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1.
Ann Surg Oncol ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969858

RESUMO

BACKGROUND: The risk for recurrence in patients with distal gastric cancer can be reduced by surgical radicality. However, dispute exists about the value of the proposed minimum proximal margin distance (PMD). Here, we assess the prognostic value of the safety distance between the proximal resection margin and the tumor. PATIENTS AND METHODS: This is a single-center cohort study of patients undergoing distal gastrectomy for gastric adenocarcinoma (2001-2021). Cohorts were defined by adequacy of the PMD according to the European Society for Medical Oncology (ESMO) guidelines (≥ 5 cm for intestinal and ≥ 8 cm for diffuse Laurén's subtypes). Overall survival (OS) and time to progression (TTP) were assessed by log-rank and multivariable Cox-regression analyses. RESULTS: Of 176 patients, 70 (39.8%) had a sufficient PMD. An adequate PMD was associated with cancer of the intestinal subtype (67% vs. 45%, p = 0.010). Estimated 5-year survival was 63% [95% confidence interval (CI) 51-78] and 62% (95% CI 53-73) for adequate and inadequate PMD, respectively. Overall, an adequate PMD was not prognostic for OS (HR 0.81, 95% CI 0.48-1.38) in the multivariable analysis. However, in patients with diffuse subtype, an adequate PMD was associated with improved oncological outcomes (median OS not reached versus 131 months, p = 0.038, median TTP not reached versus 88.0 months, p = 0.003). CONCLUSION: Patients with diffuse gastric cancer are at greater risk to undergo resection with an inadequate PMD, which in those patients is associated with worse oncological outcomes. For the intestinal subtype, there was no prognostic association with PMD, indicating that a distal gastrectomy with partial preservation of the gastric function may also be feasible in the setting where an extensive PMD is not achievable.

2.
Liver Int ; 44(7): 1483-1512, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38554051

RESUMO

Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.


Assuntos
Composição Corporal , Transplante de Fígado , Sarcopenia , Humanos , Sarcopenia/complicações , Transplante de Fígado/efeitos adversos , Fatores de Risco , Hepatopatias/complicações , Desnutrição/complicações , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia
3.
Transpl Infect Dis ; 26(1): e14196, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010975

RESUMO

INTRODUCTION: Cytomegalovirus (CMV)-infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV-IgG-status has been established for risk stratification when choosing various pharmaceutical regimens for CMV-prophylaxis in the last two decades. However, factors influencing course of CMV-infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. METHODS: All patients that underwent primary LT between 2006 and 2018 at the Charité-Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV-occurrence was conducted, and survival was examined using Kaplan-Meier analysis. RESULTS: Overall, 867 patients were included in the final analysis. CMV-infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV-IgG-status with either positivity had the largest influence on CMV-occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV-infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02). DISCUSSION: CMV-infection remains of clinical importance after LT. Undergone CMV-infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage-dependent impact of immunosuppression (IS) on long-term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients.


Assuntos
Infecções por Citomegalovirus , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Fatores de Risco , Citomegalovirus , Imunossupressores/efeitos adversos , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/diagnóstico , Imunoglobulina G/uso terapêutico , Progressão da Doença , Estudos Retrospectivos , Antivirais/uso terapêutico
4.
Eur Surg Res ; 64(1): 54-64, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34903685

RESUMO

INTRODUCTION: In an attempt to further improve surgical outcomes, a variety of outcome prediction and risk-assessment tools have been developed for the clinical setting. Risk scores such as the surgical Apgar score (SAS) hold promise to facilitate the objective assessment of perioperative risk related to comorbidities of the patients or the individual characteristics of the surgical procedure itself. Despite the large number of scoring models in clinical surgery, only very few of these models have ever been utilized in the setting of laboratory animal science. The SAS has been validated in various clinical surgical procedures and shown to be strongly associated with postoperative morbidity. In the present study, we aimed to review the clinical evidence supporting the use of the SAS system and performed a showcase pilot trial in a large animal model as the first implementation of a porcine-adapted SAS (pSAS) in an in vivo laboratory animal science setting. METHODS: A literature review was performed in the PubMed and Embase databases. Study characteristics and results using the SAS were reported. For the in vivo study, 21 female German landrace pigs have been used either to study bleeding analogy (n = 9) or to apply pSAS after abdominal surgery in a kidney transplant model (n = 12). The SAS was calculated using 3 criteria: (1) estimated blood loss during surgery; (2) lowest mean arterial blood pressure; and (3) lowest heart rate. RESULTS: The SAS has been verified to be an effective tool in numerous clinical studies of abdominal surgery, regardless of specialization confirming independence on the type of surgical field or the choice of surgery. Thresholds for blood loss assessment were species specifically adjusted to >700 mL = score 0; 700-400 mL = score 1; 400-55 mL score 2; and <55 mL = score 3 resulting in a species-specific pSAS for a more precise classification. CONCLUSION: Our literature review demonstrates the feasibility and excellent performance of the SAS in various clinical settings. Within this pilot study, we could demonstrate the usefulness of the modified SAS (pSAS) in a porcine kidney transplantation model. The SAS has a potential to facilitate early veterinary intervention and drive the perioperative care in large animal models exemplified in a case study using pigs. Further larger studies are warranted to validate our findings.


Assuntos
Ciência dos Animais de Laboratório , Humanos , Recém-Nascido , Feminino , Suínos , Animais , Projetos Piloto , Índice de Apgar , Estudos Retrospectivos , Complicações Pós-Operatórias
5.
HPB (Oxford) ; 25(11): 1354-1363, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37438185

RESUMO

BACKGROUND: Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited. METHODS: Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36). DISCUSSION: The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.

6.
Am J Transplant ; 22(8): 1943-1957, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35523584

RESUMO

Frailty, nutritional status, and body composition are increasingly under the spotlight of interest in various clinical scenarios including liver transplantation. To address the rapidly accumulating evidence in this field, recent European and North American practice guidelines have clearly underlined the clinical importance of nutritional status and body composition with adopting their assessment in patients with liver disease and in transplant candidates into their recommendations. While earlier reports, and therefore present guidelines, were focusing predominantly on quantitative alterations of the skeletal muscle mass (sarcopenia), recent studies have identified qualitative alterations such as intramuscular fat accumulation (myosteatosis) and sarcopenic obesity as emerging risk factors for poor clinical outcomes. In this review, the role of body composition in the context of liver transplantation will be discussed with a focus on the skeletal muscle compartment. A brief overview of current assessment modalities including their limitations, diagnostic challenges, prognostic significance, and pathophysiology are included. Possibilities to incorporate body composition parameters into clinical decision making are discussed. In addition, novel trends and remaining challenges in the therapeutic targeting of body composition and the skeletal muscle compartment are highlighted.


Assuntos
Transplante de Fígado , Sarcopenia , Composição Corporal/fisiologia , Humanos , Transplante de Fígado/efeitos adversos , Músculo Esquelético/patologia , Obesidade , Sarcopenia/diagnóstico , Sarcopenia/etiologia
7.
Langenbecks Arch Surg ; 407(6): 2381-2391, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35599252

RESUMO

PURPOSE: While liver resection is a well-established treatment for primary HCC, surgical treatment for recurrent HCC (rHCC) remains the topic of an ongoing debate. Thus, we investigated perioperative and long-term outcome in patients undergoing re-resection for rHCC in comparative analysis to patients with primary HCC treated by resection. METHODS: A monocentric cohort of 212 patients undergoing curative-intent liver resection for HCC between 2010 and 2020 in a large German hepatobiliary center were eligible for analysis. Patients with primary HCC (n = 189) were compared to individuals with rHCC (n = 23) regarding perioperative results by statistical group comparisons and oncological outcome using Kaplan-Meier analysis. RESULTS: Comparative analysis showed no statistical difference between the resection and re-resection group in terms of age (p = 0.204), gender (p = 0.180), ASA category (p = 0.346) as well as main preoperative tumor characteristics, liver function parameters, operative variables, and postoperative complications (p = 0.851). The perioperative morbidity (Clavien-Dindo ≥ 3a) and mortality were 21.7% (5/23) and 8.7% (2/23) in rHCC, while 25.4% (48/189) and 5.8% (11/189) in primary HCC, respectively (p = 0.851). The median overall survival (OS) and recurrence-free survival (RFS) in the resection group were 40 months and 26 months, while median OS and RFS were 41 months and 29 months in the re-resection group, respectively (p = 0.933; p = 0.607; log rank). CONCLUSION: Re-resection is technically feasible and safe in patients with rHCC. Further, comparative analysis displayed similar oncological outcome in patients with primary and rHCC treated by liver resection. Re-resection should therefore be considered in European patients diagnosed with rHCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Int J Mol Sci ; 23(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35457205

RESUMO

This editorial aims to summarize the 13 scientific articles published in the Special Issue entitled "New Frontiers in Organ Preservation and Hepatoprotection" [...].


Assuntos
Preservação de Órgãos
9.
Int J Mol Sci ; 23(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35563662

RESUMO

Organ shortage has led to the increasing utilization of livers retrieved from donors after circulatory death (DCD). These pre-damaged organs are susceptible to further warm ischemia and exhibit minimal tolerance for cold storage. The aim was thus to examine the effects of fibrinolysis combined with Venous Systemic Oxygen Persufflation (VSOP) on the preservation of DCD livers in vivo. Livers of male Lewis rats were explanted after 45 min of warm ischemia, cold-stored for 18 h, and transplanted into a recipient animal. Livers were left untreated or underwent either VSOP or fibrinolysis via Streptokinase (SK) or received combined SK and VSOP. Combined treatment exhibited improved microvascular flow at 168 h (p = 0.0009) and elevated microperfusion velocity at 24 h post-transplantation (p = 0.0007). Combination treatment demonstrated increased portal venous flow (PVF) at 3 and 24 h post-transplantation (p = 0.0004, p < 0.0001), although SK and VSOP analogously achieved increases at 24 h (p = 0.0036, p = 0.0051). Enzyme release was decreased for combination treatment (p = 0.0002, p = 0.0223) and lactate dehydrogenase (LDH) measurements were lower at 24 h post-transplantation (p = 0.0287). Further supporting findings have been obtained in terms of serum cytokine levels and in the alterations of endothelial injury markers. The combination treatment of SK + VSOP might provide improved organ integrity and viability and may therefore warrant further investigation as a potential therapeutic approach in the clinical setting of DCD.


Assuntos
Transplante de Fígado , Animais , Fibrinólise , Fígado , Masculino , Preservação de Órgãos , Oxigênio/farmacologia , Perfusão , Ratos , Ratos Endogâmicos Lew
10.
Int J Mol Sci ; 23(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36430283

RESUMO

Ischemia-reperfusion injury remains a fundamental problem during organ transplantation logistics. One key technical factor is the rapid allograft rewarming during the time of vascular reconstruction in the recipient. In this pilot study, a new thermal insulation bag (TIB) for organ transplantation was used. Insulation capacity, tissue compatibility, and usability were tested initially ex vivo on porcine kidneys (n = 24) followed by the first in vivo usage. Fourteen female German landrace pigs underwent kidney auto-transplantation after 24 h cold storage (4 °C). During the implantation process the kidney was either insulated with the new TIB, or it was not thermo-protected at all, which represents the clinical standard. In this proof-of-concept study, the usability (knife-to-skin-time) and the general thermal capacity (30 min warm storage at 38 °C ex vivo p < 0.001) was shown. The clinical outcome showed significant differences in the determination of CRP and pi-GST levels. Syndecan-1 Antibody staining showed clear significant higher counts in the control group (p < 0.01) indicating epithelial damage. However, the effect on renal outcomes in not severely pre-damaged kidneys does not appear to be conclusively significant. A close follow-up study is warranted, especially in the context of marginal organs or in cases where anastomosis-times are prolonged due to surgical complexity (e.g., multiple vessels and complex reconstructions).


Assuntos
Transplante de Rim , Preservação de Órgãos , Feminino , Suínos , Animais , Seguimentos , Projetos Piloto , Rim/irrigação sanguínea
11.
HPB (Oxford) ; 24(7): 1119-1128, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35078714

RESUMO

BACKGROUND: Pancreatic tumors are frequently diagnosed in a locally advanced stage with poor prognosis if untreated. This study assesses the safety and oncological outcomes of pancreatic surgery with arterial en-bloc resection. METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent a pancreatic resection with arterial resection between 2011 and 2020. Univariable analyses were used to assess prognostic factors for survival. RESULTS: Forty consecutive patients (22 female; 18 male) undergoing arterial resections were included. Surgical procedures consisted of 19 pancreatoduodenectomies (PD, 48%), 16 distal splenopancreatectomy (DSP, 40%), and 5 total pancreatectomies (TP, 12%). Arterial resection included hepatic arteries (HA, N = 23), coeliac trunk (TC, N = 15) and superior mesenteric artery (SMA, N = 2). Neoadjuvant therapy was applied in 22 patients (58%). Major complications after surgery were observed in 15% of cases. 90-day mortality was 5%. Median disease-free survival and median overall survival were for the R0/CRM- group 22.8 months and 27.9 months, 9.5 and 19.8 months for the R0/CRM+ group, and 10.1 and 13.1 months for the R1 group, respectively. CONCLUSION: In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Artéria Celíaca/diagnóstico por imagem , Artéria Celíaca/cirurgia , Feminino , Humanos , Masculino , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos
12.
Ann Surg ; 274(5): 705-712, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34334635

RESUMO

OBJECTIVE: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). BACKGROUND: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). METHODS: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). RESULTS: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). CONCLUSION: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.


Assuntos
Hipotermia Induzida/instrumentação , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Complicações Pós-Operatórias/prevenção & controle , Doadores de Tecidos/provisão & distribuição , Idoso , Aloenxertos , Desenho de Equipamento , Europa (Continente)/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia
13.
Transpl Int ; 34(8): 1468-1480, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34157178

RESUMO

Liver transplantation is still associated with a high risk of severe complications and post-operative mortality. This study examines the predictive value of the preoperative C-reactive-protein-to-albumin ratio (CAR) regarding perioperative morbidity and mortality in deceased-donor liver transplantation (DDLT) recipients. In total, 390 DDLT recipients between 05/2010 and 03/2020 were eligible. Predictive abilities of CAR were examined through receiver operating characteristic curve (ROC) analyses. Groups were compared using parametric and non-parametric tests as appropriate. Independent risk factors for morbidity and mortality were identified using uni- and multivariable logistic regression analyses. A good predictive ability for CAR was shown regarding perioperative morbidity (comprehensive complication index ≥75, Clavien-Dindo score ≥4a) and 12-month mortality, with an ideal cut-off of CAR = 26%. Patients with CAR>26% had significantly higher median CCI scores (60 vs. 43, P < 0.001), longer intensive care unit (ICU, 5 vs. 4 days, P < 0.001) and hospital (28 vs. 21 days, P < 0.001) stays and higher 12-month mortality rates (20% vs 6%, P < 0.001). Multivariable analyses identified CAR>26%, pre-OLT inpatient hospitalization (including ICU) and post-operative red blood cell transfusions as independent predictors of severe cumulative morbidity (CCI≥75). Preoperative CAR might be a reliable additional tool to predict perioperative morbidity and mortality in DDLT recipients.


Assuntos
Transplante de Fígado , Albuminas , Proteína C-Reativa , Humanos , Doadores Vivos , Morbidade , Estudos Retrospectivos , Fatores de Risco
14.
Transpl Int ; 34(5): 778-800, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33728724

RESUMO

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.


Assuntos
Transplante de Fígado , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
15.
Langenbecks Arch Surg ; 406(1): 75-86, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33294952

RESUMO

PURPOSE: No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. METHODS: Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) χ2 (homogeneity), linear trend (LT) χ2 (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. RESULTS: Liver resection for HCC was performed in 160 patients. Median OS was 39 months (95% confidence interval (CI): 32-46 months) and median RFS was 26 months (95% CI: 16-34 months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR χ2 30.08, LT χ2 13.90, AIC 455.27) and CLIP (LR χ2 28.65, LT χ2 18.95, AIC 460.07) being the best performing staging systems. CONCLUSIONS: ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Prognóstico
16.
Int J Mol Sci ; 22(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668478

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular-pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.


Assuntos
Fígado/metabolismo , Preservação de Órgãos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Velocidade do Fluxo Sanguíneo , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Humanos , Fígado/patologia , Traumatismo por Reperfusão/patologia
17.
HPB (Oxford) ; 23(1): 99-108, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32546423

RESUMO

BACKGROUND: Major liver resection has evolved as the mainstay of treatment for patients with perihilar cholangiocarcinoma (pCCA). Here we assessed the suitability of preoperative future liver remnant (FLR) measurement to predict perioperative complications, since surgical morbidity and mortality are high compared to other malignancies. METHODS: Between 2011 and 2016, 91 patients with pCCA underwent surgery in curative intent at our institution. The associations of surgical complications with FLR and clinico-pathological characteristics were assessed using logistic regression analyses. Different methods of FLR assessment, the calculated-FLR (cFLR; ratio of FLR to total liver volume), standardized FLR (sFLR; ratio of FLR to liver volume estimated by body surface area) and FLR to bodyweight ratio (FLR/BW) were tested for validity. RESULTS: Multivariable analysis identified preoperative cholangitis (Exp(B) = 0.236; p = 0.030) as the single significant predictor of postoperative mortality and cFLR (Exp(B) = 0.009, p = 0.004) as the single significant predictor of major postoperative morbidity (Clavien-Dindo ≥ 3b). Based on these findings we designed a futility criterion (cFLR<40% OR preoperative cholangitis) predicting in-house mortality. CONCLUSIONS: In patients with pCCA, the preoperative FLR<40% as well as preoperative cholangitis are two risk factors to independently predict perioperative morbidity and mortality. The cFLR should be the preferred method of liver volumetry.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite , Tumor de Klatskin , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Colangite/diagnóstico , Colangite/etiologia , Hepatectomia/efeitos adversos , Humanos , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Fígado , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
18.
HPB (Oxford) ; 23(10): 1565-1577, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33934958

RESUMO

BACKGROUND: While a certain degree of tumor infiltration of the portal vein is common in patients with perihilar cholangiocarcinoma (pCCA) scheduled for surgery, complete tumor-associated portal vein occlusion (PVO) is less frequently observed. Here, we analyzed the impact of PVO on perioperative and oncological outcomes in pCCA patients. METHODS: Between 2010 and 2019, 127 patients with pCCA underwent surgery in curative intent at our department of which 17.3% (22/127) presented with PVO. Extensive group comparisons were conducted and the association of cancer-specific (CSS) and disease-free survival (DFS) with PVO and other clinico-pathological characteristics were assessed using Cox regression models. RESULTS: Patients without PVO showed a median CSS of 65 months (3-year-CSS = 64%, 5-year-CSS = 53%) compared to 31 months (3-year-CSS = 43%, 5-year-CSS = 17%) in patients with PVO (p = 0.025 log rank). Patients with PVO did also display significant perioperative mortality (22.7%, 5/22) compared to patients without PVO (14.3%, 15/105, p = 0.323). Further, PVO (CSS: HR = 5.25, p = 0.001; DFS: HR = 5.53, p = 0.001) was identified as independent predictors of oncological outcome. CONCLUSIONS: PVO has been identified as an important prognostic marker playing a role in inferior oncological outcome in patients with pCCA. As PVO is also associated with notable perioperative mortality, surgical therapy should be considered carefully in pCCA patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Humanos , Tumor de Klatskin/complicações , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Prognóstico , Estudos Retrospectivos
19.
Am J Transplant ; 20(2): 493-503, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31448486

RESUMO

Muscle wasting and alterations of body composition are linked to clinical outcomes in numerous medical conditions. The role of myosteatosis in posttransplant outcomes remains to be determined. Here we investigated skeletal muscle mass and myosteatosis as prognostic factors in patients undergoing orthotopic liver transplantation (OLT). The data of 225 consecutive OLT recipients from a prospective database were retrospectively analyzed (May 2010-December 2017). Computed tomography-based skeletal-muscle-index (muscle mass), visceral-fat-area (visceral adiposity), and mean skeletal-muscle-radiation-attenuation (myosteatosis) were calculated using a segmentation tool. Cut-off values of myosteatosis resulted in a good stratification of patients into low- and high-risk groups in terms of morbidity (Clavien-Dindo ≥3b). Patients with myosteatosis had significantly higher complication rates (90-day Comprehensive Complication Index 68 ± 32 vs 44 ± 30, P < .001) and also displayed significantly longer intensive care (18 ± 25 vs 11 ± 21 days, P < .001) and hospital stay (56 ± 55 vs 33 ± 24 days, P < .001). Estimated costs were 44% higher compared to patients without myosteatosis. Multivariable analysis identified myosteatosis as an independent prognostic factor for major morbidity (odds ratio: 2.772, confidence interval: 1.516-5.066, P = .001). Adding myosteatosis to the well-established Balance-of-Risk-(BAR) score resulted in an increased prognostic value compared to the original BAR score. Myosteatosis may be a useful parameter to predict perioperative outcome in patients undergoing OLT, supporting the role of muscle quality (myosteatosis) over quantity (muscle mass) in this setting.


Assuntos
Transplante de Fígado , Atrofia Muscular/complicações , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Composição Corporal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Atrofia Muscular/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios X , Transplante Homólogo
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