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The Meso-Rex bypass (MRB) is recognized as an effective treatment for portal hypertension secondary to extrahepatic portal vein occlusion (EHPVO) both in the pediatric and adult population, within or outside the context of liver transplantation. It is the preferred surgical treatment in most centers because not only does it addresses the portal hypertension, but also restores physiologic portal hepatopetal flow. However, the Rex recess, the landmark for this technique, may not be safely accessible in some patients. We present a 22-year-old male who underwent living donor liver transplant (LDLT) for neonatal hepatitis. He presented with variceal bleeding due to EHPVO at 13 years after transplant. Various endoscopic, radiologic, and surgical interventions were employed to address the recurrent gastrointestinal bleeding, but results have been unsatisfactory. We performed a meso-intrahepatic portal vein bypass (MIPVB), an innovative alternative to the MRB, for this patient with extensive post-operative adhesions, perihilar collaterals, and cavernous transformation. MIPVB creation in patients where the Rex recess is inaccessible is technically challenging. But with a multidisciplinary team approach, meticulous preoperative planning, and close follow-up, the authors have demonstrated that it is a safe and feasible option for patients with late-onset EHPVO after liver transplantation.
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BACKGROUND: Liver transplantation is an effective treatment for preventing hepatocellular carcinoma (HCC) recurrence. This retrospective study aimed to quantitatively evaluate the attenuation in Hounsfield units (HU) on contrast-enhanced computed tomography (CECT) as a prognostic factor for hepatocellular carcinoma (HCC) following liver transplantation as a treatment. Our goal is to optimize its predictive ability for early tumor recurrence and compare it with the other imaging modality-positron emission tomography (PET). METHODS: In 618 cases of LDLT for HCC, only 131 patients with measurable viable HCC on preoperative CECT and preoperative positron emission tomography (PET) evaluations were included, with a minimum follow-up period of 6 years. Cox regression models were developed to identify predictors of postoperative recurrence. Performance metrics for both CT and PET were assessed. The correlation between these two imaging modalities was also evaluated. Survival analyses were conducted using time-dependent receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) to assess accuracy and determine optimized cut-off points. RESULTS: Univariate and multivariate analyses revealed that both arterial-phase preoperative tumor attenuation (HU) and PET were independent prognostic factors for recurrence-free survival. Both lower arterial tumor enhancement (Cut-off value = 59.2, AUC 0.88) on CT and PET positive (AUC 0.89) increased risk of early tumor recurrence 0.5-year time-dependent ROC. Composites with HU < 59.2 and a positive PET result exhibited significantly higher diagnostic accuracy in detecting early tumor recurrence (AUC = 0.96). CONCLUSION: Relatively low arterial tumor enhancement values on CECT effectively predict early HCC recurrence after LDLT. The integration of CT and PET imaging may serve as imaging markers of early tumor recurrence in HCC patients after LDLT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Donadores Vivos , Recurrencia Local de Neoplasia , Tomografía Computarizada por Rayos X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Masculino , Femenino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Tomografía de Emisión de Positrones/métodos , Medios de Contraste , Adulto , Anciano , Análisis de Supervivencia , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Biomedical information retrieval for diagnosis, treatment and prognosis has been studied for a long time. In particular, image recognition using deep learning has been shown to be very effective for cancers and diseases. In these fields, scaphoid fracture recognition is a hot topic because the appearance of scaphoid fractures is not easy to detect. Although there have been a number of recent studies on this topic, no studies focused their attention on surgical treatment recommendations and nonsurgical prognosis status classification. Indeed, a successful treatment recommendation will assist the doctor in selecting an effective treatment, and the prognosis status classification will help a radiologist recognize the image more efficiently. For these purposes, in this paper, we propose potential solutions through a comprehensive empirical study assessing the effectiveness of recent deep learning techniques on surgical treatment recommendation and nonsurgical prognosis status classification. In the proposed system, the scaphoid is firstly segmented from an unknown X-ray image. Next, for surgical treatment recommendation, the fractures are further filtered and recognized. According to the recognition result, the surgical treatment recommendation is generated. Finally, even without sufficient fracture information, the doctor can still make an effective decision to opt for surgery or not. Moreover, for nonsurgical patients, the current prognosis status of avascular necrosis, non-union and union can be classified. The related experimental results made using a real dataset reveal that the surgical treatment recommendation reached 80% and 86% in accuracy and AUC (Area Under the Curve), respectively, while the nonsurgical prognosis status classification reached 91% and 96%, respectively. Further, the methods using transfer learning and data augmentation can bring out obvious improvements, which, on average, reached 21.9%, 28.9% and 5.6%, 7.8% for surgical treatment recommendations and nonsurgical prognosis image classification, respectively. Based on the experimental results, the recommended methods in this paper are DenseNet169 and ResNet50 for surgical treatment recommendation and nonsurgical prognosis status classification, respectively. We believe that this paper can provide an important reference for future research on surgical treatment recommendation and nonsurgical prognosis classification for scaphoid fractures.
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BACKGROUND AND AIM: The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. METHODS: Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). RESULTS: Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n = 8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. CONCLUSIONS: Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.
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Carcinoma Hepatocelular , Neoplasias Colorrectales , Neoplasias Hepáticas , Microesferas , Sistema de Registros , Radioisótopos de Itrio , Humanos , Neoplasias Hepáticas/radioterapia , Radioisótopos de Itrio/efectos adversos , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Hepatocelular/radioterapia , Anciano , Neoplasias Colorrectales/radioterapia , Resultado del Tratamiento , Taiwán , Estudios Prospectivos , Adulto , Braquiterapia/métodos , Braquiterapia/efectos adversos , Anciano de 80 o más AñosRESUMEN
Acute cellular rejection (ACR) is a significant immune issue among recipients following liver transplantation. Although diffusion-weighted magnetic resonance imaging (DWI) is widely used for diagnosing liver disease, it has not yet been utilized for monitoring ACR in patients after liver transplantation. Therefore, the aim of this study was to evaluate the efficacy of DWI in monitoring treatment response among recipients with ACR. This study enrolled 25 recipients with highly suspected ACR rejection, and all subjects underwent both biochemistry and DWI scans before and after treatment. A pathological biopsy was performed 4 to 24 h after the first MRI examination to confirm ACR and degree of rejection. All patients were followed up and underwent a repeated MRI scan when their liver function returned to the normal range. After data acquisition, the DWI data were post-processed to obtain the apparent diffusion coefficient (ADC) map on a voxel-by-voxel basis. Five regions of interest were identified on the liver parenchyma to measure the mean ADC values from each patient. Finally, the mean ADC values and biochemical markers were statistically compared between ACR and non-ACR groups. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the ADC and biochemical data in detecting ACR, and correlation analysis was used to understand the relationship between the ADC values, biochemical markers, and the degree of rejection. The histopathologic results revealed that 20 recipients had ACR, including 10 mild, 9 moderate, and 1 severe rejection. The results demonstrated that the ACR patients had significantly lower hepatic ADC values than those in patients without ACR. After treatment, the hepatic ADC values in ACR patients significantly increased to levels similar to those in non-ACR patients with treatment. The ROC analysis showed that the sensitivity and specificity for detecting ACR were 80% and 95%, respectively. Furthermore, the correlation analysis revealed that the mean ADC value and alanine aminotransferase level had strong and moderate negative correlation with the degree of rejection, respectively (r = -0.72 and -0.47). The ADC values were useful for detecting hepatic ACR and monitoring treatment response after immunosuppressive therapy.
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AIM: To compare the effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) with different particle sizes in bridging and downstaging in pretransplant hepatocellular carcinoma patients. Assess the recurrent and survival rates after living donor liver transplantation (LDLT). METHODS: Retrospective review of 580 patients who underwent TACE using DEB from August 2012 to June 2020 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and post-TACE computed tomography scan images of the liver were reviewed, and treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors criteria. Patients were divided by who met the criteria (n = 342) or beyond (n = 238) the University of California San Francisco criteria for successful bridging and downstaging rate evaluation. Each group was divided into subgroups according to DEB particle sizes (group A: <100µm, group B: 100-300 µm, group C: 300-500 µm, and group D: 500-700 µm) to compare objective response rate and post-LDLT survival rate. RESULTS: Overall successful bridging and downstaging rate is 97.1% and 58.4%, respectively, in the group of patients who meet the criteria (n = 332) and are beyond (n = 139) the University of California San Francisco criteria. Group B (100-300 µm) had a higher successful bridging rate (99.5%, P = .003) and downstaging rate (63.8%, P = .443). This subgroup also demonstrated a higher objective response rate in single (93.2%, P = .038) tumors, multiple (83.3%, P = .001) tumors, and tumors with size less than 5 cm (93.9%, P = .005). There are no significant differences in post-LDLT overall survival rate between different particle sizes. CONCLUSION: TACE with 100 to 300 µm DEB particles is associated with a better chance of bridging and downstaging hepatocellular carcinoma patients to LDLT.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Trasplante de Hígado , Donadores Vivos , Tamaño de la Partícula , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Estadificación de Neoplasias , Microesferas , AncianoRESUMEN
AIMS: Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT. METHODS: 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups. RESULTS: According to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025). CONCLUSIONS: Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns.
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PURPOSE: Despite technological and immunologic innovations, some living-donor liver transplant (LDLT) recipients still face poor liver regeneration. Sarcopenia is often recognized as a biomarker for poor outcomes in surgical patients. This study aimed to evaluate associations between sarcopenia and liver regeneration in LDLT recipients. MATERIALS AND METHODS: This retrospective review included consecutive patients who had received LDLT at Chang Gung Memorial Hospital between 2005 and 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. Receiver operating characteristic curve analysis was used to determine the ability of PMI to predict relatively poor survival rates. Correlations between liver regeneration and sarcopenia were evaluated using regression analysis. RESULTS: A total of 109 LDLT recipients were included. The 1-, 3-, 5, 10-, and 15-year survival rates were 93.7%, 84.8%, 79.7%, 74.7%, and 73.3% in males and 93.3%, 83.3%, 83.3%, 71.4%, and 71.4% in females. PMIs were significantly different based on 10- and 15-year overall survival rates (P = .001 and P = .000) in male patients. Receiver operating characteristic curve analysis revealed the PMI cutoff point at 6.7 cm2/m2 (sensitivity = 48.3%, specificity = 81%, AUC (area under the ROC curve) = 0.685) based on 10-year survival. Linear regression analysis revealed that PMI was significantly associated with liver regeneration in males (P = .013). CONCLUSIONS: Sarcopenia and low PMI are associated with poor liver regeneration and long-term survival after LDLT in male patients. Further studies, including sarcopenia with conventional scores, may help to more reliably predict liver regeneration and mortality among LDLT patients with hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Regeneración Hepática , Trasplante de Hígado , Donadores Vivos , Sarcopenia , Humanos , Sarcopenia/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Adulto , Tasa de SupervivenciaRESUMEN
BACKGROUND: Langerhans cell histiocytosis affecting the thyroid commonly presents with nonspecific clinical and radiological manifestations. Thyroid Langerhans cell histiocytosis is typically characterized by non-enhancing hypodense lesions with an enlarged thyroid on computed tomography medical images. Thyroid involvement in LCH is uncommon and typically encountered in adults, as is salivary gland involvement. Therefore, we present a unique pediatric case featuring simultaneous salivary and thyroid involvement in LCH. CASE PRESENTATION: A 3-year-old boy with complaints of an anterior neck mass persisting for 1 to 2 months, accompanied by mild pain, dysphagia, and hoarseness. A physical examination revealed a 2.5 cm firm and tender mass in the left anterior neck. Laboratory examinations revealed normal thyroid function test levels. Ultrasonography revealed multiple heterogeneous hypoechoic nodules with unclear and irregular margins in both lobes of the thyroid. Contrast-enhanced neck computed tomography revealed an enlarged thyroid gland and bilateral submandibular glands with non-enhancing hypointense nodular lesions, and multiple confluent thin-walled small (< 1.5 cm) cysts scattered bilaterally in the lungs. Subsequently, a left thyroid excisional biopsy was performed, leading to a histopathological diagnosis of LCH. Immunohistochemical analysis of the specimen demonstrated diffuse positivity for S-100, CD1a, and Langerin and focal positivity for CD68. The patient received standard therapy with vinblastine and steroid, and showed disease regression during regular follow-up of neck ultrasonography. CONCLUSIONS: Involvement of the thyroid and submandibular gland as initial diagnosis of Langerhans cell histiocytosis is extremely rare. It is important to investigate the involvement of affected systems. A comprehensive survey and biopsy are required to establish a definitive diagnosis.
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Histiocitosis de Células de Langerhans , Tiroiditis , Preescolar , Humanos , Masculino , Biopsia , Histiocitosis de Células de Langerhans/diagnóstico por imagen , Histiocitosis de Células de Langerhans/complicaciones , Cuello/patología , Tiroiditis/complicacionesRESUMEN
Over the past few decades, recognition of early lung cancers was researched for effective treatments. In early lung cancers, the invasiveness is an important factor for expected survival rates. Hence, how to effectively identify the invasiveness by computed tomography (CT) images became a hot topic in the field of biomedical science. Although a number of previous works were shown to be effective on this topic, there remain some problems unsettled still. First, it needs a large amount of marked data for a better prediction, but the manual cost is high. Second, the accuracy is always limited in imbalance data. To alleviate these problems, in this paper, we propose an effective CT invasiveness recognizer by semi-automated segmentation. In terms of semi-automated segmentation, it is easy for doctors to mark the nodules. Just based on one clicked pixel, a nodule object in a CT image can be marked by fusing two proposed segmentation methods, including thresholding-based morphology and deep learning-based mask region-based convolutional neural network (Mask-RCNN). For thresholding-based morphology, an initial segmentation is derived by adaptive pixel connections. Then, a mathematical morphology is performed to achieve a better segmentation. For deep learning-based mask-RCNN, the anchor is fixed by the clicked pixel to reduce the computational complexity. To incorporate advantages of both, the segmentation is switched between these two sub-methods. After segmenting the nodules, a boosting ensemble classification model with feature selection is executed to identify the invasiveness by equalized down-sampling. The extensive experimental results on a real dataset reveal that the proposed segmentation method performs better than the traditional segmentation ones, which can reach an average dice improvement of 392.3%. Additionally, the proposed ensemble classification model infers better performances than the compared method, which can reach an area under curve (AUC) improvement of 5.3% and a specificity improvement of 14.3%. Moreover, in comparison with the models with imbalance data, the improvements of AUC and specificity can reach 10.4% and 33.3%, respectively.
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BACKGROUND: The aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone. METHODS: This multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model. RESULTS: The median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P = 0.009) and PFS (38.7% vs. 10.0%, P = 0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P = 0.032), PFS (P = 0.001), and LRC (P = 0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P = 0.034) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P = 0.039). On multivariate analyses, the use of POCRT significantly predicted superior OS (P = 0.037) and PFS (P = 0.013) for node-positive patients and LRC for patients with R2 resection (P = 0.041) or AdCC (P = 0.005). CONCLUSIONS: For surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC.
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Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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BACKGROUND: It may be difficult for pediatric patients to evaluate the impact of liver transplantation (LT) on splenomegaly due to the natural growth course. The long-term dynamics of portal vein (PV) size and PV flow after LT in pediatric patients are unclear. We aimed to evaluate the long-term transition of the splenic size, PV size, and PV flow velocity in pediatric patients who underwent successful living donor liver transplantation (LDLT) and survived >10 years. METHODS: From October 2004 to December 2010, 39 pediatric patients (25 boys; 14 girls) underwent LDLT, received pre-LDLT and post-LDLT computed tomography scans and long-term ultrasound sonography follow-up, and survived >10 years without additional intervention at our institution. We analyzed the short- to mid-term and long-term impact of LDLT on splenic size, PV size, and PV flow velocity over time. RESULTS: The PV diameter increased throughout the 10-year follow-up (P < .001). The PV flow velocity increased 1 day after LDLT (P< .001); proceeded to decrease 3 days after LDLT, reaching a low point 6 to 9 months after LDLT; and remained stable throughout the 10-year follow-up. Regression of the splenic volume at 6 to 9 months after LDLT (P < .001) was noted. However, the splenic size steadily increased on long-term follow-up. CONCLUSIONS: Although LDLT has a significant short-term reduction effect on splenomegaly, the long-term transitional trend of the splenic size and PV diameter may increase along with children's growth. The PV flow reached a stable status 6 to 9 months after LDLT and remained so until 10 years after LDLT.
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Trasplante de Hígado , Masculino , Femenino , Niño , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Estudios de Seguimiento , Donadores Vivos , Estudios Retrospectivos , Esplenomegalia/diagnóstico por imagen , Esplenomegalia/etiología , Esplenomegalia/cirugía , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Resultado del TratamientoRESUMEN
Background: Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) hepatocellular carcinoma (HCC) is highly heterogeneous; thus, identifying the most effective treatment for individual patients represents a significant clinical challenge. However, transarterial chemoembolization (TACE) is the only recommended treatment option. Therefore, we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. Methods: A total of 516 patients with BCLC stage B HCC who underwent LDLT (n=104) or did not undergo LDLT (non-LDLT; n=412) between 2004 to 2018 were analyzed by propensity score matching (PSM; 1:4) analysis. Factors influencing overall survival (OS) and recurrence were analyzed using Cox's proportional hazards models. Results: Patients treated with LDLT achieved better OS than the non-LDLT group, including liver- and non-liver related survival (all P<0.001). Multivariate Cox regression analysis showed age >60 years (P=0.006), a neutrophil-lymphocyte ratio (NLR) >4 (P=0.016) and >3 locoregional therapies (LRT) before LDLT (P<0.001) were independent risk factors for HCC recurrence. In addition, age >60 years (P<0.001) and >3 LRT before LDLT (P=0.001) were independent risk factors for OS. Using a combination of age, NLR, and LRT before liver transplantation (LT), the patients can be divided into low-risk (none of risk), intermediate-risk (one of risk), and high risk (more than two of risk) groups. There were significant differences in the cumulative HCC recurrence (P<0.001) and mortality (P<0.001) rates among the three groups. Conclusions: LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.
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Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , MicroARNs , Humanos , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/genética , Exosomas/genética , Exosomas/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , MicroARNs/genética , Estudios Retrospectivos , Microambiente Tumoral/genéticaRESUMEN
(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.
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Background: The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. Methods: From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. Results: Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. Conclusion: Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.
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PURPOSE: Barcelona Clinic Liver Cancer (BCLC) guidelines designate monofocal hepatocellular carcinoma (HCC) > 2 cm as BCLC A, and large monofocal HCC is defined at > 5 cm. We aimed to evaluate the optimal cutoff value for large monofocal HCC based on prognosis stratification. METHODS: From 2011 to 2018, 3055 patients with newly diagnosed HCC, who were managed in our institution, including 868 patients with monofocal HCC > 2 cm and 330 patients with BCLC B, were enrolled in this retrospective study. RESULTS: Monofocal HCC > 5 cm patients had worse overall survival (OS) than monofocal HCC 2-5 cm patients (5-year OS: 54% vs. 57%; p = 0.047), confirmed by multivariate analysis (hazard ratio (HR): 1.492, 95% confidence interval (CI): 1.055-2.110; p = 0.024). Monofocal HCC > 5 cm patients had better OS than BCLC B HCC patients (5-year OS: 54% vs. 25%; p < 0.001), confirmed by multivariate analysis (HR: 0.670, 95% CI: 0.481-0.934; p = 0.018). Using 7 cm as the monofocal HCC cutoff value resulted in worse OS than monofocal HCC 2-7 cm (5-year OS: 50% vs. 57%; p = 0.02), confirmed by multivariate analysis (HR: 1.625, 95% CI: 1.039-2.540; p = 0.033). Monofocal HCC > 7 cm patients had better OS than BCLC B patients (p = 0.006). However, no significant difference was identified in the multivariate analysis (HR: 0.726; 95% CI: 0.473-1.115; p = 0.144). CONCLUSIONS: The prognosis of monofocal HCC > 7 cm was similar to that of BCLC B, indicating that 7 cm represents an optimal cutoff value for prognosis stratification in large monofocal HCC.