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1.
Surgery ; 174(6): 1436-1444, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37827898

RESUMO

BACKGROUND: A new deceased donor liver allocation policy using an acuity circle-based model was implemented with the goal of providing equitable access to liver transplantation. We assessed the effect of the acuity circle policy on racial disparities in liver transplantation by analyzing waitlist mortality, transplant probability, and post-transplant outcomes. METHODS: We conducted a retrospective analysis of 23,717 adult liver transplantation candidates listed during the pre-acuity circle period and 21,051 during the post-acuity circle period (N = 44,768) in the United Network for Organ Sharing database from February 2020 to December 2021. RESULTS: Acuity circle-policy implementation was not associated with any significant difference in 90-day waitlist mortality but increased the 90-day probability of all candidates. Implementation did not decrease 90-day waitlist mortality but increased the 90-day transplant probability for all patients. One-year patient and liver graft survival were comparable between the study periods for all recipients, but Black recipients had higher rates of 1-year post-liver transplantation mortality and liver graft failure in both periods. CONCLUSION: Although the implementation of the acuity circle policy is associated with an increase in transplant probability in White, Black, and Hispanic liver transplantation candidates, it did not change their waitlist mortality, nor did it lead to any improvement in the preexistent worse post-transplant outcomes in Black liver transplantation recipients.


Assuntos
Transplante de Fígado , Adulto , Humanos , Estudos Retrospectivos , Doadores Vivos , Grupos Raciais , Políticas
2.
Surg Technol Int ; 422023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37466913

RESUMO

INTRODUCTION: Patients with cirrhosis undergoing non-liver transplant surgery have a higher risk or adverse events than those without cirrhosis. The main objectives of this study were to describe characteristics, outcomes, and outcome predictors of cirrhotic patients undergoing complex abdominal wall reconstruction (CAWR) with biologic mesh. MATERIALS AND METHODS: This study had retrospective and prospective components, including all cirrhotic patients at our center with CAWR for ventral/umbilical hernia repair with biologic mesh between December 2016 and November 2021. RESULTS: We studied 37 patients with cirrhosis. Their mean age was 57.2 years, and 64.9% were male. The median body mass index (BMI) was 28.1kg/m2. Ascites was present in 83.3% of patients. The other most common comorbidities were alcohol abuse (67.6%), hypertension (37.8%), and diabetes (24.3%). All complications in aggregate occurred in 11 patients (29.7%). Six patients (16.2%) underwent reoperation. Surgical site infections (SSIs) occurred in five patients (13.5%). Four deaths occurred within 90 days (11.2% cumulative mortality). By 120 days, there were five deaths (14.2% mortality, but none due to the operation). Seven predictor variables achieved an area under the receiver operating characteristic curve (AUROC) for SSI of 0.963, and two predictors yielded an AUROC of 0.825 for 120-day mortality. CONCLUSIONS: Our results suggest that CAWR for ventral/umbilical hernias among cirrhotic patients is feasible given a dedicated CAWR team in collaboration with transplant surgeons and a transplant hepatologist. The rates of adverse outcomes were low or at the midpoint of the range of the study-specific estimates.

3.
World J Hepatol ; 15(4): 554-563, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37206654

RESUMO

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a significant impact on routine medical care in the United States, including in fields of transplantation and oncology. AIM: To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation (LT) for hepatocellular carcinoma (HCC) in the United States. METHODS: WHO declared COVID-19 as a pandemic on March 11, 2020. We retrospectively analyzed data from the United Network for Organ Sharing (UNOS) database regarding adult LT with confirmed HCC on explant in 2019 and 2020. We defined pre-COVID period from March 11 to September 11, 2019, and early-COVID period as from March 11 to September 11, 2020. RESULTS: Overall, 23.5% fewer LT for HCC were performed during the COVID period (518 vs 675, P < 0.05). This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020. Among LT recipients for HCC, concurrent diagnosis of non-alcoholic steatohepatitis significantly increased (23 vs 16%) and alcoholic liver disease (ALD) significantly decreased (18 vs 22%) during the COVID period. Recipient age, gender, BMI, and MELD score were statistically similar between two groups, while waiting list time decreased during the COVID period (279 days vs 300 days, P = 0.041). Among pathological characteristics of HCC, vascular invasion was more prominent during COVID period (P < 0.01), while other features were the same. While the donor age and other characteristics remained same, the distance between donor and recipient hospitals was significantly increased (P < 0.01) and donor risk index was significantly higher (1.68 vs 1.59, P < 0.01) during COVID period. Among outcomes, 90-day overall and graft survival were the same, but 180-day overall and graft were significantly inferior during COVID period (94.7 vs 97.0%, P = 0.048). On multivariable Cox-hazard regression analysis, COVID period emerged as a significant risk factor of post-transplant mortality (Hazard ratio 1.85; 95%CI: 1.28-2.68, P = 0.001). CONCLUSION: During COVID period, there was a significant decrease in LTs performed for HCC. While early postoperative outcomes of LT for HCC were same, the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

4.
J Am Coll Surg ; 236(1): 73-80, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36519910

RESUMO

BACKGROUND: Liver transplant (LT) outcomes using machine perfusion (MP) in donation after brain death (DBD) is promising, but the LT outcomes of MP in donation after cardiac death (DCD) is limited in the US. The aim of this study was to compare LT outcomes of MP between DCD and DBD. STUDY DESIGN: We analyzed data from the United Network for Organ Sharing between 2016 and 2021 among adult LT recipients. Propensity score matching was performed to assess the outcomes between DCD and DBD. RESULTS: A total of 380 LTs (295 from DBD and 85 from DCD) were performed using MP. When compared with DBD, DCD group had older median recipient age (61 vs 58 years, p = 0.03), higher prevalence of diabetes (41% vs 28%, p = 0.02), lower model for end-stage liver disease score (17 vs 22, p < 0.01), longer wait time (276 vs 143 days, p < 0.01) and younger median donor age (40 vs 51 years, p < 0.01). The most common primary diagnosis was alcohol-related liver disease, and hepatocellular carcinoma was more common in the DCD group (22% vs 13%). On survival analysis, 1-year overall/graft survivals (DCD 95.4% vs DBD 92.1%, p = 0.54; DCD 91.7% vs DBD 89.8%, p = 0.86) were the same. After propensity score matching, overall/graft survivals were the same. In Cox regression analysis, DCD was not an independent risk factor of mortality (hazard ratio 0.80; 95% CI 0.25 to 2.52; p = 0.70) and graft failure (hazard ratio 0.58; 95% CI 0.17 to 1.97; p = 0.38). CONCLUSIONS: In transplant recipients who underwent LT using MP, posttransplant outcomes of overall and graft survival were similar among DCD and DBD cohorts.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Pessoa de Meia-Idade , Morte Encefálica , Doença Hepática Terminal/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença , Morte , Perfusão , Sobrevivência de Enxerto , Doadores de Tecidos
5.
World J Transplant ; 12(8): 259-267, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36159074

RESUMO

BACKGROUND: The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited. AIM: To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States. METHODS: We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old). RESULTS: Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI. CONCLUSION: While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.

6.
Transplant Proc ; 54(7): 1834-1838, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35933231

RESUMO

BACKGROUND: Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT. METHODS: We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016). RESULTS: HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival. CONCLUSIONS: DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Hepacivirus , Transplante de Fígado/efeitos adversos , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Estudos Retrospectivos , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/cirurgia
8.
J Liver Transpl ; 7: 100099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38013989

RESUMO

Background: : Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Methods: : We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Results: : Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01; 92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01). Conclusions: : During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.

9.
Cancer Immunol Immunother ; 71(3): 589-599, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34282496

RESUMO

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.


Assuntos
Carcinoma Hepatocelular/terapia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Neoplasias Hepáticas/terapia , Transplante de Fígado , Fígado/imunologia , Transferência Adotiva , Adulto , Idoso , Biomarcadores , Terapia Combinada , Estudos de Viabilidade , Feminino , Sobrevivência de Enxerto , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/metabolismo , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
10.
Transplant Proc ; 53(4): 1175-1179, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33888342

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected all facets of life and continues to cripple nations. COVID-19 has taken the lives of more than 2.1 million people worldwide, with a global mortality rate of 2.2%. Current COVID-19 treatment options include supportive respiratory care, parenteral corticosteroids, and remdesivir. Although COVID-19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID-19 infection in patients with organ transplants has not been well described in the literature. The treatment of COVID-19 differs based on the organ(s) transplanted. Preliminary data suggested that liver transplant patients with COVID-19 did not have higher mortality rates than untransplanted COVID-19 patients. Table 1 depicts a compiled list of current published data on COVID-19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID-19 within their posttransplant hospitalization course. This potential differentiation needs to be further explored. Here, we report 2 patients who underwent liver transplantation who acquired COVID-19 during their posttransplant recovery period in the hospital. CASE DESCRIPTIONS: Two patients who underwent liver transplant and contracted COVID-19 in the early posttransplant period and were treated with hydroxychloroquine, methylprednisolone, tocilizumab, and convalescent plasma. This article includes a description of their hospital course, including treatment and recovery. CONCLUSION: The management of post-liver transplant patients with COVID-19 infection is complicated. Strict exposure precaution practice after organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID-19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low-dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID-19 pneumonia in post-liver transplant patients. Future studies and experiences from posttransplant patients are warranted to better delineate the clinical features and optimal management of COVID-19 infection in liver transplant recipients.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Transplante de Fígado , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/complicações , COVID-19/terapia , COVID-19/virologia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Imunossupressores/uso terapêutico , Falência Hepática/complicações , Falência Hepática/terapia , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Soroterapia para COVID-19
11.
Int J Surg ; 78: 160-161, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32387620
12.
HPB (Oxford) ; 20(3): 216-221, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29129486

RESUMO

BACKGROUND: A retrospective review to investigate rate and outcomes of re-exploration following liver transplantation in the United States. METHODS: The NIS database was used to examine outcomes of patients who underwent re-exploration following liver transplantation from 2002 to 2012. Multivariate regression analysis was performed to compare outcomes of patients with and without reoperation. RESULTS: We sampled a total of 12,075 patients who underwent liver transplantation. Of these, 1505 (12.5%) had re-exploration during the same hospitalization. Hemorrhagic (67.9%) and biliary tract anastomosis complication (14.8%) were the most common reasons for reoperation. Patients with reoperation had a significantly higher mortality than those who did not (11.6% vs. 3.8%, AOR: 3.01, P < 0.01). Preoperative coagulopathy (AOR: 1.71, P < 0.01) and renal failure (AOR: 1.57, P < 0.01) were associated with hemorrhagic complications. Peripheral vascular disorders (AOR: 2.15, P < 0.01) and coagulopathy (AOR: 1.32, P < 0.01) were significantly associated with vascular complications. Risk of wound disruption was significantly higher in patients with chronic pulmonary disease (AOR: 1.50, P < 0.01). CONCLUSION: Re-exploration after liver transplantation is relatively common (12.5%), with hemorrhagic complication as the most common reason for reoperation. Preoperative coagulation disorders significantly increase hemorrhagic and vascular complications. Further clinical trails should investigate prophylactic strategies in high risk patients to prevent unplanned reoperation.


Assuntos
Transplante de Fígado/efeitos adversos , Hemorragia Pós-Operatória/cirurgia , Reoperação , Transtornos da Coagulação Sanguínea/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Transplante de Fígado/mortalidade , Transplante de Fígado/tendências , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/epidemiologia , Hemorragia Pós-Operatória/mortalidade , Insuficiência Renal/epidemiologia , Reoperação/efeitos adversos , Reoperação/mortalidade , Reoperação/tendências , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
13.
PLoS One ; 11(8): e0161618, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27560943

RESUMO

BACKGROUND: T-cell depleting strategies have become an integral part of immunosuppressive regimens in organ transplantation. Alemtuzumab is a humanized monoclonal antibody against CD52, a cell-surface antigen on several immune cells. It has been suggested that lymphocyte depletion increases the risk of serious infections. However, this has not been observed with short-term alemtuzumab treatment in an organ transplant setting. For induction therapy using alemtuzumab following liver transplantation, we found that T- and B-cell numbers declined rapidly after alemtuzumab therapy; however, the natural killer (NK) cell number was sustained. NK cells are important effectors of innate immunity. Since the effects of alemtuzumab on NK cell functions, especially those of liver NK cells, are unknown, this study aimed to investigate this in detail. METHODS: To assess the effect of alemtuzumab on NK cells, samples were obtained from 7 organ donors and examined by flow cytometry using Annexin V and propidium iodide. Phenotypical and functional differences within subsets of NK cells with different levels of CD52 expression were determined by flow cytometry and in vitro cytotoxicity assays. RESULTS: CD52 expression on NK cells was lower than that on other lymphocyte subsets. The liver contained a large number of CD52- NK cells compared with the peripheral blood. In vitro treatment of liver-derived NK cells with alemtuzumab did not result in cell death. In contrast, co-incubation with alemtuzumab induced cell death in peripheral blood mononuclear cells and non-NK cells in the liver. Furthermore, CD52- liver NK cells were more cytotoxic and produced more IFN-γ than CD52+ NK cells after cytokine activation. CONCLUSION: The liver contains a large number of CD52- NK cells. These cells are refractory to alemtuzumab and have robust activity. These findings indicate that CD52- NK cells persist and could protect against infection after alemtuzumab-based lymphocyte depletion.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Resistência a Medicamentos , Glicoproteínas/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Fígado/citologia , Alemtuzumab , Anticorpos Monoclonais/química , Anticorpos Antineoplásicos , Complexo CD3/metabolismo , Antígeno CD52 , Morte Celular , Citocinas/metabolismo , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Células Matadoras Naturais/citologia , Hepatopatias/cirurgia , Transplante de Fígado , Depleção Linfocítica , Doadores de Tecidos
14.
Pediatr Surg Int ; 32(4): 337-46, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26711121

RESUMO

PURPOSE: To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases. METHODS: This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months). RESULTS: LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease. CONCLUSIONS: Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.


Assuntos
Neoplasias Abdominais/cirurgia , Neoplasias do Sistema Digestório/cirurgia , Intestinos/transplante , Transplante de Órgãos/métodos , Vísceras/transplante , Adolescente , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/terapia , Humanos , Imunossupressores/uso terapêutico , Lactente , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Masculino , Mesentério/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo
16.
Ann Surg ; 259(4): 760-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24299686

RESUMO

OBJECTIVE: To identify complications associated with different techniques utilized to treat portal vein thrombosis (PVT) during primary liver transplantation and their impact on survival. BACKGROUND: PVT remains an intricate problem in liver transplantation, and the long-term outcomes of patients with PVT who undergo transplantation are not well defined. METHODS: We performed a retrospective cohort analysis of all consecutive adult patients who underwent primary isolated liver transplantation from 1998 to 2009 (median follow-up period, 89 months). The outcomes of patients with PVT were compared with those without PVT. RESULTS: Among 1379 recipients, 174 (12.6%) had PVT at the time of transplantation [83 (48%) complete and 91 (52%) partial]. Among PVT patients with reestablished physiological portal inflow (PVT: physiological group; n = 149), 123 underwent thrombectomies, 16 received interpositional vein grafts, and 10 received mesoportal jump grafts. In 25 patients, physiological portomesenteric venous circulation was not reconstituted (PVT: nonphysiological group; 18 underwent cavoportal hemitranspositions, 6 renoportal anastomoses, and 1 arterialization). The PVT: nonphysiological group suffered a significantly increased incidence of rethrombosis of the portomesenteric veins and gastrointestinal bleeding, with a marginal 10-year overall survival rate of 42% (no PVT, 61%; P = 0.002 and PVT: physiological, 55%; P = 0.043). The PVT: physiological and no PVT groups exhibited comparable survival rates (P = 0.13). No significant differences in survival were observed between complete and partial PVT as long as physiological portal flow was reestablished. CONCLUSIONS: The subset of PVT patients requiring nonphysiological portal vein reconstruction was associated with higher complication rates and suffered diminished long-term prognoses. For the most severe PVT cases, a comprehensive approach is critical to further improve outcomes.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado , Veia Porta/cirurgia , Trombectomia , Enxerto Vascular , Trombose Venosa/cirurgia , Adulto , Anastomose Cirúrgica , Estudos de Casos e Controles , Doença Hepática Terminal/complicações , Doença Hepática Terminal/mortalidade , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Incidência , Estimativa de Kaplan-Meier , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/mortalidade
17.
Curr Opin Organ Transplant ; 18(6): 690-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24220052

RESUMO

PURPOSE OF REVIEW: Natural killer (NK) cells are innate immune lymphocytes. NK cells contribute to host antimicrobial and antitumor immunity. Liver transplantation in patients with hepatocellular carcinoma (HCC) has increased recently. The possibility of NK cell immunotherapy for liver cancer has been studied. RECENT FINDINGS: Adoptive transfer of interleukin-2 (IL-2)-stimulated NK cells extracted from donor liver perfusate could increase an antitumor response without causing toxicity against 1-haplotype identical recipient intact tissues in patients with live donor liver transplant. Donor liver NK cells showed the most vigorous cytotoxicity against an HCC after in-vitro IL-2 stimulation, compared with donor and recipient peripheral blood NK cells and recipient liver NK cells. IL-2 stimulation led to an increased expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on liver NK cells. T-cell contamination and risk of graft-versus-host disease can be minimized with a T-cell depleting agent such as anti-CD3 antibody. SUMMARY: Allogeneic NK cells might have an advantage for adoptive immunotherapy. Liver NK cells from a deceased donor liver can be used safely as adoptive immunotherapy under current good manufacturing practice conditions for the treatment of liver transplantation with HCC. IL-2-stimulated liver NK cells have strong cytotoxicity, express TRAIL and secret interferon-γ.


Assuntos
Carcinoma Hepatocelular/terapia , Células Matadoras Naturais/imunologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Carcinoma Hepatocelular/cirurgia , Humanos , Imunidade Inata , Imunoterapia Adotiva , Interleucina-2/imunologia , Fígado/imunologia , Neoplasias Hepáticas/cirurgia
18.
Cell Transplant ; 21(7): 1397-406, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22469170

RESUMO

Tumor recurrence is the main limitation of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and can be promoted by immunosuppressants. However, there is no prevention or treatment for HCC recurrence after LT. Here we describe a clinical-scale method for an adoptive immunotherapy approach that uses natural killer (NK) cells derived from deceased donor liver graft perfusate to prevent tumor recurrence after LT. Liver mononuclear cells (LMNCs) that were extracted from deceased donor liver graft perfusate contained a high percentage of NK cells (45.0 ± 4.0%) compared with peripheral blood mononuclear cells (PBMCs) (21.8 ± 5.2%) from the same donor. The CD69 activation marker and the natural cytotoxicity receptors, NKp44 and NKp46, were expressed at high levels in freshly isolated liver NK cells. Furthermore, interleukin-2 (IL-2)-stimulated NK cells showed greater upregulation of activation markers and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is critical for NK cell-mediated antitumor cell death and increased production of interferon. Moreover, IL-2 stimulation induced LMNCs to exhibit a strong cytotoxicity against NK-susceptible K562 target cells compared with PBMCs (p < 0.01). Finally, we also showed that the final product contained a very low T-cell contamination (0.02 ± 10(6) cells/kg(-1)), which reduces the risk of graft-versus-host disease (GVHD). Collectively, our results suggest that the adoptive transfer of IL-2-stimulated NK cells from deceased donor liver graft perfusate could be a promising treatment for LT patients with HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Hepáticas/terapia , Transplante de Fígado , Adulto , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Apoptose , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Citocinas/metabolismo , Feminino , Rejeição de Enxerto , Humanos , Imunoterapia , Células K562 , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Lectinas Tipo C/metabolismo , Leucócitos Mononucleares/citologia , Fígado/citologia , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Receptor 2 Desencadeador da Citotoxicidade Natural/metabolismo , Prevenção Secundária , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Doadores de Tecidos , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
19.
Surgery ; 152(1): 82-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22386709

RESUMO

OBJECTIVE: To present the indications, techniques, short- and long-term outcomes after visceral exenteration, ex vivo resection, and intestinal/multivisceral autotransplantation. PATIENTS AND METHODS: All patients who have undergone this procedure at our center were studied. Technique, postoperative complications, survival, tumor recurrence, and functional status were recorded. RESULTS: Ten patients, 4 children and 6 adults, have undergone these procedures since January 1999. Seven patients are alive at 13-138 months later, 6 with functioning autografts and one after rescue with an allotransplantation. CONCLUSION: Intestinal/multivisceral autotransplantation is a potentially valuable option for some otherwise unresectable neoplasms of the root of the mesentery.


Assuntos
Intestinos/transplante , Mesentério/cirurgia , Neoplasias Peritoneais/cirurgia , Vísceras/transplante , Adolescente , Adulto , Pré-Escolar , Feminino , Seguimentos , Trato Gastrointestinal/cirurgia , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
20.
J Am Coll Surg ; 214(4): 691-8; discussion 698-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22364695

RESUMO

BACKGROUND: We aim to demonstrate the utility and efficacy of the "piggyback technique" (PBT); liver transplant (LT) with caval preservation. STUDY DESIGN: Adult LTs were performed with intent to use the PBT except in cases of juxtacaval malignancy or technical difficulty. Hepatic venous outflow was established between the donor suprahepatic cava and the joined ostia of all recipient suprahepatic veins. Technical variants with the donor cava and recipient retrohepatic cava were used as needed. The experience was divided into 2 eras: E1 (1994-2002), E2 (2002-2010). RESULTS: We completed 945 of 1080 LTs in E1 (87.5%) and 851 of 920 LTs in E2 (92.5%) using the PBT. Thirty day mortality was 4.6% in E1, 3% in E2 (p = 0.02) with 2 intra-operative deaths in E1. One, 3, 5 year patient survival was 83.7, 75.6, 69.3% in E1 vs. 86, 78.4, 73.8% in E2 (p = 0.057). Graft survival was 77.7, 69, 62.3% in E1 vs. 84, 76.2, 71.2% in E2 (p < 0.0001). Median operative time and hospital length of stay improved in E2 (p < 0.0001, 0.0001). Outflow variants were used more frequently in E2 (11.3% vs. 6.1%). Nine patients (0.5%) developed outflow obstruction, 6 in E1, and 3 in E2. Twice, it was recognized and corrected intraoperatively. Seven patients presented with refractory ascites. Six were successfully treated (4 balloon dilatation, 2 surgical revision), one patient died after attempted dilatation. CONCLUSIONS: The PBT can be used as the preferred technique in adult LT. With experience, the technique was used more frequently, with more variants, with improved outcomes. Outflow obstruction was a rare complication.


Assuntos
Hepatopatias/cirurgia , Transplante de Fígado/métodos , Veia Cava Inferior/cirurgia , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Transplante de Fígado/mortalidade , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
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