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PURPOSE: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). METHODS: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of 166Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. RESULTS: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up. CONCLUSION: Adjuvant (super-)selective infusion of 166Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm. TRIAL REGISTRATION: Clinicaltrials.gov NCT03437382 . (registered: 19-02-2018).
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Carcinoma Hepatocelular , Embolización Terapéutica , Holmio , Neoplasias Hepáticas , Radioisótopos , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/terapia , Masculino , Holmio/uso terapéutico , Femenino , Anciano , Persona de Mediana Edad , Embolización Terapéutica/métodos , Radioisótopos/uso terapéutico , Radioisótopos/administración & dosificación , Ablación por Radiofrecuencia/métodos , Dosificación Radioterapéutica , Estadificación de Neoplasias , Distribución TisularRESUMEN
BACKGROUND: The administration of contrast medium is associated with acute kidney injury; however, the effect of exposure of a deceased organ donor to contrast medium on kidney transplant outcomes has been poorly studied. METHODS: A retrospective analysis of all deceased kidney donors between 2011 and 2021 and their corresponding recipients in the Netherlands was conducted. Multivariable analyses were performed to assess the associations between contrast medium exposure and delayed graft function (DGF)/graft survival. Linear mixed models were used to assess the differences in mean estimated glomerular filtration rate values in recipients 1 to 6 y after transplantation. RESULTS: In total, 2177 donors and 3638 corresponding kidney graft recipients were included. Twenty-four percent of the donors (n = 520) were exposed to contrast medium, corresponding to 23% of recipients (n = 832). DGF was observed in 36% (n = 1321) and primary nonfunction in 3% (n = 122) of recipients. DGF rates for donation after brain death (DBD) and donation after circulatory death (DCD) donors showed no significant effect of contrast medium exposure ( P = 0.15 and P = 0.60 for DBD and DCD donors, respectively). In multivariable analyses, contrast medium administration was not significantly associated with a higher DGF risk (odds ratio 1.06; 95% confidence interval, 0.86-1.36; P = 0.63) nor was a significant predictor for death-censored graft failure (hazard ratio 1.01; 95% confidence interval, 0.77-1.33; P = 0.93). Linear mixed models showed no difference in mean estimated glomerular filtration rate values in recipients 1 to 6 y posttransplantation ( P = 0.78). CONCLUSIONS: This study indicates that contrast medium administration in DBD and DCD donors has no negative effect on early and long-term kidney graft function.
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Trasplante de Riñón , Obtención de Tejidos y Órganos , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Supervivencia de Injerto , Donantes de Tejidos , Muerte Encefálica , Funcionamiento Retardado del Injerto/etiologíaRESUMEN
Background & Aims: In the USA, inequal liver transplantation (LT) access exists between patients with and without hepatocellular carcinoma (HCC). Survival benefit considers survival without and with LT and could equalise LT access. We calculated bias-corrected LT survival benefit for patients with(out) HCC who underwent a transplant, based on longitudinal data in a recent United States cohort. Methods: Adult LT candidates with(out) HCC between 2010 and 2019 were included. Waitlist survival over time was contrasted to post-transplant survival, to estimate 5-year survival benefit from the moment of LT. Waitlist survival was modelled with a bias-corrected Cox regression, and post-transplant survival was estimated through Cox proportional hazards regression. Results: Mean HCC survival without LT was always lower than non-HCC waitlist survival. Below model for end-stage liver disease (sodium) (MELD(-Na)) 30, patients with HCC gained more life-years from LT than patients without HCC at the same MELD(-Na) score. Only patients without HCC below MELD(-Na) 9 had negative benefit. Most patients with HCC underwent a transplant below MELD(-Na) 14, and most patients without HCC underwent a transplant above MELD(-Na) 26. Liver function [MELD(-Na), albumin] was the main predictor of 5-year benefit. Therefore, during 5 years, most patients with HCC gained 0.12 to 1.96 years from LT, whereas most patients without HCC gained 2.48 to 3.45 years. Conclusions: On an individual level, performing a transplant in patients with HCC resulted in survival benefit. However, on a population level, benefit was indirectly decreased, as patients without HCC were likely to gain more survival owing to decreased liver function. For patients who underwent a transplant, a constructed online calculator estimates 5-year survival benefit given specific patient characteristics. Survival benefit scores could serve to equalise LT access. Impact and implications: Benefit is a comparison of the survival with and without liver transplantation, and it is important when deciding who should undergo a transplant. Liver function is most important when predicting possible benefit from transplantation. Patients with liver cancer die sooner on the waiting list than similar patients without liver cancer. However, patients with liver cancer more often have better liver function. Most patients without liver cancer derive more benefit from transplantation than patients with liver cancer.
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BACKGROUND: Currently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study. METHOD: Using the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed. RESULTS: The five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease. CONCLUSION: This DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies.
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BACKGROUND: Disseminated disease (DD) is often found at (re-)exploration in gallbladder cancer (GBC) patients. We aimed to assess the yield of staging laparoscopy (SL) and identify predictors for DD. METHODS: This retrospective study included patients from all Dutch academic centres with primary GBC (pGBC) and incidentally diagnosed GBC (iGBC) planned for (re-)resection. The yield of SL was determined. In iGBC, predictive factors for DD were assessed. RESULTS: In total, 290 patients were included. Of 183 included pGBC patients, 143 underwent laparotomy without SL, and 42 (29%) showed DD perioperatively. SL, conducted in 40 patients, identified DD in eight. DD was found in nine of 32 patients who underwent laparotomy after SL. Of 107 included iGBC patients, 100 underwent laparotomy without SL, and 19 showed DD perioperatively. SL, conducted in seven patients, identified DD in one. Cholecystitis (OR = 4.25; 95% CI 1.51-11.91) and primary R1/R2 resection (OR = 3.94; 95% CI 1.39-11.19) were independent predictive factors for DD. CONCLUSIONS: In pGBC patients, SL may identify DD in up to 20% of patients and should be part of standard management. In iGBC patients, SL is indicated after primary resection for cholecystitis and after initial R1/R2 resection due to the association of these factors with DD.
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Carcinoma in Situ , Colecistitis , Neoplasias de la Vesícula Biliar , Laparoscopía , Humanos , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/patología , Estudios de Cohortes , Estudios Retrospectivos , Estadificación de Neoplasias , Colecistitis/cirugía , Carcinoma in Situ/cirugíaRESUMEN
PURPOSE: To investigate the biodistribution of holmium-166 microspheres (166Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume). MATERIALS AND METHODS: This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2-5 cm, or a maximum of 3 lesions of ≤ 3 cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (99mTc-MAA). The perfused liver volume is segmented from the CBCT and 166Ho-MS is administered to this treatment volume 5-10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of ≥ 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival. DISCUSSION: This study aims to find the optimal administration dose of adjuvant radioembolization with 166Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03437382.
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Carcinoma Hepatocelular , Ablación por Catéter , Embolización Terapéutica , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Embolización Terapéutica/métodos , Holmio , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Estudios Prospectivos , Radioisótopos , Estudios Retrospectivos , Distribución Tisular , Resultado del TratamientoRESUMEN
OBJECTIVES: The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant. MATERIALS AND METHODS: Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our analyses. Liver utilization was defined by transplant status as the primary outcome to evaluate the performance of the Eurotransplant-developed Discard Risk Index. RESULTS: Of 11670 potential livers, 9565 (81%) were actually transplanted. Donor sex, age, history of diabetes, drug abuse, use of vasopressors, body mass index category, serum sodium, cause of death, donor type, and levels of C-reactive protein, bilirubin, aspartate and alanine aminotransferases, international normalized ratio, and gamma-glutamyltranspeptidase were associated with discard and combined in the Eurotransplant-developed Discard Risk Index. Correlation between the two Discard Risk Indexes was high (r = 0.86), and both achieved high C statistics of 0.72 and 0.75 (P < .001), respectively. Despite strong calibration, discard rates of 0.8% for overall donors and 6% of donors after circulatory death could be predicted with 80% accuracy. CONCLUSIONS: The Eurotransplant-developed Discard Risk Index showed a high prognostic ability to predict liver utilization in a European setting. The model could therefore be valuable for identifying livers at high risk of not being transplanted in an early stage. These organs might profit the most from modified allocation strategies or advanced preservation techniques.
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Selección de Donante , Donantes de Tejidos , Selección de Donante/métodos , Supervivencia de Injerto , Humanos , Hígado , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is usually associated with a precipitating event and results in the failure of other organ systems and high short-term mortality. Current prediction models fail to adequately estimate prognosis and need for liver transplantation (LT) in ACLF. This study develops and validates a dynamic prediction model for patients with ACLF that uses both longitudinal and survival data. METHODS: Adult patients on the UNOS waitlist for LT between 11.01.2016-31.12.2019 were included. Repeated model for end-stage liver disease-sodium (MELD-Na) measurements were jointly modelled with Cox survival analysis to develop the ACLF joint model (ACLF-JM). Model validation was carried out using separate testing data with area under curve (AUC) and prediction errors. An online ACLF-JM tool was created for clinical application. RESULTS: In total, 30,533 patients were included. ACLF grade 1 to 3 was present in 16.4%, 10.4% and 6.2% of patients, respectively. The ACLF-JM predicted survival significantly (p <0.001) better than the MELD-Na score, both at baseline and during follow-up. For 28- and 90-day predictions, ACLF-JM AUCs ranged between 0.840-0.871 and 0.833-875, respectively. Compared to MELD-Na, AUCs and prediction errors were improved by 23.1%-62.0% and 5%-37.6% respectively. Also, the ACLF-JM could have prioritized patients with relatively low MELD-Na scores but with a 4-fold higher rate of waiting list mortality. CONCLUSIONS: The ACLF-JM dynamically predicts outcome based on current and past disease severity. Prediction performance is excellent over time, even in patients with ACLF-3. Therefore, the ACLF-JM could be used as a clinical tool in the evaluation of prognosis and treatment in patients with ACLF. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) progresses rapidly and often leads to death. Liver transplantation is used as a treatment and the sickest patients are treated first. In this study, we develop a model that predicts survival in ACLF and we show that the newly developed model performs better than the currently used model for ranking patients on the liver transplant waiting list.
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Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92-0.95) and 0.87 (0.85-0.89), respectively. MELDNa-JM AUC was 0.91 (0.89-0.93) and MELD-Na AUC was 0.84 (0.81-0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Enfermedad Hepática en Estado Terminal/cirugía , Humanos , Índice de Severidad de la Enfermedad , Sodio , Listas de EsperaRESUMEN
BACKGROUND & AIMS: Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course. METHODS: Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death. RESULTS: A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision. CONCLUSIONS: Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.
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Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenoma de Células Hepáticas/cirugía , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Adulto Joven , beta Catenina/genéticaRESUMEN
BACKGROUND: Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide overview of postoperative outcomes after LLR and OLR of BLT. METHODS: This was a nationwide retrospective study including all patients who underwent liver resection for hepatocellular adenoma, haemangioma and focal nodular hyperplasia in the Netherlands from 2014 to 2019. Propensity score matching (PSM) was applied to compare 30-day overall and major morbidity and 30-day mortality after OLR and LLR. RESULTS: In total, 415 patients underwent BLT resection of whom 230 (55.4%) underwent LLR. PSM for OLR and LLR resulted in 250 matched patients. Median (IQR) length of stay was shorter after LLR than OLR (4 versus 6 days, 5.0-8.0, p < 0.001). Postoperative 30-day overall morbidity was lower after LLR than OLR (12.0% vs. 22.4%, p = 0.043). LLR was associated with reduced 30-day overall morbidity in multivariable analysis (aOR:0.46, CI:0.22-0.95, p = 0.043). Both 30-day major morbidity and 30-day mortality were not different. CONCLUSIONS: LLR for BLT is associated with shorter hospital stay and reduced overall morbidity and is preferred if technically feasible.
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Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación , Neoplasias Hepáticas/cirugía , Países Bajos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The MELD score is used in the Eurotransplant (ET) region to allocate liver grafts. Hyponatremia in cirrhotic patients is an important predictor of death but is not incorporated in MELD. This study investigated the performance of the MELD-Na score for the ET region. All adult patients with chronic liver disease on the ET liver transplantation waiting list (WL) allocated through lab MELD scores were included. The MELD-corrected effect of serum sodium (Na) concentration at listing on the 90-day WL mortality was calculated using Cox regression. The MELD-Na performance was assessed with c-indices, calibration per decile and Brier scores. The reclassification from MELD to MELD-Na score was calculated to estimate the impact of MELD-Na-based allocation in the ET region. For the 5223 included patients, the risk of 90-day WL death was 2.9 times higher for hyponatremic patients. The MELD-Na had a significantly higher c-index of 0.847 (SE 0.007) and more accurate 90-day mortality prediction compared to MELD (Brier score of 0.059 vs 0.061). It was estimated that using MELD-Na would reduce WL mortality by 4.9%. The MELD-Na score yielded improved prediction of 90-day WL mortality in the ET region and using MELD-Na for liver allocation will very likely reduce WL mortality.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Humanos , Índice de Severidad de la Enfermedad , Sodio , Listas de EsperaRESUMEN
BACKGROUND AND AIMS: The United Network for Organ Sharing's Model for End-Stage Liver Disease (UNOS-MELD) score is the basis of liver allocation in the Eurotransplant region. It was constructed 20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the United States. Therefore, this study refits the MELD (reMELD) for the Eurotransplant region. APPROACH AND RESULTS: All adult patients listed for a first liver transplantation between January 1, 2007, and December 31, 2018, were included. Data were randomly split in a training set (70%) and a validation set (30%). In the training data, generalized additive models with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log-likelihood were chosen for the final models. The refit models were tested in the validation data with C-indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS-MELD. The correlation between scores and survival of prioritized patients was calculated. A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7-2.5, bilirubin 0.3-27, international normalized ratio 0.1-2.6, and sodium 120-139. ReMELD and reMELD-Na showed C-indices of 0.866 and 0.869, respectively. ReMELD-Na prioritized patients with 1.6 times higher 90-day mortality probabilities compared to UNOS-MELD. CONCLUSIONS: Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD-Na was significantly higher than UNOS-MELD. ReMELD prioritized patients with higher 90-day mortality rates. Thus, reMELD(-Na) should replace UNOS-MELD for liver graft allocation in the Eurotransplant region.
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Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/normas , Índice de Severidad de la Enfermedad , Obtención de Tejidos y Órganos/normas , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/mortalidad , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Listas de Espera/mortalidadRESUMEN
BACKGROUND: Predicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models is of great interest.Nowadays, there is a strong discussion in the medical field about machine learning (ML) and whether it has greater potential than traditional regression models when dealing with complex data. Criticism to ML is related to unsuitable performance measures and lack of interpretability which is important for clinicians. METHODS: In this paper, ML techniques such as random forests and neural networks are applied to large data of 62294 patients from the United States with 97 predictors selected on clinical/statistical grounds, over more than 600, to predict survival from transplantation. Of particular interest is also the identification of potential risk factors. A comparison is performed between 3 different Cox models (with all variables, backward selection and LASSO) and 3 machine learning techniques: a random survival forest and 2 partial logistic artificial neural networks (PLANNs). For PLANNs, novel extensions to their original specification are tested. Emphasis is given on the advantages and pitfalls of each method and on the interpretability of the ML techniques. RESULTS: Well-established predictive measures are employed from the survival field (C-index, Brier score and Integrated Brier Score) and the strongest prognostic factors are identified for each model. Clinical endpoint is overall graft-survival defined as the time between transplantation and the date of graft-failure or death. The random survival forest shows slightly better predictive performance than Cox models based on the C-index. Neural networks show better performance than both Cox models and random survival forest based on the Integrated Brier Score at 10 years. CONCLUSION: In this work, it is shown that machine learning techniques can be a useful tool for both prediction and interpretation in the survival context. From the ML techniques examined here, PLANN with 1 hidden layer predicts survival probabilities the most accurately, being as calibrated as the Cox model with all variables. TRIAL REGISTRATION: Retrospective data were provided by the Scientific Registry of Transplant Recipients under Data Use Agreement number 9477 for analysis of risk factors after liver transplantation.
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Trasplante de Hígado , Humanos , Aprendizaje Automático , Redes Neurales de la Computación , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. METHODS: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. RESULTS: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. CONCLUSION: Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging.
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Neoplasias de la Vesícula Biliar , Ictericia , Estudios de Cohortes , Neoplasias de la Vesícula Biliar/complicaciones , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Ictericia/diagnóstico , Ictericia/etiología , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: The success of pancreas transplantation, in combination with a stable number of available allografts has resulted in an increasing waiting list. This study investigated donor potential by expanding age and Body Mass Index (BMI) criteria. METHODS: All reported donors in the Netherlands between 2013 and 2017 were analysed. Risk assessment of extended criteria donors was done by in-depth analysis of donor reports and calculation of the Pancreas Donor Risk Index (PDRI). The PDRI of these extended criteria donors was compared to standard criteria donors to evaluate the increased risk on graft failure. RESULTS: A total of 1273 donors were reported. Of these donors, 405 donors were reported as pancreas donor, of which 93 (23%) pancreata were transplanted. Extending age criterion with 5 years could result in additional 40 Donation after Brain Death donors and 37 Donation after Circulatory Death donors reported. In 24 (31%) extended age criteria donors the PDRI was below the upper limit of currently transplanted pancreata. Extending BMI criteria to 35â¯kg/m2 could result in an additional 19 (6%) donors reported. CONCLUSIONS: Extending BMI criteria could result in a slight increase of reported donors. Extending age criteria increased significantly the number of reported donors. In 24 (31%) of the older donors the PDRI showed a reduced risk compared to currently transplanted pancreata. This study suggest that, if other risk factors are absent, pancreata of extended age and/or BMI criteria donors should be considered for transplantation.
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Selección de Donante , Trasplante de Páncreas , Páncreas , Donantes de Tejidos , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Selección de Paciente , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Several risk models to predict outcome after liver transplantation (LT) have been developed in the last decade. This study compares the predictive performance of 7 risk models. METHODS: Data on 62 294 deceased donor LTs performed in recipients ≥18 years old between January 2005 and December 2015 in the United Network for Organ Sharing region were used for this study. The balance of risk, donor risk index (DRI), Eurotransplant-DRI, donor-to-recipient model (DRM), simplified recipient risk index, Survival Outcomes Following Liver Transplantation (SOFT), and donor Model for End-stage Liver Disease scores were calculated, and calibration and discrimination were evaluated for patient, overall graft, and death-censored graft survival. Calibration was evaluated by outcome of high-risk transplantations (>80th percentile of the respective risk score) and discrimination by concordance index (c-index). RESULTS: Patient survival at 3 months was best predicted by the SOFT (c-index: 0.68) and Balance of Risk score (c-index: 0.64), while the DRM and SOFT score had the highest predictive capacity at 60 months (c-index: 0.59). Overall, graft survival was best predicted by the SOFT score at 3-month follow-up (c-index: 0.65) and by the SOFT and DRM at 60-month follow-up (c-index: 0.58). Death-censored graft survival at 60-month follow-up is best predicted by the DRI (c-index: 0.59) and Eurotransplant-DRI (c-index: 0.58). For patient and overall graft survival, high-risk transplantations were best defined by the DRM. For death-censored graft survival, this was best defined by the DRI. CONCLUSIONS: This study shows that models dominated by recipient factors have the best performance for short-term patient survival. Models that also include sufficient donor factors have better performance for long-term graft survival. Death-censored graft survival is best predicted by models that predominantly included donor factors.