A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation.

OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). BACKGROUND: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%-94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.

The Impact of Neoadjuvant Treatment on Survival in Patients Undergoing Pancreatoduodenectomy With Concomitant Portomesenteric Venous Resection: An International Multicenter Analysis.

OBJECTIVE: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers. SUMMARY OF BACKGROUND DATA: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients. METHODS: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018. RESULTS: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS. CONCLUSION: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry.

BACKGROUND: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. METHODS: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. RESULTS: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). CONCLUSION: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Defining Benchmark Outcomes for Pancreatoduodenectomy With Portomesenteric Venous Resection.

OBJECTIVE: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers. SUMMARY BACKGROUND DATA: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection. METHODS: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998). RESULTS: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%. CONCLUSION: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

A 5-Year Follow-Up of The Benefits of an Exercise Training Program in Liver Recipients Transplanted Due to Familial Amyloidotic Polyneuropathy.

BACKGROUND: Supervised (SE) and home-based exercise (HBE) training regimes are effective on reconditioning patients with familial amyloidotic polyneuropathy (FAP) after liver transplantation, but research of the long-term retention of the benefits attained in patients with FAP has not yet been conducted. PURPOSE: In this 5-year follow-up study, we aimed to determine whether the exercise training gains in body composition, physical activity, and function promoted by a 24-week SE or HBE training regimes are retained in patients with FAP who resume normal activity. METHODOLOGY: Sixteen liver-transplanted patients with FAP were reassessed for body composition (dual X-ray absorptiometry), physical activity (questionnaire), and function (handgrip strength and 6-minute walk test). RESULTS: Total body fat increased with both exercise regimes during follow-up ( P < .05; η2 = 0.432-0.625) as well as femoral neck bone density ( P = .048; η2 = 0.119). However, gains in upper limbs muscle quality during follow-up ( P < .001; η2 = 0.597) were only found in the SE group ( P = .042; η2 = 0.245). Both exercise regimes showed retaining aptitudes in walking capacity ( P < .05; η2 = 0.329-0.460) and muscle mass ( P = .05; η2 = 0.245). Still, none could retain the physical activity levels. CONCLUSION: Long-term resumption of normal activity following a 24-week SE or HBE regime in patients with FAP resulted in loss of exercise induced increases in physical activity but counterweighted postoperative losses in bone mineral density and substantially retained the benefits in walking capacity, muscle mass, and quality, in particular, in the SE group.

Acute-on-Chronic Liver Failure: A Portuguese Single-Center Reference Review.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of a patient with cirrhosis, frequently associated with multi-organ failure and a high short-term mortality rate. We present a retrospective study that aims to characterize the presentation, evolution, and outcome of patients diagnosed with ACLF at our center over the last 3 years, with a comparative analysis between the group of patients that had ACLF precipitated by infectious insults of bacterial origin and the group of those with ACLF triggered by a nonbacterial infectious insult; the incidence of acute kidney injury and its impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were enrolled, the majority of them being male (89.6%), and the mean age was 53 years. Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and 9 of them died (64.2%, overall mortality rate 31%); however, no statistical significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again there was no statistical significance (p < 0.7). Twenty-four patients (83%) developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28-day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic transplant was performed in 3 patients, with a 100% survival at the 28-day and 90-day follow-up (p < 0.023). Higher grades of ACLF were associated with increased mortality (p < 0.02; overall mortality 69%). CONCLUSIONS: ACLF is a heterogeneous syndrome with a variety of precipitant factors and different grades of extrahepatic involvement. Most cases will have some degree of renal dysfunction, with an increased risk of mortality. Hepatic transplant is an efficient form of therapy for this syndrome.

A Doença Hepática Crónica Agudizada/Falência é um síndrome caracterizado por uma deterioração aguda de um doente com cirrose, frequentemente associada com falência multiorgânica e elevada mortalidade a curto prazo. Apresentamos estudo retrospetivo que teve como objetivo caracterizar a apresentação, evolução e prognóstico de doentes diagnosticados com Doença Hepática Crónica Agudizada/Falência no nosso Centro nos últimos 3 anos, comparando o grupo de doentes que tiveram Doença Hepática Crónica provocada por infeções bacterianas e os doentes com Doença Hepática Crónica Agudizada/Falência desencadeada por precipitantes que não a infeção bacteriana; foi também analisada a incidência de lesão renal aguda e o seu impacto no prognóstico na Doença Hepática Crónica Agudizada/Falência. Vinte e nove doente foram incluídos no estudo, a maioria do género masculino (89.6%), idade media de 53 anos. Catorze doentes (48.3%) desenvolveram Doença Hepática Crónica Agudizada devido a infeção bacteriana, 9 dos quais faleceram (64.2%, mortalidade global 31%), contudo, sem significado estatístico (p < 0.7); dos restantes 15 (51.7%) sem infeção bacteriana, 11 faleceram (73.3%, mortalidade global 37.9%), também sem significado estatístico (p < 0.7%). Vinte e quatro doentes (83%) desenvolveram lesão renal, mortalidade global de 65.5% (p < 0.022) aos 28 e 90 dias de seguimento. Doze doentes desenvolveram lesão renal aguda com necessidade de terapêutica de substituição da função renal (41.37%), mortalidade global de 37.9% (p < 0.043). O transplante hepático foi realizado em 3 doentes, com uma sobrevida de 100% aos 28 e 90 dias de seguimento (p < 0.023); Graus elevados de Doença Hepática Crónica Agudizada estão associadas a mortalidade mais elevada (p < 0.02); mortalidade global de 69%. CONCLUSIONS: A Doença Hepática Crónica Agudizada é um síndrome heterogéneo, com uma variedade de fatores precipitantes e diferentes graus de envolvimento extra-hepático; a maioria das situações estará associada a disfunção renal, com aumento do risco de mortalidade; O transplante hepático será uma eficaz de tratamento deste síndrome.

A Fair Chance for Everyone: Total Tumor Volume as a Selection Tool in Liver Transplantation for Hepatocellular Carcinoma.

Total tumor volume (TTV) has been proposed as a more accurate means of selecting patients for liver transplantation (LT) due to hepatocellular carcinoma (HCC). We aim to analyze the role of TTV in a population with a short waiting time on list. METHODS: Analysis of a prospective database of patients submitted to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC), UCSF (University of California San Francisco), and "Up to Seven" criteria were calculated both with preoperative imaging exams and histological data. RESULTS: The study population consisted of 231 out of patients. Median waiting time on list was 62.5 days. MC included 187 patients, while TTV ≤115 cm3 included 214. Microvascular invasion (HR 2.601, 95% CI 1.529-4.426), MC (HR 1.666, 95% CI 0.990-2.804), UCSF criteria (HR 2.995, 95% CI 1.875-4.875), TTV ≤115 cm3 (HR 2.898, 95% CI 1.398-6.007), and "Up to Seven" criteria (HR 2.139, 95% CI 1.353-3.383) proved to be independent factors for prognosis for disease-free survival. CONCLUSIONS: TTV ≤115 cm3 may be a useful tool to properly identify the best HCC candidates for LT in a population with a short waiting time on list. TTV gives more patients the opportunity of undergoing LT while maintaining similar rates of tumor recurrence and patient survival.

Preoperative metabolic status is associated with different evolution of resting energy expenditure after liver transplant in adults.

INTRODUCTION: The resting energy expenditure (REE) evolution after liver transplantation is not fully understood. OBJECTIVE: To assess longitudinally the REE evolution in adults undergoing liver transplantation, in association with other nutritional measurements that characterize the metabolic profile. METHODS: A single-center cohort of consecutive end-stage liver disease patients with indication for liver transplantation was recruited. REE, subjective global assessment (SGA), handgrip strength and body composition measurements were assessed before transplantation (T0) and at median nine (T1) and 36 (T2) days after transplantation. Mixed effects regression models were used for analysis. RESULTS: Fifty-six patients with a mean age of 53.7 (8.5) years were included; 87.5% were males. In T0, 41% of patients were normometabolic, 37.5% were hypometabolic and 21.4% were hypermetabolic. After transplantation, the mean REE decreased progressively in patients initially hypermetabolic and the opposite occurred in those initially hypometabolic. The REE evolution was positively associated with body weight (ß = 9.6, p < 0.001) and energy intake (ß= 13.6, p = 0.005) in the whole sample; it was positively associated with body weight (ß= 7.1, p = 0.018) and percentage of energy intake from lipids (ß= 18.9, p = 0.003) in initially hypometabolic patients, and positively associated with body weight (ß= 14.1, p < 0.001) and negatively associated with SGA-undernourishment (ß = -171, p = 0.007) in initially normometabolic patients. CONCLUSION: Different REE evolutions after liver transplantation are associated with the preoperative metabolic status. In patients initially hypometabolic, the REE evolution is positively associated with body weight and percentage of energy intake from lipids, and in those initially normometabolic, it is positively associated with body weight and negatively associated with SGA-undernourishment.

Preoperative metabolic status is associated with different evolution of resting energy expenditure after liver transplant in adults / Influencia del estado metabólico preoperatorio sobre los cambios en el gasto energético en reposo después del trasplante hepático en adultos

Introduction: The resting energy expenditure (REE) evolution after liver transplantation is not fully understood. Objective: To assess longitudinally the REE evolution in adults undergoing liver transplantation, in association with other nutritional measurements that characterize the metabolic profile. Methods: A single-center cohort of consecutive end-stage liver disease patients with indication for liver transplantation was recruited. REE, subjective global assessment (SGA), handgrip strength and body composition measurements were assessed before transplantation (T0) and at median nine (T1) and 36 (T2) days after transplantation. Mixed effects regression models were used for analysis. Results: Fifty-six patients with a mean age of 53.7 (8.5) years were included; 87.5% were males. In T0, 41% of patients were normometabolic, 37.5% were hypometabolic and 21.4% were hypermetabolic. After transplantation, the mean REE decreased progressively in patients initially hypermetabolic and the opposite occurred in those initially hypometabolic. The REE evolution was positively associated with body weight (β = 9.6, p < 0.001) and energy intake (β = 13.6, p = 0.005) in the whole sample; it was positively associated with body weight (β = 7.1, p = 0.018) and percentage of energy intake from lipids (β = 18.9, p = 0.003) in initially hypometabolic patients, and positively associated with body weight (β = 14.1, p < 0.001) and negatively associated with SGA-undernourishment (β = -171, p = 0.007) in initially normometabolic patients. Conclusion: Different REE evolutions after liver transplantation are associated with the preoperative metabolic status. In patients initially hypometabolic, the REE evolution is positively associated with body weight and percentage of energy intake from lipids, and in those initially normometabolic, it is positively associated with body weight and negatively associated with SGA-undernourishment (AU)

Introducción: el gasto energético en reposo (GER) después del trasplante hepático no está totalmente esclarecido. Objetivo: evaluar longitudinalmente la evolución del GER y de otros parámetros nutricionales que caracterizan el perfil metabólico en adultos que recibieron un trasplante hepático. Métodos: cohorte consecutiva de pacientes con enfermedad hepática terminal con indicación para trasplante, reclutada en un centro. Las siguientes variables fueron medidas antes del trasplante (T0) y en las medianas de nueve (T1) y 36 (T2) días de postoperatorio: GER, valoración global subjetiva (VGS), dinamometría manual y composición corporal. Se utilizaron modelos de regresión de efectos mixtos. Resultados: se incluyeron 56 pacientes con una edad media de 53,7 (8,5) años; el 87,5% de ellos eran varones. En T0, el 41% de los pacientes eran normometabólicos; el 37,5%, hipometabólicos, y el 21%, hipermetabólicos. Después del trasplante, el GER disminuyó progresivamente en los pacientes inicialmente hipermetabólicos y lo contrario ocurrió en los inicialmente hipometabólicos. La evolución del GER se asoció positivamente con el peso (β = 9,6, p < 0,001) y la ingesta energética (β = 13,6, p = 0,005) en toda la muestra. Asimismo, se asoció positivamente con el peso (β = 7,1, p = 0,018) y el porcentaje de ingesta energética de grasas (β = 18,9, p = 0,003) en los inicialmente hipometabólicos, mientras que en los inicialmente normometabólicos se relacionó positivamente con el peso (β = 14,1, p < 0,001) y negativamente con la subnutrición por VGS (β = -171, p = 0,007). Conclusión: la evolución del GER después del trasplante hepático se asocia con el estado metabólico preoperatorio, de forma positiva con el peso y el porcentaje de ingesta energética de grasas en los inicialmente hipometabólicos, mientras que en los pacientes inicialmente normometabólicos se relaciona positivamente con el peso y negativamente con la subnutrición valorada por VGS (AU)

Acute Liver Failure due to Trazodone and Diazepam.

Most antidepressant agents have the potential to cause liver injury, even at therapeutic doses. Nevertheless, drug-induced liver injury (DILI) from antidepressant agents is a rare event. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. We describe a rare case of a 63-year-old man presenting with acute liver failure after 3 months of trazodone and diazepam administration at normal therapeutic doses, requiring liver transplantation. This report should increase physicians' awareness of this complication and call attention to the regular monitoring of liver tests in patients taking trazodone, in order to prevent life-threatening complications.

A maioria dos antidepressivos tem o potencial de causar lesão hepática, mesmo em doses terapêuticas. Contudo, a hepatite tóxica por antidepressivos é um evento raro. Não existe forma de prevenir a hepatite tóxica, mas a sua gravidade pode ser minimizada com o diagnóstico precoce e a retirada antecipada do fármaco. Apresentamos um caso raro de um homem de 63 anos com insuficiência hepática aguda após 3 meses de terapêutica com trazodona e diazepam em doses terapêuticas, com necessidade de transplante hepático. Com este caso pretende-se alertar os clínicos para a possibilidade desta entidade e da necessidade de monitorização regular das provas hepáticas em doentes sob tratamento com trazodona, de forma a prevenir morbilidade e mortalidade.

Tuberculosis in Liver Transplant Recipients: A Report of Eight Cases During a Five Year Period.

INTRODUCTION: Tuberculosis incidence in Portugal ranged from 20 to 22 cases per 100 000 inhabitants between 2010 and 2014. Tuberculosis incidence in liver transplant recipients is not precisely known, but it is estimated to be higher than among the general population. Tuberculosis in liver transplant recipients is particularly challenging because of the atypical clinical presentation and side effects of the antibacillary drugs and their potential interactions with immunosuppressive therapies. MATERIAL AND METHODS: We retrospectively reviewed the clinical records of liver transplant recipients with post-transplant tuberculosis occurring from January 2010 to December 2014 at a liver transplantation unit in Lisbon, Portugal. Demographic data, baseline and clinical features, as well as treatment regimen, toxicities and outcomes, were analyzed. RESULTS: Among 1005 recipients, active tuberculosis was diagnosed in eight patients between January 2010 and December 2014 (frequency = 0.8%). Late onset tuberculosis was more frequent than early tuberculosis. Mycobacterium tuberculosis complex was isolated from cultures in almost every case (7; 87.5%). Extra-pulmonary involvement and disseminated tuberculosis were frequent. Two patients developed rejection without allograft loss. Crude mortality was 37.5%, with 2 deaths being related to tuberculosis. DISCUSSION: Despite the uncertainty regarding treatment duration in liver transplant recipients, disease severity, as well as number of active drugs against TB infection, should be taken into account. There was a need for a rifampin-free regimen and immunosuppression adjustment in patients who experienced acute graf rejection. CONCLUSION: Although the number of cases of tuberculosis is low, its post-transplant frequency is significant and the observed mortality rate is not to be neglected. The cases of hepatotoxicity and graft rejection seen in this case series demonstrate the challenges associated with tuberculosis diagnosis in liver transplant recipients and management of the interactions between immunosuppressors and rifampin. This study strengthens the recommendation of latent tuberculosis infection screening and treatment in liver transplant candidates or recipients.

Introdução: A incidência de tuberculose em Portugal entre 2010 - 2014 foi de 20 a 22 casos por 100 000 habitantes. A incidência de tuberculose em transplantados hepáticos não é conhecida, estimando-se que seja mais elevada do que a da população em geral. O manejo da tuberculose em transplantados hepáticos constitui um desafio, não só pela apresentação clínica frequentemente atípica, mas também pelos efeitos secundários da terapêutica antibacilar e suas interações farmacológicas com a medicação imunossupressora, necessária no período pós-transplante. Material e Métodos: Os autores fizeram uma revisão retrospetiva dos casos de doentes transplantados hepáticos com tuberculose pós- transplante diagnosticada durante o período entre janeiro 2010 e dezembro 2014 num centro de transplantação hepática em Lisboa, Portugal. Foram analisados os dados demográficos, características clínicas, a par do regime antibacilar, toxicidade e evolução. Resultados: Num total de 1005 transplantados foi diagnosticada tuberculose ativa em oito doentes entre janeiro de 2010 e dezembro de 2014 (frequência de 0,8%). O desenvolvimento de tuberculose tardia foi mais frequente do que a doença precoce. Foi isolado Mycobacterium tuberculosis complex no exame cultural de sete doentes (87,5%). Foram frequentes a presença de envolvimento extrapulmonar, assim como doença tuberculosa disseminada. Dois doentes desenvolveram rejeição aguda, sem perda de enxerto. A taxa de mortalidade global foi de 37,5%, com duas mortes directamente atribuíveis à tuberculose. Discussão: Apesar da incerteza quanto à duração do tratamento da tuberculose em transplantados hepáticos, deverão ser tidos em conta a gravidade da doença, assim como o número de fármacos com actividade antibacilar. Nesta série, os doentes que desenvolveram rejeição aguda necessitaram da utilização de um regime sem rifampicina, e ajuste da terapêutica imunossupressora. Conclusão: Apesar do baixo número de casos de tuberculose, a sua frequência pós-transplante é significativa e a mortalidade associada não é negligenciável. Os casos de hepatotoxicidade e rejeição de enxerto demonstram os desafios no diagnóstico da tuberculose em transplantados hepáticos e a dificuldade do manejo das interações entre imunossupressores e a rifampicina. Este estudo reforça a recomendação de rastreio e tratamento de tuberculose latente em transplantados ou candidatos a transplante hepático.

[Biliary Anastomosis in Liver Transplantation: With or Without T-Tube?] / Anastomose Biliar no Transplante Hepático: Com ou Sem Tubo em T?

INTRODUCTION: Biliary complications occur in 10-30% of liver transplants. The aim of this study was to compare the incidence of these complications in liver transplants when the T-tube was or was not used during the biliary anastomosis. MATERIAL AND METHODS: Analysis of 2 groups of patients undergoing liver transplantation between 2008 and 2012. Patients were divided considering if the T-tube was used (G1) or if it was not (G2). We sought explanatory models of the occurrence of biliary complications by logistic regression, including the variables identified in the univariate analysis. RESULTS: We reviewed 506 consecutive patients who underwent a first liver transplant (G1 = 363, G2 = 143). The overall incidence of biliary complications was 24.7% (95% CI 21.1 to 28.6): 27.0% in G1 and 18.9% in G2 (p = 0.057). The incidences of stenosis and biliary fistula tended to be higher in G1: 19.6% (95% CI 15.7 to 23.8) vs 15.4% (95% CI 10.1 to 22.0) (p = 0.275) and 6.6% (95% CI 4.4 to 9.5) vs 2.8% (95% CI 0.9 to 6.6) (p = 0.091). We did not find statistically significant differences in the rates of endoscopic retrograde cholangiopancreatography, reoperation and retransplantation. There were two deaths in G1. There was no association between the occurrence of biliary complications and the diameters of the biliary tract nor the time of cold ischemia. The explanatory model, adjusted to the recipient and the donor age's and to the initial diagnosis, identifies the use of the T-tube as increasing the possibility of the occurrence of biliary complications (AdjOR 1.71, 95% CI 1.04 to 2.80; p = 0.034). DISCUSSION AND CONCLUSION: The use of the T-tube should be a decision taken on a case-based intraoperative judgment of experienced surgeons.

Introdução: Complicações biliares ocorrem em 10% - 30% dos transplantes hepáticos. O objetivo deste trabalho é comparar as incidências dessas complicações nos transplantes hepáticos em que foi ou não utilizado tubo em T na anastomose biliar. Material e Métodos: Análise de dois grupos de doentes submetidos a transplante hepático entre 2008 e 2012. Consideraram-se os doentes em que o tubo em T foi utilizado (G1) e em que não o foi (G2). Procuraram-se depois modelos explicativos da ocorrência de complicações biliares por regressão logística, incluindo as variáveis identificadas na análise univariável. Resultados: Estudaram-se 506 doentes consecutivos submetidos a um primeiro transplante hepático (G1 = 363; G2 = 143). A incidência global de complicações biliares foi 24,7% (IC 95% 21,1 - 28,6): 27,0% no G1 e 18,9% no G2 (p = 0,057). As incidências de estenose e de fístula biliar foram tendencialmente mais elevadas em G1: 19,6% (IC 95% 15,7-23,8) vs 15,4% (IC 95% 10,1 - 22,0) (p = 0,275) e 6,6% (IC 95% 4,4 - 9,5) vs 2,8% (IC 95% 0,9 - 6,6) (p = 0,091). Não se encontraram diferenças estatisticamente significativas nas taxas de colangiopancreatografia retrógrada endoscópica, reoperação e retransplante. Verificaram-se dois óbitos no G1. Não se encontrou associação entre a ocorrência de complicações biliares e os diâmetros das vias biliares ou o tempo de isquemia fria. O modelo explicativo ajustado à idade do recetor e do dador, e ao diagnóstico de base identifica o uso do tubo em T como aumentando a possibilidade da ocorrência de complicações biliares (AdjOR 1,71; IC 95% 1,04 - 2,80; p = 0,034). Discussão e Conclusão: A utilização do tubo em T deve ser uma decisão tomada caso a caso e baseada no julgamento intra-operatório de cirurgiões experientes.

Outcomes of parenchyma-preserving hepatectomy and right hepatectomy for solitary small colorectal liver metastasis: A LiverMetSurvey study.

BACKGROUND: Occasionally, right hepatectomy, rather than parenchyma-preserving hepatectomy, has been performed for solitary small colorectal liver metastasis. The relative oncologic benefits of parenchyma-preserving hepatectomy and right hepatectomy are unclear. This study compared the outcomes of patients with solitary small colorectal liver metastasis in the right liver who underwent parenchyma-preserving hepatectomy and those who underwent right hepatectomy. METHODS: The study population consisted of a multicentric cohort of 21,072 patients operated for colorectal liver metastasis between 2000 and 2015 whose data were collected in the LiverMetSurvey registry. Patients with a pathologically confirmed solitary tumor of less than 30 mm in size in the right liver were included. The short- and long-term outcomes of patients who underwent parenchyma-preserving hepatectomy were compared to those of patients who underwent right hepatectomy. RESULTS: Of the 1,720 patients who were eligible for the study, 1,478 (86%) underwent parenchyma-preserving hepatectomy and 242 (14%) underwent right hepatectomy. The parenchyma-preserving hepatectomy group was associated with lower rates of major complications (3% vs 10%; P < .001) and 90-day mortality (1% vs 3%; P = .008). Liver recurrence occurred similarly in both groups (20% vs 22%; P = .39). The 5-year recurrence-free survival and overall survival rates were similar in both groups. However, in patients with liver-only recurrence, repeat hepatectomy was more frequently performed in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (67% vs 31%; P < .001), and the overall 5-year survival rate was significantly higher in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (55% vs 23%; P < .001). CONCLUSION: Parenchyma-preserving hepatectomy should be considered the standard procedure for solitary small colorectal liver metastasis in the right liver when technically feasible.

Resection of colorectal liver metastases after second-line chemotherapy: is it worthwhile? A LiverMetSurvey analysis of 6415 patients.

PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2. CONCLUSION: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.

The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis.

BACKGROUND: Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM). METHODS: Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed. RESULTS: Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS. DISCUSSION: In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection.