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1.
Liver Transpl ; 29(7): 683-697, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37029083

RESUMO

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Fatores de Risco , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Recidiva
2.
Liver Transpl ; 29(1): 34-47, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630156

RESUMO

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Fatores de Risco
3.
Mol Ther Methods Clin Dev ; 28: 190-207, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36700123

RESUMO

Viral replication places oncolytic viruses (OVs) in a unique niche in the field of drug pharmacokinetics (PK) as their self-amplification obscures exposure-response relationships. Moreover, standard bioanalytical techniques are unable to distinguish the input from replicated drug products. Here, we combine two novel approaches to characterize PK and biodistribution (BD) after systemic administration of vesicular stomatitis virus pseudotyped with lymphocytic choriomeningitis virus glycoprotein (VSV-GP) in healthy mice. First: to decouple input drug PK/BD versus replication PK/BD, we developed and fully characterized a replication-incompetent tool virus that retained all other critical attributes of the drug. We used this approach to quantify replication in blood and tissues and to determine its impact on PK and BD. Second: to discriminate the genomic and antigenomic viral RNA strands contributing to replication dynamics in tissues, we developed an in situ hybridization method using strand-specific probes and assessed their spatiotemporal distribution in tissues. This latter approach demonstrated that distribution, transcription, and replication localized to tissue-resident macrophages, indicating their role in PK and BD. Ultimately, our study results in a refined PK/BD profile for a replicating OV, new proposed PK parameters, and deeper understanding of OV PK/BD using unique approaches that could be applied to other replicating vectors.

4.
JAMA Surg ; 156(11): 1051-1057, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34495291

RESUMO

Importance: Acuity circles (AC) liver allocation policy was implemented to eliminate donor service area geographic boundaries from liver allocation and to decrease variability in median Model of End-stage Liver Disease (MELD) score at transplant and wait list mortality. However, the broader sharing of organs was also associated with more flights for organ procurements and higher costs associated with the increase in flights. Objective: To determine whether the costs associated with liver acquisition changed after the implementation of AC allocation. Design, Setting, and Participants: This single-center cost comparison study analyzed fees associated with organ acquisition before and after AC allocation implementation. The cost data were collected from a single transplant institute with 2 liver transplant centers, located 30 miles apart, in different donation service areas. Cost, recipient, and transportation data for all cases that included fees associated with liver acquisition from July 1, 2019, to October 31, 2020, were collected. Exposures: Primary liver offer acceptance with associated organ procurement organization or charter flight fees. Main Outcomes and Measures: Specific fees (organ acquisition, surgeon, import, and charter flight fees) and total fees per donor were collected for all accepted liver donors with at least 1 associated fee during the study period. Results: Of 213 included donors, 171 were used for transplant; 90 of 171 (52.6%) were male, and the median (interquartile range) age of donors was 41.0 (30.0-52.8) years in the pre-AC period and 36.9 (24.0-48.8) years in the post-AC period. There was no significant difference in the post-AC compared with pre-AC period in median (range) MELD score (24 [8-40] vs 25 [6-40]; P = .27) or median (range) match run sequence (15 [1-3951] vs 10 [1-1138]; P = .31), nor in mean (SD) distance traveled (155.83 [157.00] vs 140.54 [144.33] nautical miles; P = .32) or percentage of donors requiring flights (58.5% [69 of 118] vs 56.8% [54 of 95]; P = .82). However, costs increased significantly in the post-AC period: total cost increased 16% per accepted donor (mean [SD] of $52 966 [13 278] vs $45 725 [9300]; P < .001) and 55% per declined donor (mean [SD] of $15 865 [3942] vs $10 217 [4853]; P < .001). Contributing factors included more than 2-fold increases in the proportions of donors incurring import fees (31.4% [37 of 118] vs 12.6% [12 of 95]; P = .002) and surgeon fees (19.5% [23 of 118] vs 9.5% [9 of 95]; P = .05), increased acquisition fees (10% increase; mean [SD] of $43 860 [3266] vs $39 980 [2236]; P < .001), and increased flight expenses (43% increase; mean [SD] of $12 904 [6066] vs $9049 [5140]; P = .002). Conclusions and Relevance: The unintended consequences of implementing broader sharing without addressing organ acquisition fees to account for increased importation between organ procurement organizations must be remedied to contain costs and ensure viability of transplant programs.


Assuntos
Doença Hepática Terminal/cirurgia , Honorários e Preços , Política de Saúde/economia , Obtenção de Tecidos e Órgãos/economia , Adulto , Custos e Análise de Custo , Doença Hepática Terminal/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Seleção de Pacientes , Listas de Espera , Adulto Jovem
5.
Clin Nephrol ; 96(1): 47-50, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33960298

RESUMO

Serum sickness is an immune-complex-mediated hypersensitivity reaction that was first noted in the early 1900s in patients receiving heterologous antisera, such as horse antitetanus or antidiphtheria serum. This condition is primarily self-limited; however, in its acute state, it can cause severe symptoms of fever, rash, polyarthritis, or polyarthralgias. In solid organ transplantation, this condition is frequently reported in association with the use of rabbit anti-thymocyte globulin and chimeric murine monoclonal antibodies such as rituximab. Alemtuzumab, designed as a humanized monoclonal antibody against CD52, is expected to be less immunogenic. Here, we report a case of serum sickness associated with alemtuzumab induction therapy in a kidney-pancreas dual-organ recipient.


Assuntos
Alemtuzumab/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Transplante de Rim , Transplante de Pâncreas , Doença do Soro , Humanos , Doença do Soro/induzido quimicamente , Doença do Soro/diagnóstico
6.
Clin Transplant ; 35(7): e14331, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33914373

RESUMO

Non-contrast pelvic computed tomography (CT) can detect severe iliac artery calcifications that present technical contraindications to kidney transplantation (TCT). We screened 454 asymptomatic patients with a history of any of the following: hemodialysis >10 years, diabetes mellitus >20 years, coronary artery disease (CAD) with percutaneous or surgical interventions, carotid disease, diabetes with below-/above-knee amputations, and heart-kidney transplantation candidacy. Patients with normal dorsalis pedis and/or tibialis posterior pulses were not screened. A total of 8.4% had severe calcifications with TCT; CT determined laterality for implantation in 13.9%. No patients with the following characteristics were classified as TCT: age <40 years, hemodialysis >10 years, carotid arterial disease, prior lower extremity amputation, or heart-kidney transplantation candidacy. CAD was associated with TCT in univariate though not multivariate analysis. Limiting screening to patients >40 years, with DM >20 years, or with CAD, 9.8% had a TCT and CT determined transplant laterality in 14.2%. Screening for severe iliac artery calcifications is useful for selected kidney transplantation candidates over age 40. It can assist with laterality choice or surgeon determination of TCT. Cost and radiation exposure risks should be weighed against the morbidity risks from unnecessary surgery.


Assuntos
Doença da Artéria Coronariana , Transplante de Rim , Adulto , Humanos , Programas de Rastreamento , Diálise Renal , Tomografia Computadorizada por Raios X
7.
Transplantation ; 105(1): 225-230, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32150040

RESUMO

BACKGROUND: Uterus transplantation is a treatment for absolute uterine infertility and can be performed with living and deceased donors. Given the safety and increased utilization of robotic assistance with other gynecologic and transplant donor operations, we adopted a robot-assisted approach to donor hysterectomy. This study compared early outcomes and morbidity of the robot-assisted approach to donor hysterectomy with the traditionally performed open approach and addressed whether the robot-assisted approach is safe and offers advantages for the donor. METHODS: Our institution has performed 18 living donor hysterectomies for uterus transplantation. This retrospective review compared the last 5 cases utilizing a robot-assisted technique and vaginal extraction of the uterus graft with the first 13 cases performed with an open laparotomy technique. Demographic, intraoperative, and postoperative data were examined. RESULTS: There were no differences between the robot-assisted and the open living donor group with respect to age, body mass index, or gynecological history. Although the median operative time was shorter for the open approach (6.27 versus 10.46 h), the donors' median estimated blood loss, length of hospital stay, and length of sick leave were less with the robot-assisted approach. There was no conversion to open hysterectomy in the robot-assisted cases, and the incidence of complications was similar between the 2 groups. There was no difference in early graft function. CONCLUSIONS: These preliminary results show that robot-assisted living donor hysterectomy is feasible and safe for the donors; it allows a faster postoperative recovery and the same early graft function.


Assuntos
Histerectomia , Doadores Vivos , Procedimentos Cirúrgicos Robóticos , Útero/transplante , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Histerectomia/efeitos adversos , Tempo de Internação , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Licença Médica , Texas , Fatores de Tempo , Resultado do Tratamento
8.
Liver Transpl ; 27(5): 684-698, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33306254

RESUMO

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia
9.
Ann Surg ; 272(3): 411-417, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657928

RESUMO

OBJECTIVE: We report the results of the first 20 uterus transplants performed in our institution. SUMMARY BACKGROUND DATA: Uterus transplantation (UTx) aims at giving women affected by absolute uterine-factor infertility the possibility of carrying their own pregnancy. UTx has evolved from experimental to an established surgical procedure. METHODS: The Dallas Uterus Transplant Study (DUETS) program started in 2016. The uterus was transplanted in orthotopic position with vascular anastomoses to the external iliac vessels and removed when 1 or 2 live births were achieved. Immunosuppression lasted only for the duration of the uterus graft. RESULTS: Twenty women, median age 29.7 years, enrolled in the study, with 10 in phase 1 and 10 in phase 2. All but 2 recipients had a congenital absence of the uterus. Eighteen recipients received uteri from living donors and 2 from deceased donors. In phase 1, 50% of recipients had a technically successful uterus transplant, compared to 90% in phase 2. Four recipients with a technical success in phase 1 have delivered 1 or 2 babies, and the fifth recipient with a technical success is >30 weeks pregnant. In phase 2, 2 recipients have delivered healthy babies and 5 are pregnant. CONCLUSIONS: UTx is a unique type of transplant; whose only true success is a healthy child birth. Based on results presented here, involving refinement of the surgical technique and donor selection process, UTx is now an established solution for absolute uterine-factor infertility.


Assuntos
Seleção do Doador/métodos , Fertilidade/fisiologia , Infertilidade Feminina/cirurgia , Doadores Vivos , Transplante de Órgãos/métodos , Útero/transplante , Adulto , Feminino , Seguimentos , Humanos , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Hepatology ; 72(6): 2014-2028, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32124453

RESUMO

BACKGROUND AND AIMS: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.


Assuntos
Técnicas de Ablação/métodos , Carcinoma Hepatocelular/terapia , Doença Hepática Terminal/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Técnicas de Ablação/estatística & dados numéricos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/patologia , Feminino , Seguimentos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/efeitos da radiação , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Obtenção de Tecidos e Órgãos/normas , Carga Tumoral/efeitos da radiação , Estados Unidos/epidemiologia , Listas de Espera/mortalidade
11.
Ann Surg ; 271(4): 616-624, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30870180

RESUMO

OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Carcinoma Hepatocelular/cirurgia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Carga Tumoral , Estados Unidos
12.
Liver Transpl ; 24(8): 1011-1018, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29637692

RESUMO

Bile duct size discrepancy in liver transplantation may increase the risk of biliary complications (BCs). The aim of this study was to evaluate the safety and outcomes of the eversion bile duct anastomosis technique in deceased donor liver transplantation (DDLT) with duct-to-duct anastomosis. A total of 210 patients who received a DDLT with duct-to-duct anastomosis from 2012 to 2017 were divided into 2 groups: those who had eversion bile duct anastomosis (n = 70) and those who had standard bile duct anastomosis (n = 140). BC rates were compared between the 2 groups. There was no difference in the cumulative incidence of biliary strictures (P = 0.20) and leaks (P = 0.17) between the 2 groups. The BC rate in the eversion group was 14.3% and 11.4% in the standard anastomosis group. All the BCs in the eversion group were managed with endoscopic stenting. A severe size mismatch (≥3:1 ratio) was associated with a significantly higher incidence of biliary strictures (44.4%) compared with a 2:1 ratio (8.2%; P = 0.002). In conclusion, the use of the eversion technique is a safe alternative for bile duct discrepancy in DDLT. However, severe bile duct size mismatch may be a risk factor for biliary strictures with such a technique.


Assuntos
Ductos Biliares/cirurgia , Endoscopia do Sistema Digestório/instrumentação , Transplante de Fígado/métodos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Ductos Biliares/anatomia & histologia , Ductos Biliares/patologia , Estudos de Casos e Controles , Criança , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Endoscopia do Sistema Digestório/métodos , Feminino , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de Risco , Stents , Resultado do Tratamento , Adulto Jovem
13.
Am J Surg ; 216(2): 331-336, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28859922

RESUMO

BACKGROUND: To assess the impact of participation of multiorgan procurement (MP) by general surgery (GS) residents on surgical knowledge and skills, a prospective cohort study of GS residents during transplant surgery rotation was performed. METHODS: Before and after participation in MPs, assessment of knowledge was performed by written pre and post tests and surgical skills by modified Objective Structured Assessment of Technical Skill (OSATS) score. Thirty-nine residents performed 84 MPs. RESULTS: Significant improvement was noted in the written test scores (63.3% vs 76.7%; P < 0.001). Better surgical score was associated with female gender (15.4 vs 13.3, P = <0.01), prior MP experience (16.2 vs 13.7, P = 0.03), and senior level resident (15.1 vs 13.0, P = 0.03). Supraceliac aortic dissection (P = 0.0017) and instrument handling (P = 0.041) improved with more MP operations. CONCLUSIONS: Participation in MP improves residents' knowledge of abdominal anatomy and surgical technique.


Assuntos
Abdome/cirurgia , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Cirurgia Geral/educação , Internato e Residência , Transplante de Órgãos/educação , Obtenção de Tecidos e Órgãos/métodos , Adulto , Avaliação Educacional/métodos , Feminino , Humanos , Masculino , Estudos Prospectivos
14.
Ann Surg ; 266(3): 525-535, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28654545

RESUMO

OBJECTIVE: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013). RESULTS: Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044). CONCLUSIONS: Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
15.
Proc (Bayl Univ Med Cent) ; 27(4): 346-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25484508

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication associated with the transplant recipient. We chronicle a case of PTLD in a failed graft presenting as a small bowel obstruction in a pancreas-only transplant patient. While typical symptoms may be elusive in the complex immunosuppressed patient, graft pain along with persistent graft pancreatitis and a positive Epstein-Barr viremia should raise suspicion for an underlying PTLD.

16.
Rev. MED ; 21(1): 46-53, ene.-jun. 2013. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-700585

RESUMO

Introducción: el manejo del dolor debe ser adaptado y optimizado de acuerdo con las condiciones de cada hospital, tipo de cirugía y paciente. Objetivos: ealuar la percepción del dolor de los pacientes intervenidos en el postoperatorio del Hospital Universitario San Jorge de Pereira. Materiales y métodos: Se realizó un estudio de corte, prospectivo en pacientes mayores de 18 años entre 2 de septiembre y 28 de octubre de 2011. La valoración de intensidad del dolor postoperatorio se realizó mediante Escala Visual Analógica a las 24 horas del postquirúrgico. Se consideraron variables sociodemográficas, clínicas (tipo de cirugía, anestesia, riesgo) y farmacológicas (medicamentos empleados, dosis, intervalos dosificación). El análisis se hizo con SPSS 20.0 para Windows. Resultados: Se evaluaron 153 pacientes en postoperatorio, 80 (52,3%) mujeres y 73 (47,7%) hombres, con edad promedio de 47,6 ± 20,2 años. El 38,8% de los pacientes no tenía controlado el dolor. Las variables de cirugía ortopédica, el empleo de anestesia general por vía intravenosa, y el incumplimiento de los intervalos recomendados de dosificación de los analgésicos, se asociaron de manera estadísticamente significativa con la falta de control. Discusión: El control del dolor fue inadecuado haciendo evidente la necesidad de replantear su manejo ajustado a guías de práctica clínica, formalizando el uso de medicamentos, en dosis e intervalos adecuados que garanticen una analgesia efectiva.


Introduction: Pain management should be adapted and optimized according to the conditions of each hospital, type of surgery and patient. Objectives: To evaluate the perception of pain in postoperative patients at Hospital Universitario San Jorge of Pereira. Materials and methods: A descriptive observational study in patients older than 18 years, between September 2nd to October 28, 2011. The assessment of postoperative pain intensity was performed by visual analogue scale 24 hours after surgery. We considered socio-demographic, clinical (type of surgery, anesthesia, risk) and pharmacological variables (drugs used, dosage, dosage intervals). The analysis was done with SPSS 20.0 for Windows. Results: We evaluated 153 patients in the postoperative period, 80 (52.3%) women and 73 (47.7%) males, mean age 47.6 ± 20.2 years. 38.8% of patients did not obtain pain control. The variables of orthopedic surgery, the use of intravenous general anesthesia, and suboptimal dosage was statistically significantly associated with lack of control. Conclusions: Pain control was inadequate thus showing the need to redefine its management by following clinical practice guidelines, through the use of analgesics in doses and appropriate intervals.


Introdução: o manejo da dor deve ser adaptado e otimizado de acordo com as condições de cada hospital, tipo de cirurgia e paciente. Objetivos: avaliar a percepção da dor dos pacientes intervindos no pós operatório do Hospital Universitário San Jorge de Pereira. Materiais e métodos: Realizou-se um estudo de corte, prospectivo em pacientes maiores de 18 anos entre 2 de setembro e 28 de outubro de 2011. A valoração de intensidade da dor pós-operatória se realizou mediante Escala Visual Analógica às 24 horas do pós-cirúrgico. Consideraram-se variáveis sociodemográficas, clínicas (tipo de cirurgia, anestesia, risco) e farmacológicas (medicamentos empregados, doses, intervalos, dosagem). A análise se fez com SPSS 20.0 para Windows. Resultados: Se avaliaram 153 pacientes em pós-operatório, 80 (52,3%) mulheres e 73 (47,7%) homens, com idade média de 47,6 ± 20,2 anos. O 38,8% dos pacientes não tinha controlada a dor. As variáveis de cirurgia ortopédica, o emprego de anestesia geral por via intravenosa, e o descumprimento dos intervalos recomendados de dosagem dos analgésicos, se associaram de maneira estatisticamente significativa com a falta de controle. Discussão: O controle da dor foi inadequado fazendo evidente a necessidade de repensar o seu manejo ajustado a guias de prática clínica, formalizando o uso de medicamentos, em doses e intervalos adequados que garantam uma analgesia efetiva.


Assuntos
Humanos , Adulto , Dor Pós-Operatória , Guia de Prática Clínica , Colômbia , Analgésicos Opioides , Anti-Inflamatórios
17.
Clin Transplant ; 27(2): 311-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23351129

RESUMO

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre-transplant locoregional therapy (LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty-five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha-fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five-yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre-transplant LRT did not affect post-transplant outcomes in patients meeting Milan criteria but did result in lower three-yr HCC recurrence (7% vs. 75%, p < 0.001) and better three-yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre-transplant LRT are important factors that determine the post-transplant outcomes in patients with HCC who meet R4T3 criteria.


Assuntos
Carcinoma Hepatocelular/terapia , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Transplante de Fígado , Terapia Neoadjuvante , Adulto , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
18.
Liver Transpl ; 18(4): 455-60, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22139972

RESUMO

Whether a positive crossmatch result has any relevance to liver transplantation (LT) outcomes remains controversial. We assessed the impact of a positive crossmatch result on patient and graft survival and posttransplant complications. During a 20-year period, 2723 LT procedures with crossmatch results were identified: 2479 primary transplants and 244 retransplants. The rates of positive B cell and T cell crossmatches were 10.1% and 7.4%, respectively, for primary transplants and 14.6% and 6.4%, respectively, for retransplants (P = 0.049 for a B cell crossmatch). Across all primary transplants, females (P < 0.001) and patients with autoimmune hepatitis (P < 0.001) had greater frequencies of positive crossmatches. There was no effect from race or age. For both primary transplants and retransplants, patient survival and graft survival were not affected by the presence of a positive crossmatch. With respect to posttransplant complications, there were no differences in rejection episodes (hyperacute, acute, or chronic) or technical complications (biliary and vascular) between negative and positive crossmatch groups. However, there were significant differences in the pathological findings of preservation injury (PI) on liver biopsy samples taken at the time of transplantation and within the first week of transplantation (P = 0.003 for B cells and P = 0.03 for T cells). In summary, a positive crossmatch had no significant impact on patient survival or graft outcomes. However, there was a significantly higher incidence of PI in primary LT recipients with a positive crossmatch. This finding is important for a broader understanding of PI, which may include a significant immunological component.


Assuntos
Linfócitos B/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Histocompatibilidade , Transplante de Fígado/imunologia , Linfócitos T/imunologia , Tolerância ao Transplante , Biópsia , Distribuição de Qui-Quadrado , Feminino , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Texas , Fatores de Tempo , Resultado do Tratamento
19.
Proc (Bayl Univ Med Cent) ; 24(4): 287-94, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22046060

RESUMO

Different renal-sparing immunosuppressive protocols have been used in liver transplantation. At our institution, muromonab-CD3 (OKT3) is used in patients with acute renal failure (ARF), along with a delay in starting a calcineurin inhibitor. This study was conducted to compare outcomes in liver transplant patients with ARF who received OKT3 and those who did not. From 1988 to 2007, ARF was present in 1685 of 2587 patients (65%). OKT3 was used in 109 patients (OKT3 group). The control group (1416 patients) received a low-dose calcineurin inhibitor. The OKT3 group was more critically ill. In spite of this, the OKT3 group patients who were on renal replacement therapy (RRT) achieved long-term survival similar to that of the control group on RRT. Among the patients who were not on RRT, the OKT3 group had a higher complete recovery rate, but this did not translate into improved long-term survival. Bacterial and fungal infections were more common in the OKT3 group; however, there was no increased risk of malignancy or death from hepatitis C recurrence. The use of OKT3 in patients with ARF allowed more critically ill patients on RRT to achieve survival rates similar to those of patients who did not receive OKT3.

20.
Clin Transplant ; 24(6): 807-11, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20002463

RESUMO

The frequency of combined liver and kidney transplants (CLKT) persists despite the pronounced scarcity of organs. In this review, we sought to ascertain any factors that would reduce the use of these limited commodities. Seventy-five adult CLKT were performed over a 23-yr period at our center, 29 (39%) of which occurred during the Model for End-stage Liver Disease (MELD) era. Overall, patient survival rates were 82%, 73%, and 62% at one, three, and five yr, respectively. There was no difference in patient survival based either on pre-transplant hemodialysis status or by glomerular filtration rate (GFR) at the time of transplant. Patients undergoing a second CLKT or a liver retransplantation at the time of CLKT had a survival rate of 30% at three months. In the MELD era, patient survival was unchanged (p = NS) despite an older recipient population (p = 0.0029) and a greater number of hepatitis C patients (p = 0.0428). In summary, patients requiring liver retransplantation with concomitant renal failure should be denied CLKT. Renal allografts may also be spared by implementing strict criteria for renal organ allocation (GFR < 30 mL/min at the time of evaluation) and considering the elimination of preemptive kidney transplantation in CLKT.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Fígado , Adulto , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Alocação de Recursos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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