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The canonical role of the transcription factor E2F is to control the expression of cell cycle genes by binding to the E2F sites in their promoters. However, the list of putative E2F target genes is extensive and includes many metabolic genes, yet the significance of E2F in controlling the expression of these genes remains largely unknown. Here, we used the CRISPR/Cas9 technology to introduce point mutations in the E2F sites upstream of five endogenous metabolic genes in Drosophila melanogaster. We found that the impact of these mutations on both the recruitment of E2F and the expression of the target genes varied, with the glycolytic gene, Phosphoglycerate kinase (Pgk), being mostly affected. The loss of E2F regulation on the Pgk gene led to a decrease in glycolytic flux, tricarboxylic acid cycle intermediates levels, adenosine triphosphate (ATP) content, and an abnormal mitochondrial morphology. Remarkably, chromatin accessibility was significantly reduced at multiple genomic regions in PgkΔE2F mutants. These regions contained hundreds of genes, including metabolic genes that were downregulated in PgkΔE2F mutants. Moreover, PgkΔE2F animals had shortened life span and exhibited defects in high-energy consuming organs, such as ovaries and muscles. Collectively, our results illustrate how the pleiotropic effects on metabolism, gene expression, and development in the PgkΔE2F animals underscore the importance of E2F regulation on a single E2F target, Pgk.
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Proteínas de Drosophila , Drosophila , Factores de Transcripción E2F , Fosfoglicerato Quinasa , Animales , Cromatina , Drosophila/genética , Factores de Transcripción E2F/genética , Fosfoglicerato Quinasa/genética , Fosfoglicerato Quinasa/metabolismo , Regiones Promotoras Genéticas , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismoRESUMEN
Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.
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Carcinoma Hepatocelular , Virus de la Hepatitis B , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Transducción de Señal , Sorafenib , Superóxido Dismutasa-1 , Serina-Treonina Quinasas TOR , Sorafenib/farmacología , Sorafenib/uso terapéutico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Especies Reactivas de Oxígeno/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Superóxido Dismutasa-1/metabolismo , Superóxido Dismutasa-1/genética , Animales , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones , Virus de la Hepatitis B/efectos de los fármacos , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Apoptosis/efectos de los fármacos , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Ditiocarba/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones Desnudos , Proliferación Celular/efectos de los fármacos , Transactivadores , Proteínas Reguladoras y Accesorias ViralesRESUMEN
Biological tubes are essential for animal survival, and their functions are dependent on tube shape. Analyzing the contributions of cell shape and organization to the morphogenesis of small tubes has been hampered by the limitations of existing programs in quantifying cell geometry on highly curved tubular surfaces and calculating tube-specific parameters. We therefore developed QuBiT (Quantitative Tool for Biological Tubes) and used it to analyze morphogenesis of the embryonic Drosophila trachea (airway). In the main tube, we find previously unknown anterior-to-posterior (A-P) gradients of cell apical orientation and aspect ratio, and periodicity in the organization of apical cell surfaces. Inferred cell intercalation during development dampens an A-P gradient of the number of cells per cross-section of the tube, but does not change the patterns of cell connectivity. Computationally 'unrolling' the apical surface of wild-type trachea and the hindgut reveals previously unrecognized spatial patterns of the apical marker Uninflatable and a non-redundant role for the Na+/K+ ATPase in apical marker organization. These unexpected findings demonstrate the importance of a computational tool for analyzing small diameter biological tubes.
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Drosophila/embriología , Epitelio/embriología , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Tráquea/embriología , Adenosina Trifosfato/química , Animales , Tipificación del Cuerpo , Sistemas CRISPR-Cas , Linaje de la Célula , Biología Computacional/instrumentación , Cruzamientos Genéticos , Proteínas de Drosophila/metabolismo , Proteínas de la Membrana/metabolismo , Modelos Biológicos , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
PURPOSE: Spleen-preserving distal pancreatectomy (SPDP) such as splenic vessel preservation (SVP) for solid pseudopapillary neoplasms (SPNs) in the body or tail of the pancreas in children prevents post-splenectomy infection and hematologic disorders. However, SVP could be technically challenging, and the Warshaw technique (WT) could be an alternative technique that has been reported to be safe and effective in adults. We, therefore, compared the perioperative outcomes of SVP and WT in pediatric patients. METHODS: We retrospectively reviewed the medical records of pediatric patients with SPN who underwent SPDP using SVP or WT between November 2002 and November 2018 at a large-sized tertiary referral center. RESULTS: Twenty-eight patients were included. Sixteen (57.1%) patients underwent SVP and 12 (42.9%) patients underwent WT. There were no significant differences in the baseline characteristics between the two groups. Postoperative complications occurred in 8 patients each in the SVP (50%), and the WT (66.7%) groups. Two (12.5%) in the SVP group and 1 (8.3%) in the WT group required additional intervention. During a median follow-up duration of 49 months, there were no significant differences in the incidence of splenic infarctions or perigastric varices between the two groups. CONCLUSIONS: There were no significant differences in the surgical outcomes between WT and SVP in pediatric patients with SPN. WT could be a safe and feasible alternative technique for SVP in challenging cases.
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Laparoscopía , Neoplasias Pancreáticas , Adulto , Niño , Humanos , Laparoscopía/métodos , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Bazo/cirugía , Resultado del TratamientoRESUMEN
Hypercapnia, elevated partial pressure of CO2 in blood and tissue, develops in many patients with chronic severe obstructive pulmonary disease and other advanced lung disorders. Patients with advanced disease frequently develop bacterial lung infections, and hypercapnia is a risk factor for mortality in such individuals. We previously demonstrated that hypercapnia suppresses induction of NF-κB-regulated innate immune response genes required for host defense in human, mouse, and Drosophila cells, and it increases mortality from bacterial infections in both mice and Drosophila. However, the molecular mediators of hypercapnic immune suppression are undefined. In this study, we report a genome-wide RNA interference screen in Drosophila S2* cells stimulated with bacterial peptidoglycan. The screen identified 16 genes with human orthologs whose knockdown reduced hypercapnic suppression of the gene encoding the antimicrobial peptide Diptericin (Dipt), but did not increase Dipt mRNA levels in air. In vivo tests of one of the strongest screen hits, zinc finger homeodomain 2 (Zfh2; mammalian orthologs ZFHX3/ATBF1 and ZFHX4), demonstrate that reducing zfh2 function using a mutation or RNA interference improves survival of flies exposed to elevated CO2 and infected with Staphylococcus aureus. Tissue-specific knockdown of zfh2 in the fat body, the major immune and metabolic organ of the fly, mitigates hypercapnia-induced reductions in Dipt and other antimicrobial peptides and improves resistance of CO2-exposed flies to infection. Zfh2 mutations also partially rescue hypercapnia-induced delays in egg hatching, suggesting that Zfh2's role in mediating responses to hypercapnia extends beyond the immune system. Taken together, to our knowledge, these results identify Zfh2 as the first in vivo mediator of hypercapnic immune suppression.
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Proteínas de Unión al ADN/inmunología , Proteínas de Drosophila/inmunología , Hipercapnia/inmunología , Infecciones Estafilocócicas/complicaciones , Animales , Western Blotting , Modelos Animales de Enfermedad , Drosophila , Técnicas de Silenciamiento del Gen , Hipercapnia/microbiología , Inmunidad Innata/inmunología , Interferencia de ARN , Infecciones Estafilocócicas/inmunología , Staphylococcus aureusRESUMEN
BACKGROUND: The outcomes of revascularization of nonatherosclerotic occlusive popliteal artery disease are unknown. Therefore, the objective of this study was to analyze the outcomes of recanalization of nonatherosclerotic occlusive popliteal artery disease, the results of which would be useful in creating surgical strategies for such cases. METHODS: From January 2000 to December 2015, a total of 22 patients with nonatherosclerotic occlusive popliteal artery disease underwent open surgical repair. We retrospectively analyzed the data of these patients. Thrombectomy with angioplasty on the occluded popliteal artery, graft interposition, and bypass surgery were conducted for revascularization of the affected region. We analyzed the overall primary patency rate, type of graft, and surgical approach. Furthermore, we compared the primary patency rate after surgical treatment. RESULTS: Of 22 patients, 3 (13.6%) had cystic adventitial disease, 16 (72.7%) had popliteal artery entrapment syndrome, and 3 (13.6%) were diagnosed as having thromboangiitis obliterans. Five patients (22.7%) underwent thrombectomy with patch angioplasty, 8 (36.3%) underwent bypass surgery, and 9 (40.9%) underwent graft interposition of the popliteal artery. All graft interpositions and thrombectomies with patch angioplasty were performed through a posterior approach, whereas all bypass surgeries were performed through a medial approach except in 1 case. The mean follow-up period was 54.95 ± 42.99 months. The overall primary patency rate at 1, 3, and 10 years was 100%, 86.9%, and 69.5%, respectively. In the bypass group, the primary patency rate at 1, 3, and 10 years was 100%, 66.7%, and 44.4%, respectively. In the other groups, the primary patency rate was 100% during the follow-up period. The difference in primary patency rate was statistically significant (P ≤ 0.05). CONCLUSIONS: The result of surgical treatment for nonatherosclerotic occlusive popliteal artery disease was better than that of atherosclerotic popliteal artery disease. Direct popliteal artery reconstruction, such as graft interposition or thrombectomy with patch angioplasty, showed better short- and long-term patency than did bypass surgery.
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Arteriopatías Oclusivas/cirugía , Arteria Poplítea/cirugía , Adulto , Adventicia/cirugía , Implantación de Prótesis Vascular , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombectomía , Tromboangitis Obliterante/cirugía , Trombosis/cirugía , Injerto Vascular , Grado de Desobstrucción VascularRESUMEN
This study was conducted to investigate the inhibited influences on and solution to the degradation of four types of dense non-aqueous phase liquids (DNAPLs) (i.e. perchloroethylene [PCE], trichloroethylene [TCE], chloroform [CF], and carbon tetrachloride [CT]) all at the same instance in groundwater (GW). Degradations of DNAPLs in de-ionized water (DW) and GW were carried out by applying an ultraviolet radiation-activated persulphate (UV/PS) system. PCE and TCE were degraded by over 90% and CT was only degraded by 25% in both DW and GW. However, CF was degraded by over 90% in DW, while it was only degraded by 50% in GW. First of all, degradations with an inorganic anion (either Cl- or HCO3-) indicated that the lower degradation of CF in GW was caused by the existence of the chloride ion. Moreover, the low CF degradation in GW was overcome by the additional injection of a base solution (sodium hydroxide [NaOH]) into the UV/PS system. The results showed that PCE, TCE, and CF were degraded by over 90%, respectively, when a molar ratio of [base]0:[PS]0 was larger than 0.5:1, but CT was still not effectively degraded in the UV/PS system. To achieve effective CT degradation, UV/PS with the ethanol (EtOH) system was evaluated and it was found that it degraded CT over 90%. However, at this time, CF was not effectively degraded in the UV/PS/EtOH system. Finally, degradations of DNAPLs in the UV/PS/EtOH system with the additional injection of a base solution were conducted and it showed that multi-DNAPLs were degraded by over 90%, respectively, when the molar ratio of [PS]0:[EtOH]0:[base]0 was 1:1:3.
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Hidrocarburos Clorados/química , Contaminantes Químicos del Agua/química , Bicarbonatos , Cloruros , Etanol , Hidrocarburos Clorados/efectos de la radiación , Sulfatos , Rayos Ultravioleta , Contaminantes Químicos del Agua/efectos de la radiaciónRESUMEN
Purpose: Although surgical management of Hirschsprung disease (HD) is effective in most patients, some patients experience long-term postoperative complications, and require redo pull-through (PT). The present study evaluated clinical outcomes of redo PT in HD patients at a single center. Methods: Patients with HD who underwent redo PT procedures between 2003 and 2019 were retrospectively reviewed. Results: Thirteen patients were included. Five (38.5%) had undergone initial PT surgery at our center and 8 (61.5%) at other centers. Redo PT procedures were transanal endorectal PT in 12 patients (92.3%) and the posterior sagittal approach in 1 patient (7.7%). Indications for redo PT included pathologic misdiagnosis in 8 patients (61.5%); stricture in 2 (15.4%); and rectal stenosis, obstructing Duhamel pouch and remnant septum in 1 each (7.7%). At a median follow-up of 68 months (range, 3-227 months) after redo PT, 8 patients (61.5%) had normal bowel function, 2 (15.4%) had incontinence, and 1 (7.7%) had constipation. Conclusion: Redo PT procedures could be an effective approach for improving obstructive symptoms in HD patients with anatomic or pathologic reasons following primary PT. Careful selection of patients and discreet indications for redo PT are crucial.
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Cystic fibrosis (CF) is a fatal hereditary disorder that primarily affects Caucasians and is rare in Asian populations, including Koreans. Diagnosing CF is often challenging and delayed owing to its rarity and its overlapping features with non-CF diseases, ultimately affecting the patient prognosis. Radiologists can provide initial clues for clinically unsuspected cases and play a crucial role in establishing an early childhood diagnosis. This pictorial essay reviews the clinical and imaging features of genetically confirmed CF in Korean children and increases awareness of this rare disease, thereby facilitating early diagnosis.
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BACKGROUND: We investigated the prognostic significance of body mass index in small-cell lung cancer and explored whether skeletal muscle status affects the body mass index-survival relationship. METHODS: This retrospective study evaluated data from patients who underwent platinum-etoposide chemotherapy for small-cell lung cancer between March 2010 and December 2021. Skeletal muscle status was assessed using non-contrast computed tomography images of baseline positron-emission tomography-computed tomography, with the skeletal muscle index defined as the cross-sectional area of skeletal muscle divided by height squared, and the average attenuation values of skeletal muscle. Cox proportional hazards regression analysis was used to determine the correlations of body mass index, skeletal muscle metrics, and overall survival. RESULTS: We analysed the data of 1146 Asian patients (1006 men and 140 women, with a median age of 67 years [interquartile range: 61-72 years]), including 507 and 639 patients with limited and extensive disease, respectively. Being underweight, defined as a body mass index <18.5 kg/m2 , was associated with shorter overall survival, independent of clinical covariates in both the limited-disease (hazard ratio, 1.77; 95% confidence interval, 1.01-3.09) and extensive-disease (hazard ratio, 1.71; 95% confidence interval, 1.18-2.48) groups. The prognostic value of being underweight remained significant after additional adjustment for skeletal muscle index and attenuation in both limited-disease (hazard ratio, 1.96; 95% confidence interval, 1.09-3.51) and extensive-disease (hazard ratio, 1.75; 95% confidence interval, 1.17-2.61) groups. CONCLUSIONS: Being underweight is an independent poor prognostic factor for shorter overall survival in Asian patients with small-cell lung cancer, regardless of skeletal muscle status.
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Neoplasias Pulmonares , Sarcopenia , Carcinoma Pulmonar de Células Pequeñas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Neoplasias Pulmonares/patología , Índice de Masa Corporal , Sarcopenia/patología , Delgadez , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor Clock is crucial for a robust longevity and fecundity response to DR in Drosophila. To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets. In contrast to more chronic DR regimens, we did not detect significant changes in the rhythmic expression of core clock genes. Yet we discovered that DR induced de novo rhythmicity or increased expression of rhythmic clock output genes. Network analysis revealed that DR increased network connectivity in one module comprised of genes encoding proteasome subunits. Adult, fat body specific RNAi knockdown demonstrated that proteasome subunits contribute to DR-mediated lifespan extension. Thus, clock control of output links DR-mediated changes in rhythmic transcription to lifespan extension.
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PURPOSE: To evaluate the diagnostic performance and inter-observer variability of differentiating T1 and T2 gallbladder (GB) cancers using multi-detector row CT (MDCT). METHODS: This retrospective study included 151 patients with surgically confirmed T1 (n = 49)- or T2 (n = 102)-stage GB cancer who underwent contrast-enhanced MDCT from 2016 to 2020. Five radiologists (two experienced and three less experienced) evaluated the T-stage with a confidence level calculated using a six-point scale. GB cancers were morphologically classified into three types: polypoid, polypoid with wall thickening, and wall thickening. The diagnostic performance of T-staging was assessed using receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated based on a binary scale (T1 = positive). Inter-observer agreement was assessed using Fleiss κ statistics. RESULTS: The area under the receiver operating characteristic (ROC) curve of each reviewer for T-staging ranged from 0.69 to 0.80 (median 0.77). The overall accuracy of the five radiologists was 78% (95% confidence interval [CI] 71-84%). Sensitivity was higher and specificity was lower in experienced radiologists than in less experienced radiologists (P < 0.001). The overall inter-observer agreement was fair (κ = 0.36; 95% CI 0.31, 0.41). The overall accuracy for T-stage was 63% (95% CI 48-76), 78% (95% CI 63-88), and 87% (95% CI 77-93) for polypoid, polypoid with wall thickening, and wall thickening type, respectively. CONCLUSION: The accuracy of MDCT for differentiating T1 and T2 GB cancer is limited, and there is considerable inter-observer variability.
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Neoplasias de la Vesícula Biliar , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Humanos , Variaciones Dependientes del Observador , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Our purpose was to investigate the interfraction and intrafraction reproducibility and practical applicability of continuous positive airway pressure (CPAP) for left breast volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Interfraction reproducibility of the position of the heart was evaluated by measuring the heart-to-target distance on 20 planning computed tomography (CT) and 300 daily cone beam CT of 20 patients with left breast cancer treated with a 15-fraction VMAT. The dosimetric metrics of the whole heart and its substructures were compared between CPAP and free-breathing based VMAT plans. Intrafraction reproducibility was evaluated by measuring the motions of the breast target and diaphragm in 4-dimensional CT of 20 female patients with nonbreast cancer. Lastly, we analyzed the CPAP compliance data of 237 consecutive patients with left-sided breast cancer with and without internal mammary node irradiation (IMNI). RESULTS: The heart position was reproducible as evidenced by an absolute average heart-to-target distance error of 2.0 ± 2.0 mm. Compared with free-breathing, CPAP significantly reduced the mean heart dose and the dose to the left ventricle and left anterior descending artery. The average intrafraction position variation of the breast target was 0.5 ± 0.5, 2.5 ± 2.0, and 1.8 ± 1.4 mm in the mediolateral, craniocaudal, and anteroposterior directions, respectively. CPAP was successfully applied in 221 patients (93%), with a mean heart dose of 1.6 ± 0.7 Gy (IMNI: 2.0 Gy and no IMNI: 1.1 Gy). CONCLUSIONS: CPAP has adequate heart-sparing capability and sufficient reproducibility in VMAT for left-sided breast cancer treatment, with a high compliance rate. Thus, CPAP is applicable in routine practice for left-sided breast cancer radiation therapy.
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Neoplasias de la Mama , Radioterapia de Intensidad Modulada , Neoplasias de Mama Unilaterales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/etiología , Neoplasias de la Mama/radioterapia , Presión de las Vías Aéreas Positiva Contínua , Femenino , Tomografía Computarizada Cuatridimensional , Humanos , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Reproducibilidad de los Resultados , Neoplasias de Mama Unilaterales/diagnóstico por imagen , Neoplasias de Mama Unilaterales/radioterapiaRESUMEN
The left lateral section (LLS) can have an unusual variant left hepatic vein (LHV) anatomy. We present a case of customized funneling venoplasty of the graft LHV in a 22-month-old girl diagnosed with ornithine transcarbamylase deficiency undergoing deceased donor liver transplantation (LT) using a split LLS graft. The split LLS graft weighed 350 g, yielding a graft-to-recipient weight ratio of 3.2%. Notably, the graft LHV opening was located at the graft liver cut surface, which was only 1 cm in size and 2 cm away from the cephalad apex of the LLS graft. Since such a variant location of the small LHV opening was unsuitable for direct anastomosis, we performed a funneling venoplasty using an inferior vena cava fragment homograft obtained from the same donor. The graft implantation was performed according to standard procedures of infant split LT. Follow-up imaging studies showed no vascular complications. The patient recovered uneventfully from the LT operation. She had normal blood test findings, including normal ammonia level. She has been doing well for 6 months after the transplantation. In conclusion, our surgical technique using a funneling venoplasty enabled successful reconstruction of the anomalous graft LHV. Our results suggest that individualized reconstruction techniques should be applied to infant patients undergoing LT using a LLS graft with variant types of graft LHV anatomy.
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Graft size matching is essential for successful liver transplantation in infant recipients. We present our technique of graft dextroplantation used in an infant who underwent living donor liver transplantation (LDLT) using a reduced left lateral section (LLS) graft. The patient was an 11-month-old female infant weighing 7.8 kg with hepatoblastoma. She was partially responsive to systemic chemotherapy. Thus, LDLT was performed to treat the tumor. The living donor was a 34-year-old mother of the patient. After non-anatomical size reduction, the weight of the reduced LLS graft was 235 g, with a graft-to-recipient weight ratio of 3.0%. Recipient hepatectomy was performed according to the standard procedures of pediatric LDLT. At the beginning of graft implantation, the graft was temporarily placed at the abdomen to determine the implantation location. The graft portal vein was anastomosed with an interposed external iliac vein homograft. As the liver graft was not too large and it was partially accommodated in the right subphrenic fossa, thus the abdominal wall wound was primarily closed. The patient recovered uneventfully. An imaging study revealed deep accommodation of the graft within the right subphrenic fossa. The patient has been doing well for six months without any vascular complications. This case suggests that dextroplantation of a reduced LLS graft can be a useful technical option for LDLT in infant patients.
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OBJECTIVE: Recently, sirolimus has emerged as a safe and effective treatment modality for unresectable vascular lesions. In the present study, we investigated the effectiveness and safety of sirolimus from our early experience with patients with unresectable vascular anomalies. METHODS: The medical records and radiologic images of all patients with unresectable vascular anomalies treated with sirolimus at our center from January 2018 to November 2019 were retrospectively reviewed. All patients were administered oral doses of sirolimus 0.8 mg/m2 every 12 hours as the initial dose, followed by maintenance of a target serum concentration (5-10 ng/mL) with therapeutic drug monitoring. RESULTS: Six patients with unresectable vascular anomalies were treated with sirolimus for ≥10 months. Their median age at the initiation of sirolimus treatment was 17 months (range, 8-67 months). The median duration of treatment was 13 months (range, 10-16 months). One patient had a good response, four had an intermediate response, and one had no response to sirolimus therapy. None of the patients had discontinued sirolimus therapy because of adverse effects. CONCLUSIONS: Sirolimus can be used effectively and safely for patients with unresectable vascular anomalies. However, further prospective studies are warranted to evaluate the long-term effects of sirolimus and clarify the indications for early intervention.
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Antibióticos Antineoplásicos/uso terapéutico , Hemangioma/tratamiento farmacológico , Sirolimus/uso terapéutico , Malformaciones Vasculares/tratamiento farmacológico , Antibióticos Antineoplásicos/efectos adversos , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Sirolimus/efectos adversos , Resultado del TratamientoRESUMEN
Background: Currently, indocyanine green (ICG) fluorescence imaging enables radical surgical resection in hepatoblastoma (HB) and has beneficial uses; however, its usage in pediatric patients is still limited. Methods: From 2015 to 2019, 17 hepatoblastoma patients underwent 22 fluorescence-guided surgery using ICG. ICG (0.3 mg/kg) was intravenously injected 24-48 h before the operation. With ICG/NIR camera, intraoperative identification of biological structures and demarcation of mass were conducted. Results: ICG fluorescence-guided surgery was performed for hepatoblastoma in 22 cases: 16, 1, and 2 cases underwent anatomic resection, partial hepatectomy, and liver transplantation, respectively. Six patients accompanied lung metastasis at the time of surgery, and two patients underwent lung surgery using ICG. The median interval from ICG injection to surgery was 38.3 h (range, 20.5-50.3 h). The median tumor size was 36.5 mm (range, 2-132 mm). According to the pathologic finding, the median safety margin was secured for 6 mm (range, 0-11 mm) and there was no residual finding at the liver at the follow-up computed tomography (CT). Conclusions: ICG fluorescence imaging in children with HB was feasible and safe for tumor demarcation and enhancing the accuracy of radical tumor resection.
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PURPOSE: Autologous adipose tissue-derived stem cells (ASCs) have been proposed for patients with refractory Crohn disease, but research is lacking in pediatric patients. This Phase IV study evaluated the efficacy and safety of ASCs in children with refractory Crohn's fistulae. METHODS: Patients with a refractory Crohn's fistula who did not have conventional therapy for more than 3 months or with a recurrent complex Crohn's fistula were included. All patients were at least 14 years old. Patients with infection, poor condition, or active Crohn disease with a disease activity index of 450 and above were excluded. Five patients were treated with ASCs from 2014 to 2015 in Asan Medical Center. ASC administration was adjusted according to fistula size (1 mL per cm2). We evaluated the efficacy and safety 8 weeks after injection and followed patients for 6 months. RESULTS: Fistulae were healed in 4 patients by 8 weeks after ASC injection. Of these 4 patients, 1 had complete fistula closure and sustainability after 6 months. The other 3 with healing effects had less than 50% fistula closure by 6 months. None of these 4 patients have persistent fistulae. One patient had no healing effect, and seton ligation was performed 8 months after ASC injection. There were no adverse effects related to ASC administration. CONCLUSION: ASC therapy is a simple and well-tolerated therapeutic option for children with refractory Crohn's complex fistulae. Complete closure was well-sustained. However, more data from a larger number of patients are needed.
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We present a case of third retransplantation using a whole liver graft in a 13-year-old girl who suffered graft failure and hepatopulmonary syndrome following split liver retransplantation with endovascular stenting of the hepatic and portal veins as an infant. She was diagnosed with biliary atresia-polysplenia syndrome, and thus underwent living donor liver transplantation from her mother at 9 months of age. The first liver graft failed due to stenosis of the portal vein. She underwent the second liver transplantation with a split left lateral section graft. Endovascular stenting was performed to the portal vein stenosis 2 months and hepatic vein stenosis 9 months after transplantation. During the next 9 years, 11 sessions of balloon angioplasty for hepatic vein stent stenosis were performed. Ten years after the second transplantation, she underwent third transplantation using a whole liver graft recovered from a 12-year-old-girl. The double inferior vena cava technique was used for outflow vein reconstruction. The graft portal vein was anastomosed with the stent-containing portal vein stump because it was not possible to remove the stent and the inner diameter of the portal vein stent was large enough. An aorto-hepatic jump graft was used for arterial reconstruction. The patient recovered slowly and is doing well for 6 months posttransplant. In conclusion, because stenting of the hepatic vein or portal vein can induce graft failure leading to late retransplantation, we emphasize secure vascular reconstruction to prevent endovascular stenting during LT in infants.
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The present study deals with structural transformations induced by high-energy ball-milling of an amorphous Fe90Zr10 alloy prepared by melt-spinning. The amorphous melt-spun ribbons were found to undergo crystallization into BCC alpha-Fe(Zr) nanocrystallites under high-energy ball milling. The decomposition degree of the amorphous phase increased with increasing milling time and intensity. Our results suggest that the observed crystallization is a deformation-induced process rather than a thermally induced one.