RESUMO
Primary sclerosing cholangitis (PSC) is a progressive liver disease for which there is no effective therapy. Hepatocytes and cholangiocytes from a PSC patient were cocultured with mesenchymal stem cells (MSCs) to assess in vitro change. A single patient with progressive PSC was treated with 150 million MSCs via direct injection into the common bile duct. Coculture of MSCs with cholangiocytes and hepatocytes showed in vitro improvement. Local delivery of MSCs into a single patient with progressive PSC was safe. Radiographic and endoscopic evaluation showed stable distribution of multifocal structuring in the early postoperative period. MSCs may be effective for the treatment of PSC.
Assuntos
Colangite Esclerosante , Células-Tronco Mesenquimais , Humanos , Colangite Esclerosante/terapia , Células EpiteliaisRESUMO
Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial.
Assuntos
Anemia , Telangiectasia Hemorrágica Hereditária , Anemia/tratamento farmacológico , Anemia/etiologia , Epistaxe/tratamento farmacológico , Epistaxe/etiologia , Humanos , Indazóis , Pirimidinas , Estudos Retrospectivos , Sulfonamidas , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológicoRESUMO
SARS-CoV2, first described in December 2019, was declared a pandemic by the World Health Organization in March 2020. Various surgical and medical societies promptly published guidelines, based on expert opinion, on managing patients with COVID-19, with a consensus to postpone elective surgeries and procedures. We describe the case of an orthotopic liver transplantation (OLT) in a young female who presented with acute liver failure secondary to acetaminophen toxicity to manage abdominal pain and in the setting of a positive SARS-CoV2 test. Despite a positive test, she had no respiratory symptoms at time of presentation. The positive test was thought to be residual viral load. The patient had a very favorable outcome, likely related to multiple factors including her young age, lack of respiratory COVID-19 manifestations and plasma exchange peri-operatively. We recommend a full work-up for OLT in COVID-19 patients with uncomplicated disease according to standard of care, with careful interpretation of COVID-19 testing in patients presenting with conditions requiring urgent or emergent surgery as well as repeat testing even a few days after initial testing, as this could alter management.
Assuntos
Acetaminofen/intoxicação , COVID-19/virologia , Overdose de Drogas/complicações , Falência Hepática Aguda/induzido quimicamente , Transplante de Fígado/métodos , Pandemias , SARS-CoV-2/genética , Adulto , Analgésicos não Narcóticos/intoxicação , COVID-19/epidemiologia , Feminino , Humanos , Falência Hepática Aguda/cirurgia , RNA Viral , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND AND AIMS: Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS: Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS: Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.
Assuntos
Antivirais/uso terapêutico , DNA Viral/análise , Transplante de Coração , Hepacivirus/genética , Hepatite C/prevenção & controle , Transplante de Rim , Transplante de Fígado , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Feminino , Hepatite C/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Complicações Pós-Operatórias/virologia , Resposta Viral Sustentada , Doadores de Tecidos , Viremia/virologiaRESUMO
OBJECTIVE: To develop machine learning models that can predict post-transplantation major adverse cardiovascular events (MACE), all-cause mortality, and cardiovascular mortality in patients undergoing liver transplantation (LT). DESIGN: Retrospective cohort study. SETTING: High-volume tertiary care center. PARTICIPANTS: The study comprised 1,459 consecutive patients undergoing LT between January 2008 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MACE, all-cause mortality, and cardiovascular mortality were modeled using logistic regression, least absolute shrinkage and selection surgery regression, random forests, support vector machine, and gradient-boosted modeling (GBM). All models were built by splitting data into training and testing cohorts, and performance was assessed using five-fold cross-validation based on the area under the receiver operating characteristic curve and Harrell's C statistic. A total of 1,459 patients were included in the final cohort; 1,425 (97.7%) underwent index transplantation, 963 (66.0%) were female, the median age at transplantation was 57 (11-70) years, and the median Model for End-Stage Liver Disease score was 20 (6-40). Across all outcomes, the GBM model XGBoost achieved the highest performance, with an area under the receiver operating curve of 0.71 (95% confidence interval [CI] 0.63-0.79) for MACE, a Harrell's C statistic of 0.64 (95% CI 0.57-0.73) for overall survival, and 0.72 (95% CI 0.59-0.85) for cardiovascular mortality over a mean follow-up of 4.4 years. Examination of Shapley values for the GBM model revealed that on the cohort-wide level, the top influential factors for postoperative MACE were age at transplantation, diabetes, serum creatinine, cirrhosis caused by nonalcoholic steatohepatitis, right ventricular systolic pressure, and left ventricular ejection fraction. CONCLUSION: Machine learning models developed using data from a tertiary care transplantation center achieved good discriminant function in predicting post-LT MACE, all-cause mortality, and cardiovascular mortality. These models can support clinicians in recipient selection and help screen individuals who may be at elevated risk for post-transplantation MACE.
Assuntos
Doenças Cardiovasculares , Doença Hepática Terminal , Transplante de Fígado , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Aprendizado de Máquina , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Volume Sistólico , Função Ventricular EsquerdaRESUMO
There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID-19) in solid organ transplant recipients but negligible data-driven guidance on clinical management. A biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), beginning with a flu-like illness followed by an intense inflammatory response characterized by elevated c-reactive protein (CRP), interleukin 6 (IL-6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL-6. Tocilizumab is an IL-6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T-cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS-CoV-2-related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS-CoV-2-related ARDS that received tocilizumab with favorable short-term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/epidemiologia , Rejeição de Enxerto/prevenção & controle , Transplante de Órgãos/métodos , Pandemias , SARS-CoV-2 , Idoso , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , TransplantadosRESUMO
Coronavirus disease 2019 (COVID-19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with flu-like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID-19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well-controlled HIV who successfully recovered from a mild, flu-like illness attributed to SARS-CoV-2.
Assuntos
Fármacos Anti-HIV/efeitos adversos , COVID-19/diagnóstico , Infecções por HIV/tratamento farmacológico , Transplante de Fígado/efeitos adversos , SARS-CoV-2/imunologia , Adulto , Fármacos Anti-HIV/administração & dosagem , COVID-19/imunologia , COVID-19/virologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Infecções por HIV/imunologia , Humanos , Hidroxicloroquina/administração & dosagem , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Prednisona/administração & dosagem , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
PURPOSE: To compare overall survival and toxicities after yttrium-90 (90Y) radioembolization and chemoembolization with drug-eluting embolics (DEE) in patients with infiltrative hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Retrospective review of 50 patients with infiltrative HCC without main portal vein invasion who were treated with 90Y radioembolization (n = 26) or DEE chemoembolization (n = 24) between March 2007 and August 2012 was completed. Infiltrative tumors were defined by cross-sectional imaging as masses that lacked well-demarcated boundaries, and treatment allocations were made by a multidisciplinary tumor board. Median age was 63 years; median tumor diameter was 9.0 cm; and there were no significant differences between groups in performance status, severity of liver disease, or HCC stage. Toxicities were graded by Common Terminology Criteria for Adverse Events v4.03. Overall survival from treatment was assessed by Kaplan-Meier analysis, with analysis of potential predictors of survival with log-rank test. RESULTS: There was no difference in the average number of procedures performed in each treatment group (DEE, 1.5 ± 1.1; 90Y, 1.6 ± 0.5; P = .97), and technical success was achieved in all cases. Abdominal pain (73% vs 33%; P = .004) and fever (38% vs 8%; P = .01) were more frequent after DEE chemoembolization. There was no significant difference in median overall survival between treatment groups after treatment (DEE, 9.9 months; 90Y, 8.1 months; P = .11). CONCLUSIONS: 90Y radioembolization and DEE chemoembolization provided similar overall survival in the treatment of infiltrative HCC without main portal vein invasion. Abdominal pain and fever were more frequent after DEE chemoembolization.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Biópsia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Radioisótopos de ÍtrioRESUMO
Vascular endothelial growth factor (VEGF) is pivotal in the development of hepatocellular carcinoma (HCC). Studies have demonstrated the prognostic value of circulating VEGF levels in patients undergoing liver resection or locoregional therapy (LRT) for HCC. We investigated the significance of preoperative plasma VEGF levels in patients with HCC undergoing liver transplantation (LT) at a Western transplant center. Pre-LT plasma VEGF levels were measured with an enzyme-linked immunoassay for 164 patients with HCC undergoing LT. The preoperative plasma VEGF level was correlated with clinicopathological variables and overall and recurrence-free post-LT survival. A higher pre-LT plasma VEGF level was significantly associated with pre-LT LRT (P = 0.01), multiple tumors (P = 0.02), a total tumor diameter ≥ 5 cm (P = 0.01), bilobar tumor distribution (P = 0.03), tumor vascular invasion (VI; P < 0.001), and HCC beyond the Milan criteria (P < 0.001). Patients with a plasma VEGF level > 44 pg/mL had significantly worse overall and disease-free survival than those with VEGF levels ≤ 44 pg/mL (P = 0.04 and P = 0.02, respectively). In a multivariate analysis, a plasma VEGF level > 44 pg/mL was independently associated with tumor VI (P < 0.001) and recurrence-free survival (hazard ratio = 2.12, 95% confidence interval = 1.08-4.14, P = 0.03). In conclusion, in patients with chronic end-stage liver disease and HCC, a pre-LT plasma VEGF level > 44 pg/mL may be a predictor of tumor VI and recurrence-free post-LT survival.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Recidiva Local de Neoplasia , Ohio , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Regulação para CimaRESUMO
Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period.
Assuntos
Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/prevenção & controle , Falência Hepática/cirurgia , Transplante de Fígado , Micoses/prevenção & controle , Rifamicinas/uso terapêutico , Idoso , Infecções Bacterianas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Micoses/complicações , Estudos Retrospectivos , RifaximinaRESUMO
BACKGROUND/AIMS: Balloon-assisted enteroscopy (BAE) provides higher-resolution of imaging and allows both diagnosis and treatment in the small intestine. However, the role of BAE in portal hypertensive enteropathy (PHE) is not clear. The purpose of this study is to define BAE findings and its utility in patients with PHE. METHODOLOGY: This study included 20 cirrhotic patients with PHE and 20 control patients, matched by age and gender, who underwent BAE. The indications were to investigate the cause of obscure gastrointestinal bleeding and to achieve a diagnosis in patients with abnormal video capsule endoscopy and/ or abnormal radiological imaging. We evaluated the diagnostic yield and safety of BAE in PHE. RESULTS: BAE revealed significantly abnormal small bowel mucosa including angiodysplasia-like lesions, friability, edema, erythema, and punctate hemorrhage in PHE. There was a significantly higher prevalence of small bowel angiodysplasia- like lesions (65%) in the cirrhotic patients as compared with that (10%) in the controls (p = 0.01). Among the patients with small bowel angiodysplasialike lesions (65%), seven patients (35%) exhibited a diffuse pattern, which was not found in the control group (p = 0.008). CONCLUSIONS: Our study has shown that small bowel angiodysplasia-like lesion, particularly, the diffuse form of the lesion, is the dominant mucosal abnormality in PHE.
Assuntos
Angiodisplasia/patologia , Enteroscopia de Duplo Balão , Hemorragia Gastrointestinal/patologia , Hipertensão Portal/etiologia , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Cirrose Hepática/complicações , Idoso , Angiodisplasia/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT. METHODS: A prospectively maintained LT database was retrospectively analyzed for patients with recurrent HCC following LT between 2001 and 2011-34 patients. Patients were divided into two groups based on whether they were prescribed sorafenib (n = 17) or not prescribed sorafenib (n = 17). The primary endpoint was overall survival. RESULTS: There were no significant differences between the two groups analyzed. Seventeen patients were on sorafenib for recurrent HCC, with a mean daily dose of ~444 mg. Mean duration of treatment was ~10 months. Side effects included: thrombocytopenia, diarrhea, rising transaminases, fatigue, hand-foot skin reaction, and nausea. Survival in the sorafenib vs. non-sorafenib group was greater at three-, six-, nine-, and 12-month intervals and overall survival. CONCLUSION: Sorafenib can be well tolerated and safe in patients with recurrent HCC following LT and may be associated with a modest survival benefit. To our knowledge, this is the largest single-center retrospective analysis of patients prescribed sorafenib for recurrent HCC after LT.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado , Recidiva Local de Neoplasia/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Complicações Pós-Operatórias , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Niacinamida/uso terapêutico , Prognóstico , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , SorafenibeRESUMO
BACKGROUND: Locoregional therapies (LRTs) are treatments to achieve local control of hepatocellular carcinoma (HCC). Correlation between radiologic response to LRT and degree of induced tumor necrosis is not well understood. The aim of this study was to evaluate different levels of radiologic response after pre-liver transplant (LT) LRT and its correlation with percentage of tumor necrosis on explanted histopathology. METHODS: Institutional Review Board approved LT database was queried for treated HCC in patients undergoing LT. Radiologic response was evaluated to predict tumor necrosis in the explanted liver. Tumor response was evaluated 1 to 3 months after LRT with computed tomography or MRI via Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) guidelines. LRT was repeated as needed until time of LT. Histological tumor necrosis was graded as complete (100%), partial (50%-99%), or poor (<50%). RESULTS: Between 2002 and 2011, 128 patients (97 men and 31 women) received pre-LT LRT including transarterial therapy (93), radiofrequency ablation (20), or combination of both (15). The mean age of the patients was 58+/-9 years. Their mean follow-up was 35+/-27 months. The median waitlist time was 55 days. One hundred (78%) patients had HCC within the Milan criteria at the initial radiologic diagnosis. Nineteen (15%) of the patients had complete tumor necrosis on histopathology analysis. Fifty (39%) of the patients exhibited partial necrosis, 52 (41%) showed poor or no necrosis and 7 (5%) showed progressive disease. The overall pre-LT radiologic staging was correlated with explant pathology in 73 (57%) of the patients. Underestimated tumor stage was noted in 49 (38%) patients, and overestimated tumor stage in 6 (5%) patients. The post-LT 3-year overall survival and disease free survival were 82% and 80%, and the rates for complete and partial tumor necrosis were 100% vs 78% (P=0.02) and 100% vs 75% (P=0.03), respectively. CONCLUSIONS: In the current era, interpretation of radiologic response after LRT for HCC does not correlate accurately with histologic tumor necrosis. Total tumor necrosis is the goal of LRT; therefore, evolution in its performance is needed. Similarly, ways to predict therapy induced tumor necrosis via radiological investigation need to be improved.
Assuntos
Carcinoma Hepatocelular/mortalidade , Ablação por Cateter/mortalidade , Quimioembolização Terapêutica/mortalidade , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Terapia Combinada/mortalidade , Bases de Dados Factuais/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/mortalidade , Análise de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and extracolonic tumors. Adenocarcinoma of the pancreas and hepatocellular carcinoma are rare in FAP. In this case series, we describe a mother and daughter with FAP who developed a hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas, respectively.
Assuntos
Adenocarcinoma , Polipose Adenomatosa do Colo , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/patologia , Pâncreas/patologia , Adenocarcinoma/patologiaRESUMO
BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.
Assuntos
Doença da Artéria Coronariana , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/cirurgia , Cirrose Hepática/cirurgia , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.
Assuntos
Síndrome Hepatorrenal , Transplante de Rim , Insuficiência Renal , Humanos , Transplante de Rim/efeitos adversos , Recuperação de Função Fisiológica , Creatinina , Rim/diagnóstico por imagem , Rim/cirurgia , Taxa de Filtração Glomerular , Cintilografia , Estudos RetrospectivosRESUMO
BACKGROUND: The pattern and severity of postoperative complications after colectomy and total proctocolectomy with ileoanal pouch for patients with IBD with liver cirrhosis from primary sclerosing cholangitis have not been well characterized. OBJECTIVE: This study aimed to evaluate the immediate and long-term outcomes for patients with cirrhosis from primary sclerosing cholangitis undergoing colectomy for IBD. DESIGN: This is a retrospective study. SETTING: This study was conducted at Cleveland Clinic, a tertiary medical center. PATIENTS: From 1989 to 2009, 23 patients (22 ulcerative colitis and 1 Crohn's disease) who underwent colectomy were included. RESULTS: The mean duration of primary sclerosing cholangitis before surgery was 6.8 ± 4.9 years, and the mean duration of IBD was 18 ± 10.7 years. All patients had cirrhosis; the mean Model for Endstage Liver Disease score was 9.3 ± 1.6, and most patients were Child Pugh class A or early B. Eight patients were on the orthotopic liver transplantation list. Indications for colectomy were dysplasia (n = 13), failure or complications of medical therapy (n = 7), cancer (n = 2), and colonic perforation at colonoscopy (n = 1). Nineteen patients (82.6%) developed postoperative complications including bleeding (43.5%), ileus (17.4%), wound infection (8.7%), worsening liver function (34.8%), pelvic abscess (13%), and deep vein thrombosis (8.7%). Two patients, both after total proctocolectomy/IPAA, died of septic shock after pelvic abscess in the postoperative period. Two patients underwent transjugular intrahepatic portosystemic shunt procedure before total proctocolectomy/IPAA; none developed pelvic abscess or mortality. There were no differences in mortality or morbidity between patients who underwent an ileoanal pouch procedure or colectomy with ileostomy. CONCLUSIONS: Colectomy in patients with IBD complicated with cirrhotic primary sclerosing cholangitis is associated with a high early postoperative morbidity rate. Due consideration needs to be given to strategies to reduce pelvic sepsis, especially after ileoanal pouch, because this is associated with mortality.
Assuntos
Colangite Esclerosante/complicações , Doenças Inflamatórias Intestinais/cirurgia , Cirrose Hepática/etiologia , Complicações Pós-Operatórias/epidemiologia , Proctocolectomia Restauradora , Adulto , Colectomia , Feminino , Humanos , Ileostomia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Liver transplantation (LT) in Milan Criteria (MC) hepatocellular carcinoma (HCC) has excellent outcomes. Pre-transplant loco-regional therapy (LRT) has been used to downstage HCC to meet the MC. However, its benefit in patients with a brief waiting time to transplant remains unclear. This study evaluated outcomes in patients with short waitlist times to LT for MC-compliant HCC. METHODS: Patients undergoing LT for MC HCC at either of two transplant centres between 2002 and 2009 were retrospectively evaluated for outcome. Patients for whom post-transplant follow-up amounted to <12 months were excluded. RESULTS: A total of 225 patients were included, 93 (41.3%) of whom received neoadjuvant LRT. The median waiting time to transplant was 48 days. Mean post-transplant follow-up was 32.2 months. Overall and disease-free survival at 1 year, 3 years and 5 years were 93.1%, 82.4% and 72.6%, and 91.3%, 79.3% and 70.6%, respectively. There was no difference in overall (P= 0.94) and disease-free survival (P= 0.94) between groups who received and did not receive pre-LT LRT. There were also no disparities in survival or tumour recurrence among categories of patients (with single tumours measuring <3 cm, with single tumours measuring 3-5 cm, with multiple tumours). CONCLUSIONS: Loco-regional therapy followed by rapid transplantation in MC HCC appears not to have an impact on post-transplant outcome.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Terapia Neoadjuvante , Listas de Espera , Idoso , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Ohio , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Objective: This paper examines the incidence, clinical presentation, and pathophysiology of portal vein thrombosis (PVT) in cirrhosis. Additionally, we have reviewed the literature regarding the current status of medical and interventional radiology management of PVT and have proposed a novel algorithm for the management given different clinical scenarios. Lastly two representative cases displaying endovascular treatment options are provided. Background: Portal vein thrombus in the setting of cirrhosis is an increasingly recognized clinical issue with debate on its pathophysiology, natural course, and optimal treatment. Approximately one-third of patients are asymptomatic, and detection of the thrombus is an incidental finding on imaging performed for other reasons. In 30% to 50% of patients, PVT resolves spontaneously. However, there is increased post-transplant mortality in patients with completely occlusive PVT, therefore effective early revascularization strategies are needed for patients with complete PVT who are expected to undergo liver transplant. Additionally, no consensus has been reached regarding PVT treatment in terms of timing and type of interventions as well as type and duration of anticoagulation. Methods: Computerized literature search as well as discussion with experts in the field. Conclusions: Management of PVT is complex, as many variables affect which treatments can be used. Anticoagulation appears to be the optimal first-line treatment in patients with acute PVT but without bleeding varices or mesenteric ischemia. Minimally invasive treatments include various methods of mechanical thrombectomy, chemical thrombolysis, and transjugular intrahepatic portosystemic shunt (TIPS) placement with or without variceal embolization. Definitive recommendations are difficult due to lack of high quality data and continued research is needed to evaluate the efficacy of different anticoagulants as well as the timing and use of various minimally invasive therapies in specific circumstances.
RESUMO
Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH. Methods: This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH. Results: Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03). Conclusions: Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.