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1.
J Hepatol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774638

RESUMO

BACKGROUND & AIMS: In Italy, since August 2014, LT candidates with MELD≥30 receive a national allocation priority. This multi-center cohort study aims to evaluate waiting time in the list, dropout rate, and graft survival before and after introducing the macroarea sharing policy. METHODS: 4,238 patients registered from 2010 to 2018 have been enrolled and categorized in an ERA-1 Group (n=2,013; before August 2014) and an ERA-2 Group (n=2,225; during and after August 2014). Cox proportional hazard model was used to estimate the HR of receiving LT or death between the two ERAs. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: MELD≥30 patients had a lower median waiting time in the list for LT (4vs.12 days, p<0.001) and a higher probability to be transplanted (HR=2.27, 95%CI 1.78-2.90; p=0.001) in the ERA-2 when compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio=0.56, 95%CI=0.46-0.68; p=0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high volume center and ERA-2, while MELD≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD≥30 priority allocation was associated with improved patient outcomes, although MELD≥30 had a higher risk of graft loss. The transplant centers volume and competition among centers may have a role in the recipient prioritization and outcome. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: After introducing the Italian national MELD≥30 priority, more LT, fewer dropouts, and shorter waiting times were observed in patients with MELD≥30. However, a higher risk of graft loss still burdens these cases compared to MELD<30. The volume of transplant centers and competitions among centers may have a role in the recipient prioritization and outcome.

2.
Updates Surg ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807412

RESUMO

The correct timing of use of direct acting agents (DAAs) among transplanted patients remains unknown. The aim of this paperwork is to evaluate the impact of DAAs treatment in pre- or peri-operative period in liver transplantation when grafts ≥ 70 years are used. This is a retrospective analysis comparing adult liver transplant performed for HCV-related cirrhosis and/or hepatocarcinoma using a graft ≥ 70 in the period 2015-2018 (Group DAA-HCV-OLD, study group) to three different groups: (a) anti-HCV-Ab-negative patients receiving graft ≥ 70 (no-HCV-OLD), (b) anti-HCV-Ab-negative patients receiving a graft aged 18-69 years (no-HCV-YOUNG), and (c) anti-HCV-Ab-positive patients receiving a donor graft ≥ 70 in the period 2007-2011 (no-DAA-HCV-OLD). Totally, 528 liver transplants were considered: 164 in DAA-HCV-OLD, 143 in no-HCV-OLD, 120 in no-HCV-YOUNG and 101 in no-DAA-HCV-OLD Group. Graft survival rates at 1 and 3 years were 88% and 81% in DAA-HCV-OLD Group, 82% and 68% in no-DAA-HCV-OLD (p = 0.007), 89% and 84% in no-HCV-OLD (p = 0.76), and 94% and 92% in no-HCV-YOUNG (p = 0.02). No differences were observed among groups in the incidence of primary non-function, primary dysfunction, vascular or biliary complications. DAAs were able to zero HCV-related graft loss, with a 3-year graft survival > 80%. The outcomes of older graft recipients became equal irrespectively of their HCV serological status.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34648952

RESUMO

BACKGROUND & AIMS: Missed or inappropriate referrals of potential candidates for liver transplantation (LT) are common and traditional referral methods (tRs) do not allow for efficient triage. We investigated the effects of a website developed for electronic outpatient referral to LT (eRW-LT) on these issues. METHODS: We prospectively collected data on all consecutive outpatient referrals to 2 Italian LT centers from January 2015 to December 2019. In the second half of the study, starting from July 2017, referring physicians had the option of using eRW-LT, quickly obtaining the judgment on the appropriateness and urgency of the visit from a transplant hepatologist. RESULTS: In the second half of the study, there were 99 eRW-LTs and 96 traditional referrals (new tRs), representing a 17.4% increase over the 161 traditional referrals (old tRs) of the first half. With eRW-LT, 11.1% of referrals were judged inappropriate online without booking a visit. Appropriateness, judged at the time of the first visit, was 59.6%, 56.2%, and 94.3% with old tRs, new tRs, and eRW-LT, respectively. Considering the appropriate visits, the median waiting time in days between referral date and first visit appointment was significantly shorter for urgent visits referred with eRW-LT (5.0; 95% CI, 4.8-9.3) compared with nonurgent visits sent with the same system (17.0; 95% CI, 11.5-25.0; P < .0001), those referred with old tRs (14.0; 95% CI, 8.0-23.0; P < .001) and with new tRs (16.0; 95% CI, 10.0-23.0; P < .001). CONCLUSIONS: eRW-LT allows an increase in the number of referrals for LT, ensuring effective triage and better appropriateness of visits.

4.
Updates Surg ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487336

RESUMO

Adult-to-adult living-donor liver transplantation (A2ALDLT) represents a challenging procedure, mainly when the right hepatic lobe is donated. Therefore, especially in Western countries, the medical community still considers it a "risky procedure". The present meta-analysis investigated the postoperative results reported in donors undergoing right hepatectomy for A2ALDLT through a minimally invasive liver resection (MILR) vs. open liver resection (OLR) approach, with the intent to clarify the hypothesis that the MILR approach should minimize the risks for the donor. A systematic literature search was performed using MEDLINE-PubMed, Cochrane Library, and EMBASE electronic databases. The primary outcome investigated was the complication rate after transplant. Fifteen studies were included (n = 2094; MILR = 553 vs. OLR = 1541). The MILR group only merged the statistical relevance in terms of advantage in terms of a lower number of complications (OR = 0.771, 95% CI 0.578-1.028; P value = 0.077). Investigating the complications ≥ IIIa according to the Dindo-Clavien classification, the estimated blood loss, and the length of hospital stay, no statistical difference was reported between the two groups. MILR represents a novel and promising approach for improving the results in A2ALDLT. However, no benefits have been reported regarding blood loss, length of stay, and postoperative complications. More extensive experiences are needed to re-evaluate the impact of MILR in right lobe live donation.

5.
Clin Transplant ; : e14495, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34569101

RESUMO

Solid organ transplant patients are at a higher risk for poor CoronaVirus Disease-2019 (COVID-19)-related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two-dose vaccination cycle with mRNA-based COVID-19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post-vaccine days, a SARS-CoV-2 anti-Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody-mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de novo HLA-donor-specific antibodies (DSA) were detected during the follow-up period. Only one patient with pre-vaccination HLA-DSA did not experience an increased intensity of the existing HLA-DSA. During the follow-up, only one infection (mild COVID-19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two-dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P = .02) and use of anti-metabolite as an immunosuppressant drug (OR = 5.26; P = .004). Among younger patients not taking anti-metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID-19 vaccination strategy in transplanted patients.

6.
J Clin Med ; 10(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361985

RESUMO

Immune checkpoint inhibitors (ICIs) are the new frontier for the treatment of advanced hepatocellular carcinoma (HCC). Since the first trial with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 inhibitor, increasing evidence has confirmed that these drugs can significantly extend the survival of patients with advanced hepatocellular carcinoma (HCC). As a matter of fact, the overall survival and objective response rates reported in patients with advanced HCC treated with ICIs are the highest ever reported in the second-line setting and, most recently, the combination of the anti-programmed death ligand protein-1 atezolizumab with bevacizumab-an anti-vascular endothelial growth factor monoclonal antibody-demonstrated superiority to sorafenib in a Phase III randomized clinical trial. Therefore, this regimen has been approved in several countries as first-line treatment for advanced HCC and is soon expected to be widely used in clinical practice. However, despite the promising results of trials exploring ICIs alone or in combination with other agents, there are still some critical issues to deal with to optimize the prognosis of advanced HCC patients. For instance, the actual proportion of patients who are deemed eligible for ICIs in the real-life ranges from 10% to 20% in the first-line setting, and is even lower in the second-line scenario. Moreover, long-term data regarding the safety of ICIs in the population of patients with cirrhosis and impaired liver function are lacking. Lastly, no biomarkers have been identified to predict response, and thus to help clinicians to individually tailor treatment. This review aimed to summarize the state of the art immunotherapy in HCC and, by analyzing a large, multicenter cohort of Italian patients with HCC, to assess the potential applicability of the combination of atezolizumab/bevacizumab in the real-life setting.

7.
Biology (Basel) ; 10(8)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34439960

RESUMO

(1) Background: To demonstrate correlation between skeletal muscle depletion measured before and after one month of TARE treatment and its induced local response rate. (2) Material and methods: For this retrospective, single center study, we evaluated 86 patients with HCC treated with TARE. Sarcopenia status was measured using the psoas muscle index (PMI). The PMI was calculated according to the formula: PMI [mm/m2]: [(minor diameter of left psoas + major diameter of left psoas + minor diameter of right psoas + major diameter of right psoas)/4]/height in m2. Population was divided in two groups according to the delta value of PMI measured at the time of TARE and one month after TARE, a group in which the delta PMI was stable or increased (No-Sarcopenia group; n = 42) vs. a group in which the delta-PMI decreased (Sarcopenia group; n = 44). Patient response was evaluated at 1, 3 and 6 months after TARE treatment with CT/MRI. (3) Results: When the radiological response of the tumor was evaluated according to the mRECIST criteria, the two groups were similar in terms of rates of complete response (p = 0.42), partial response (p = 0.26) and stable disease (p = 0.59). Progressive disease (PD) was more commonly observed in the Sarcopenia group (38.6% vs. 11.9%; p = 0.006). (4) Conclusions: Worsening of sarcopenia status measured one month after TARE is able to predict patients who will undergo disease progression.

8.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198853

RESUMO

In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving ≥50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by α-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipase/genética , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Idoso , Feminino , Regulação da Expressão Gênica/genética , Hepacivirus/genética , Hepatócitos/virologia , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Gotículas Lipídicas/virologia , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/virologia , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos
10.
JAMA Surg ; 156(9): e213112, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259797

RESUMO

Importance: Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). Objective: To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. Design, Setting, and Participants: This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. Main Outcomes and Measures: Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. Results: A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. Conclusions and Relevance: This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

11.
Sci Rep ; 11(1): 15184, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312420

RESUMO

This study aimed to ascertain, for the first time, whether serum magnesium (Mg) concentration is affected by the presence of hepatocellular carcinoma (HCC). We retrospectively enrolled consecutive cirrhotic patients with a diagnosis of HCC (n = 130) or without subsequent evidence of HCC during surveillance (n = 161). Serum levels of Mg were significantly (P < 0.001) lower in patients with HCC than in those without (median [interquartile range]: 1.80 [1.62-1.90] mg/dl vs. 1.90 [1.72-2.08] mg/dl). On multivariate logistic regression, low serum Mg was associated with the presence of HCC (OR 0.047, 95% CI 0.015-0.164; P < 0.0001), independently from factors that can influence magnesaemia and HCC development. In a subset of 94 patients with HCC, a linear mixed effects model adjusted for confounders showed that serum Mg at diagnosis of HCC was lower than before diagnosis of the tumor (ß = 0.117, 95% CI 0.039-0.194, P = 0.0035) and compared to after locoregional treatment of HCC (ß = 0.079, 95% CI 0.010-0.149, P = 0.0259), with two thirds of patients experiencing these changes of serum Mg over time. We hypothesize that most HCCs, like other cancers, may be avid for Mg and behave like a Mg trap, disturbing the body's Mg balance and resulting in lowering of serum Mg levels.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Magnésio/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Hepáticas/terapia , Deficiência de Magnésio/sangue , Deficiência de Magnésio/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Am J Transplant ; 21 Suppl 3: 17-59, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245223

RESUMO

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante de Rim , Transplante de Pâncreas , Sobrevivência de Enxerto , Humanos , Qualidade de Vida , Diálise Renal
13.
Pol J Pathol ; 72(1): 89-96, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060293

RESUMO

Lymphomas presenting and mimicking soft-tissue masses are important to recognize, to avoid unnecessary treatment delays or extensive surgery. We describe a case of primary anaplastic large cell lymphoma (ALCL) arising from a deep skeletal muscle in a middle-aged male. He presented with a two-month history of swelling of his right thigh and mild fever, which led to a diagnosis of abscess formation. Antibiotics were prescribed for two weeks, with little improvement of symptoms. Subsequently, an exploratory surgery, with excision of the mass, demonstrated a ALCL of the psoas muscle, ALK-1 positive.


Assuntos
Linfoma Anaplásico de Células Grandes , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Psoas/diagnóstico por imagem
14.
Cancers (Basel) ; 13(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067521

RESUMO

The XXL trial represents the first prospective validation of "biological downstaging" in liver transplantation (LT) for hepatocellular carcinoma. The aim of this study was to compare the Padua downstaging protocol to the XXL protocol in terms of downstaging failure rates and patient outcome. A total of 191 patients undergoing aggressive surgical downstaging and potentially eligible for LT from 2012 to 2018 at our center were retrospectively selected according to XXL trial criteria. Unlike the XXL trial, patients with a complete response to downstaging did not receive any prioritization for LT. Downstaging failure was defined as stable progressive disease or post-treatment mortality. The statistical method of "matching-adjusted indirect comparison" was used to match the study group to the XXL population. Downstaging failure rate was considerably lower in the study group than in the XXL trial (12% vs. 32%, d value = |0.683|). The survival curves of our LT group (n = 68) overlapped with those of the LT-XXL group (p = 0.846). Survival curves of non-LT candidates with a sustained complete response (n = 64) were similar to those of transplanted patients (p = 0.281). Our study represents a validation of the current Padua and Italian policies of denying rapid prioritization to patients with complete response to downstaging. Such a policy seems to spare organs without worsening patient outcome.

15.
JAMA Surg ; 156(6): 559-567, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33950167

RESUMO

Importance: Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. Objective: To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models. Design, Setting, and Participants: A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020. Main Outcomes and Measures: The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome. Results: Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0. Conclusions and Relevance: This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.

16.
Updates Surg ; 73(5): 1599-1614, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34003479

RESUMO

The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Seleção de Pacientes , Estudos Retrospectivos
17.
Liver Int ; 41(7): 1629-1640, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33793054

RESUMO

BACKGROUND & AIMS: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility. METHODS: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). RESULTS: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra point of MELDNa was added for each 0.5 cm2 /m2 reduction of total psoas area (TPA) < 6.0 cm2 /m2 . At external validation, the Sarco-Model2 showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P = .003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model2 . As for the futility threshold, transplanted patients with TPA < 6.0 cm2 /m2 and MELDNa 35-40 (n = 16/833, 1.9%) had the worse results (6-month graft loss = 25.5%). CONCLUSIONS: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco-Model2 should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco-Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, 'futile' transplantation should be considered.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Adulto , Doença Hepática Terminal/cirurgia , Humanos , Cirrose Hepática , Prognóstico , Índice de Gravidade de Doença , Listas de Espera
18.
Eur J Clin Invest ; 51(8): e13575, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33866547

RESUMO

BACKGROUND: Prophylaxis with hepatitis B immunoglobulin (HBIG) represents an efficient strategy for reducing the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). Unfortunately, the long-term use of HBIG presents high costs. Therefore, the use of prophylaxis based only on nucleos(t)ide analogues (NUC) has been recently postulated. The present meta-analysis aimed to evaluate the impact of HBIG ± NUC vs HBIG alone or NUC alone in post-LT HBV recurrence prophylaxis. MATERIALS AND METHODS: A systematic literature search was performed using PubMed and Cochrane databases. The primary outcome investigated was the HBV recurrence after LT. Three analyses were done comparing the effect of (a) HBIG + NUC vs HBIG alone; (b) HBIG+NUC vs NUC alone; and (c) HBIG alone vs NUC alone. Sub-analyses were also performed investigating the effect of low and high genetic barrierto-recurrence NUC. RESULTS: Fifty-one studies were included. The summary OR (95%CI) showed a decreased risk with the combination of HBIG + NUC vs HBIG alone for HBV recurrence, being 0.36 (95% CI = 0.22-0.61; P < .001). HBIG + NUC combined treatment reduced HBV reappearance respect to NUC alone (OR = 0.22; 95% CI = 0.16-0.30; P < .0001). Similarly, HBIG alone was significantly better than NUC alone in preventing HBV recurrence (OR = 0.20; 95% CI = 0.09-0.44; P < .0001). CONCLUSIONS: Prophylaxis with HBIG is relevant in preventing post-LT HBV recurrence. Its combination with NUC gives the best results in terms of protection. The present results should be considered in light of the fact that also old studies based on lamivudine use were included. Studies exploring in detail high genetic barrier-to-recurrence NUC and protocols with definite use of HBIG are needed.

19.
Hepatobiliary Surg Nutr ; 10(2): 210-225, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33898561

RESUMO

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) represents an innovative surgical technique used for the treatment of large hepatic lesions at high risk for post-resection liver failure due to a small future liver remnant. The most significant amount of literature concerns the use of ALPPS for the treatment of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and colorectal liver metastases (CRLM). On the opposite, few is known about the role of ALPPS for the treatment of uncommon liver pathologies. The objective of the present study was to evaluate the current literature on this topic. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible articles published up to February 2020 were included using the MEDLINE, Scopus, and Cochrane databases. Among the 486 articles screened, 45 papers met the inclusion criteria, with 136 described cases of ALPPS for rare indications. These 136 cases were reported in 18 different countries. Only in two countries, namely Germany and Brazil, more than ten cases were observed. As for the ALPPS indications, we reported 41 (30.1%) cases of neuroendocrine tumor (NET) metastases, followed by 27 (19.9%) cases of gallbladder cancer (GBC), nine (6.6%) pediatric cases, six (4.4%) gastrointestinal stromal tumors, six (4.4%) adult cases of benign primary liver disease, four (2.9%) adult cases of malignant primary liver disease, and 43 (31.6%) adult cases of malignant secondary liver disease. According to the International ALPPS Registry data, less than 10% of the ALPPS procedures have been performed for the treatment of uncommon liver pathologies. NET and GBC are the unique pathologies with acceptable numerosity. ALPPS for NET appears to be a safe procedure, with satisfactory long-term results. On the opposite, the results observed for the treatment of GBC are poor. However, these data should be considered with caution. The rationale for treating benign pathologies with ALPPS appears to be weak. No definitive response should be given for all the other pathologies. Multicenter studies are needed with the intent to clarify the potentially beneficial effect of ALPPS for their treatment.

20.
Updates Surg ; 73(4): 1381-1389, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33792888

RESUMO

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.


Assuntos
Transplante de Fígado , Adulto , Criança , Hábitos , Humanos , Itália/epidemiologia , Doadores Vivos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
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