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Purpose: Numerous efforts have been made to achieve minimally invasive surgery, such as single-port laparoscopic surgery. However, few studies have provided long-term follow-up information, and the number of patients with hepatocellular carcinoma (HCC) in previous studies has been small. The purpose in this study is to compare the long-term oncological outcomes of HCC patients who underwent single-port laparoscopic hepatectomy (SPLH) with those of patients who underwent multiport laparoscopic hepatectomy (MPLH). Methods: We retrospectively reviewed the medical records of 135 patients with HCC who underwent laparoscopic liver between January 2008 and December 2018. Of the 135 patients, 53 underwent MPLH, and 82 underwent SPLH. Results: From January 2008 to December 2018, 135 patients underwent laparoscopic hepatectomy for HCC. Among them, 82 patients underwent SPLH, and 53 patients underwent MPLH. Neither long-term overall survival (P = 0.849) nor recurrence-free survival (P = 0.057) differed significantly between the 2 groups, even though the recurrence rate was higher in the SPLH group. In the univariable analysis of risk factors for recurrence, multiple tumors, SPLH method, and portal vein invasion were statistically significant (P < 0.05). Multivariable analysis showed that the SPLH method and portal vein invasion were independent adverse prognostic factors for recurrence-free survival. Conclusion: In terms of both short-term and long-term outcomes, the SPLH method seems to be a feasible approach for HCC in select patients. Because the potential risk of margin recurrence might produce poor oncological outcomes, strict patient selection is essential to ensure that an adequate safety margin can be secured.
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Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.
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Liposomas , Nanoestructuras , Humanos , Ratones , Animales , Liposomas/química , Células HEK293 , Espectroscopía Infrarroja por Transformada de Fourier , Proteínas de la Membrana , Lípidos/químicaRESUMEN
Purpose: Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Methods: Upon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models. Results: In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker). Conclusion: These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.
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BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. APPROACH AND RESULTS: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05). CONCLUSIONS: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.
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BACKGROUND: Despite advances in surgical techniques, biliary complications are still considered to be a technical "Achilles' heel" of liver transplantation (LT). The purpose of this study was to evaluate the effect of loupe magnification in reducing biliary complications after LT. MATERIALS AND METHODS: From April 2017 to February 2022, LT was performed on 307 patients in our center. Among them, except for 3 patients who underwent hepaticojejunostomy, 304 adult patients with LT were enrolled. They were divided into 3 groups according to the loupe magnification: 2.5 times (×2.5 group, n = 105), 3.5 times (×3.5 group, n = 95), and 5.0 times (×5.0 group, n = 105). RESULTS: Biliary complications occurred in 63 (20.7%) patients. Anastomosis site leakage occurred in 37 patients (12.2%), and stricture occurred in 52 patients (17.1%). Anastomosis site leakage occurred in 15 patients (14.3%) in the ×2.5 group, 15 patients (16.0%) in the ×3.5 group, and 7 patients (6.7%) in the ×5.0 group (P = .097). Biliary stricture occurred in 26 patients (24.8%) in the ×2.5 group, 15 patients (16.0%) in the ×3.5 group, and 11 patients (10.5%) in the ×5.0 group (P = .021). Total biliary complications occurred in 31 patients (29.5%) in the ×2.5 group, 19 patients in the ×3.5 group (20.2%), and 13 patients in the ×5.0 group (12.4%) (P = .009). CONCLUSION: The use of a high magnification loupe can reduce biliary complications in liver transplantation. Further large-scale analyses of clinical data or randomized controlled trials are required to support this study.
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Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Enfermedades de las Vías Biliares/etiología , Enfermedades de las Vías Biliares/prevención & control , Anastomosis Quirúrgica , Estudios Retrospectivos , AncianoRESUMEN
BACKGROUND: Liver transplantation (LT) is typically performed at specialized, high-volume centers. However, some smaller centers also offer liver transplantation services, but their outcomes and safety have been a subject of debate. To overcome these difficulties, we tried to build a Catholic Medical Center (CMC) network to share our experiences and overcome the lack of volume. In this study, we reviewed the overall outcome of patients undergoing LT at a small-volume procedure center, with a focus on patient and graft survival rates. METHODS: Between July 2014 and September 2021, 60 adults underwent LT at Bucheon Saint Mary's Hospital. The overall outcomes were analyzed in terms of perioperative outcomes, complications, and overall survival rate. In addition, the patients were divided into a benign end-stage liver disease (ESLD) group (n = 44) and a hepatocellular carcinoma (HCC) group (n = 16). The baseline characteristics, perioperative outcomes, complications, and overall survival rate were analyzed between the 2 groups. RESULTS: Of a total of 60 LT, living donor liver transplantation (LDLT) was 26, and deceased donor liver transplantation was 34. LDLT was 14 (31.8%) in the ESLD group and 12 (75.0%) in the HCC group. The overall 1-year, 3-year, and 5-year survival rates were 86.7%, 79.7%, and 77.7%, respectively. The survival difference was not statistically significant (P = .214) between the 2 groups. CONCLUSION: We suggest that with appropriate patient selection and adequate resources, LT can be safely performed at smaller centers with the assistance of the CMC network, thus expanding access to this life-saving procedure.
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Trasplante de Hígado , Humanos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Adulto , Supervivencia de Injerto , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Resultado del Tratamiento , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Living donor liver transplantation (LDLT) is currently widespread due to organ shortage. Because LDLT is a high-risk surgery for the donor, donor safety becomes an important issue. In adult LDLT, right lobe grafts are usually used, posing a greater risk to the donor than a left lobe. Reports have demonstrated that branched-chain amino acids help patients recover after hepatectomy. This study aimed to evaluate the effect of Livact granule on donor safety and recovery. METHODS: From January 2016 to December 2021, LDLT was performed on 258 patients at our center. Among them, 148 were in the non-Livact group, and 110 were in the Livact group. Six of 110 patients in the Livact group stopped taking the granules due to nausea and vomiting, leaving 104 patients in the Livact group to be analyzed. Various preoperative and postoperative factors were evaluated to assess donor safety and recovery. RESULTS: In the non-Livact group, the mean donor age was 35.8; in the Livact group, it was 40. There were no differences between the 2 groups in preoperative liver function tests and no difference in future liver remnant or steatosis. There was no difference in total bilirubin level between the 2 groups at 5 days postoperatively; however, in the Livact group, the prothrombin time international normalized ratio was lower, and albumin was higher. The days taken for total bilirubin to normalize were the same in both groups, but fewer days were needed for Livact to realize an international normalized ratio. More patients in the non-Livact group were discharged with the Jackson-Pratt drain because the drainage did not decrease. CONCLUSIONS: In donor right hepatectomy patients, taking Livact granules and branched-chain amino acids helps donor recovery. For donor safety, administration of Livact granules during the perioperative period should be considered.
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Hepatectomía , Trasplante de Hígado , Donadores Vivos , Recuperación de la Función , Humanos , Adulto , Masculino , Femenino , Pruebas de Función Hepática , Hígado/cirugía , Persona de Mediana Edad , Aminoácidos de Cadena Ramificada , Estudios Retrospectivos , Bilirrubina/sangreRESUMEN
INTRODUCTION: Liver transplantation (LT) is a complex and demanding procedure associated with significant perioperative challenges and risks. Concerns have arisen regarding LT outcomes in low-volume centers. We implemented an integrated training and surgical team network to address these concerns within the Catholic Medical Center (CMC) network. This study presents a comprehensive review of our 9-year LT experience within the CMC medical network. METHOD: A retrospective study of LT procedures conducted between January 2013 and August 2021 in 6 CMC-affiliated hospitals was performed. One center was categorized as a high-volume center, conducting over 60 cases annually, and the remaining 5 were considered small-volume centers. The primary endpoints assessed were 1-year and 5-year survival rates. RESULTS: A total of 793 LTs were performed during the study period. The high-volume center performed 411 living donor LT (LDLT) cases and 127 deceased donor LT (DDLT) cases. Also, 146 LDLT cases and 109 DDLT cases were performed in 5 small-volume centers. One-year and 5-year patient survival for LDLT recipients was 88.3% and 78.8% in the high-volume center and 85.6% and 80.6% in the low-volume center. Five-year survival was not significantly different in small-volume centers (P = .903). For DDLT recipients, 1-year and 5-year patient survival was 80.3% and 70.6% in the high-volume center and 76.1% and 67.6% in the low-volume center. In DDLT cases, 5-year survival was not significantly different in small-volume centers (P = .445). CONCLUSION: In conclusion, comparable outcomes for liver transplantation can be obtained in a small-volume center with a high level of integrated training systems and networks.
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Trasplante de Hígado , Trasplante de Hígado/mortalidad , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Hospitales de Alto Volumen , Hospitales de Bajo Volumen , Adulto , Resultado del TratamientoRESUMEN
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Asia , Hígado , Trasplante de Hígado/métodos , Donadores VivosRESUMEN
OBJECTIVE: We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification. MATERIALS AND METHODS: This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan-Meier curves were used to estimate RFS and OS for the different risk-score groups. RESULTS: In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2-5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62-0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05). CONCLUSION: Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.
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Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Carcinoma Hepatocelular/patología , Gadolinio DTPA , Imagen por Resonancia Magnética , Medios de Contraste , PronósticoRESUMEN
BACKGROUND: Clinical factors predicting graft survival (GS) after ABO-incompatible (ABOi) liver transplantation (LT), and differences between recipients with and without hepatocellular carcinoma (HCC) are unclear. AIM: To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without HCC) in ABOi living-donor liver transplantation (LDLT). METHODS: We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT, including 47 patients with HCC. RESULTS: The 1-, 3-, 5-, and 10-year GS rates were 85.9%, 73.3%, 71.4%, and 71.4%, respectively, and there were no significant differences between HCC and non-HCC recipients. In multivariate Cox-regression analyses, tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT, in addition to the antibody-mediated rejection (AMR) were associated with poor-graft outcomes. In HCC patients, AMR [hazard ratio (HR) = 63.20, P < 0.01] and HCC recurrence (HR = 20.72, P = 0.01) were significantly associated with poor graft outcomes. HCCs outside Milan criteria, and tacrolimus concentrations at 4 wk post-LT > 7.3 ng/mL were significant predictive factors for HCC recurrence. After propensity score matching, patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival. CONCLUSION: Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence. Therefore, careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.
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BACKGROUND: The size of gallbladder (GB) polyps is a representative risk factor for neoplastic polyps. However, whether growth rate during follow-up is associated with neoplastic polyps remains unclear. METHODS: From 2009 to 2019, a cohort of patients with GB polyps who underwent cholecystectomy was enrolled. We included only patients who underwent at least two abdominal ultrasonography procedures at least 6 months apart prior to cholecystectomy. Performance and optimal cutoff value of polyp growth rate for predicting neoplastic polyps were estimated using receiver operating characteristic (ROC) analysis. In addition to growth rate, several other variables considered suitable for predicting neoplastic polyps were also investigated. A nomogram was created to predict neoplastic polyps. RESULTS: A total of 239 patients with neoplastic polyps (n = 27, 11.3%) and non-neoplastic polyps (n = 212, 88.7%) were included. The median follow-up period was 28.5 months. The area under the ROC curve (AUROC) of polyp growth rate for neoplastic polyps was 0.66 (95% confidence interval, 0.59-0.72). The growth rate cutoff value for prediction of neoplastic polyps was 3 mm/year (sensitivity, 37.0%; specificity, 86.3%). Multivariate analysis identified several factors predicting neoplastic polyps: polyp size ≥10 mm (odds ratio [OR], 3.74, p = 0.041), solitary polyp (OR, 3.92, p = 0.004), and polyp growth rate ≥ 3 mm/year (OR, 2.75, p = 0.031). The AUROC of the nomogram using these three significant factors in multivariate analysis was 0.71. CONCLUSION: GB polyps with a growth rate of over 3 mm per year on ultrasonography during follow-up should be considered a risk factor for neoplastic polyps.
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Enfermedades de la Vesícula Biliar , Neoplasias de la Vesícula Biliar , Neoplasias Gastrointestinales , Pólipos , Diagnóstico Diferencial , Neoplasias de la Vesícula Biliar/diagnóstico , Humanos , Pólipos/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND: Hypoxic preconditioning (HP) is a stem cell preconditioning modality designed to augment the therapeutic effects of mesenchymal stem cells (MSCs). Although autophagy is expected to play a role in HP, very little is known regarding the relationship between HP and autophagy. METHODS AND RESULTS: The adipose-derived stem cell (ASC)-secretome obtained under normoxia (NCM) and ASC-secretome obtained under HP (HCM) were obtained by culturing ASCs for 24 h under normoxic (21% partial pressure of O2) and hypoxic (1% partial pressure of O2) conditions, respectively. Subsequently, to determine the in vivo effects of HCM, each secretome was injected into 70% partially hepatectomized mice, and liver specimens were obtained. HCM significantly reduced the apoptosis of thioacetamide-treated AML12 hepatocytes and promoted the autophagic processes of the cells (P < 0.05). Autophagy blockage by either bafilomycin A1 or ATG5 siRNA significantly abrogated the anti-apoptotic effect of HCM (P < 0.05), demonstrating that HCM exerts its anti-apoptotic effect by promoting autophagy. The effect of HCM - reduction of cell apoptosis and promotion of autophagic process - was also demonstrated in a mouse model. CONCLUSIONS: HP appears to induce ASCs to release a secretome with enhanced anti-apoptotic effects by promoting the autophagic process of ASCs.
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Tejido Adiposo , Secretoma , Adipocitos , Tejido Adiposo/metabolismo , Animales , Autofagia , Humanos , Ratones , Células MadreRESUMEN
ABBREVIATIONS: LT, liver transplantation; HCC, hepatocellular carcinoma; IS, immunosuppressants; DC, dendritic cells; Treg, regulatory T; Th17, T helper 17; AST, aspartate transaminase; ALT, alanine transaminase; OUT, operational taxonomic unit; LEfSe, linear discriminant analysis effect size; LDA, linear discriminant analysis; IL, interleukin; TGF, transforming growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; TNF-α, tumor necrosis factor-α; MIP-1α, macrophage inflammatory protein-1α; IP-10, interferon γ-induced protein; MCP-1, monocyte chemoattractant protein-1; ACR, acute cellular rejection; NF-κB, nuclear factor κB; PT INR, prothrombin time; QC, quality check; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Trasplante de Hígado , Citocinas , Faecalibacterium/metabolismo , Homeostasis , Humanos , Leucocitos Mononucleares/metabolismo , FN-kappa B , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Persistent left superior vena cava (PLSVC) is the most common congenital thoracic venous anomaly. It is usually found incidentally on examination or during invasive procedures. In most cases, the blood flows back to the right atrium through the coronary sinus without hemodynamic abnormalities and it is usually asymptomatic. There is some controversy regarding the clinical use of PLSVC. In a few cases, a PLSVC has been used for hemodialysis or large-bore intravenous access. CASE REPORT: A 62-year-old woman with a previous hepatectomy for hepatocellular carcinoma and liver cirrhosis developed hepatic failure. Owing to her worsening condition, she needed liver transplantation (LT). However, a superior vena cava thrombus was found between the right atrium and proximal superior vena cava on preoperative transesophageal echocardiography. Usually, right-sided central venous catheterization is performed for LT preparation, but the embolic risk was very high in our patient. Fortunately, she had already been diagnosed with PLSVC. Therefore, we decided to perform fluoroscopy-guided catheterization through the PLSVC. For the safe use of a PLSVC catheter during surgery, the rapid infusion system pressure, coronary sinus inflow pressure, and intraoperative transesophageal echocardiography were monitored. The patient successfully underwent LT. CONCLUSIONS: Based on a literature review and this case, PLSVC can be used clinically when accompanied by a detailed history, preoperative imaging examination, and close intraoperative monitoring. We suggest that a PLSVC is a feasible alternative to central venous access for LT.
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Trasplante de Hígado , Vena Cava Superior Izquierda Persistente , Síndrome de la Vena Cava Superior , Trombosis , Malformaciones Vasculares , Femenino , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Persona de Mediana Edad , Síndrome de la Vena Cava Superior/complicaciones , Trombosis/complicaciones , Malformaciones Vasculares/complicaciones , Vena Cava Superior/anomalías , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/cirugíaRESUMEN
Circulating tumor cells (CTCs) are a promising prognostic biomarker for cancers. However, the paucity of CTCs in peripheral blood in early-stage cancer is a major challenge. Our study aimed to investigate whether portal venous CTCs can be a biomarker for early recurrence and poor prognosis in pancreatic cancer. Patients who underwent upfront curative surgery for resectable pancreatic cancer were consecutively enrolled in this prospective study. Intraoperatively, 7.5 mL of portal and peripheral blood was collected, and CTC detection and identification were performed using immunofluorescence staining. Peripheral blood CTC sampling was performed in 33 patients, of which portal vein CTC sampling was performed in 28. The median portal venous CTCs (2.5, interquartile ranges (IQR) 1−7.75) were significantly higher than the median peripheral venous CTCs (1, IQR 0−2, p < 0.001). Higher stage and regional lymph node metastasis were related with a larger number of CTCs (≥3) in portal venous blood. Patients with low portal venous CTCs (≤2) showed better overall (p = 0.002) and recurrence-free (p = 0.007) survival than those with high portal venous CTCs (≥3). If validated, portal CTCs can be used as a prognostic biomarker in patients with resectable pancreatic cancer.
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BACKGROUND: Biliary strictures frequently occur in living-donor liver transplant (LDLT) recipients. However, long-term clinical outcomes and their associated factors are unclear. METHODS: We analyzed an historical cohort of 228 recipients who underwent LDLT with post-liver transplantation biliary strictures. Endoscopic retrograde cholangiography or percutaneous transhepatic biliary drainage were performed to treat biliary strictures. Patients that experienced persistent jaundice over 3 mo after the initial treatment were defined as a remission-failure group. RESULTS: Median observation period was 8.5 y after the diagnosis of biliary stricture. The 15-y graft survival (GS) rate was 70.6%, and 15-y rate of developing portal hypertension (PH) was 26.1%. Remission failure occurred in 25.0% of study participants. In the multivariate analysis, biopsy-proven acute rejection, and portal vein/hepatic artery abnormalities were risk factors for remission failure. Development of PH, retransplantation, and death were significantly more frequent in the remission-failure group. Remission failure and PH were associated with poor GS. In multivariate analyses, hepatic artery abnormality and biloma were common significant factors that were associated with a poor GS and development of PH. CONCLUSIONS: The insufficient blood supply reflected by hepatic artery abnormality and biloma might be the most important factor that can predict poor long-term survival in LDLT patients with biliary strictures. Future large-scale prospective studies are needed to validate our observations.
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Colestasis , Trasplante de Hígado , Colangiopancreatografia Retrógrada Endoscópica , Colestasis/diagnóstico , Colestasis/etiología , Colestasis/cirugía , Constricción Patológica/complicaciones , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Although rejection or tolerance can occur in liver transplantation (LT) patients, there are no reliable non-invasive methods for predicting immune homeostasis. In this study, we developed a humanized mouse model to predict liver immune homeostasis in patients who underwent LT. The patient-derived avatar model was developed by injecting peripheral blood mononuclear cells from healthy controls (HCs) or LT patients with stable, rejection, or tolerance into NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJ (NSG) mice, followed by injection of human hepatic stellate cells and Carbone tetrachloride (CCl4). After 7 weeks, the patient's T-cell engraftment and liver inflammation in the avatar model were evaluated and compared with the liver histology of LT patients. Changes in liver inflammation following treatment with tacrolimus and/or biguanide derivatives were also examined. The C-X-C Motif Chemokine Receptor 3 (CXCR3)-dependently engrafted patient T cells led to differences in liver inflammation in our model according to the status of LT patients. The livers of avatar models from rejection patients had severe inflammation with more T helper 17 cells and fewer regulatory T cells compared to those of models from tolerance and HCs showing only mild inflammation. Moreover, our model classified stable post-LT patients into severe and mild inflammation groups, which correlated well with liver immunity in these patients. Our models revealed alleviation of inflammation after combination treatment with tacrolimus and biguanide derivatives or monotherapy. Consequently, using our new patient-derived avatar model, we predicted liver immune homeostasis in patients with stable LT without biopsy. Moreover, our avatar model may be useful for preclinical analysis to evaluate treatment responses while reducing risks to patients.
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Trasplante de Hígado , Animales , Biguanidas , Modelos Animales de Enfermedad , Homeostasis , Humanos , Inflamación , Leucocitos Mononucleares , Hígado , Trasplante de Hígado/efectos adversos , Ratones , Ratones Endogámicos NOD , TacrolimusRESUMEN
OBJECTIVES: In HCC, locoregional therapy (LRT) is performed as a bridging or downstaging treatment before curative surgery. The impact of the LI-RADS Treatment Response (LR-TR) algorithm on surgical outcomes remains unknown. We aimed to evaluate radiologic and clinical factors predicting recurrence-free survival (RFS) and overall survival (OS) after curative surgery for LRT-treated HCC. MATERIALS AND METHODS: Consecutive HCC patients who underwent liver transplantation or curative resection after LRT from 2010 to 2016 and had baseline and follow-up post-LRT CT/MRI up to the point of surgery were included. The LR-TR category at the time of surgery and other features were assessed using Cox proportional hazard models. RFS was estimated and compared using the Kaplan-Meier method with log-rank tests. RESULTS: We evaluated 73 patients with 115 lesions. The LR-TR viable category at the time of surgery (hazard ratio [HR], 3.84; 95% confidence interval [CI]: 1.04, 14.16), preoperative AFP > 200 ng/mL (HR, 3.63; 95% CI: 1.63, 8.10), LRT sessions > 3 (HR, 4.99; 95% CI: 1.73, 14.38), and resection (HR, 3.35; 95% CI: 1.39, 8.09) independently predicted recurrence. The risk score categorized the patients into poor, intermediate, and favorable-risk groups with 1-year RFS rates of 35.0%, 78.3%, and 97.0%, respectively (p < 0.001). Outside Milan at the time of surgery (HR, 5.79; 95% CI: 1.94, 17.07) and recurrence within the first postoperative year (HR, 17.66; 95% CI: 6.42, 48.56) predicted death. CONCLUSION: In LRT-treated HCC, non-LR-TR viable disease achieved within fewer LRT sessions and removed by liver transplantation recurred less. KEY POINTS: ⢠The Liver Imaging Reporting and Data System treatment response (LR-TR) viable disease (hazard ratio [HR], 3.84; p = 0.043), preoperative serum AFP level > 200 ng/mL (HR, 3.63; p = 0.002), more than three locoregional treatment (LRT) sessions (HR, 4.99; p = 0.003), and resection compared to liver transplantation (HR, 3.35; p = 0.001) were the independent predictors for postsurgical recurrence in LRT-treated HCCs. ⢠A scoring system combining LR-TR categories and key clinical factors stratifies the patients into poor, intermediate, and favorable recurrence risk groups, with 1-year RFS rates of 35.0%, 78.3%, and 97.0%, respectively (p < 0.001). ⢠Outside Milan at the time of surgery (HR, 5.79; p = 0.001) and recurrence within the first postoperative year (HR, 17.66; p < 0.001) were associated with poor overall survival.