de internação.CONCLUSÃO:Esta análise proporciona uma compreensão significativa dos custos do seguimento ambulatorial pós-transplante de fígado por IHA e a participação de cada componente de custo no cenário brasileiro.

CONTEXT AND OBJECTIVE:Data on the costs of outpatient follow-up after liver transplantation are scarce in Brazil. The purpose of the present study was to estimate the direct medical costs of the outpatient follow-up after liver transplantation, from the first outpatient visit after transplantation to five years after transplantation.DESIGN AND SETTING:Cost description study conducted in a university hospital in São Paulo, Brazil.METHODS:Cost data were available for 20 adults who underwent liver transplantation due to acute liver failure (ALF) from 2005 to 2009. The data were retrospectively retrieved from medical records and the hospital accounting information system from December 2010 to January 2011.RESULTS:Mean cost per patient/year was R$ 13,569 (US$ 5,824). The first year of follow-up was the most expensive (R$ 32,546 or US$ 13,968), and medication was the main driver of total costs, accounting for 85% of the total costs over the five-year period and 71.9% of the first-year total costs. In the second year after transplantation, the mean total costs were about half of the amount of the first-year costs (R$ 15,165 or US$ 6,509). Medication was the largest contributor to the costs followed by hospitalization, over the five-year period. In the fourth year, the costs of diagnostic tests exceeded the hospitalization costs.CONCLUSION:This analysis provides significant insight into the costs of outpatient follow-up after liver transplantation due to ALF and the participation of each cost component in the Brazilian setting.