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BACKGROUND: The optimal approach for managing hepatic hemangioma is controversial. AIM: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience. METHODS: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated. RESULTS: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 (P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 (P > 0.05; χ² = 1.68, P > 0.05). CONCLUSION: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed.
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Barium sulfate (BaSO4) content is used to evaluate the grade of barite ore. In the present study, we report a method to determine the BaSO4 content in barite ore by phase conversion-headspace gas chromatography with partial pressure correction. In this method, the ore sample is roasted with sodium carbonate and potassium carbonate after pretreatment with hydrochloric acid. The roasted product is subsequently placed in a closed headspace bottle to react with hydrochloric acid. The ratio of CO2 to O2 signals is detected by a thermal conductivity detector for gas chromatography. Finally, the BaSO4 content in barite ore is calculated using this ratio. The method demonstrates good precision (relative standard deviation < 0.84%) and accuracy (relative error < 3.40%), with the uncertainty at 95% confidence interval at approximately +/- 0.57%. Moreover, this approach is expected to be used for the batch testing of BaSO4 content in barite ores in industrial applications.
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Sulfato de Bário , Dióxido de Carbono , Sulfato de Bário/química , Pressão Parcial , Ácido Clorídrico , Cromatografia Gasosa/métodosRESUMO
OBJECTIVES: Leiomyosarcoma of inferior vena cava (IVC) is a rare clinical entity with severe vascular involvement. Surgical management of leiomyosarcoma is still challenging. METHODS: This a retrospective study of consecutive patients referred to our hospital from January 2017 to June 2019. Depending on the anatomical site of affected IVC, leiomyosarcomas were categorized into zone I-II. The clinical data including baseline information, surgical parameters, peri-operative management, short- and mid-term outcomes were observed. RESULTS: Four patients with leiomyosarcoma of zone I-III underwent radical resection without intraoperative mortality. Prosthetic grafts were interpositioned in all patients to instruct vena cava. Renal vein reconstruction was perfumed in two patients due to involvement to renal veins. Median blood loss was 450âmL (200-600âmL), median operative time was 215 minutes (150-240âminutes). No Clavien-Dindo IIIa or higher complication was observed. No organ dysfunction and recurrence were observed with median follow-up of 25.5âmonths. CONCLUSIONS: Curative resection of zone I-II leiomyosarcoma is associated with longer survival in selected cases, en-bloc resection with complex vascular reconstruction could be considered.
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Leiomiossarcoma , Neoplasias Vasculares , Humanos , Leiomiossarcoma/cirurgia , Veias Renais , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/cirurgiaRESUMO
BACKGROUND: As an early complication after liver transplantation, early allograft dysfunction (EAD) indicates a poor prognosis. This study analyzes the risk factors related to early allograft dysfunction (EAD) after liver transplantation using grafts from donation after citizen death (DCD) to provide a reference for the prevention of EAD after DCD liver transplantation. METHODS: A total of 32 patients who underwent DCD liver transplantation in the organ transplantation center of our hospital from September 2013 to January 2021 were enrolled in this study. The patients were divided into the EAD group and non-EAD group according to whether they developed EAD after transplantation. The general data of the donors and recipients before transplantation, intraoperative conditions, and clinical data within one week after transplantation were compared between the two groups, and related complications were statistically analyzed. The follow-up time was one week postoperatively or, if they died within the first week postoperatively, until the patient died. RESULTS: The subjects included 10 females and 22 males, and the incidence of postoperative EAD was 25% (8/32). Four patients (12%) had primary malignant tumors (primary liver cancer and cholangiocarcinoma), and five donors (15%) had fatty liver. The univariate analysis revealed that the donor BMI (P = 0.005), degree of fatty liver (P = 0.025), aspartate aminotransferase (P = 0.001), alanine aminotransferase (P < 0.001), and total bilirubin (P = 0.009) were related to the occurrence of EAD after DCD liver transplantation. By analyzing the correlation between the incidence EAD and postoperative complications after liver transplantation using grafts from DCD donors, it was shown that the incidence of primary nonfunction (PNF) is related to EAD (P = 0.024). CONCLUSION: Donor BMI, the degree of fatty liver, and preoperative liver function are risk factors for EAD after DCD liver transplantation, and the occurrence of EAD after DCD liver transplantation significantly increases the probability of PNF.
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Fígado Gorduroso , Hepatopatias , Transplante de Fígado , Fígado Gorduroso/etiologia , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate potential biomarkers for distinguishing biological viability of hepatic cystic echinococcosis. METHODS: Using Luminex assay we measured plasma concentrations of cytokine and chemokine in patients with active and non-active cysts (hepatic cystic echinococcosis (HCE), n = 47) and stable/progressive hepatic alveolar echinococcosis (HAE, n = 38), and in comparable infection-free volunteers (n = 48). Disease progression was staged according to the classification standard. RESULTS: Compared with healthy controls, enhanced elevation was found of T helper 22 type cytokine interleukin (IL)-22 and chemokines Eotaxin, interferon-γ inducible protein-10, monocyte chemoattractant protein-1, and stromal cell-derived factor-1α concentrations in HAE patients, and IL-22, growth-related oncogene α, monocyte chemoattractant protein-1, regulated on activation normal T-expressed and secreted, and stromal cell-derived factor-1α concentrations in HCE patients (P < 0.05-0.001). For HCE patients, only IL-27 concentrations in non-active HCE were significantly lower than in active HCE. In logistic regression analysis, IL-27 <20.79 pg/mL was an independent risk factor for HCE biological viability with receiver operating characteristic analysis at a 44.23 pg/mL cut-off resulting in 0.72 area under the curve. CONCLUSIONS: Our findings correlate multiple cytokine and chemokine secretion patterns in HAE and HCE patients with different disease progression stages. IL-27 could serve as a referring biomarker for distinguishing HCE biological viability and provide a preliminary foundation for clinical decision-making.
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Equinococose Hepática , Equinococose , Interleucina-27 , Citocinas , Equinococose Hepática/diagnóstico , Humanos , Interleucinas , PrognósticoRESUMO
We report the first documented case of leiomyosarcoma at zone II-III of inferior vena cava with thrombi in three hepatic veins undergoing ex vivo liver resection and autotransplantation (ELRA) and hepatic veins thrombectomy. A 33-year-old female patient presented with abdominal distention and lower extremities edema. Abdominal wall varicosis and shifting dullness were positive on physical examination. Her liver function was classified as Child-Pugh B and a solid tumor at retro-hepatic vena cava extending to right atrium with thrombi in three hepatic veins were confirmed. The diagnosis of leiomyosarcoma with Budd-Chiari syndrome was highly suspected with preoperative ultrasound, echocardiogram, CT scan, and three-dimensional reconstruction. A zone II-III leiomyosarcoma of IVC origin was confirmed at surgery and ex vivo liver resection and autotransplantation, and hepatic vein thrombectomy with atrial reconstruction were performed under cardiopulmonary bypass (CPB). Operative time, anhepatic time, and CPB time were 12 h, 128 min, and 84 min, respectively. The patients experienced post-operative liver dysfunction and was cured with conservative therapy. Hepatic recurrence two years after surgery was managed with radiofrequency. The patient was alive with liver metastasis three years after surgery. Despite being regarded as an extremely aggressive procedure, ELRA could be considered in the treatment of advanced leiomyosarcoma with Budd-Chiari syndrome and hepatic vein thrombi.
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OBJECTIVE: Alveolar echinococcosis (AE) is a zoonosis caused by the larval stage of the metacestode Echinococcosis multilocularis with a tumor-like behavior in the targeted organ, especially in the liver. Surgery with albendazole is first-line modality for AE. Drug discontinuation is usually based upon the parasitic viability shown by the positron emission tomography (PET) scan. However, as a demanding and expensive method, it is not widely practiced in majority of the endemic regions. Further understanding on the cytokine and chemokine response profiles in AE patients may provide an interesting insight for potential markers in viability assessment. METHODS: Mice were inoculated with Echinococcus multilocularis intrahepatically to develop the hepatic AE murine model. Oral albendazole administration was then applied for three months after the first inoculation, and peripheral and regional immune cells including type 1 T helper cells (Th), Th2, Th17, regulatory T (Treg) cells, related cytokines, and chemokines were examined. RESULTS: The hepatic AE lesion was confirmed by ultrasound examination resulting in a successful rate of 70%. Among the 17 cytokines and chemokines detected, plasma levels of IL-23 were significantly higher in E. multilocularis-infected mice when compared to the control group; furthermore, more obvious increasing levels were found after albendazole treatment (p < 0.05). All chemokine levels other than eotaxin and MCP-3 were slightly higher in E. multilocularis-infected mice compared to the control group (p > 0.05). Eotaxin levels were significantly decreased in mice with E. multilocularis infection followed by albendazole treatment (p < 0.05). Both IL-17A and IL-23 expressions in hepatic AE lesions were significantly higher and related with disease activity. CONCLUSION: Albendazole administration influenced the balance of immune response and promotes the secretion of proinflammatory factors which is beneficial to parasite clearance. IL-23 seems to be associated with the successful albendazole treatment in mice with E. multilocularis infection; such a change could be translated into clinical application in the near future.
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Albendazol/uso terapêutico , Quimiocinas/imunologia , Citocinas/imunologia , Equinococose/tratamento farmacológico , Echinococcus multilocularis/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Equinococose/parasitologia , Equinococose/patologia , Equinococose Hepática/tratamento farmacológico , Equinococose Hepática/parasitologia , Equinococose Hepática/patologia , Feminino , Humanos , Imunidade , Interleucina-23 , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologiaRESUMO
OBJECTIVES: The clinical safety, efficacy and feasibility of laparoscopic appendectomy (LA) compared with open appendectomy (OA) in pregnancy are still controversial. Herein, we are aiming to compare the clinical outcomes of LA and OA in patients with acute appendicitis during their pregnancy. MATERIALS AND METHODS: This was a systematic review and meta-analysis of studies comparing laparoscopic and OA in pregnancy identifying using PubMed, Web of science, Embase, The Cochrane Library, Ovid and Scopus. Two independent reviewers extracted data on surgical complication, fetal loss, preterm delivery, hospital stay, Apgar score in both groups. RESULTS: Twenty-seven studies with total of 6497 patients (4464 in open and 2031 in laparoscopic group) were included. LA was associated with lower rate of wound infection [odds risk (OR)=3.13, 95% confidence interval (CI): 1.77-5.56, P<0.0001] overall complications (OR=2.15, 95% CI: 1.47-3.14, P<0.0001) and shorter hospitalization (mean difference=0.72, 95% CI: 0.43-1.02, P<0.00001) compared with open group. LA was in a lower risk for 5-minute Apgar score (mean difference=0.09, 95% CI: 0.02-0.17, P=0.01) group than open group. No difference was found regarding preterm delivery between 2 groups. LA was associated with higher fetal loss (OR=0.57, 95% CI: 0.41-0.79, P=0.0007) compared with open surgery. However, laparoscopy was not associated with increased fetal loss after 2010 (OR=0.74, 95% CI: 0.44-1.24, P=0.26) compared with open group. CONCLUSIONS: LA in pregnancy seems to be feasible with acceptable outcome, especially in patients with early and mid-trimester period, with sophisticated hands and experienced centers.
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Apendicite , Laparoscopia , Doença Aguda , Apendicectomia , Apendicite/cirurgia , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Thioredoxin-like protein-1 (TXNL1; also known as thioredoxin-related 32 kDa protein, TRP32) is a thioredoxin involved in the regulation of oxidative stress, which protects cells from damage through redox balance. Studies have shown that TXNL1 has a variety of functions, including cell signal transduction, cell cycle regulation, protein synthesis, modification and degradation, vesicle transport, transcriptional regulation, cell apoptosis, virus replication and oxidative stress regulation, etc., and plays an important role in the occurrence and development of human diseases. Therefore, TXNL1 has a strong correlation with the treatment of cancer and oxidative stress diseases. In this paper, the basic structure, function and potential application value of TXNL1 in diseases are reviewed, so as to open up new targets for the treatment of cancer and oxidative stress-related diseases.
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Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo , Tiorredoxinas/metabolismo , Animais , Epilepsia/patologia , Humanos , Neoplasias/terapia , Traumatismos da Medula Espinal/patologia , Tiorredoxinas/químicaRESUMO
[This corrects the article DOI: 10.3389/fonc.2020.00326.].
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BACKGROUND: Emerging evidence indicates a regulatory role of long non-coding RNAs (lncRNAs) in the development of gastric cancer (GC), but the mechanisms underlying their function have remained largely unknown. Recent microarray-based expression profiling has led to the identification of a novel differentially expressed lncRNA, LINC00858, in GC. Subsequently, LINC00858 was found to be highly expressed in GC tissues and cells. This study was designed to clarify the functional role of LINC00858 in GC, including its effect on methylation of the WNK2 gene promoter and its downstream MAPK signaling pathway. METHODS: After exogenous over-expression and knockdown of LINC00858 and the addition of a MAPK pathway inhibitor in GC cells, we explored the effects of LINC00858 and the MAPK signaling pathway on GC cell behavior using various in vitro and in vivo assays. RESULTS: LINC00858 was found to negatively regulate WNK2 expression by enhancing its promoter methylation and to activate the MAPK signaling pathway. Moreover, we found that knockdown of LINC00858 or inhibition of the MAPK signaling pathway resulted in decreased GC cell growth, migration and invasion, as well as decreased cell cycle progression, along with increased apoptosis and decreased tumorigenicity. CONCLUSIONS: Together, these findings indicate that silencing of LINC00858 increases WNK2 expression and inhibits the MAPK signaling pathway, thereby inhibiting GC growth and development. Our data highlight LINC00858 as a potential target in GC therapy.
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Regulação Neoplásica da Expressão Gênica/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Apoptose/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Metilação de DNA/genética , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Regiões Promotoras Genéticas/genéticaRESUMO
Nest survival is a vital component of breeding success, and affects population dynamics, as the loss of nests is the main cause of reproductive failure in birds. To identify key factors for the conservation of Chinese grouse Tetrastes sewerzowi, we tested the effects of nest concealment, nest age, nesting season, and habitat edge on nest daily survival rate (DSR) of Chinese grouse using 54 nests found at Lianhuashan Nature Reserve, Gansu, China, 2009-2012. Moreover, we controlled for the effect of research activity by testing the effect of nest checks on DSR. Overall, mammal predation caused 93% of nest failures. DSR was 0.986 ± 0.0038 in the constant model and the probability of a nest with a full clutch of 6 eggs surviving the entire 40-day nesting period was 0.526 ± 0.090. DSR decreased with nest age and nesting season (from 19 May to 3 July). Mammals instead of avian predators being responsible for most nest failures suggest that nest sites might be selected to avoid visual avian predators, but not olfactory mammalian predators, and the decreasing trend of DSR with nest age and nesting season could attribute to an additive exposure effect. Moreover, nest checks conducted by investigators significantly lowered nest DSR, especially during the late period of nesting season and for older nests. Mammalian predators might locate the nest site by following the investigator's odor. Based on our results, we suggest that the late incubation stage is a particularly vulnerable period for nest survival of Chinese grouse and those researchers should adjust their activities around nests to balance the need of acquiring accurate data and decreasing nest predation risk.
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Hypoxia-exposed lung cancer-released exosomal microRNA-23a (miR-23a) has been shown to enhance angiogenesis as well as vascular permeability, contributing to the close correlation between exosomal miR-23a and tumorigenesis. The current study aimed to investigate whether gastric cancer (GC) cell-derived exosomal miR-23a could induce angiogenesis and to elucidate the potential mechanisms associated with the process. Differentially expressed miRNAs in GC were initially screened from the Gene Expression Omnibus database. Target genes were selected following miRNA-mRNA prediction and subsequently verified by dual luciferase reporter assay. RT-qPCR was conducted to detect miR-23a and PTEN expression in GC tissues, cells and exosomes. Human umbilical venous endothelial cells (HUVECs) were co-cultured with GC cell-derived exosomes to assess the angiogenesis mediated by exosomes in vitro. Additionally, PTEN was overexpressed in HUVECs to analyze the mechanism by which miR-23a regulates angiogenesis. miR-23a was highly expressed in GC tissues and cells and GC cell-derived exosomes. Angiogenesis was promoted by the co-culture of HUVECs and GC cells-derived exosomes, as evidenced by the increased expression of VEGF but decreased expression of TSP-1. PTEN was targeted by miR-23a and was lowly expressed in GC tissues. In a co-culture system, miR-23a carried by GC cells-derived exosomes promoted angiogenesis via the repression of PTEN. Collectively, GC cell-derived exosomal miR-23a could promote angiogenesis and provide blood supply for growth of GC cells. This study contributes to advancement of miRNA-targeted therapeutics.
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BACKGROUND: China is facing challenges of the shifting presentation of tuberculosis (TB) from younger to elderly due to an ageing population, longer life expectancy and reactivation disease. However, the burden of elderly TB and influence factors are not yet clear. To fill the gap, we generated a cohort study to measure the magnitude of TB incidence and associated factors among the elderly population aged 65 years and above in China. METHODS: In this cohort established in 2013 through a prevalence survey conducted in selected sites, a total of 34 076 elderlies without TB were enrolled into two-year follow-up. We used both active and passive case findings to find out all TB patients among them. The person-year (PY) incidence rates for both bacteriologically positive TB and active TB were calculated. Cox proportional regression model was performed to test effect of risk factors, and the population attributable fraction (PAF) of each risk factor contributing to incident TB among elderlies was calculated. RESULTS: Over the two-year follow-up period, a total of 215 incident active TB were identified, 62 of which were bacteriologically positive. The incidence rates for active TB and bacteriologically positive TB were 481.8 per 100 000 PY (95% CI: 417.4-546.2 per 100 000 PY) and 138.9 per 100 000 PY (95% CI: 104.4-173.5 per 100 000 PY), respectively. Incident cases detected by active case finding were significantly higher (P < 0.001). Male, non-Han nationality, previously treated TB, ex/current smoker and body mass index (BMI) < 18.5 presented as independent predictors for developing TB disease. For developing bacteriologically positive TB, the biggest contribution was from self-reported ex or current smoker (18.06%). And, for developing active TB, the biggest contribution was from non-Han nationality (35.40%), followed by male (26.80%) and age at 75 years and above (10.85%). CONCLUSIONS: Ageing population in China had a high TB incidence rate and risk to develop TB disease, implying that National TB Program (NTP) needs to prioritize for elderly. Active case finding should be applied capture more active TB cases among this particular population, especially for male, non-Han nationality, and those with identified risk factors.
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Tuberculose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Humanos , Incidência , Estudos Prospectivos , Fatores de RiscoRESUMO
The mediator complex is an essential link between transcription factors and RNA polymerase II, and mainly functions in the transduction of diverse signals to genes involved in different pathways. Limited information is available on the role of soybean mediator subunits in growth and development, and their participation in defense response regulation. Here, we performed genome-wide identification of the 95 soybean mediator subunits, which were unevenly localized on the 20 chromosomes and only segmental duplication events were detected. We focused on GmMED16-1, which is highly expressed in the roots, for further functional analysis. Transcription of GmMED16-1 was induced in response to Phytophthora sojae infection. Agrobacterium rhizogenes mediated soybean hairy root transformation was performed for the silencing of the GmMED16-1 gene. Silencing of GmMED16-1 led to an enhanced susceptibility phenotype and increased accumulation of P. sojae biomass in hairy roots of transformants. The transcript levels of NPR1, PR1a, and PR5 in the salicylic acid defense pathway in roots of GmMED16-1-silenced transformants were lower than those of empty-vector transformants. The results provide evidence that GmMED16-1 may participate in the soybean-P. sojae interaction via a salicylic acid-dependent process.
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Estudo de Associação Genômica Ampla , Glycine max/genética , Glycine max/parasitologia , Interações Hospedeiro-Parasita/genética , Complexo Mediador/metabolismo , Phytophthora/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Phytophthora/classificação , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Subunidades Proteicas , TranscriptomaRESUMO
BACKGROUND: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy in end-stage hepatic alveolar echinococcosis patients who underwent ex-situ liver resection and autotransplantation (ELRA). METHODS: A total of 81 patients received ELRA from August 2010 to March 2018. They were allocated into UW (nâ¯=â¯48) and HTK groups (nâ¯=â¯33) based on the type of solutions used. Demographic and operational data were retrospectively analyzed. Primary outcomes included 90-day mortality, incidence of early graft loss, primary dysfunction, and postoperative complications. RESULTS: Demographic and operational characteristics were similarly distributed in the two groups. No statistically significant differences were observed with regard to 90-day mortality (12.77% vs. 12.12%) and early graft loss rate (8.51% vs. 9.09%) between the two groups. Patients in the UW and HTK groups showed a primary dysfunction rate of 27.66% and 27.27%, respectively. The UW group exhibited a higher incidence tendency of biliary complications, albeit with no statistical significance. CONCLUSIONS: This is the largest cohort study comparing the efficacy of the UW and HTK organ-preserving solutions in end-stage hepatic alveolar echinococcosis patients in ELRA settings. UW and HTK solutions presented similar efficacy and safety. A randomized clinical trial with larger scale is needed for further investigation in future clinical applications.
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Equinococose Hepática/cirurgia , Doença Hepática Terminal/cirurgia , Transplante de Fígado , Soluções para Preservação de Órgãos/química , Adulto , Autoenxertos/fisiopatologia , Equinococose Hepática/complicações , Doença Hepática Terminal/parasitologia , Feminino , Sobrevivência de Enxerto , Hepatectomia , Histidina , Humanos , Ácidos Cetoglutáricos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Triptofano , Universidades , Wisconsin , Adulto JovemRESUMO
Alveolar echinococcosis (AE) is caused by the larval stage of echinococcus multilocularis (E. multilocularis), and hepatectomy is the main modality in hepatic AE patients. Liver regeneration after partial hepatectomy (PHx) in such patients is challenging, and further investigation is needed. Thus far, knowledge regarding the possible impact of E. multilocularis on liver regeneration after PHx is limited. Herein, a subcutaneous infection model of E. multilocularis was developed in C57 BL/6 mice, and after 3 months, PHx was performed. Plasma and liver samples were harvested under inhalational isofluorane (2%) anaesthesia at designated post-PHx time points (0, 24, 48, 96 and 168 h). The parameters included the future remnant liver/body weight ratio (FLR/BW), liver function tests (AST and ALT) and related cytokines (TNF-α, IL-6, Factor V, HMGB1, TGF-ß, TSP-1, and TLR4) and proteins (MyD88 and STAT3). To assess the proliferation intensity of hepatocytes, BrdU, Ki67 and PAS staining were carried out in regenerated liver tissue. The FLR/BW in the infected group from 48 h after surgery was lower than that in the control group. The BrdU positive hepatocyte proportions reached their peak at 48 h in the control group and 96 h in the infected group and then gradually decreased. During the first 48 h after surgery, both the AST and ALT levels in the infected group were lower; however, these levels were altered from 96 h after surgery. In the infected group, the concentrations and mRNA expression levels of the pre-inflammatory cytokines TNF-α and IL-6 demonstrated a delayed peak. Moreover, post-operatively, the TGF-ß and TSP-1 levels showed high levels in the infected group at each different time-point compared to those in the control group; however, high levels of TGF-ß were observed at 96 h in the control group. The MyD88 and STAT3 protein expression levels in the infected group were markedly higher than those in the control group 96 h after surgery. Delayed liver regeneration after PHx was observed in the C57 BL/6 mice with the subcutaneous infection of E. multilocularis in the current study. This phenomenon could be partially explained by the alteration in the pro-inflammatory cytokines in the immunotolerant milieu induced by chronic E. multilocularis infection.
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Equinococose Hepática/parasitologia , Equinococose/parasitologia , Echinococcus multilocularis/fisiologia , Regeneração Hepática , Dermatopatias Parasitárias/parasitologia , Animais , Biomarcadores , Citocinas/genética , Citocinas/metabolismo , Equinococose Hepática/diagnóstico , Equinococose Hepática/metabolismo , Equinococose Hepática/cirurgia , Expressão Gênica , Hepatectomia , Mediadores da Inflamação/metabolismo , Testes de Função Hepática , Camundongos , Dermatopatias Parasitárias/metabolismoRESUMO
BACKGROUND & AIMS: Radical resection is the best treatment for patients with advanced hepatic alveolar echinococcosis (AE). Liver transplantation is considered for selected advanced cases; however, a shortage of organ donors and the risk of postoperative recurrence are major challenges. The aim of this study was to assess the clinical outcomes of ex vivo liver resection and autotransplantation for end-stage AE. METHODS: In this prospective study, 69 consecutive patients with end-stage hepatic AE were treated with ex vivo resection and liver autotransplantation between January 2010 and February 2017. The feasibility, safety and long-term clinical outcome of this technique were assessed. RESULTS: Ex vivo extended hepatectomy with autotransplantation was successful in all patients without intraoperative mortality. The median weight of the graft and AE lesion were 850 (370-1,600)â¯g and 1,650 (375-5,000)â¯g, respectively. The median duration of the operation and anhepatic phase were 15.9 (8-24)â¯h and 360 (104-879)â¯min, respectively. Six patients did not need any blood transfusion. Complications higher than IIIa according to Clavien classification were observed in 10 patients. The 30-day-mortality and overall mortality (>90â¯days) were 7.24% (5/69) and 11.5% (8/69), respectively. The mean hospital stay was 34.5 (12-128) days. Patients were followed-up systematically for a median of 22.5â¯months (14-89) without recurrence. CONCLUSION: This is the largest series assessing ex vivo liver resection and autotransplantation in end-stage hepatic AE. This technique could be an effective alternative to liver transplantation in patients with end-stage hepatic AE, with the advantage that it does not require an organ nor immunosuppressive agents. LAY SUMMARY: Ex vivo liver resection and autotransplantation were performed in a large series of patients with end-stage hepatic alveolar echinococcosis. The results showed that this surgical option was feasible, with acceptable postoperative mortality, but 100% disease-free survival in survivors. Careful patient selection, as well as precise assessment for size and quality of the remnant liver are key to successful surgery.
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Equinococose Hepática/cirurgia , Hepatectomia/métodos , Transplante de Fígado/métodos , Adolescente , Adulto , Feminino , Hepatectomia/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Transplante Homólogo , Adulto JovemRESUMO
Fluorodeoxyglucose (FDG) uptake by alveolar echinococcosis (AE) liver lesions is a signal of their metabolic activity and of disease progression. In order to find a surrogate marker for this status, we investigated whether parameters of the peripheral and/or periparasitic immune responses were associated with metabolic activity in a prospective case-control study of 30 AE patients and 22 healthy controls. Levels of 18 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in plasma and peripheral cells of two groups of patients with (MAAE) and without (MIAE) metabolically active lesions, and in the liver of MAAE patients. Mixed cytokine profile was observed in the peripheral blood of AE patients, with a predominance of Th2, Th17 and Treg responses. Among the detected markers only plasma IL-5 and IL-23, more elevated in MAAE patients, were found discriminant. Discrimination between MAAE and MIAE patients obtained by using IL-23 was improved when IL-5 was used in combination. The combination of elevated levels of IL-5 and IL-23 is significantly associated with FDG uptake at PET scan. It offers a new tool for the follow-up of AE patients which could substitute to FDG-PET whenever non-available to assess disease progression.